neuropeptide-y and Myocardial-Infarction

Topics: Animals; Heart; Heart Failure; Humans; Myocardial Infarction; Neuropeptide Y

Increased sympathetic activity is assumed to contribute substantially to the occurrence of malignant arrhythmias in patients with coronary heart disease, since the rate of sudden cardiac death is significantly reduced by beta-adrenoceptor blockade, but not by antiarrhythmic agents such as flecainide or encainide. During acute myocardial ischaemia, adrenergic stimulation of the ischaemic myocardium is independent of plasma catecholamines. Rather, it is caused by the combination of excessively high local noradrenaline concentrations and an enhanced responsiveness of the myocyte to catecholamines. Myocardial ischaemia of 15 min duration results in a 100-fold increase in catecholamine concentrations within the extracellular space of the ischaemic zone, a two-fold increase in functionally coupled alpha-adrenoceptors, and a 30% increase in beta-adrenoceptors. Within the first 10 min of ischaemia, the myocardium is protected from excessive catecholamine release. Ischaemia-associated metabolic alterations, such as extracellular potassium accumulation, acidosis, and especially the accumulation of adenosine reduce the transmitter release caused by central sympathetic activation. Furthermore, the functional neuronal amine reuptake (uptake1) prevents excessive local accumulation of noradrenaline. With progression of ischaemia to more than 10 min, local nonexocytotic catecholamine release becomes predominant. This release is independent of central sympathetic nerve activity, availability of extracellular calcium, activation of both neuronal calcium channels and protein kinase C, and it is not accompanied by the release of sympathetic cotransmitters such as neuropeptide Y. It has been demonstrated to be nonexocytotic and to be caused by a carrier-mediated transport of noradrenaline from the sympathetic nerve ending into the synaptic cleft. This release is not modulated through presynaptic receptors. It is, however, suppressed by blockers of uptake1 and by inhibitors of sodium-proton exchange. Depletion of cardiac catecholamine stores by chronic surgical or chemical sympathectomy effectively suppresses malignant arrhythmias induced by experimental coronary ligature. Accordingly, inhibitors of nonexocytotic noradrenaline release, such as uptake1 blocking agents or sodium-proton exchange inhibitors, effectively reduce the occurrence of ischaemia-associated ventricular fibrillation, emphasizing the relevance of nonexocytotic release mechanisms in myocardial ischaemia.

Topics: Animals; Arrhythmias, Cardiac; Heart; Humans; Myocardial Infarction; Neuropeptide Y; Norepinephrine

Few studies have described how neurohormonal activation is influenced by treatment with beta-receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta(1) receptor-antagonist compared to a partial beta(1) receptor-agonist.. Double-blind, randomized comparison of metoprolol 50-100 mg b.i.d. (n=74), and xamoterol 100-200 mg b.i.d (n=67). Catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed.. N-ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY-LI which was greater (by 3.9 pmol/l, 95% CI 1.2-6.6) in the metoprolol group. N-ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209-607). Increase above median of NPY-LI (>25.2 pmol/l, odds ratio 2.8, P=0.0050) and N-ANF (>1043 pmol/l, odds ratio 2.8, P=0.0055) were related to long term (mean follow-up 6.8 years) cardiovascular mortality.. Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin-angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta-receptor antagonists. The small increase in NPY-LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N-ANF may be explained by changes in cardiac preload, renal function, and differences in beta-receptor mediated inhibition of atrial release of N-ANF. NPY-LI, and N-ANF at discharge were related to long term cardiovascular mortality.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chi-Square Distribution; Dopamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography, Doppler; Epinephrine; Female; Follow-Up Studies; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Probability; Proportional Hazards Models; Prospective Studies; Survival Rate; Treatment Outcome; Xamoterol

Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY wild-type/knockout (WT/KO) mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, and excessive apoptosis but impairing angiogenesis. All of these changes were reversed when the NPY KO mice were treated with exogenous NPY in a dose-dependent manner. Interestingly, treatment with NPY also dose dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart-failure patients and AMI mice. Mechanistically, NPY was induced by transforming growth factor (TGF)-β1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/nuclear factor κB (NF-κB)-mediated M1 macrophage activation while promoting the reparative M2 phenotype in vivo and in vitro. In conclusion, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI.

