cyclic-gmp and Coronary-Disease

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adrenergic alpha-Antagonists; Arteriosclerosis; Blood Pressure; Carbolines; Contraindications; Coronary Disease; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Interactions; Endothelium, Vascular; Erectile Dysfunction; Heart Rate; Humans; Hypotension; Imidazoles; Isosorbide Dinitrate; Male; Molecular Structure; Myocardial Infarction; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilation; Vasodilator Agents

Topics: Angina Pectoris; Coronary Circulation; Coronary Disease; Cyclic GMP; Cytochrome P-450 Enzyme System; Humans; Muscle, Smooth, Vascular; Nitrates; Nitric Oxide

Topics: Adenosine; Animals; Aprotinin; Coronary Disease; Cyclic AMP; Cyclic GMP; Heart Arrest, Induced; Lysosomes; Myocardium; Protease Inhibitors; Tissue Survival

Nitrate tolerance is defined as an attenuation or even loss of hemodynamic and anti-ischemic effects during continuous nitrate medication. The blunted response may be due to the development of pseudotolerance and true pharmacologic tolerance. Pseudotolerance is the result of volume and salt retention, as well as the stimulation of counter-regulatory mechanisms which may alter the baseline hemodynamics of a patient during nitrate therapy. Far less important are changes in nitrate pharmacokinetics. True pharmacological tolerance may also be of practical importance. Diminished uptake of nitrates into the vascular smooth muscle cell, a decrease in intracellular SH groups, inhibition of the guanylate-cyclase, and stimulation of a specific phosphodiesterase may result in a decrease of cyclic GMP formation and hence to a decrease in nitrate induced vasodilatation. Tolerance development may be prevented by intermittent nitrate administration providing intervals with low plasma and tissue nitrate levels. In consequence, nitrates should be used predominantly for treatment of ischemic episodes, but 24-hour anti-ischemic action for the prevention of ischemia can be better achieved by treatment with a beta-blocker and/or a calcium antagonist. Nitrates should be added in times of maximum susceptibility to ischemia, while allowing nitrate levels to fall at other times.

Topics: Coronary Disease; Cyclic GMP; Drug Tolerance; Enzyme Activation; Guanylate Cyclase; Hemodynamics; Humans; Nitrates; Water-Electrolyte Balance

Topics: Adenylyl Cyclases; Animals; Arrhythmias, Cardiac; Calcium; Calcium-Transporting ATPases; Cholinergic Fibers; Coronary Disease; Cyclic AMP; Cyclic GMP; Heart Rate; Hormones; Humans; Myocardial Contraction; Myocardium; Myosins; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Phosphorylation; Phosphotransferases; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta

To examine whether the prophylactic antianginal agent perhexiline potentiates platelet responsiveness to nitric oxide (NO) in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS: unstable angina pectoris or non-Q-wave myocardial infarction).. Blood samples were obtained from patients before and after initiation of treatment with perhexiline. ADP-induced platelet aggregation and its inhibition by the NO donor sodium nitroprusside (SNP) were determined via impedance aggregometry in whole blood (WB) and platelet-rich plasma (PRP). Intraplatelet cGMP content was assayed by RIA, and superoxide (O(2)(-)) level by lucigenin-derived chemiluminescence. In patients with ACS not receiving perhexiline (n=12), platelet responsiveness to SNP did not vary significantly over the first 3 days post admission to hospital. Therapy with perhexiline for 3 days was associated with increases in SNP-induced inhibition of aggregation from 29+/-2% to 43+/-4% (n=50,P <0.001) in WB and from 20+/-5% to 42+/-7% (n=12, P<0.01) in PRP. Resolution of symptomatic ischaemia (n=39) was associated with significantly greater (P<0.01) increases than non-resolution (n=11). Similar increases in SNP responsiveness (P<0.001) occurred following institution of perhexiline therapy in patients with SAP (n=30), associated with a 85% decrease in anginal frequency. Treatment with perhexiline potentiated the cGMP-elevating effects of SNP in platelets (n=9,P =0.03). Although perhexiline did not alter whole blood O(2)(-) concentration ex vivo, it inhibited (P<0.01) O(2)(-) release from neutrophils in vitro.. Perhexiline potentiates platelet responsiveness to NO both in SAP and ACS patients; in the latter group this improvement was predictive of resolution of ischaemic symptoms. The predominant mechanism of perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for NO clearance by neutrophil-derived O(2)(-).

Topics: Aged; Angina Pectoris; Blood Platelets; Cardiovascular Agents; Coronary Disease; Cyclic GMP; Female; Humans; Male; Neutrophils; Nitric Oxide; Nitric Oxide Donors; Nitroprusside; Perhexiline; Platelet Aggregation; Superoxides

In experimental animal models, long-term in vivo treatment with nitroglycerin (NTG) induces both endothelial dysfunction and tolerance to nitrates. However, it is still controversial whether nitrate tolerance in humans is associated with both endothelial dysfunction and impaired vascular response to nitrovasodilator-derived NO.. Patients undergoing elective bypass surgery were randomized to receive 48 hours of continuous NTG infusion (NTG group) or no nitrate therapy (control group). Segments of surgically removed arteria mammaria, vena saphena, and arteria radialis not required for the bypass procedure were used to examine (1) the vascular responsiveness to NTG and the endothelium-dependent vasodilator acetylcholine; (2) the expression of the NO target, the soluble guanylyl cyclase; (3) the expression of the soluble guanylyl cyclase/cGMP effector target, the cGMP-dependent protein kinase (cGK); and (4) the cGK activity as assessed by the phosphorylation state of its vascular substrate, the vasodilator-stimulated phosphoprotein at serine(239) (P-VASP). NTG treatment caused a marked degree of nitrate tolerance in all 3 vessel types studied and a significant cross-tolerance to the endothelium-dependent vasodilator acetylcholine in A. mammaria and A. radialis. Although soluble guanylyl cyclase, cGK-I, and VASP expression levels were not modified by NTG treatment, a marked decrease of P-VASP, a surrogate parameter for in-vivo cGK-I activity, was observed.. We conclude that long-term NTG treatment induces endothelial dysfunction and impaired vascular NO/cGMP signaling in humans, which can be monitored by measuring P-VASP levels.

Topics: Aged; Blood Vessels; Cell Adhesion Molecules; Coronary Artery Bypass; Coronary Disease; Cyclic GMP; Cyclic GMP-Dependent Protein Kinase Type I; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Drug Tolerance; Endothelium, Vascular; Female; Guanylate Cyclase; Humans; Immunohistochemistry; In Vitro Techniques; Male; Mammary Arteries; Microfilament Proteins; Middle Aged; Nitric Oxide; Nitroglycerin; Phosphoproteins; Phosphorylation; Radial Artery; Receptors, Cytoplasmic and Nuclear; Saphenous Vein; Signal Transduction; Soluble Guanylyl Cyclase; Vasodilation; Vasodilator Agents

The possibility that systemic formation of cyclic guanosine monophosphate (cGMP) could reflect the level of cardiovascular fitness was investigated. The relations between physical activity and systemic formation of cGMP were evaluated in healthy volunteers and in patients with coronary artery disease (CAD). No significant differences were observed in the basal urinary excretion of cGMP in highly trained runners, sedentary subjects, and in patients with CAD, despite the large differences in aerobic exercise training between groups. In addition, the basal levels of cGMP in CAD patients failed to increase after a 12-week cardiac rehabilitation program. Short-term exercise, on the other hand, was associated with significant increases in urinary cGMP excretion. A 42-km marathon increased urinary cGMP excretion by 272%. The 15-km race increased urinary cGMP excretion by 330%. In CAD patients, 30 min of supervised exercise on a treadmill, at 80% of patient's maximal heart rate, induced a 60% increase in urinary cGMP, which returned to preexercise levels 90 min after termination of the exercise. Completion of the 12-week cardiac rehabilitation program improved exercise capacity and the magnitude of increase in cGMP levels induced by short-term treadmill exercise. Our findings suggest that cGMP increases during and shortly after short-term exercise and that the magnitude of the increase seems dependent on the intensity of the exercise and on physical fitness. Exercise training in healthy subjects and in CAD patients enhanced the amount of cGMP produced during short-term exercise, which might be responsible for some of the protective cardiovascular actions of exercise. The short half-life of cGMP may explain why the basal resting levels of cGMP are not appropriate predictors of a subject's physical fitness.

