cyclic-gmp and Postoperative-Complications

We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined.. The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 μg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group.. It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.

Topics: Aged; Aldosterone; Angiotensin II; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Coronary Artery Bypass; Creatine Kinase, MB Form; Cyclic GMP; Dose-Response Relationship, Drug; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Heart Arrest, Induced; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Renin; Troponin I

A prospective randomized study was performed to test whether removal of endothelin-1, by ultrafiltration techniques, will reduce pulmonary hypertension after operations for congenital heart disease.. Twenty-four patients with pulmonary hypertension (systolic pulmonary/systemic arterial pressure ratio > 60%) undergoing cardiac operations were randomized into a control group (n = 12) having conventional ultrafiltration and an experimental group (n = 12) undergoing dilutional ultrafiltration during and modified ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10 minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation in both groups, as well as in the ultrafiltrates and after modified ultrafiltration in the experimental group. Both groups received alpha-blockers (chlorpromazine and/or prazosin) postoperatively using the same guidelines.. The ultrafiltrates contained significant amounts of endothelin-1 (1.81 +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate). Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower in experimental compared with control patients. Nitric oxide metabolites and cyclic guanosine monophosphate increased similarly in both groups for 12 hours after the operation (p = not significant). Three of 12 control patients (25%) but no experimental patients had pulmonary hypertensive crises (p = 0.07). The experimental patients required significantly less ventilatory support (67 +/- 47 hours vs 178 +/- 139 hours for control patients, p = 0.048).. Dilutional and modified ultrafiltration reduce endothelin-1 and the pulmonary/systemic pressure ratio postoperatively and may become an important adjunct for preventing pulmonary hypertension after operations for congenital heart disease in high-risk patients.

Topics: Cardiopulmonary Bypass; Cyclic GMP; Endothelin-1; Female; Heart Defects, Congenital; Hemofiltration; Humans; Hypertension, Pulmonary; Infant; Male; Nitric Oxide; Postoperative Complications; Prospective Studies

As the pathogenesis of postoperative ileus (POI) involves inflammation and oxidative stress, comparable to ischaemia/reperfusion injury which can be ameliorated with nitrite, we investigated whether nitrite can protect against POI and explored the mechanisms involved.. We used intestinal manipulation (IM) of the small intestine to induce POI in C57BL/6J mice. Sodium nitrite (48 nmol) was administered intravenously just before IM. Intestinal transit was assessed using fluorescent imaging. Bethanechol-stimulated jejunal circular muscle contractions were measured in organ baths. Inflammatory parameters, neutrophil infiltration, inducible NOS (iNOS) activity, reactive oxygen species (ROS) levels, mitochondrial complex I activity and cGMP were measured in the intestinal muscularis.. Pre-treatment with nitrite markedly improved the delay in intestinal transit and restored the reduced intestinal contractility observed 24 h following IM. This was accompanied by reduced protein levels of TNF-α, IL-6 and the chemokine CCL2, along with reduced iNOS activity and ROS levels. The associated neutrophil influx at 24 h was not influenced by nitrite. IM reduced mitochondrial complex I activity and cGMP levels; treatment with nitrite increased cGMP levels. Pre-treatment with the NO scavenger carboxy-PTIO or the soluble guanylyl cyclase inhibitor ODQ abolished nitrite-induced protective effects.. Exogenous nitrite deserves further investigation as a possible treatment for POI. Nitrite-induced protection of POI in mice was dependent on NO and this effect was not related to inhibition of mitochondrial complex I, but did involve activation of soluble guanylyl cyclase.

Topics: Animals; Chemokine CCL2; Cyclic GMP; Gastrointestinal Transit; Ileus; Interleukin-6; Jejunum; Male; Mice, Inbred C57BL; Muscle Contraction; Neutrophils; Nitric Oxide Synthase Type II; Postoperative Complications; Reactive Oxygen Species; Sodium Nitrite; Tumor Necrosis Factor-alpha

Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have been located in the arterial wall: endothelial NOS (eNOS), inducible NOS, and neuronal NOS (nNOS). We have studied the role of NOS in a murine model of aortic allograft rejection.. The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (-/-) for a knockout of the eNOS gene (eNOS(-/-)).. After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS(-/-) recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS.. Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Cell Adhesion; Cell Division; Cyclic GMP; DNA Primers; Homozygote; Kidney; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Postoperative Complications; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tunica Intima

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Biopsy; Cyclic GMP; Escherichia coli Infections; Histiocytes; Humans; Ischemia; Kidney; Kidney Diseases; Malacoplakia; Male; Middle Aged; Periodic Acid-Schiff Reaction; Postoperative Complications; Pyelonephritis; Transplants; Urinary Tract Infections

