(Circulation. 1997;96:2675-2682.)
© 1997 American Heart Association, Inc.
Articles |
Inotropic Effects of Glyceryl Trinitrate and Spontaneous NO Donors in the Dog Heart
From the Physiologisches Institut I (B.P., D.E., V.T.), the Institut für Pharmakologie (G.K., K.K., E.N.), and the Institut für Klinische Anaesthesiologie (W.S.), Heinrich-Heine-Universität, Düsseldorf.
Correspondence to Prof Dr Volker Thämer, Physiologisches Institut I, Abteilung für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, Postfach 10 10 07, D-40001 Düsseldorf, Germany. E-mail benedikt{at}herzkreis.uni-duesseldorf.de
Background In vitro, NO has a biphasic effect on myocardial inotropy. To determine the inotropic effect of NO in vivo, we investigated the activity of glyceryl trinitrate (GTN) and the NO donors S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and sodium-(2)-1-(N,N-diethyl-amino)-diazen-1-ium-1,2-diolat (DEA/NO) in dogs.
Methods and Results Eight anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressures (tip manometers) and coronary flow (ultrasonic flow probes). Regional myocardial function was assessed by sonomicrometry as systolic wall thickening (sWT), mean systolic thickening velocity (Vs), and regional myocardial stroke work index (RSW). GTN, SNAP, and DEA/NO were infused into the left anterior descending coronary artery (LAD) to achieve defined coronary plasma concentrations of GTN, SNAP (both 10 to 100 µmol/L), and DEA/NO (2 to 20 µmol/L). All drugs increased LAD flow and myocardial contractile function in the LAD-dependent myocardium within the first 120 seconds. The greatest inotropic effect was noted after infusion of DEA/NO (20 µmol/L), which increased sWT by 9.7±3.1% from 28.5±2.2%, Vs by 10.3±3.4% from 9.1±1.1 mm/s, and RSW by 7.1±2.1% from 200.0±22.1 mm Hgxmm (P<.05). At the same time, systemic hemodynamics remained unchanged. Prevention of the flow response to GTN by external narrowing of the LAD did not influence the inotropic effect of GTN.
Conclusions Organic nitrates and NO donors evoke a small but constant positive inotropic effect in vivo that is not caused by coronary vasodilation.
Key Words: endothelium-derived factors • myocardial contraction • contractility • nitroglycerin
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