Topics: Adult; Coronary Disease; Cyclic GMP; Exercise; Humans; Male; Middle Aged; Rehabilitation; Running; Time Factors

The endothelial EDRF/NO-mediated relaxing mechanism is impaired in atherosclerotic and in hypertensive arteries. Recently, it was suggested that primary pulmonary hypertension might be another disease in which the endothelial EDRF/NO pathway is disturbed. We tested the hypothesis that intravenous administration of L-arginine (L-ARG), the physiological precursor of EDRF/NO, stimulates the production of NO, subsequently increasing plasma cGMP levels and reducing systemic and/or pulmonary blood pressure, in patients with coronary artery disease (CAD, n = 16) or with primary pulmonary hypertension (PPH, n = 5). L-ARG (30 g, 150 ml, 15 min) or placebo (150 ml NaCl) was infused in CAD patients, and L-ARG was infused in PPH patients during cardiac catheterization. Mean aortic (Pao) and pulmonary (PAPmean) arterial pressures were continuously monitored. Cardiac output (CO, by thermodilution), total peripheral resistance (TPR), and pulmonary vascular resistance (PVR) were measured before and during the infusions. In CAD patients Pao decreased from 87.2 +/- 4.9 to 81.8 +/- 5.1 mmHg during L-ARG (p < 0.05), whereas PAPmean and PVR were unchanged. TPR decreased from 1008.9 +/- 87.9 to 845.0 +/- 81.7 dyne x sec x cm-5 during L-ARG administration (p < 0.01). CO significantly increased during L-ARG (from 7.3 +/- 2.8 to 8.1 +/- 0.9 l/min, p < 0.05). Placebo did not significantly influence any of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased by 12.2 +/- 9.6% during L-ARG, but slightly decreased during placebo (-12.3 +/- 9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no significant change in Pao, TPR, and CO, PAPmean was 59.4 +/- 8.5 mmHg at the beginning of the study and was not significantly reduced by L-ARG nor was PVR (basal: 1042.4 +/- 211.4 dyne x sec x cm-5) changed by L-ARG. Plasma cGMP was not significantly affected by L-ARG in these patients. We conclude that L-ARG stimulates NO production and induces vasorelaxation in CAD patients but not in patients with primary pulmonary hypertension.

Topics: Adult; Arginine; Blood Pressure; Coronary Disease; Cyclic GMP; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Pilot Projects; Signal Transduction; Vascular Resistance

The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Cyclic GMP; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Ventricular Dysfunction, Left

Nitric oxide (NO) and atrial natriuretic peptide (ANP) relax vascular smooth muscle increasing levels of cyclic guanosine 3':5' monophosphate (cGMP). Nitrovasodilators act as exogenous nitric oxide donors. The aim of this study was to ascertain the response of cGMP to exercise without medication and after the administration of 20 mg of isosorbide-5-mononitrate (IS-5-MN) in coronary patients (n = 8) and healthy control subjects (n = 9). A third group of 10 normal volunteers was studied to test plasma cGMP response to second exercise test without IS-5-MN administration. Plasma cGMP increased significantly in both patients (P < 0.02) and controls (P < 0.01) after the first ergometry. After IS-5-MN administration, plasma cGMP did not increase either before or after exercise. In normal volunteers without IS-5-MN plasma cGMP increased significantly after first (P < 0.004) and second (P < 0.0008) exercise test. In conclusion, plasma cGMP increases during exercise. Administration of IS-5-MN does not raise plasma cGMP and neither does performance of further exercise after its administration.

Topics: Angina Pectoris; Coronary Disease; Cyclic GMP; Exercise; Exercise Test; Female; Humans; Isosorbide Dinitrate; Male; Middle Aged; Vasodilator Agents

Ibopamine is a novel oral dopamine analogue with positive inotropy and diuretic effects. In a double-blind, randomized study, the drug was investigated in 10 patients (mean age 49 +/- 10 years, six male, four female) with mild heart failure (NYHA classes II: six patients, III: four patients). Effects of single oral doses of 200 mg ibopamine, of 40 mg furosemide, and of 200 mg ibopamine plus 40 mg furosemide were compared in each patient at 3-day-intervals. One h after application, systolic and diastolic blood pressure increased from 119 +/- 11 to 124 +/- 8, and from 75 +/- 4 to 80 +/- 6 mm Hg (p less than 0.01) in the ibopamine group, while changes in both other groups and changes of the heart rate were insignificant. During 2 h after drug ingestion urinary flow was raised from 124 +/- 81 to 227 +/- 166 ml/2 h in the ibopamine group (p less than 0.05), while the application of furosemide (with or without ibopamine) resulted in several fold increases of urinary flow. After ibopamine, the 2-h-creatinine-clearance rose from 123 +/- 73 to 130 +/- 85 ml/min (not significant). Sodium excretion remained unchanged by ibopamine, potassium excretion was increased from 2.9 +/- 1.7 to 4.0 +/- 3.3 mmol/h (p less than 0.05), while effects of furosemide were several fold of those of ibopamine. Atrial natriuretic factor concentrations in plasma increased significantly after ibopamine and after ibopamine plus furosemide (p less than 0.01), but remained constant after furosemide alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Coronary Disease; Cyclic GMP; Deoxyepinephrine; Diuretics; Dopamine; Electrolytes; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuresis; Urodynamics

Background Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular disease (ASCVD). We hypothesized that plasma cGMP levels would be associated with lower risk for incident HFpEF, any HF, ASCVD, and coronary heart disease (CHD). Methods and Results We conducted a case-cohort analysis nested in the ARIC (Atherosclerosis Risk in Communities) study. Plasma cGMP was measured in 875 participants at visit 4 (1996-1998), with oversampling of incident HFpEF cases. We used Cox proportional hazard models to assess associations of cGMP with incident HFpEF, HF, ASCVD (CHD+stroke), and CHD. The mean (SD) age was 62.4 (5.6) years and median (interquartile interval) cGMP was 3.4 pmol/mL (2.4-4.6). During a median follow-up of 9.9 years, there were 283 incident cases of HFpEF, 329 any HF, 151 ASCVD, and 125 CHD. In models adjusted for CVD risk factors, the hazard ratios (95% CI) associated with the highest cGMP tertile compared with lowest for HFpEF, HF, ASCVD, and CHD were 1.88 (1.17-3.02), 2.18 (1.18-4.06), 2.84 (1.44-5.60), and 2.43 (1.19-5.00), respectively. In models further adjusted for N-terminal-proB-type natriuretic peptide, associations were attenuated for HFpEF and HF but remained statistically significant for ASCVD (2.56 [1.26-5.20]) and CHD (2.25 [1.07-4.71]). Conclusions Contrary to our hypothesis, higher cGMP levels were associated with incident CVD in a community-based cohort. The associations of cGMP with HF or HFpEF may be explained by N-terminal-proB-type natriuretic peptide, but not for ASCVD and CHD.

Topics: Aged; Atherosclerosis; Biomarkers; Case-Control Studies; Coronary Disease; Cyclic GMP; Female; Heart Disease Risk Factors; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; United States

Platelet and endothelial production of bioactive nitric oxide (NO) is known to be impaired in acute coronary syndromes, thus compounds that release NO are useful candidates to restore NO-vascular functions.. We have studied whether donation of NO with a novel platelet-selective S-nitrosothiol compound (LA810) at a systemic level can inhibit thrombosis elicited by damaged vessel wall (eroded and disrupted vessel wall) at hemodynamic conditions typical of patent and stenotic coronary arteries.. Thrombogenicity was measured in the porcine experimental model and assessed as platelet-thrombus formation in the ex vivo Badimon perfusion chamber. After baseline perfusions, female pigs (Large WhitexLandrace) were given intravenous infusion of LA810 or GSNO standard S-nitrosothiol during 2 h. Changes in blood pressure, heart rate and in vitro platelet aggregation were measured.. LA810 significantly decreased thrombus formation at any degree of vascular damage and shear rate (p<0.001) without hypotensive side-effects or heart rate variations. In contrast, inhibition of thrombus formation by GSNO required high doses associated to hypotensive episodes. Platelet aggregation induced by collagen was inhibited after nitrosothiol infusion in whole blood (LA810) and platelet rich plasma (LA810 and GSNO). In addition, there was a drug-dependent rise in platelet guanosine 3',5'-cyclic monophosphate (cGMP) levels.. This new anti-ischemic NO-donor (NOd) LA810 that inhibits platelet function without hypotensive side-effects seems a highly efficacious strategy to reduce acute thrombosis triggered by coronary artery disease.