Topics: Animals; Humans; Mice; Mice, Knockout; Myocardial Infarction; Neuropeptide Y; Ventricular Remodeling

Acute myocardial infarction (AMI) is considered a major cause of death and disability. Myocardial perfusion scintigraphy (MPS) as a non-invasive diagnostic imaging procedure and certain biomarkers associated with myocardial ischemia (ISCH), such as ischemia-modified albumin (IMA), neuropeptide Y (NPY), N-terminal pro b-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) could probably aid in the detection of myocardial infarction.. Between December 2011 and June 2012, we prospectively analyzed patients who underwent a MPS study with the clinical question of myocardial ISCH. An exercise test was performed along with a MPS. Blood was drawn from the patients before exercise and the within 3 minutes from achieving maximum load and was analyzed for the aforementioned biomarkers.. A total of 71 patients (56 men and 15 women) were enrolled with a mean age of 61 ± 12 years. Twenty-six patients (36.6%) showed reduced uptake on stress MPS images that normalized at rest, a finding consistent with ISCH. Between ISCH and non-ISCH groups, only hsTnT levels showed a significant difference with the highest levels pertaining to the former group both before (0.0075 ng/ml vs 0.0050 ng/ml, P = 0.023) and after stress exercise (0.0085 vs 0.0050, P = 0.015). The most prominent differences were seen in higher stages of the Bruce protocol (stress duration > 9.05 minutes - P < 0.017). None of the IMA, NPY, and NP-pro BNP showed significant differences in time between the two groups.. Although IMA, NPY, and NT-pro BNP may not detect minor ischemic myocardial insults, serum hsTnT holds a greater ability of detecting not only myocardial infarction but also less severe ischemia. Further studies with larger cohorts of patients are warranted in order to better define the role of hsTnT as a screening tool for myocardial ischemia.

Topics: Aged; Area Under Curve; Biomarkers; Exercise; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Neuropeptide Y; Peptide Fragments; Probability; Prospective Studies; Sensitivity and Specificity; Serum Albumin, Human; Troponin T

The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium.. Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (. RDN in the infarcted pig model leads to reduction of postinfarction VAs and myocardial sympathetic effectors. This may form the basis for a potential therapeutic role of RDN in postinfarct VAs.

Topics: Animals; Disease Models, Animal; Female; Heart; Heart Rate; Kidney; Male; Myocardial Infarction; Myocardium; Nerve Growth Factor; Neuropeptide Y; Renal Artery; Sus scrofa; Sympathectomy; Sympathetic Nervous System; Tachycardia, Ventricular; Time Factors

Myocardial infarction (MI) induces remodeling in stellate ganglion neurons (SGNs).. We investigated whether infarct site has any impact on the laterality of morphologic changes or neuropeptide expression in stellate ganglia.. Yorkshire pigs underwent left circumflex coronary artery (LCX; n = 6) or right coronary artery (RCA; n = 6) occlusion to create left- and right-sided MI, respectively (control: n = 10). At 5 ± 1 weeks after MI, left and right stellate ganglia (LSG and RSG, respectively) were collected to determine neuronal size, as well as tyrosine hydroxylase (TH) and neuropeptide Y immunoreactivity.. Compared with control, LCX and RCA MIs increased mean neuronal size in the LSG (451 ± 25 vs 650 ± 34 vs 577 ± 55 μm(2), respectively; P = .0012) and RSG (433 ± 22 vs 646 ± 42 vs 530 ± 41 μm(2), respectively; P = .002). TH immunoreactivity was present in the majority of SGNs. Both LCX and RCA MIs were associated with significant decreases in the percentage of TH-negative SGNs, from 2.58% ± 0.2% in controls to 1.26% ± 0.3% and 0.7% ± 0.3% in animals with LCX and RCA MI, respectively, for LSG (P = .001) and from 3.02% ± 0.4% in controls to 1.36% ± 0.3% and 0.68% ± 0.2% in LCX and RCA MI, respectively, for RSG (P = .002). Both TH-negative and TH-positive neurons increased in size after LCX and RCA MI. Neuropeptide Y immunoreactivity was also increased significantly by LCX and RCA MI in both ganglia.. Left- and right-sided MIs equally induced morphologic and neurochemical changes in LSG and RSG neurons, independent of infarct site. These data indicate that afferent signals transduced after MI result in bilateral changes and provide a rationale for bilateral interventions targeting the sympathetic chain for arrhythmia modulation.