Recently, the infarct reducing and cardioprotective effects of phosphodiesterase-5-inhibitors were described. In this study, we investigated these effects on ischemia/reperfusion injury in a rat model of heart transplantation. Three groups were assigned for our study: a vardenafil preconditioning group, an ischemic control, and a nonischemic control. Hemodynamic parameters were significantly increased in the vardenafil group (Pmax: 82+/-4 vs. 110+/-12 vs. 127+/-13 mm Hg; dP/dtmax: 1740+/-116 vs. 3197+/-599 vs. 4397+/-602 mm Hg/sec; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Furthermore, we recorded increased ATP levels and significantly less apoptosis in the treatment group after terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (apoptosis index: 27.23%+/-1.54% vs. 16.77%+/-1.42% vs. 18.86%+/-1.07%; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Our current results support the concept that the cGMP-PKG-pathway plays an important role in ischemia/reperfusion injury. We could show that up-regulating this pathway has a preconditioning-like effect and can effectively reduce ischemia/reperfusion injury.

Topics: Animals; Aorta, Abdominal; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Heart Transplantation; Hemodynamics; Imidazoles; Male; Myocardial Contraction; Phosphodiesterase Inhibitors; Piperazines; Postoperative Complications; Rats; Rats, Inbred Lew; Reperfusion Injury; Sulfones; Systole; Transplantation, Heterotopic; Transplantation, Isogeneic; Triazines; Vardenafil Dihydrochloride; Vena Cava, Inferior; Ventricular Function, Left

The etiology of placental dysfunction after fetal cardiopulmonary bypass remains unknown. The placental nitric oxide (NO) pathway has been implicated in this pathophysiology. We set out to examine possible perturbations in this pathway in an ovine model of fetal bypass.. Ovine fetuses (n = 14) between 100 and 114 days of gestation, instrumented to measure hemodynamics and umbilical blood flow, were placed on bypass for 30 minutes and followed after bypass for 2 hours. Sham controls (n = 6) were instrumented but did not undergo bypass. Real-time, in-vivo NO concentrations were measured in the placental circulation. To examine other components of the NO pathway, fetal plasma samples were analyzed by immunoassays for total NO metabolite and cyclic guanosine 3',5'-cyclic monophosphate (cGMP) levels. In addition, the expression of phosphodiesterase-5 was examined in placenta by immunohistochemistry. Statistical analysis was performed using analysis of variance with least significant difference post hoc tests (p < or = 0.05).. With the onset of bypass, an immediate increase occurs in umbilical NO concentrations. These return to baseline with cessation of bypass, and decline thereafter. In contrast, there was a linear increase in fetal plasma cGMP levels and a decline in NO metabolite concentrations through the post-bypass period. There was a dramatic increase in placental phosphodiesterase-5 expression with 30 minutes of bypass. The changes occur simultaneously with decreasing umbilical flows, increased placental vascular resistance, and worsening placental gas exchange.. Fetal bypass leads to significant reductions in placental NO concentrations despite increases in fetal plasma cGMP and placental phosphodiesterase-5 levels, indicative of perturbations in the fetal-placental NO pathway.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Carbon Dioxide; Cardiopulmonary Bypass; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Female; Fetus; Nitrates; Nitric Oxide; Nitrites; Oxygen; Placenta; Placenta Diseases; Postoperative Complications; Pregnancy; Sheep; Signal Transduction

The aim of this study was to investigate the changes in atrial natriuretic peptide (ANP) levels and lung cyclic guanosine 3',5'-monophosphate (cGMP) concentrations caused by pneumonectomy (Pn), and the effect of inhaled nitric oxide (NO) after Pn in a canine model. The mean pulmonary arterial pressure (PAP) and plasma ANP levels were measured over 180 min in two groups of dogs, one subjected to 60 min of 5 ppm NO inhalation (Pn + NO group, n = 5) and one subjected to 180 min without NO inhalation (Pn group, n = 5). The ANP and cGMP levels in the lung were also measured before and after Pn. Both the PAP and ANP levels increased significantly. Inhaled NO rapidly reduced the PAP and plasma ANP to levels similar to those before Pn. The lung ANP level was significantly increased after Pn, but inhaled NO reduced it to a level similar to that before Pn. The lung cGMP level, which was significantly decreased after Pn, was significantly increased by NO inhalation. These results indicate that NO administration may be effective for preventing post-Pn pulmonary hypertension, although an elevation in ANP does not reduce the PAP.