Topics: Animals; Blood Platelets; Coronary Disease; Coronary Thrombosis; Coronary Vessels; Cyclic GMP; Female; Glycine; Models, Animal; Nitric Oxide Donors; Nitroso Compounds; Platelet Aggregation Inhibitors; S-Nitrosothiols; Stress, Mechanical; Sulfhydryl Compounds; Swine

Endothelial dysfunction of the pulmonary arterial tree occurring after cardiopulmonary bypass (CPB) contributes to pulmonary hypertension and respiratory failure in the postoperative period. The goal of the present study was to characterize the alterations of endothelial cell signal transduction pathways in pulmonary arteries following CPB, the effect of ventilation and nitric oxide (NO) inhalation on endothelium-dependent relaxations and the alterations in hemodynamics and oxygenation.. Six groups of Landrace swine were compared: control, sham without CPB, CPB 150min+no reperfusion, CPB 150min+reperfusion 60 min, CPB 150min+ventilation (tidal volume 12 ml/kg)+reperfusion 60 min, and CPB 150min+NO inhalation (with ventilation, NO 40 ppm)+60 min of reperfusion. No cross-clamping was applied, the heart was left beating, empty. Pulmonary artery reactivity was evaluated in organ chambers to assess the endothelium-dependent relaxations.. CPB alone did not alter endothelial function. CPB and pulmonary reperfusion induced a statistically significant decrease in endothelium-dependent relaxations to acetylcholine. Mechanical ventilation during CPB prevented the reduction of relaxations to acetylcholine. Ventilation and NO inhalation during CPB did not differ from ventilation alone in terms of endothelium-dependent relaxations. There were no differences between groups for relaxations to bradykinin. There was a significant increase in arterial oxygen tension in the ventilated group compared to the non-ventilated group.. Pulmonary reperfusion after CPB causes a selective dysfunction of Gi-protein-mediated relaxations. Mechanical ventilation prevents the pulmonary endothelial dysfunction due to reperfusion after CPB. Ventilation also improves oxygenation after CPB. Mechanical ventilation could be used as a preventive approach for patients undergoing cardiac surgery with extracorporeal circulation.

Topics: Administration, Inhalation; Animals; Cardiopulmonary Bypass; Coronary Disease; Cyclic GMP; Endothelium, Vascular; Female; Male; Models, Animal; Nitric Oxide; Oxygen; Perfusion; Pulmonary Artery; Respiration, Artificial; Swine; Vascular Resistance

Vascular reactivity to nitric oxide (NO) is mediated by NO-sensitive soluble guanylyl cyclase (sGC). Since a diminished activity of vascular sGC has been reported in an animal model of type 2 diabetes, the sGC activity was assayed in vitro in internal mammary artery specimens obtained during bypass surgery from patients with and without type 2 diabetes. The sensitivity of sGC to NO, which is dependent on Fe(2+)-containing heme, was measured in vitro using stimulation with diethylamine NONOate (DEA/NO). In addition, the novel cyclic guanosine monophosphate-elevating compound HMR-1766 was used to test the stimulation of the oxidized heme-Fe(3+)-containing form of sGC. Basal activity of sGC and its sensitivity to stimulation by DEA/NO and HMR-1766 were not different between control and type 2 diabetic patients: maximum stimulation by DEA/NO amounted to 475 +/- 67 and 418 +/- 59 pmol. mg(-1). min(-1) in control and type 2 diabetic patients, respectively. The maximum effects of HMR-1766 were 95 +/- 18 (control subjects) and 83 +/- 11 pmol. mg(-1). min(-1) (type 2 diabetic patients). Hypertension, hyperlipidemia, drug treatment with statins, ACE inhibitors, or nitrates had no effect on sGC activity. In conclusion, the present findings do not support the hypothesis that desensitization of sGC contributes to the pathogenesis of diabetic vascular dysfunction in humans.

Topics: Aged; Coronary Disease; Cyclic GMP; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Guanylate Cyclase; Humans; Hydrazines; Male; Mammary Arteries; Middle Aged; Nitric Oxide; Nitric Oxide Donors; Nitrogen Oxides; Ventricular Dysfunction, Left

To investigate the dynamics of plasma cAMP/cGMP in patients during cardiac surgery, and its relationship to traumatic stress.. Sixteen patients, aged 19.31 years+/-10.4 years, who underwent an open heart operation with cardiopulmonary bypass (CPB) and hypothermia were served as subjects. The arterial plasma concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured by radioimmunoassay 2 hours before operation, after heparinization, 20 minutes following CPB, at the end of the operation, and 24 and 72 hours postoperatively, respectively. The patients' preoperative blood samples were heparinized and the venous blood samples of 30 healthy blood donors were taken to measure the levels of cAMP and cGMP as heparin and normal controls separately.. There were no statistical difference among the heparin control, preoperative level and normal control. The peak values of cAMP and cGMP occurred during CPB and plasma cAMP levels changed synchronously with intensities of operative stimulus to human body. However cGMP level was mainly related to the operative stimulus to the heart and CPB. The cAMP value was positively correlated with the cGMP value (r=0.6313, P<0.001).. Dynamic variation of plasma cyclic ribonucleotide can be considered as a reference parameter for intensity of traumatic stress.

Topics: Adolescent; Adult; Biomarkers; Cardiopulmonary Bypass; Coronary Disease; Cyclic AMP; Cyclic GMP; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Postoperative Period; Preoperative Care; Radioimmunoassay; Reference Values; Sensitivity and Specificity; Stress, Psychological

We sought to determine whether coronary vascular nitric oxide (NO) release in vivo modulates platelet activation.. Nitric oxide modulates vasodilator tone and platelet activity via the cyclic guanosine monophosphate (cGMP) pathway, but whether coronary endothelial dysfunction influences platelet activation in humans is unknown.. In 26 patients, we measured coronary blood flow, epicardial diameter and coronary sinus platelet cGMP content during intracoronary infusions of acetylcholine (ACH), L-NG monomethyl arginine (L-NMMA) and sodium nitroprusside.. Acetylcholine increased platelet cGMP content (p = 0.013), but its magnitude was lower in patients with endothelial dysfunction; thus, patients with epicardial constriction with ACH had a 7 +/- 6%, p = ns change compared with a 32 +/- 13%, p = 0.05 increase in platelet cGMP in those with epicardial dilation. Similarly, patients with atherosclerosis or its risk factors had a smaller increase (9 +/- 6%) compared with those having normal coronary arteries without risk factors (51 +/- 22%, p = 0.019). L-NG monomethyl arginine decreased platelet cGMP content to a greater extent in patients with epicardial dilation with ACH (- 15 +/- 7%, p = 0.06) compared to those with constriction (+5 +/- 6% change, p = 0.5). Sodium nitroprusside produced a similar increase in platelet cGMP content in patients with and without endothelial dysfunction (p = 0.56). The effects of sodium nitroprusside, but not ACH or L-NMMA, were reproduced in vitro.. Platelet cGMP levels can be modulated by basal and stimulated release of NO. The platelet inhibitory effect of NO is reduced in patients with endothelial dysfunction, which may explain their increased risk from thrombotic events and the improved survival associated with strategies designed to improve vascular function.

Topics: Acetylcholine; Adult; Aged; Coronary Circulation; Coronary Disease; Coronary Thrombosis; Cyclic GMP; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Nitric Oxide; Nitroprusside; omega-N-Methylarginine; Platelet Activation

Recently, it was proposed that soluble intercellular adhesion molecule (sICAM)-1 plasma levels may allow subgroup identification of patients at risk for cardiovascular complications during sepsis. However, the impact of preexisting coronary artery disease (CAD) on these results has not yet been tested. The aim of this study was to investigate whether plasma levels of adhesion molecules, nitric oxide, and cytokines differ between septic patients with or without preexisting CAD.. Prospective study.. Surgical ICU.. Forty-four septic patients, 24 of whom met the criteria of CAD.. Hemodynamic measurements were performed and blood samples were taken within 12 h after onset of sepsis (early sepsis) and again 72 h thereafter (late sepsis). Soluble adhesion molecules and cytokines were determined using commercially available enzyme-linked immunosorbent assay kits, cyclic guanosinomonophosphate (cGMP) by competitive radioimmunoassay, and nitrite/nitrate photometrically by Griess reaction.. In CAD patients, sICAM-1 (p < 0.02) was significantly elevated in early and late sepsis, whereas soluble endothelial-linked adhesion molecule (sE-selectin; p < 0.01) and cGMP (p < 0.03) were only increased in late sepsis. Oxygen consumption did not significantly differ between groups. Oxygen delivery and mixed venous oxygen saturation during early and late sepsis were significantly diminished and the oxygen extraction ratio significantly increased in the CAD group (p < 0.05).. Increased endothelial injury may be indicated by the elevated levels of sICAM-1, sE-selectin, and cGMP in septic patients with preexisting CAD. These parameters, however, failed to serve as predictors for unknown CAD or chances for survival in early sepsis.

