neuropeptide-y and Ventricular-Fibrillation

ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors.. In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P < 0.05) higher venous NPY levels despite the absence of classical risk factors including late presentation, larger infarct size, and beta-blocker usage. Receiver operating curve identified an NPY threshold of 27.3 pg/mL with a sensitivity of 0.83 and a specificity of 0.71. RT-qPCR demonstrated the presence of NPY mRNA in both human and rat stellate ganglia. In the isolated Langendorff perfused rat heart, prolonged (10 Hz, 2 min) stimulation of the stellate ganglia caused significant NPY release. Despite maximal beta-blockade with metoprolol (10 μmol/L), optical mapping of ventricular voltage and calcium (using RH237 and Rhod2) demonstrated an increase in magnitude and shortening in duration of the calcium transient and a significant lowering of ventricular fibrillation threshold. These effects were prevented by the Y1 receptor antagonist BIBO3304 (1 μmol/L). Neuropeptide Y (250 nmol/L) significantly increased the incidence of VT/VF (60% vs. 10%) during experimental ST-elevation ischaemia and reperfusion compared to control, and this could also be prevented by BIBO3304.. The co-transmitter NPY is released during sympathetic stimulation and acts as a novel arrhythmic trigger. Drugs inhibiting the Y1 receptor work synergistically with beta-blockade as a new anti-arrhythmic therapy.

Topics: Animals; Heart; Humans; Neuropeptide Y; Percutaneous Coronary Intervention; Rats; ST Elevation Myocardial Infarction; Ventricular Fibrillation

The implanted cardioverter defibrillator represents an alternative therapy for patients with drug-refractory malignant ventricular arrhythmias. Implantation and testing of the device requires that ventricular fibrillation be evoked and converted, thus providing a situation in which cardiovascular haemodynamics can be studied. In this study we have evaluated the effects of electrically induced ventricular fibrillation, followed by defibrillation, on coronary sinus blood flow and cardiac outflow of endothelin- and neuropeptide Y-like immunoreactivity (-LI) and of noradrenaline. Twelve patients were studied during implantation of a defibrillator. Ventricular fibrillation was induced and terminated after 17 +/- 1 s 5 +/- 1 times in each patient. In six patients coronary sinus blood flow was measured continuously. Plasma samples were obtained from four of these patients and another six patients, from the coronary sinus, radial artery and central vein before and during fibrillation and at two time points ( < 30 s and 5 min). Basal coronary sinus blood flow decreased to 38% at 14 +/- 2 s of ventricular fibrillation. Immediately following defibrillation there was a short-lasting increase in coronary sinus blood flow to 244% and a significant increase in the levels of neuropeptide Y-LI (146%) and noradrenaline (158%) in the coronary sinus while endothelin-LI remained unchanged (97%). Neither fibrillation nor defibrillation evoked any changes in the peripheral arterial and venous levels of endothelin-, neuropeptide Y-LI or noradrenaline. It is concluded that coronary sinus blood flow is markedly reduced during fibrillation and that restoration of normal impulse activity is followed by short-lasting hyperaemia. There was no evidence for effects on the vascular endothelium as assessed by endothelin levels.

Topics: Adult; Aged; Cardiac Pacing, Artificial; Coronary Circulation; Defibrillators, Implantable; Electrocardiography; Endothelins; Female; Hemodynamics; Humans; Hyperemia; Male; Middle Aged; Myocardium; Neuropeptide Y; Norepinephrine; Reference Values; Ventricular Fibrillation