Sodium nitroprusside enhances in vivo left ventricular function in beta-adrenergically stimulated rabbit hearts.
OBJECTIVE
Sodium nitroprusside (SNP) is an activator of soluble guanylate cyclase, which depresses myocardial contractility. These exclusively negative inotropic effects of SNP were recently challenged by in vitro data.. In isolated rat ventricular myocytes, a moderate increase of cGMP improved the contractile response at baseline and in isoprenaline-stimulated conditions. The present study evaluated in vivo the inotropic effects of SNP at baseline and during administration of low dose dobutamine.


METHODS
Anesthetized open-chest rabbits (n = 18) were instrumented with micromanometers, ultrasound crystals and atrial pacing wires. Measurements were obtained during caval occlusion with ventilation suspended at end-expiration. Systolic function was assessed with dP/dtmax and the slope Ees of the end-systolic pressure-volume relation. Diastolic function was assessed with the time constant tau and the stiffness constant Kc of the diastolic pressure-volume relation. SNP (0.02, 0.08, 0.32 microgram x kg-1) was administered at baseline and during low dose dobutamine.


RESULTS
At baseline, SNP reduced dP/dtmax from 3750 +/- 88 to 3470+/- 88 mmHg/s (mean +/- s.e.m.) and Ees from 148 +/- 16 to 103 +/- 13 mmHg/ml (P < 0.01) . During dobutamine infusion, SNP increased dP/dtmax from 4340 +/- 125 to 4681 +/- 230 mmHg/s and Ees from 148 +/- 19 to 190 +/- 30 mmHg/ml (P < 0.01). Effects of SNP on dP/dtmax and Ees were different at baseline and during dobutamine (interaction P < 0.01). SNP did not alter Kc at baseline nor during dobutamine.


CONCLUSIONS
SNP enhances in vivo systolic function in beta-adrenergically stimulated rabbits.
De Mulder
P A
PA
Department of Anesthesiology, University of Antwerp, Belgium.
De Hert
S G
SG
Van Kerckhoven
R J
RJ
Adriaensen
H F
HF
Gillebert
T C
TC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006162:Guanylate Cyclase / Q000187:drug effects*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical; D013599:Systole; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D014665:Vasodilator Agents; D009599:Nitroprusside; D004280:Dobutamine; D006162:Guanylate Cyclase