Topics: Animals; Coronary Vessels; Disease Models, Animal; Electrocardiography; Myocardial Infarction; Neuronal Plasticity; Neurons; Neuropeptide Y; Spatial Analysis; Stellate Ganglion; Swine; Tyrosine 3-Monooxygenase

The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI).. Prospective observational study.. University hospital heart centre.. 64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction.. PPCI.. NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance.. Plasma NPY levels were highest before PPCI (17.4 (8.8-42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5-26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6-21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI.. Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance.

Topics: Aged; Analysis of Variance; Biomarkers; Chi-Square Distribution; Coronary Angiography; Coronary Circulation; Electrocardiography; England; Enzyme-Linked Immunosorbent Assay; Female; Hospitals, University; Humans; Male; Microcirculation; Middle Aged; Myocardial Infarction; Neuropeptide Y; No-Reflow Phenomenon; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Risk Factors; Stents; Time Factors; Treatment Outcome; Vascular Resistance

Topics: Coronary Angiography; Coronary Circulation; Electrocardiography; Female; Humans; Male; Myocardial Infarction; Neuropeptide Y; Percutaneous Coronary Intervention

Neuropeptide Y (NPY) induced reentry of differentiated rat neonatal and adult cardiomyocytes into the cell cycle. NPY also induced differentiation of bone marrow-derived mesenchymal stem cells (MSC) into cardiomyocytes following transplantation into infarcted myocardium. Rat neonatal and adult cardiomyocytes were treated in vitro with vehicle, NPY, fibroblast growth factor (FGF; 100 ng/ml), or FGF plus NPY. DNA synthesis, mitosis, and cytokinesis were determined by immunocytochemistry. NPY-induced MSC gene expression, cell migration, tube formation, and endothelial cell differentiation were analyzed. Male rat green fluorescent protein-MSC (2 x 10(6)), pretreated with either vehicle or NPY (10(-8) M) for 72 h, were injected into the border zone of the female myocardium following left anterior descending artery ligation. On day 30, heart function was assessed, and hearts were harvested for histological and immunohistochemical analyses. NPY increased 5-bromo-2'-deoxy-uridine incorporation and promoted both cytokinesis and mitosis in rat neonatal and adult myocytes. NPY also upregulated several genes required for mitosis in MSC, including aurora B kinase, FGF-2, cycline A2, eukaryotic initiation factor 4 E, and stromal cell-derived factor-1alpha. NPY directly induced neonatal and adult cardiomyocyte cell-cycle reentry and enhanced the number of differentiated cardiomyocytes from MSC in the infarcted myocardium, which corresponded to improved cardiac function, reduced fibrosis, ventricular remodeling, and increased angiomyogenesis. It is concluded that a combined treatment of NPY with MSC is a novel approach for cardiac repair.

Topics: Animals; Blotting, Western; Cell Differentiation; Cell Movement; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Heart Function Tests; Hypoxia; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Infarction; Myocytes, Cardiac; Neovascularization, Physiologic; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation; Vascular Endothelial Growth Factor A; Ventricular Remodeling

Cardiac ischemia-reperfusion alters sympathetic neurotransmission in the heart, but little is known about its effect on neuropeptide expression in sympathetic neurons. Ischemia followed by reperfusion induces the production of inflammatory cytokines in the heart, including interleukin-6 and cardiotrophin-1. These cytokines and related molecules inhibit the expression of neuropeptide Y (NPY), and stimulate the expression of vasoactive intestinal peptide (VIP), substance P (SubP), and galanin (GAL) in cultured sympathetic neurons. Therefore, we quantified NPY, VIP, SubP, and GAL mRNA in neurons of the stellate ganglia 1 week after ischemia-reperfusion to determine if neuropeptide expression was altered in cardiac sympathetic neurons. NPY, VIP, and SubP mRNAs were unchanged compared to unoperated control animals, but GAL mRNA was increased significantly. The increased GAL mRNA was not accompanied by elevated GAL peptide content in the stellate ganglia. Galanin content was increased significantly in the heart, however, indicating that elevated GAL mRNA led to increased peptide production. GAL content was increased in the left ventricle below the coronary artery ligation, but was not increased significantly in the atria or the base of the heart above the ligation. The buildup of GAL specifically in the damaged left ventricle is consistent with previous reports that GAL is transported to regenerating nerve endings after axon damage.