Topics: Case-Control Studies; Cell Adhesion Molecules; Coronary Disease; Cyclic GMP; Cytokines; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Nitric Oxide; Oxygen Consumption; Prospective Studies; Radioimmunoassay; Sepsis; Time Factors

Carperitide, a recombinant form of alpha-hANP, possesses potent diuretic, natriuretic, and vasodilatory activity, and inhibits the renin-aldosterone system and sympathetic nervous activity. However, its beneficial effects on ischemic myocardium have not been studied fully. We examined carperitide's effects on infarct size, hemodynamics, and arrhythmia frequency in anesthetized dogs (n = 20) subjected to a 90-min coronary artery occlusion/6-h reperfusion protocol. Intravenous infusion of carperitide (0.2 microg/kg/min) commenced 15 min after occlusion and continued during occlusion/reperfusion. Ventricular fibrillation developed in two of 10 control versus three of 10 treated dogs (p = NS). Hemodynamics, collateral blood flow to the ischemic wall measured 10 min after occlusion, and extent of area at risk were comparable for the two groups. Infarct size/area at risk was smaller in treated than in control dogs (4.5 +/- 2.1% vs. 27.8 +/- 7.8%, respectively; p < 0.05). During occlusion, carperitide tended to increase collateral blood flow (+39%) and significantly decreased left ventricular systolic pressure (-13%) and end-diastolic pressure (-40%) compared with baseline. In control dogs, collateral blood flow tended to decrease (-8.3%), whereas most hemodynamic parameters did not change significantly with respect to baseline. The number of arrhythmias recorded during occlusion/reperfusion was similar in the two groups. Intravenous administration of carperitide limited infarct size, but did not reduce incidence of ventricular arrhythmias after 90-min coronary occlusion/6-h reperfusion in anesthetized dogs. Although the beneficial effects of carperitide may be attributable to concomitant changes in hemodynamics and collateral blood flow, the precise mechanisms require further investigation.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Collateral Circulation; Coronary Disease; Cyclic GMP; Dogs; Female; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments

Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66%, significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.

Topics: Coronary Disease; Cyclic GMP; Endothelins; Exercise Test; Female; Humans; Postmenopause

Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge.. Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay.. Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05).. From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.

Topics: Abdominal Muscles; Arteries; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Culture Techniques; Cyclic GMP; Epoprostenol; Humans; Internal Mammary-Coronary Artery Anastomosis; Iodine Radioisotopes; Mammary Arteries; Nitric Oxide; Omentum; Platelet Aggregation Inhibitors; Radiopharmaceuticals; Saphenous Vein; Vascular Patency; Vasodilator Agents

To investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on nitrate tolerance during continuous nitrate therapy, coronary artery diameters and platelet cyclic guanosine monophosphate (cGMP) levels were measured before and 2 minutes after intracoronary injection of nitroglycerin 200 microg in 60 patients with coronary artery disease and were compared among 20 patients treated with nitrates (nitrate group), 20 patients treated with both nitrates and enalapril (enalapril group), and 20 untreated patients (control group). The percent increase in platelet cGMP and coronary dilatation in the nitrate group was significantly less than in the control group, but the percent increase in the enalapril group was significantly greater than that in the nitrate group. These results indicate that enalapril may be helpful as concomitant therapy to maintain the effect of nitrates during continuous nitrate therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Platelets; Case-Control Studies; Coronary Angiography; Coronary Disease; Coronary Vessels; Cyclic GMP; Drug Administration Schedule; Enalapril; Female; Humans; Hypertension; Isosorbide Dinitrate; Male; Middle Aged; Nitroglycerin; Norepinephrine; Renin; Vasodilator Agents

We investigated intracoronary cyclic-guanosine monophosphate (c-GMP) levels during percutaneous transluminal coronary angioplasty (PTCA) since experimental studies have shown the endothelial origin of c-GMP production. Intracoronary c-GMP and cyclic adenosine monophosphate (c-AMP) were measured during coronary angioplasty in 24 patients with chronic coronary artery disease. Four coronary blood samples were taken through a catheter from the coronary artery the first sample before coronary angiography and the other three from distal to coronary obstruction, as follows: before the balloon inflation, at the maximum inflation and 5 min after restoration of coronary flow. c-GMP increased from 7.9 +/- 1.0 pmol/ml and 7.5 +/- 0.9 pmol/ml before angiography and balloon inflation to 11.1 +/- 1.3 pmol/ml at the maximum inflation (P < 0.01), with a trend to decrease 5 min after the end of the intervention (9.5 +/- 1.0 pmol/ml, P: NS). Intracoronary c-AMP levels remained almost unchanged. Five venous samples were taken to measure c-AMP before coronary angiography, before PTCA, and 5 min, 2 h and 24 h after PTCA. c-AMP values 2 and 24 h after PTCA (17.8 +/- 1.7 pmol/ml and 17.5 +/- 1.7 pmol/ml, respectively) were lower than the highest value (22.1 +/- 2.1 pmol/ml) found 5 min after PTCA, (P < 0.001). c-GMP increases distal to coronary obstructive lesion during PTCA at the time of balloon inflation, while c-AMP remains unchanged. c-AMP rises in venous circulation only. PTCA stimulates the mechanism of c-GMP release, while systemic c-AMP increase seems to be related to the stress occurring during catheterisation and PTCA.

Topics: Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Coronary Disease; Cyclic AMP; Cyclic GMP; Female; Humans; Male; Middle Aged

Endothelin-1 and cyclic guanosine monophosphate (c-GMP) peripheral vein plasma levels increase during coronary angioplasty, but the reason for this increase has not been elucidated. The purpose of this study was to investigate whether these changes are related to myocardial ischaemia, or to mechanical artery injury induced during the procedure. Thirty-two patients with stable angina pectoris and a single lesion were studied. They were aged 56 +/- 8 and were undergoing balloon angioplasty. Eight arteries were totally occluded and 24 were partially occluded. Blood samples were drawn from a peripheral vein after coronary artery engagement with the guiding catheter (baseline), after the first balloon inflation, immediately after the end of the procedure, and 4 h later. In the total occlusion group endothelin-1 increased by 7% (P ns), whereas in the partial occlusion group it increased by 45% after the procedure (P < 0.001). c-GMP in the partial occlusion group increased by 41% (P < 0.001) after the procedure whereas in the total occlusion group it increased by 5% (P ns). Thus, the increase in endothelin-1 and c-GMP peripheral vein plasma levels after coronary angioplasty is related to myocardial ischaemia rather than to mechanical artery injury.

Topics: Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Coronary Disease; Coronary Vessels; Cyclic GMP; Diagnosis, Differential; Endothelins; Female; Humans; Male; Middle Aged; Myocardial Ischemia

Disorders in arterial production of PGI2 and NO occur in atherosclerosis. Exogenous PGI2 and NO are capable of interacting pharmacologically. We claim that no such direct interactions occur between endogenous endothelial PGI2 and NO. Studying mechanisms of cardiac reactive hyperemia in guinea pigs and of thrombolysis in cats, we surmise that in vivo vascular intima releases PGI2 intraluminally while NO is secreted abluminally and thus these two ephemeral mediators do not see each other. Hence, in any disease, the disturbances in endothelial generation of PGI2 or NO have to be scrutinized separately. It may well be that endogenous PGI2 maintains endothelial thromboresistance while NO controls arterial myocytes and tissues in which microcirculation is embedded. These responsibilities remain unshared. Interactions between PGI2 and NO are confined to pharmacological domains.

