EFFECTS OF VASOACTIVE-INTESTINAL-PEPTIDE ON MYOCARDIAL PERFORMANCE

It is now recognized that stimulation of the vagus releases both acetylcholine (ACh) and vasoactive intestinal peptide (VIP). Whereas ACh depresses cardiac function, recent data indicate that VIP may have a cardiostimulatory effect. Exogenously administered VIP appears to enhance left ventricular (LV) contractile function; however, whether endogenously released VIP alters LV performance is not known. Accordingly, we evaluated the effects of exogenous VIP and endogenously released VIP during vagal stimulation after muscarinic and beta-adrenergic blockade (VS-B) on LV performance using pressure-volume analysis. Eight anesthetized open-chest dogs instrumented to measure LV pressure and volume (conductance catheter) were pretreated with atropine (0.1 mg/kg) and propranolol (1 mg/kg). The cervical vagi were transected. Hemodynamic data were obtained at steady state and during transient vena caval occlusion. Exogenous intravenous VIP (0.05 mu g.kg(-1).min(-1)) increased HR minimally [2.1 +/- 0.9% increase; P = not significant (NS)] but significantly increased maximum first time derivative of left ventricular pressure (dP/dt(max) 29.4 +/- 19.9% increase; P < 0.05) and the slope of the end-systolic pressure-volume relation (E(es); 3.1 +/- 1.3 to 8.9 +/- 4.2 mmHg/ml; P < 0.05). Minimum first time derivative of left ventricular pressure (dP/dt(min)) decreased 22 +/- 16.2% (P < 0.05), and the time constant of isovolumic relaxation (tau) decreased 38 +/- 18% (P < 0.05). During VS-B (20 Hz, 15 v, 5 min), HR increased significantly (98 +/- 11 to 130 +/- 26 beats/min; P < 0.05). E(es) also increased significantly (3.3 +/- 1.6 vs. 5.2 +/- 2.8 mmHg/ml; P < 0.05). However, E(es) after VS-B was not significantly different from control at a similar heart rate (4.3 +/- 1.7 mmHg/ml; P = NS). No significant change was noted in dP/dt(min) (-1,882 +/- 692 mmHg/s to -1,905 +/- 785 mmHg/s; P = NS) and tau (71 +/- 23 ms to 69 +/- 24 ms; P = NS). In conclusion, exogenous VIP has positive chronotropic, inotropic, and lusitropic effects. How ever, endogenous VIP released during VS-B enhances cardiac performance primarily by increasing heart rate, without any direct effect on LV contractility or relaxation.