Topics: Animals; Coronary Vessels; Galanin; Gene Expression; Heart; Ligation; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Neurons; Neuropeptide Y; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; RNA, Messenger; Substance P; Sympathetic Nervous System; Vasoactive Intestinal Peptide

Neuropeptide Y (NPY) has been recently characterised as one of the strongest circulating vasoconstrictor peptides, its elevated level may cause coronary artery spasm and increase of peripheral vascular resistance. All this contributes to ischemic myocardial damage and decrease of regional and global left ventricular function. The aim of the study was the examination of NPY plasma levels in patients with acute myocardial infarction (AMI) after thrombolytic therapy with or without reperfusion. The survey was made in 82 patients with AMI after thrombolytic therapy: 40 of them without reperfusion and 42 with reperfusion. The control group consisted of 20 healthy persons. Plasma levels of NPY were measured before thrombolysis, then 1, 3 and 5 days after, using a radioimmunologic method. All patients were treated with aspirin, glyceryl trinitrate and thrombolytic therapy (TT) with alteplase (r-TPA). In patients with AMI, NPY plasma levels were normal before and 1 day after TT, and were significant elevated 3 days after TT 5 days after TT, plasma NPY levels were still high in patients without reperfusion, but they decreased in patients with reperfusion. There was significant negative correlation between NPY level and left ventricular ejection fraction measured 5 days after AMI. During 30-days follow up systolic dysfunction of left ventricle with ejection fraction under 40% occurred in 21 patients and in 11 of them clinical symptoms of heart failure were observed. Using the multivariable regression analysis we showed that NPY concentration over 60 pg/ml is the independent factor leading to left ventricle systolic dysfunction. The results of our study suggest the contribution of NPY to the left ventricular remodeling after AMI.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y

To investigate the change characteristics of neuropeptide Y (NPY) release during acute myocardial ischemia period.. The animal test was carried out in in situ perfused guinea pig hearts with intact sympathetic innervation. Electrical stimulation-evoked exocytotic release of NPY during ischemia and reperfusion was tested by radioimmunoassay (RIA). The plasma NPY concentrations were measured in patients with acute myocardial infarction (AMI) and angina pectoris (AP) in different times.. Electric stimulation of the left ganglion in guinea pig heart evoked an exocytic release of neuropeptide Y. Stimulation after 20 minutes of global ischemia (S2), compared with control period stimulation (S1) produced the inhibition of NPY to a certain extent (S2/S1: 0.72, P < 0.05), whereas the inhibition of NPY release disappeared after 5 minutes reperfusion (with S2/S1 of 1.01, P > 0.05). Ischemia alone, without the electric stimulation, did not apparently induce NPY release. The clinical test found that the plasma NPY level was increased significantly during the acute ischemia attack period of coronary heart disease (CHD). The plasma NPY level reached peak (136.3 +/- 66.5 pg/ml) in patients during the first day after AMI. It began to decrease from the third day and came to normal level in the end of the first week. The plasma NPY level was 159.3 +/- 98.5 pg/ml in AP patients during angina attack. After two weeks treatment, the plasma NPY level was decreased to 118.9 +/- 54.3 pg/ml (P < 0.05).. The NPY release of global ischemia have some relation with sympathetic nerve activity. At the early stage of ischemia, NPY release is inhibited to some degree and the inhibition factors will fade away on reperfusion. NPY interferes with the pathogenesis and the pathophysiolgy.