Topics: Animals; Arteriosclerosis; Blood Pressure; Cats; Coronary Disease; Cyclic GMP; Epoprostenol; Guinea Pigs; Hyperemia; In Vitro Techniques; Male; Myocardium; Nitric Oxide; Thrombosis; Thromboxane B2

The concentrations of plasma ANF and plasma and urinary cyclic GMP were measured at rest and during exercise in 12 normal subjects (reference group) and 20 patients with coronary artery disease (coronary group). In both groups, plasma ANF and c GMP increased during exercise and fell one hour after (F = 3.8, p = 0.029 and F = 13.3, p = 0.0001, respectively) whereas the urinary c GMP increased one hour after exercise (F = 5.3, p = 0.029). In the control group, ANF increased on effort and fell during recovery to above its resting value whereas the plasma c GMP remained unchanged throughout the test. In the coronary group, no significant increase in ANF was observed on effort (wide dispersion of values) whereas the c GMP increased during effort and fell to below testing value during the recovery phase. The ANF of the coronary group was globally higher than the ANF of the control group (F = 4.7, p = 0.04). The plasma c GMP of the coronary group was comparable to that of the controls (F = 2.1, p = 0.15) despite higher concentrations at rest (p < 0.05) and during exercise (p < 0.05). However, there was a positive interaction between the efforts of exercise and the pressure of coronary disease on the concentration of plasma c GMP (F = 6.7, p = 0.0024). There was no difference in urinary c GMP between control and coronary subjects (F = 1, p = 0.33).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Disease; Cyclic GMP; Female; Humans; Male; Middle Aged; Physical Exertion; Reference Values

There is accumulating evidence that oestrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The aim of this study was to measure the effects of 17 beta-oestradiol on human epicardial coronary artery tone.. Coronary artery rings were obtained from explanted hearts during cardiac transplantation. The rings were suspended in organ baths for isometric tension measurements. The rings were precontracted with prostaglandin F2 alpha, and were then exposed to either 17 beta-oestradiol (0.3 nM-3 microM) or solvent control (0.2% ethanol v/v). In some rings, cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate content were measured by radioimmunoassay.. 17 beta-Oestradiol induced a significant relaxation [maximum effect: 84(SD 18)%]. The onset of the relaxant effect occurred within 5 min, and was maximal within 40 min. The relaxation in response to 3 microM 17 beta-oestradiol was of similar magnitude in rings with and without intact endothelium. The maximum relaxation induced by 3 microM 17 beta-oestradiol was greater in arteries from hearts obtained from women than in those obtained from men [-100.0(3.0)% v -77.5(17.6)%, respectively]. The exposure of rings to 3 microM 17 beta-oestradiol for 30 min resulted in a significant increase in both cyclic AMP and cyclic GMP content, by 88% and 182%, respectively.. 17 beta-Oestradiol produced an endothelium independent relaxation of precontracted human coronary arteries in vitro, and this effect was associated with an increase in both cyclic AMP and the cyclic GMP content. This direct relaxant effect of oestrogens on coronary arteries may contribute to the beneficial effects of oestrogen replacement therapy in postmenopausal women.

Topics: Adult; Coronary Disease; Coronary Vessels; Culture Techniques; Cyclic AMP; Cyclic GMP; Estradiol; Estrogen Replacement Therapy; Female; Humans; Male; Menopause; Middle Aged; Muscle, Smooth, Vascular; Pericardium; Sex Factors; Vasoconstriction

We assayed the concentrations of atrial natriuretic factor and guanosine 3',5'-phosphate in the plasma and urine of six healthy subjects, 12 patients with coronary artery disease and 11 patients with congestive heart failure. Patients with coronary artery disease had normal levels of atrial natriuretic factor in the plasma and urine and a normal excretion of guanosine 3',5'-phosphate, while those with congestive heart failure had a raised level of atrial natriuretic factor in the plasma, an increased excretion of 3',5'-guanosine phosphate and normal excretion of atrial natriuretic factor. Thus, measurement of atrial natriuretic factor in the urine can not replace the assay of the peptide in plasma.

Topics: Aged; Atrial Natriuretic Factor; Coronary Disease; Cyclic GMP; Female; Heart Failure; Humans; Male; Middle Aged; Reference Values

To evaluate the role of nitric oxide (NO) in the flow response after brief coronary arterial occlusion, NO formation by the isolated guinea pig heart was assessed by a specific difference spectrophotometric assay. Release of NO under basal conditions was 121.8 +/- 10.5 pmol x min-1 and increased to 211.1 +/- 16.8 pmol x min-1 after 60 seconds of coronary occlusion. Simultaneously, release of cGMP and adenosine increased by 87% and 652%, respectively. The kinetics of NO release paralleled the reactive hyperemic flow response. Inhibition of NO synthesis with nitro-L-arginine methyl ester (L-NAME, 30 microM) significantly reduced basal flow and attenuated reactive hyperemia, flow repayment, and repayment ratio. L-NAME decreased release of cGMP but significantly increased adenosine release under basal conditions and during reactive hyperemia. Oxyhemoglobin (5 microM) potentiated the effects of L-NAME. The stereoisomer nitro-D-arginine methyl ester was ineffective. Our results suggest 1) NO is an important regulator of coronary flow during reactive hyperemia as well as under basal flow conditions and 2) the significance of the increased adenosine release when NO synthesis is inhibited remains to be determined.

Topics: Adenosine; Animals; Arginine; Coronary Circulation; Coronary Disease; Cyclic GMP; Hyperemia; In Vitro Techniques; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rabbits; Spectrophotometry

In ten anaesthetized open chest cats the ligation of left descending coronary artery (LLDCA) resulted in 80 percent of mortality with survival time of 40.9 +/- 8.6 min. The death of animals was preceded by premature ventricular contractions which occurred with frequency 7.3 +/- 0.6/min after 2.1 +/- 0.3 min following LLDCA. Molsidomine as a dose of 20 micrograms/kg given i.v. to 10 cats 15 min before LLDCA affected none of the above characteristics of acute myocardial ischemia. The pretreatment with iloprost (2 micrograms/kg given i.v. to 10 cats) diminished frequency of premature ventricular contractions and elongated a period of time required for their occurrence after LLDCA, however, iloprost was also unable to diminish mortality of LLDCA cats. Only a combined administration of molsidomine and iloprost significantly diminished mortality among LLDCA cats down to 20 percent and doubled their survival time as compared to the controls. It is concluded that NO-donors (molsidomine) exert permissive effect towards the cardioprotective action of prostacyclin analogues (iloprost) in cats with myocardial ischemia. LLDCA cats pretreated with molsidomine + iloprost enjoyed a more complete cardioprotection than those pretreated with a high dose (3000 units/kg i.v.) of superoxide dismutase.

Topics: Animals; Blood Platelets; Blood Pressure; Cats; Coronary Disease; Coronary Vessels; Cyclic GMP; Electrocardiography; Epoprostenol; Heart; Iloprost; Leukocytes; Molsidomine

This study investigates biochemical and functional interactions between NO and PGI2 that generate pathways in two different in vitro assays: porcine aortic endothelial cells (PAEC) and reperfused ischemic Langendorff hearts of rabbits. Using cGMP as an index of NO generation and 6-oxo-PGF1 alpha as an index for PGI2 production in endothelial cells, it is demonstrated that the two metabolic pathways for NO and prostacyclin formation act independent of each other. Moreover, NO appears to have an autocrine function in endothelial cells which does not exist with PGI2, probably because of a lack of PGI2 receptors. Endothelial damage in the course of myocardial ischemia is associated with a marked increase in mediator release whose inhibition has consequences for both myocardial and coronary function: inhibition of NO formation also inhibits PGI2 release and the recovery of coronary vessel tone with only minor if any effect on myocardial contractility. In contrast, inhibition of PGI2-generation results in marked deterioration of myocardial recovery with only minor changes in coronary perfusion. It is concluded from these data that PGI2 in endothelial injury is important for preservation of myocardial function while NO might mainly be involved in control of local vessel tone.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Calcimycin; Cells, Cultured; Coronary Disease; Cyclic AMP; Cyclic GMP; Endothelium, Vascular; Epoprostenol; Heart; Myocardial Reperfusion; Nitric Oxide; Rabbits; Swine

The secretion of atrial natriuretic factor (ANF) and its adaptation to pharmacologic and hemodynamic interventions were investigated in 36 patients with sinus rhythm. To provoke standardized secretion of ANF all patients underwent two periods of rapid right ventricular pacing for 4 min with a 15 min interval. Immediately after the first pacing eight patients received 5 mg verapamil, 10 patients 5 mg atenolol and 10 patients 4 mg molsidomine intravenously. Eight patients remained untreated and served as controls. The amounts of atrial pressure increments due to pacing were identical (70% over basal pressure) in all patients. After molsidomine, but not after the other drugs, basal right atrial pressure was lowered. In controls the secretion of ANF due to the second stimulation was significantly (2.5-fold) larger than the secretion induced by the first stimulation. In patients receiving verapamil the secretion response after the second pacing was blunted. Atenolol did not affect the release of ANF. After molsidomine the upward regulation of the ANF secretion rate - seen in controls - was abolished. Thus, the myoendocrine cells are capable for a fast upward regulation of their ANF secretion rate after repeated stimuli. Verapamil directly blocks stimulated ANF secretion, whereas beta-blockade shows no effect. Molsidomine seems to impair enhanced ANF release by lowering basal atrial pressure.

