BACKGROUND AND AIMS: The effect of nitric oxide (NO) manipulation in acute heart failure has not been sufficiently investigated. Therefore, we assessed the impact of NO-synthase (NOS) inhibition on left ventricular (LV) function and energetics as well as overall hemodynamics, in a porcine model of acute ischemic LV failure. METHODS: Acute heart failure was induced by left coronary artery microembolization in fourteen anesthetized pigs. LV pressure-volume relationships and mechanical work (PVA) were assessed 30 min after stable heart failure, using pressure-conductance catheters. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. Microembolization led to a significant decrease in cardiac output, arterial pressure and LV systolic and diastolic performance. Animals were then randomized to a control group (n=7) or to receive 15 mg/kg N(omega)-Nitro-L-arginine-metyl ester (n=7), an inhibitor of NO synthase (NOS). RESULTS: Measurements 15 min later revealed that NOS inhibited animals had significantly reduced cardiac output (1.53+/-0.45 vs. 2.13+/-0.49 l/min, P=0.003) and stroke work (1054+/-461 vs. 1296+/-348 mmHg ml, P=0.03), and also displayed a significant increase in the slope of the MVO(2)-PVA relationship (2.57+/-0.53 vs. 1.92+/-0.15, P=0.008), i.e. an inefficient chemomechanical coupling. NOS inhibition did not alter contractility, diastolic function or arterial pressure, but afterload was significantly increased compared to controls (arterial elastance 6.03+/-1.48 vs. 2.74+/-0.34 mmHg/ml, P=0.009). CONCLUSION: Inhibition of NOS in experimental acute heart failure increased afterload without altering left ventricular systolic and diastolic function. Consequently, cardiac output was reduced. Furthermore, mechanoenergetic efficiency was severely impaired. NOS inhibition in acute heart failure and cardiogenic shock warrants further investigations.
BACKGROUND AND AIMS: The effect of nitric oxide (NO) manipulation in acute heart failure has not been sufficiently investigated. Therefore, we assessed the impact of NO-synthase (NOS) inhibition on left ventricular (LV) function and energetics as well as overall hemodynamics, in a porcine model of acute ischemic LV failure. METHODS:Acute heart failure was induced by left coronary artery microembolization in fourteen anesthetized pigs. LV pressure-volume relationships and mechanical work (PVA) were assessed 30 min after stable heart failure, using pressure-conductance catheters. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenousoxygen difference. Microembolization led to a significant decrease in cardiac output, arterial pressure and LV systolic and diastolic performance. Animals were then randomized to a control group (n=7) or to receive 15 mg/kg N(omega)-Nitro-L-arginine-metyl ester (n=7), an inhibitor of NO synthase (NOS). RESULTS: Measurements 15 min later revealed that NOS inhibited animals had significantly reduced cardiac output (1.53+/-0.45 vs. 2.13+/-0.49 l/min, P=0.003) and stroke work (1054+/-461 vs. 1296+/-348 mmHg ml, P=0.03), and also displayed a significant increase in the slope of the MVO(2)-PVA relationship (2.57+/-0.53 vs. 1.92+/-0.15, P=0.008), i.e. an inefficient chemomechanical coupling. NOS inhibition did not alter contractility, diastolic function or arterial pressure, but afterload was significantly increased compared to controls (arterial elastance 6.03+/-1.48 vs. 2.74+/-0.34 mmHg/ml, P=0.009). CONCLUSION: Inhibition of NOS in experimental acute heart failure increased afterload without altering left ventricular systolic and diastolic function. Consequently, cardiac output was reduced. Furthermore, mechanoenergetic efficiency was severely impaired. NOS inhibition in acute heart failure and cardiogenic shock warrants further investigations.