Topics: Aged; Angina Pectoris; Animals; Electric Stimulation; Guinea Pigs; Humans; In Vitro Techniques; Middle Aged; Myocardial Infarction; Neuropeptide Y; Sympathetic Nervous System

We examined the possible effect of neuropeptide Y in modulating central sympathetic activity after myocardial infarction in rats.. Previous studies have shown the coexistence of neuropeptide Y and norepinephrine in the brain and a possible functional interaction between the two. Neuropeptide Y inhibits the release of norepinephrine at the presynaptic level and can be considered to act as a neuromodulator.. Two groups of rats were examined in this study-an experimental group, defined as those rats undergoing left coronary artery ligation, and a sham group without coronary artery ligation, serving as the control group. The animal in both groups underwent microdialysis in the paraventricular nucleus at 2, 4 and 8 weeks after operation. Microdialysis samples were collected with and without injecting neuropeptide Y in the paraventricular nucleus. The concentration of norepinephrine was determined by injecting purified microdialysate samples during high performance liquid chromatography. To explore the receptor's possible role, autoradiographic localization of neuropeptide Y receptors in the paraventricular nucleus was also carried out in the experimental and sham groups.. The concentration of norepinephrine measured in the samples was decreased by 50% with neuropeptide Y in 2- and 4-week old rats after infarction, but by only 20% (p < 0.05) in 8-week old rats after infraction. The diminished inhibitory effects of neuropeptide Y on norepinephrine release was associated with increased sympathetic activity, as reflected by plasma norepinephrine; 8-week old rats after infarction had almost a 100% (p < 0.05) increase in their plasma norepinephrine level compared with the sham group. Autoradiography revealed a significant decrease in density of neuropeptide Y receptors in the paraventricular nucleus in 8-week old rats after infarction (p < 0.05).. The data presented in this report suggest that the reduction of the inhibitory activation of neuropeptide Y on sympathetic release may contribute to elevated norepinephrine levels after myocardial infarction.

Topics: Animals; Autoradiography; Male; Microdialysis; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Sympathetic Nervous System

Topics: Adult; Female; Humans; Magnesium; Magnesium Sulfate; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Raynaud Disease; Sympathetic Nervous System; Sympathomimetics

We wished to determine if chronic neuropeptide Y (NPY) infusion (1 ng/min for 1 week by Alzet minipump) could decrease plasma renin activity (PRA) and norepinephrine (NE) in a rat myocardial infarction (MI) model of moderate compensated congestive heart failure (CHF). CHF was produced by prior (6-8 weeks) ligation of the left coronary artery; control rats were sham-operated. Carotid arterial blood was drawn for PRA and NE in conscious unrestrained rats that had been instrumented 24 h earlier. MI rats had increased PRA as compared with sham-operated rats [8.73 +/- 1.27 vs. 5.10 +/- 0.91 ng angiotensin (AI) I/ml.h, mean +/- SE]. During chronic NPY infusion, PRA was reduced to normal in the MI group (4.78 +/- 0.91) but was not affected in the sham group (5.65 +/- 0.51). Plasma NE was altered similarly, but the changes did not reach statistical significance. These data suggest that NPY has the capacity to restrain renin release in moderate compensated CHF.

Topics: Animals; Heart; Heart Failure; Infusions, Intravenous; Male; Models, Cardiovascular; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Rats; Rats, Sprague-Dawley; Renin

Plasma neuropeptide Y-like immunoreactivity (NPY-LI) is elevated in patients with acute myocardial ischaemia and congestive heart failure (CHF) owing to increased activity of the sympathetic nervous system. The prognostic value of plasma NPY-LI with regard to mortality was studied in 324 random patients admitted to a coronary care unit. The one-year mortality was 37% in 113 patients with acute myocardial infarction (AMI) and 18% in those without AMI. Several factors were tested by multiple logistical regression analysis to predict the one-year mortality. Plasma NPY-LI > 60 pmol.l-1, advanced age and previous CHF were independent prognostic factors for an increased risk of mortality in patients without AMI. The mortality rate after one year in non-AMI patients with plasma NPY-LI < or = 60 pmol.l-1 was 14% compared to 69% in those with plasma NPY-LI > 60 pmol.l-1. Increased heart rate was the only independent prognostic factor for increased mortality in AMI patients. Plasma NPY-LI on admission was an independent predictor of mortality in CCU patients without AMI and thus resembles plasma noradrenaline.