Topics: Adult; Aged; Atenolol; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Cardiac Pacing, Artificial; Coronary Disease; Cyclic GMP; Female; Humans; Male; Middle Aged; Molsidomine; Verapamil

The acid phosphatase and cathepsin D activities and cAMP and cGMP levels in isolated perfused rat heart were investigated during various periods of ischaemic myocardial injury and postischaemic reperfusion. The effect of phosphodiesterase inhibitor--caffeine was also studied. Free acid hydrolases activities and cyclic nucleotide content were increased under 40 and 60 min ischemia and 20 min postischaemic reperfusion. Addition of 50 microM caffeine to perfusion solution after 30 min of ischaemia resulted in increase of cAMP level, cAMP/cGMP ratio, lysosomal bound activities of acid hydrolase and decrease of free acid hydrolase activities. The obtained results suggested that defect in cAMP synthesis might be present in lysosomal membranes labilization in cardiomyocytes injured during ischaemic conditions. Addition of such agents, as caffeine, which increased heart cAMP level, may be effective in lysosomal membranes stabilization under reversible heart ischaemia and reperfusion.

Topics: Acid Phosphatase; Animals; Caffeine; Cathepsin D; Coronary Disease; Cyclic AMP; Cyclic GMP; Male; Myocardial Reperfusion; Myocardium; Rats; Time Factors

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Coronary Disease; Cyclic GMP; Electric Stimulation; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged

Topics: Adult; Antioxidants; Coronary Disease; Cyclic AMP; Cyclic GMP; Humans; Lipid Peroxides; Male; Middle Aged; Niacinamide

The adaptation of the secretory rate of atrial natriuretic factor to repeated adequate stimuli and the influence of the calcium antagonist verapamil on the release of atrial natriuretic factor were investigated in 16 patients. In eight patients (Group 1) right atrial pressure was abruptly increased by rapid right ventricular pacing for 4 min (stimulation I). After a 15 min interval, the identical stimulation was repeated (stimulation II). Eight patients (Group 2) underwent the same protocol but received 5 mg of verapamil intravenously after stimulation I. Pacing increased right atrial pressure in both groups identically by 70%. In Group 1, release of atrial natriuretic factor caused by the second stimulation (median 290 pg/ml over basal) was significantly (2.5-fold) larger than atrial natriuretic factor release induced by the first stimulation (median 116 pg/ml over basal). In the verapamil-treated patients (Group 2), the effect of right atrial pressure increase on release of atrial natriuretic factor was abolished after stimulation II. In both groups, changes in plasma concentrations of cyclic guanosine monophosphate corresponded to changes in atrial natriuretic factor concentrations. Thus, the myoendocrine cells are apparently capable of a fast upward regulation of their response to repeated secretory stimuli. Verapamil appears to block the stimulatory effect of a sudden increase in right atrial pressure upon release of atrial natriuretic factor.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Cyclic GMP; Female; Heart Atria; Humans; Male; Middle Aged; Verapamil

Plasma levels of cyclic nucleotides were determined by radioimmunoassay in patients with (1) angina-like chest pain and normal coronary arteries (suspected spasm angina), (2) exercise-induced angina, and (3) heart diseases other than angina pectoris, as well as in (4) normal subjects. The concentration of cyclic GMP in plasma was significantly lower (by at least three-fold) in patients with suspected spasm angina, as compared with the other groups. No statistically significant difference in the plasma levels of cAMP was observed between the different patient groups. The low cGMP levels in plasma from patients with angina-like chest pain and normal coronary arteries might be an indication of a defect in the vasculature, making it more sensitive to contractile stimuli.

Topics: Adult; Angina Pectoris; Coronary Angiography; Coronary Disease; Coronary Vasospasm; Cyclic AMP; Cyclic GMP; Female; Humans; Male; Middle Aged

The effect of pretreatment on the 3 hrs globally ischemic heart assessed from the myocardial enzymes, lysosomal enzymes and cyclic nucleotides in coronary sinus blood was studied in mongrel dogs. Combined administration of CoQ10, Aprotinin, Betamethasone and Nifedipine was done as pretreatment.. m-AST, NAG and beta-Glucuronidase were significantly lower in the pretreatment group. Significant positive correlations were obtained in order between beta-Glucuronidase and NAG (r = 0.6869), m-AST and beta-Glucuronidase (r = 0.6590), m-AST and NAG (r = 0.5381), m-AST and CK-MB (r = 0.49), respectively. Significant increase in cAMP/cGMP ratio was observed in the control group after reperfusion. Before aortic occlusion, significant negative correlations were obtained between cAMP and beta-Glucuronidase, NAG, m-AST, and after 5 min of reperfusion, significant negative correlations were obtained between cGMP and NAG, m-AST and significant positive correlations between cAMP/cGMP ratio and NAG, m-AST. These data suggested the effectiveness of pretreatment, the relation between lysosomal enzyme release and the ischemic myocardial injury, and the usefulness of m-AST to evaluate the degree of myocardial injury. Moreover, the increase of cAMP/cGMP ratio suggested the ischemic myocardial injury, and cGMP in the ischemic condition, and cAMP in the non-ischemic condition affected lysosomal enzyme release.

Topics: Animals; Aprotinin; Betamethasone; Coronary Disease; Creatine Kinase; Cyclic AMP; Cyclic GMP; Dogs; Heart Arrest, Induced; Isoenzymes; Lysosomes; Myocardium; Nifedipine; Perfusion; Ubiquinone

In anesthetized rats a 30-min intravenous infusion of adenosine (2.5 mg/kg/min) performed after the coronary artery ligation significantly decreased the incidence and severity of early ischemic arrhythmias. After the infusion of adenosine, there was an increase in cGMP level in the left ventricular myocardium, cAMP content remained unchanged.

Topics: Adenosine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Cyclic AMP; Cyclic GMP; Drug Evaluation, Preclinical; Heart; Male; Myocardium; Rats; Time Factors

A total of 64 male patients with varying forms of coronary heart disease (CHD), aged 43 to 65 years, and free of diabetes mellitus, obesity and arterial hypertension symptoms, were studied in conditions of emotional stress simulated, using the method of mental calculations with shifts of attention under time shortage. Pre- and post-exercise blood levels of cyclic nucleotides (cAMP and cGMP), the somatotropic hormone and immunoreactive insulin were measured. Stress-induced decrease in platelet cAMP/cGMP ratios, indicative of further increase in the functional activity of platelets, was demonstrated in coronary patients with marked coronary atherosclerosis, as contrasted to normal subjects and patients with milder disease. They also showed a more considerable (sixfold) increase in the somatotropic hormone levels and a tendency to decreased levels of immunoreactive insulin under stress, apparently as a consequence of the prevailing activation of alpha-adrenoreceptor pathways.

