neuropeptide-y and Arrhythmias--Cardiac

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

Topics: Arrhythmias, Cardiac; Heart; Humans; Neuropeptide Y; ST Elevation Myocardial Infarction; Sympathetic Nervous System

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

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