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Dogs; Hypertension, Pulmonary; Nitric Oxide; Pneumonectomy; Postoperative Complications; Vasodilator Agents

Atrial natriuretic peptide (ANP) is a cardiac hormone which affects endothelial cell function through a receptor-mediated process. Pneumonectomy is a common thoracic surgical procedure that can cause pulmonary oedema in the remaining lung. Few reports have investigated the aetiology of this complication. The aim of this study was to determine the changes in ANP concentration and expression of its receptors following pneumonectomy as a possible aetiology for postpneumonectomy pulmonary oedema (PPE). We compared plasma ANP concentrations, cGMP concentrations, and natriuretic peptide receptor (NPR)-A mRNA and NPR-C mRNA expression in rat lung 3 h after pneumonectomy (n=5) or a sham operation (n=5). The ANP concentrations in plasma and lung tissue in the pneumonectomy group were significantly higher than in the control group (749.5 versus 202.7 pg x ml(-1), P<0.01; 33.1 versus 6.8 ng x g(-1) wet tissue, P<0.01 respectively). The level of ANP mRNA expression in the pneumonectomy group was significantly higher than in the control group (1.44 versus 0.41 relative ANP mRNA expression, P<0.05). The concentration of cGMP and the level of NPR-A mRNA expression were not significantly different between the pneumonectomy and control groups. The level of NPR-C mRNA expression in the pneumonectomy group was significantly higher than in the control group (4.17 versus 2.19 relative NPR-C mRNA expression, P<0.01). These findings suggest that changes in pulmonary ANP and NPR-C expression may contribute to the development of PPE in the remaining lung in the acute phase following pneumonectomy.

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Lung; Male; Pneumonectomy; Postoperative Complications; Pulmonary Edema; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; RNA, Messenger

Pulmonary hypertension causes major morbidity and mortality after congenital heart surgery, but its mechanism remains unclear.. Plasma endothelin-1 (ET-1), nitric oxide (NO), and cyclic GMP (cGMP) were assayed at 6 intervals in 50 children undergoing cardiopulmonary bypass (CPB): before CPB, 10 minutes into CPB, and 0, 3, 6, and 12 hours after CPB. Three groups based on pulmonary flow and pressure were analyzed: low flow (LF, n=21), high flow/low pressure (systolic pulmonary pressure/systemic pressure ratio, Pp/Ps<50%, HF-LP, n=11), and high flow/high pressure (Pp/Ps> or =50%, HF-HP, n=19). HF-HP and HF-LP received alpha-blockers (chlorpromazine and/or prazosin). HF-HP patients received nitric oxide donors (nitroglycerin/sodium nitroprusside). ET-1 peaked at 6 hours, with its highest level in the HF-HP group (P<.01, by ANOVA). ET-1 correlated significantly with Pp/Ps at 6 hours (r2=.43, P<.005). In the HF-HP group, ET-1 remained above the other groups at 12 hours (12.7+/-2.5 pg/mL versus 6.4+/-1.1 pg/mL versus 6.5+/-3.8 pg/mL P<.05 by ANOVA). NO metabolites were elevated equivalently for the HF-HP and HF-LP groups (5.7+/-2.6 micromol/L versus 0.3.5+/-2.5 micromol/L at 12 hours, P=NS) despite nitric oxide donors and the excess ET-1 in HF-HP patients. Levels of cGMP were similarly elevated in HF-HP and HF-LP patients during this study.. Endogenous NO may decrease vascular tone and maintain low pulmonary pressure in HF-LP patients. High levels of ET-1, inadequate NO production, and/or impaired responses to NO may increase pulmonary pressure in HF-HP patients.

Topics: Blood Pressure; Cardiopulmonary Bypass; Child, Preschool; Cyclic GMP; Endothelin-1; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Male; Nitric Oxide; Postoperative Complications

The effects of graded supine ergometry on blood pressure, heart rate, and plasma hormones were studied in 14 hypertensive heart transplant recipients before and after 2 weeks and 6 months of enalapril (20 mg/day) plus furosemide (20-80 mg/day) alone or combined with verapamil (120-360 mg/day). Each time, measurements were obtained at rest and at 25 and 50 W exercise. Antihypertensive therapy normalized blood pressure, while heart rate and the blood pressure response to exercise remained unaltered. Pretreatment resting plasma renin activity and catecholamine levels were normal, while atrial natriuretic factor and cyclic guanosine monophosphate concentrations were elevated. All hormones increased significantly with exercise. During treatment, plasma renin activity increased and atrial natriuretic factor and cyclic guanosine monophosphate levels decreased significantly, with a blunted exercise response; concentration of catecholamines increased significantly, with augmented exercise response. Thus, the chosen regimen allowed effective, lasting BP control in hypertensive transplant patients but was associated with significant changes in plasma hormones. Whereas the rise in plasma renin activity may be attributed to converting enzyme inhibition, the decreases in atrial natriuretic factor and cyclic guanosine monophosphate and increases in catecholamine levels seem to indicate marked changes in resting and particularly exercise hemodynamics during antihypertensive therapy.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Drug Therapy, Combination; Enalapril; Epinephrine; Exercise Test; Female; Follow-Up Studies; Furosemide; Heart Rate; Heart Transplantation; Hormones; Humans; Hypertension; Male; Middle Aged; Norepinephrine; Postoperative Complications; Renin; Verapamil