Topics: Adult; Blood Platelets; Coronary Disease; Cyclic AMP; Cyclic GMP; Growth Hormone; Humans; Insulin; Male; Middle Aged; Nucleotides, Cyclic; Stress, Psychological

Topics: Adolescent; Adult; Aged; Catecholamines; Coronary Disease; Cyclic AMP; Cyclic GMP; Female; Humans; Hypertension; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Middle Aged; Pneumonia

The aims of this study were to determine whether a relationship exists between the occurrence of coronary artery occlusion-induced arrhythmias in the anaesthetized rat and the levels of cyclic AMP and cyclic GMP in both normal and ischaemic myocardium, and to assess whether such arrhythmias were modified by pretreatment with the phosphodiesterase inhibitors, quazodine and isobutyl methylxanthine (IBMX), or with the butyryl derivatives of cyclic AMP and cyclic GMP. At 5 min after coronary artery ligation (when only a few arrhythmias had occurred) both cyclic AMP and cyclic GMP levels were elevated in normal myocardium whereas in ischaemic tissue only cyclic AMP was raised. As the peak of the arrhythmic activity and after cessation of the arrhythmias, i.e. at 10 and 30 min post-ligation respectively, levels of both nucleotides had fallen in ischaemic although not in normal tissue. The severity of these occlusion-induced arrhythmias was exacerbated by pretreatment intravenously with quazodine, IBMX, dibutyryl cyclic AMP and dibutyryl cyclic GMP. Pretreatment with IBMX was also shown to elevate significantly both cyclic AMP and cyclic GMP content of left ventricular tissue before occlusion. None of the drug pretreatments markedly affected mean arterial blood pressure but heart rate was significantly increased following quazodine and IBMX administration. We conclude that in the pentobarbitone-anaesthetized rat the occurrence of occlusion-induced arrhythmias was not accompanied by a rise in cyclic nucleotide content of the ischaemic myocardium but agents which may elevate either myocardial cyclic AMP or cyclic GMP levels exacerbate such arrhythmias.

Topics: 1-Methyl-3-isobutylxanthine; Anesthesia; Animals; Arrhythmias, Cardiac; Bucladesine; Coronary Disease; Cyclic AMP; Cyclic GMP; Dibutyryl Cyclic GMP; Heart; Male; Myocardium; Quinazolines; Rats; Rats, Inbred Strains

Plasma prostanoids and levels of cyclic nucleotides were studied in forty-nine outpatients with precordial pains and subjected to the treadmill exercise test. Blood samples were drawn before, immediately after and 30 minutes after exercise, from antecubital veins. Plasma TXB2, 6-keto PGF1 alpha, cyclic AMP and cyclic GMP levels were measured by radioimmunoassay. The results of exercise tests were evaluated according to the treadmill exercise score (TES) of Hollenberg et al. Patients were divided into two groups; those with TES (-) with ischemic findings in exercise and those with TES (+) with normal exercise response. There were no differences in TXB2 levels between the two groups before exercise. Immediately after exercise statistically significant differences in TXB2 levels were present between the two groups. There were increased levels in the TES (-) group and decreased levels in the TES (+) group (p less than 0.01). Although the 6-keto PGF1 alpha levels were the same between the two groups before exercise, 6-keto PGF1 alpha levels in the TES (+) group increased significantly immediately after exercise. Similar changes were noted in the case of cyclic nucleotides, and the differences increased immediately after exercise. We conclude that high responses of cyclic nucleotides and PGI2 are required to counteract increases in levels of TXA2 and diminution of these responses may be an important phenomenon involved in the physiological status of ischemic heart disease.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Coronary Disease; Cyclic AMP; Cyclic GMP; Exercise Test; Female; Humans; Male; Middle Aged; Physical Exertion; Thromboxane B2; Thromboxanes

The effects of 8-bromo cyclic GMP (1 X 10(-5)M) on the levels of lactate, NAD+, NADH, AMP, ADP, ATP, creatine phosphate (CrP) and creatine were studied in the ischaemic Langendorff-perfused rat heart. The NAD+/NADH ratio and the energy charge were also calculated. The dependence of the effect of 8-bromo-cGMP on substrate availability was also studied by adding pyruvate (5 mM and 10 mM) to the perfusate, and by comparing the changes to those during perfusion with glucose alone. When glucose (11 mM) was used as the only substrate, 8-bromo-cGMP administration resulted during ischaemia, in a decrease of the NADH level, and in an increase of the energy charge. When pyruvate (5 mM) was added to the perfusate, 8-bromo-cGMP administration resulted in an increase in the NAD+/NADH ratio and in an increase of the energy charge. When the pyruvate concentration was further increased (10 mM), no changes were seen in the beforementioned variables after 8-bromo-cGMP administration. It is concluded that the effects of 8-bromo-cGMP may be exerted by an enhancement of carbohydrate oxidation.

Topics: Animals; Coronary Disease; Cyclic GMP; Energy Metabolism; Glucose; In Vitro Techniques; Lactates; Lactic Acid; Male; Myocardium; NAD; Oxidation-Reduction; Perfusion; Pyruvate Dehydrogenase Complex; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains

Topics: Aged; Antigens; Coronary Disease; Cyclic AMP; Cyclic GMP; Factor VIII; Female; Humans; Male; Middle Aged; Platelet Adhesiveness; Platelet Aggregation; von Willebrand Factor

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Female; Guinea Pigs; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Mice; Myocardium; Oxygen Consumption; Plant Extracts; Plants, Medicinal

Topics: Animals; Carbachol; Coronary Disease; Cyclic AMP; Cyclic GMP; Epinephrine; Female; In Vitro Techniques; Male; Perfusion; Rats; Ventricular Fibrillation

Langendorff perfused rat hearts show synchronous, statistically significant, systematic variations in ATP and ADP. Here we show that AMP and IMP also vary in register with ATP and ADP and we suggest that the synchronizing trigger for these oscillations may be ischaemia. Oscillations in the ATP/ADP ratio were found to be significantly correlated with creatine phosphate content but by contrast these quantities vary quite differently from the GTP/GDP ratio. Cyclic GMP oscillations showed a significant negative correlation with variations in ADP. Epinephrine raised mean cyclic AMP content and stabilized cyclic GMP oscillations, but had little other effect on the purine nucleotide variations.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Epinephrine; Guanosine Diphosphate; Guanosine Triphosphate; Heart; Inosine Monophosphate; Kinetics; Male; Myocardium; Perfusion; Purine Nucleotides; Rats; Rats, Inbred Strains

Experiments made on 127 white random-bred male rats weighing 200 +/- 10 g with transitory coronary insufficiency (TCI) with varying duration of myocardial ischemia (MI) have revealed consistent changes in the heart cAMP and cGMP. During MI, there was a biphasic variation in the concentration of cyclic nucleotides: an initial appreciable increase in the concentration was replaced by its lowering. At the same time the time course of cGMP content was more mobile in nature as compared to cAMP Reperfusion made at an early period (within the first 40 min) did not normally bring about the normalization of heart content of cyclic nucleotides whose concentration time course depended on the duration of the preceding MI. The pattern of changes in the concentration of cyclic nucleotides in the heart in TCI correlated to a significant degree with the previously described time course of the activity of the sympath- and cholinergic mechanisms by which heart work, contractile function and rhythm are controlled during TCI.

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Male; Myocardium; Rats; Time Factors

The effect of the left anterior descending (LAD) coronary artery ligation on myocardial cyclic nucleotides and the role of these nucleotides in the development of ventricular fibrillation (VF) were studied in 135 mongrel dogs by means of sequential punching biopsies from the left ventricle. VF occurred in 50% of the non-premedicated groups. Significant increases of cyclic AMP (c-AMP) concentrations in the ischemic zone were observed after the ligation in VF group. C-AMP concentrations in the ischemic zone were significantly higher after the ligation compared with the border and non-ischemic zone as well as with the non-VF group. They also increased significantly from 30 sec before the onset of VF compared with 2 to 25 min before. No significant change was observed in the control group. In 41 dibutyryl cyclic AMP (DBc-AMP) premedicated dogs, the incidence of VF significantly increased, and c-AMP concentrations were significantly higher than in the non-premedicated group before and after the ligation. They were significantly higher in the ischemic zone 10, 15 and 20 min after the ligation than in the non-ischemic zone. There was a discrepancy of c-AMP concentration between the ischemic zone and the non-ischemic zone in VF induced group, whether DBc-AMP was premedicated or not. Significantly decreased cyclic GMP (c-GMP) levels in the ischemic and the non-ischemic zone were observed after the ligation. C-GMP concentrations with the DBc-AMP premedicated were significantly lower after the ligation compared with the non-premedicated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bucladesine; Coronary Disease; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dogs; Ligation; Myocardium; Ventricular Fibrillation

Following coronary artery ligation (CAL), levels of cAMP and the activity ratio of cAMP-dependent protein kinase, of phosphorylase kinase, and of phosphorylase are significantly elevated in both ischemic and nonischemic areas of the canine left ventricle. The aerobic level of cAMP was found to be 0.4 to 0.6 pmol/mg myocardium only after a precooled clamp or a cryobiopsy device was employed to guarantee tissue freezing in situ. Maximal changes in response to ischemia are observed within 2 min in both parts of the heart. Twenty minutes after the onset of ischemia, different responses have been found in the nonischemic and ischemic tissue. Whereas the levels of cAMP and the activity ratio of protein kinase, of phosphorylase kinase, and of phosphorylase returned to aerobic values in the nonischemic area, these parameters remained elevated in the ischemic area. The changes in the levels of myocardial cAMP and in the cAMP-dependent protein kinase activity ratio following CAL could be prevented by propranolol.