Topics: Aged; Arrhythmias, Cardiac; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y; Prognosis; Risk Factors; Sensitivity and Specificity; Survival Rate

The sympathetic nervous system is activated in acute myocardial infarction (MI). Scarce data exist, however, regarding the release of the sympathetic cotransmitter neuropeptide Y (NPY) during the acute and early convalescent phases after acute MI. Plasma NPY determination was obtained on days 1 and 3 after admission from 47 patients with acute MI and from eight control patients with acute chest pain without MI. Samples were also obtained on day 30 from the 39 survivors from the original MI cohort. Plasma NPY peaked on day 3 in the MI group (day 1: mean = 46.0 pmol/L, SEM = 6.4 pmol/L; day 3: mean = 60.8 pmol/L, SEM = 5.7 pmol/L; day 30: mean = 27.2 pmol/L, SEM = 4.1 pmol/L; days 1 to 3: p = 0.002; days 3 to 30: p < 0.001), whereas in the control group a nonsignificant decrease from day 1 (mean = 42.6 pmol/L, SEM = 12.3 pmol/L) to day 3 (mean = 34.0 pmol/L, SEM = 5.6 pmol/L) was observed. Plasma NPY levels were significantly increased in patients with MI on day 3 (p = 0.044), but not at baseline compared with the control group. No significant association between plasma NPY and plasma catecholamines, clinical heart failure, or 1-month survival was evident. These results suggest that increased plasma levels of the vasoconstrictory and cardiodepressant sympathetic neurotransmitter NPY are present in the recovery phase of MI, but with a plasma profile distinct from that of catecholamines.

Topics: Age Factors; Aged; Case-Control Studies; Convalescence; Epinephrine; Female; Humans; Male; Multivariate Analysis; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Sex Factors; Survival Rate

A time course (48 hours) of plasma neuropeptide Y (NPY) levels has been carried out in a male, 66 years old, admitted to Coronary Care Unit with inferior acute myocardial infarction within 1 hour from the onset of chest pain. On admission an increase of plasma NPY levels (38 pg/ml) has been observed. The plasma NPY value decreased to normal range (15-25 pg/ml) within 12 hours and increased again (53 pg/ml) within 12 and 24 hours. A decrease in plasma NPY values to normal range has been observed within the second day in the Coronary Care Unit. A clearcut diuresis decrease, without pulmonary signs of heart failure, was present from 12 to 24 hours followed by marked polyuria within the second day. These data point out a relative importance of NPY in the diuresis adjustments. Thus, plasma NPY measurement might be a more reliable prognostic indicator of heart failure than plasma catecholamine levels. However, further investigations have to be performed.

Topics: Aged; Coronary Care Units; Emergencies; Humans; Italy; Male; Myocardial Infarction; Neuropeptide Y

The aim of the study was to measure plasma neuropeptide Y (NPY) in patients with acute myocardial infarction (AMI). Eighteen patients (13 females and 5 males; range 55 to 75 years) admitted both early (n 12; mean preadmission time 3 +/- 2 hours) and late (n 6; mean preadmission time 25 +/- 16 hours) to Coronary Care Unit were studied. Plasma NPY values significantly above normal range (15-25 pg/ml) and early admitted patients (26 +/- 10 pg/ml) have been found in late admitted patients (72 +/- 28 pg/ml; p < 0.05) both on the admission and during the stay in the Coronary Care Unit (96 hours). In early admitted patients no significant correlation was found between both AMI localization and the thrombolytic treatment. A significant increase in plasma NPY levels has been observed in all patients with complicated myocardial infarction (both in subclinic and clinic heart failure or extension of infarct size). According with the literature data our results have shown a significant correlation between increase of plasma NPY levels and failure of myocardial pump. Moreover, the plasma NPY increase which has been observed in preclinic heart failure when plasma catecholamine levels is usually not significantly different from normal values, may be a useful and reliable prognostic marker.

