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 micromol/L), and DEA/NO (2 to 20 micromol/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 micromol/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 Hg x mm (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.
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 micromol/L), and DEA/NO (2 to 20 micromol/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 micromol/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 Hg x mm (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.
Authors: Kalkidan Bishu; Nazha Hamdani; Selma F Mohammed; Martina Kruger; Tomohito Ohtani; Ozgur Ogut; Frank V Brozovich; John C Burnett; Wolfgang A Linke; Margaret M Redfield Journal: Circulation Date: 2011-12-05 Impact factor: 29.690
Authors: N Paolocci; W F Saavedra; K M Miranda; C Martignani; T Isoda; J M Hare; M G Espey; J M Fukuto; M Feelisch; D A Wink; D A Kass Journal: Proc Natl Acad Sci U S A Date: 2001-08-21 Impact factor: 11.205
Authors: Tieying Dai; Ye Tian; Carlo Gabriele Tocchetti; Tatsuo Katori; Anne M Murphy; David A Kass; Nazareno Paolocci; Wei Dong Gao Journal: J Physiol Date: 2007-03-01 Impact factor: 5.182