SODIUM-NITROPRUSSIDE ENHANCES IN-VIVO LEFT-VENTRICULAR FUNCTION IN BETA-ADRENERGICALLY STIMULATED RABBIT HEARTS

Objective: Sodium nitroprusside (SNP) is an activator of soluble guany late cyclase, which depresses myocardial contractility. These exclusiv ely negative inotropic effects of SNP were recently challenged by in v itro data. In isolated rat ventricular myocytes, a moderate increase o f cGMP improved the contractile response at baseline and in isoprenali ne-stimulated conditions. The present study evaluated in vivo the inot ropic effects of SNP at baseline and during administration of low dose dobutamine, Methods: Anesthetized open-chest rabbits (n = 18) were in strumented with micromanometers, ultrasound crystals and atrial pacing wires. Measurements were obtained during caval occlusion with ventila tion suspended at end-expiration. Systolic function was assessed with dP/dt(max) and the slope E-es of the end-systolic pressure-volume rela tion. Diastolic function was assessed with the time constant tau and t he stiffness constant K-c of the diastolic pressure-volume relation. S NP (0.02, 0.08, 0.32 mu g . kg(-1) . min(-1)) was administered at base line and during low dose dobutamine. Results: At baseline, SNP reduced dP/dt(max) from 3750 +/- 88 to 3470 +/- 88 mmHg/s (mean +/- s.e.m.) a nd E-es from 148 +/- 16 to 103 +/- 13 mmHg/ml (P < 0.01). During dobut amine infusion, SNP increased dP/dt(max) from 4340 +/- 125 to 4681 +/- 230 mmHg/s and E-es from 148 +/- 19 to 190 +/- 30 mmHg/ml (P < 0.01). Effects of SNP on dP/dt(max) and E-es were different at baseline and during dobutamine (interaction P < 0.01). SNP did not alter K-c at bas eline nor during dobutamine. Conclusions: SNP enhances in vivo systoli c function in beta-adrenergically stimulated rabbits. (C) 1998 Elsevie r Science B.V.