EFFECTS OF VASOACTIVE-INTESTINAL-PEPTIDE ON MYOCARDIAL PERFORMANCE

It is now recognized that stimulation of the vagus releases both acety lcholine (ACh) and vasoactive intestinal peptide (VIP). Whereas ACh de presses cardiac function, recent data indicate that VIP may have a car diostimulatory effect. Exogenously administered VIP appears to enhance left ventricular (LV) contractile function; however, whether endogeno usly released VIP alters LV performance is not known. Accordingly, we evaluated the effects of exogenous VIP and endogenously released VIP d uring vagal stimulation after muscarinic and beta-adrenergic blockade (VS-B) on LV performance using pressure-volume analysis. Eight anesthe tized open-chest dogs instrumented to measure LV pressure and volume ( conductance catheter) were pretreated with atropine (0.1 mg/kg) and pr opranolol (1 mg/kg). The cervical vagi were transected. Hemodynamic da ta were obtained at steady state and during transient vena caval occlu sion. Exogenous intravenous VIP (0.05 mu g.kg(-1).min(-1)) increased H R minimally [2.1 +/- 0.9% increase; P = not significant (NS)] but sign ificantly 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 ve ntricular 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 significan tly (98 +/- 11 to 130 +/- 26 beats/min; P < 0.05). E(es) also increase d significantly (3.3 +/- 1.6 vs. 5.2 +/- 2.8 mmHg/ml; P < 0.05). Howev er, 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 chan ge was noted in dP/dt(min) (-1,882 +/- 692 mmHg/s to -1,905 +/- 785 mm Hg/s; P = NS) and tau (71 +/- 23 ms to 69 +/- 24 ms; P = NS). In concl usion, exogenous VIP has positive chronotropic, inotropic, and lusitro pic effects. How ever, endogenous VIP released during VS-B enhances ca rdiac performance primarily by increasing heart rate, without any dire ct effect on LV contractility or relaxation.