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Dogs; Enzyme Activation; Ligation; Myocardium; Protein Kinases

The effects of 8-bromo-cGMP on tissue lactate and NADH levels were studied under conditions of high oxygen saturation (95-100%) and hypoxia (50%) in spontaneously beating rat atria. The induction of hypoxia caused a rapid decline in contractility with a simultaneous increase in tissue lactate and NADH. 8-bromo-cGMP (10(-4) mol/l) prevented the accumulation of lactate occurring during hypoxia. It also lowered the level of lactate during high oxygen saturation. Furthermore, 8-bromo-cGMP inhibited the hypoxia-induced increase in NADH and lowered the level of NADH in high oxygen saturation. 8-bromo-cGMP did not affect contractility or heart rate during hypoxia. It is concluded that cGMP may influence the redox-state and metabolism in a direction which is beneficial for the hypoxic myocyte. It is also suggested that antianginal nitro compounds which enhance the level of cGMP might exert an effect similar to that of 8-bromo-cGMP.

Topics: Animals; Coronary Disease; Cyclic GMP; In Vitro Techniques; Lactates; Lactic Acid; Male; Myocardium; NAD; Oxygen Consumption; Rats; Rats, Inbred Strains

Developing myocardial infarction is shown to be accompanied by raised plasma cAMP and cGMP levels which peak within the first few hours of the disease. Two patterns of changes were noted in the content of cyclic nucleotides: cAMP increase prevailing (a more typical pattern) and cGMP increase prevailing. Primary ventricular fibrillation was recorded in some patients belonging to the latter group. The development of cardiac failure is accompanied by a more stable rise of plasma cAMP.

Topics: Adult; Aged; Angina Pectoris; Coronary Disease; Cyclic AMP; Cyclic GMP; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Time Factors

Topics: Acetylcholine; Animals; Atropine; Blood Pressure; Calcium; Coronary Disease; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Hypoxia; Male; Myocardial Contraction; Perfusion; Purine Nucleotides; Rats; Rats, Inbred Strains

Topics: Animals; Calcium; Cats; Coronary Disease; Cyclic AMP; Cyclic GMP; Haplorhini; Heart Diseases; Hypoxia; Myocardial Contraction; Myocardium; Papio; Rats; Swine

The effects of ischemic and beta-blocker on myocardial cyclic nucleotides (cyclic AMP and cyclic GMP) of dogs were studied. The concentration of cyclic AMP in both infarcted and noninfarcted area 60 min after the ligation of the proximal part of the left anterior descending coronary artery to significantly higher than in sham-operated control animals. The concentration of cyclic GMP in infarcted area is also significantly elevated compared with control 15 min after the ligation. The cAMP/cGMP (A/G) ratio in the infarcted group was also elevated at 60 min and returned to control level after 5 hr. When propranolol was given, the concentration of cyclic AMP of both infarcted and noninfarcted area remained at control level. In propranolol-treated animals, the concentration of cyclic GMP in both infarcted and noninfarcted area increased significantly compared with control at 15 min and 60 min. The A/G ratio was also decreased below control level after the administration of propranolol. These results suggest that the stability of the ischemic cardiac muscle was enhanced by the administration of beta-blockers.

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Dogs; Heart; Nucleotides, Cyclic; Propranolol

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Coronary Disease; Cyclic AMP; Cyclic GMP; Dogs; Myocardial Infarction; Myocardium; Propranolol

Topics: Adolescent; Adult; Cerebrovascular Disorders; Coronary Disease; Cyclic AMP; Cyclic GMP; Female; Humans; Hypertension; Male; Middle Aged; Vascular Diseases

Topics: Adenosine Triphosphatases; Animals; Carbon Dioxide; Coronary Disease; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dogs; Ligation; Myocardial Infarction; Myocardium; Myosins

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Dogs; Glucuronidase; In Vitro Techniques; Lysosomes; Male; Myocardium; Nucleotides, Cyclic; Rats; Time Factors

Topics: Animals; Arteries; Coronary Disease; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dogs; Hemodynamics; Ligation; Myocardium; Propranolol

The isolated isovolumic rat heart was used as a model of cardiac hypoxia. Force of cardiac contraction and cardiac cyclic nucleotide levels (cyclic GMP and cyclic AMP) were monitored in hearts subjected to hypoxia for 5 min and allowed to recover by reoxygenation. Hearts were obtained from both control animals and animals pretreated with methylprednisolone at 18 hr and 1 hr prior to sacrifice. Myocardial levels of cyclic GMP which were significantly (p less than 0.05) elevated above control during all periods of hypoxia were found to be lower when hearts were pretreated with methylprednisolone prior to hypoxic exposure. Hearts of animals pretreated with methylprednisolone also demonstrated better recovery during reoxygenation than did control hearts. These studies suggest that methylprednisolone may be beneficial in the prevention of myocardial failure following hypoxia via a modulation in myocardial cyclid GMP content.

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Hypoxia; In Vitro Techniques; Male; Methylprednisolone; Myocardial Contraction; Myocardium; Rats

Although corticosteroids have been shown to stabilize lysosomal membranes and prevent release of hydrolytic enzymes, the mechanism of membrane stabilization remains obscure. The few reports regarding the use of steroids in myocardial ischemia have been conflicting. This study was undertaken to determine if a pharmacologic dose of the glucocorticoid methylprednisolone would protect the heart during ischemic cardiac arrest. A randomized double-blind study was performed in 25 dogs. Biochemical and hemodynamic parameters were assessed during and after cardiopulmonary bypass and after 30 minutes of ischemic cardiac arrest. Animals were divided into two groups. Group I served as controls and consisted of dogs injected intravenously with the vehicle of methylprednisolone 18 hours and 1 hour prior to experiment. Group II comprised dogs injected with methylprednisolone, 30 mg. per kilogram, IV, at the same time periods. Blood pH, gases, and electrolytes were measured; aortic, left atrial, and left ventricular pressures were monitored; the first derivative of the left ventricular pressure (dp/dt max.) was also determined. Arterial and coronary sinus blood samples were assayed for lactate levels and activity of the lysosomal enzyme, beta-glucuronidase. Left ventricular muscle was assayed for the nucleotides cyclic adenosine 3',5' monophosphate (AMP) and cyclic guanosine 3',5' monophosphate (GMP). Following restoration of coronary flow, mean aortic and left ventricular systolic pressures and left ventricular contractility as determined by dp/dt max. and dp/dt max./IP were depressed in both groups as expected but were significantly higher in Group II than in Group I (p less than 0.05). An increase in levels of both cyclic nucleotides occurred in each group during ischemia, but this increase in cyclic GMP was significantly greater in Group I (p less than 0.05). beta-glucuronidase activity and myocardial potassium loss as determined in coronary sinus blood were both significantly greater in Group I than in Group II (p less than 0.05). Results of this study demonstrate that pretreatment with a pharmacologic dose of methylprednisolone significantly enhances cardiac recovery after ischemia. Lysosomal membrane stability and modulation of cyclic GMP levels may be critical determinants in the mechanism of cardiac ischemia.

Topics: Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Dogs; Glucuronidase; Heart Arrest, Induced; Hemodynamics; Lactates; Methylprednisolone; Myocardial Contraction; Myocardium; Oxygen; Potassium

Topics: Adrenal Glands; Ammonium Sulfate; Animals; Barium; Carrier Proteins; Chemical Precipitation; Coronary Disease; Cyclic AMP; Cyclic GMP; Dogs; Glucagon; Humans; Methods; Microchemistry; Myocardial Infarction; Norepinephrine; Protein Binding; Rats; Saliva; Species Specificity; Tritium; Zinc