Topics: Aged; Coronary Care Units; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y

Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease. On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels. The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris. Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris. Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris. Levels of NPY-LI returned to normal within 25 h in all patients. Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels. A positive correlation was found between noradrenaline and NPY-LI in plasma. It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Blood Pressure; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Pain Measurement; Sampling Studies; Time Factors

STUDY OBJECTIVE - The aim of the study was to measure plasma neuropeptide Y, which is related to sympathetic nerve stimulation, in patients admitted to a coronary care unit and to relate the findings to clinical information. DESIGN - Plasma neuropeptide Y was measured on admission and the results were related to the cause of admission and to clinical information collected prospectively and retrospectively. SUBJECTS - Plasma subjects were obtained from 377 consecutive daytime admissions to the coronary care unit at Södersjukhuset. Results of only the first sample in each patient are included in this study, so 45 cases observed more than once (readmitted patients) were omitted. Six samples were abandoned because of technical failures. The study therefore comprises 326 patients. Clinical diagnoses were defined as acute myocardial infarction, arrhythmia, angina pectoris, and miscellaneous (all other diagnoses). Heart failure was defined according to a modified Killip scheme. MEASUREMENTS and RESULTS - Neuropeptide Y like immunoreactivity was measured by radio-immunoassay. Plasma concentrations above normal (greater than 30 pmol.litre-1) were found in association with: increased age, female sex, diuretic treatment, tachycardia, arterial hypotension, increased respiratory rate, and mortality in the unit. There was a strong relationship between high neuropeptide Y concentrations and: moderate left heart failure (63%), pulmonary oedema (90%), and cardiogenic shock (100%). Of patients without heart failure only 25% had raised neuropeptide Y. In multivariate analysis, the severity of heart failure (Killip class), heart rate and respiratory rate were the only variables that were significantly and independently related to plasma neuropeptide Y. CONCLUSIONS - The presence and degree of circulatory disturbance, in particular tachycardia and left heart failure, were strongly related to increased plasma concentrations of neuropeptide Y in coronary care patients.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Coronary Care Units; Diuretics; Epinephrine; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Pilot Projects; Pulmonary Edema; Risk Factors; Shock, Cardiogenic

Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099 +/- 0.014% for synaptophysin- and 0.037 +/- 0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin- and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide. When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as non-ischemic myocardium.

Topics: Animals; Autonomic Nervous System; Coronary Vessels; Dogs; Female; Heart; Heart Atria; Heart Ventricles; Immunohistochemistry; Ligation; Male; Membrane Proteins; Myocardial Infarction; Myocardium; Neuropeptide Y; Synaptophysin; Tissue Distribution

We have investigated the hypothesis that neuropeptide Y (NPY) is released from noradrenergic sympathetic nerves during experimentally induced myocardial infarction. A left thoracotomy was performed, the left main coronary artery ligated, and the animals sacrificed 4 or 48 h later. NPY levels in heart tissue from these rats and sham-operated controls were measured with radioimmunoassay. Levels of NPY in the right atrium were greater than other regions of the rat heart. After ligation of the left coronary artery, the concentration of NPY in the infarcted area of the left ventricle was reduced at 4 and 48 h when compared to a similar area in sham-operated rats. NPY levels in the septum were unchanged. The results suggest that during myocardial infarction, NPY is released from nerves in the infarcted region and may deleteriously affect increased collateral blood flow surrounding the infarcted tissue.

Topics: Animals; Coronary Vessels; Heart; Heart Atria; Heart Septum; Heart Ventricles; Ligation; Male; Myocardial Infarction; Myocardium; Neuropeptide Y; Rats; Rats, Inbred Strains; Sympathetic Nervous System

Neuropeptide Y was infused into a coronary artery of 6 patients with typical angina but no significant coronary stenosis. 3 patients had transient myocardial ischaemia, shown by typical pain and electrocardiographic change, at doses of 0.2 pmol/kg per min in 2 patients and 1.0 pmol/kg per min in 1 patient. The arteriographic appearances suggested constriction of small vessels rather than constriction of epicardial coronary arteries. The ischaemia was completely reversed by intracoronary administration of isosorbide dinitrate with no adverse sequelae. This is the first demonstration of myocardial ischaemia in man induced by a peptide neurotransmitter.

Topics: Adult; Aged; Angina Pectoris; Angiography; Coronary Angiography; Female; Humans; Infusions, Intra-Arterial; Isosorbide Dinitrate; Middle Aged; Myocardial Infarction; Neuropeptide Y

Topics: Arginine Vasopressin; Coronary Circulation; Humans; Myocardial Infarction; Neuropeptide Y; Neurotransmitter Agents