Decrease In Left Ventricular Stroke Work Research Articles

A pharmacologic activator of endothelial KCa channels increases systemic conductance and reduces arterial pressure in an anesthetized pig model

SKA-31, an activator of endothelial KCa2.3 and KCa3.1 channels, reduces systemic blood pressure in mice and dogs, however, its effects in larger mammals are not well known. We therefore examined the hemodynamic effects of SKA-31, along with sodium nitroprusside (SNP), in anesthetized, juvenile male domestic pigs. Experimentally, continuous measurements of left ventricular (LV), aortic and inferior vena cava (IVC) pressures, along with flows in the ascending aorta, carotid artery, left anterior descending coronary artery and renal artery, were performed during acute administration of SKA-31 (0.1, 0.3, 1.0, 3.0 and 5.0mg/ml/kg) and a single dose of SNP (5.0μg/ml/kg). SKA-31 dose-dependently reduced mean aortic pressure (mPAO), with the highest dose decreasing mPAO to a similar extent as SNP (−23±3 and −28±4mmHg, respectively). IVC pressure did not change. Systemic conductance and conductance in coronary and carotid arteries increased in response to SKA-31 and SNP, but renal artery conductance was unaffected. There was no change in either LV stroke volume (SV) or heart rate (versus the preceding control) for any infusion. With no change in SV, drug-evoked decreases in LV stroke work (SW) were attributed to reductions in mPAO (SW vs. mPAO, r2=0.82, P<0.001). In summary, SKA-31 dose-dependently reduced mPAO by increasing systemic and arterial conductances. Primary reductions in mPAO by SKA-31 largely account for associated decreases in SW, implying that SKA-31 does not directly impair cardiac contractility.

SKA‐31, a positive modulator of SKCa and IKCa channels, increases systemic conductance and lowers arrterial pressure in an anesthetized pig model

SKA‐31 regulates microvascular tone, tissue perfusion and blood pressure by acting on endothelial SKCa and IKCa channels. In this study, we have examined the hemodynamic effects of SKA‐31 in comparison to the established vasodilator sodium nitroprusside (SNP) in anesthetized domestic pigs. We measured left ventricular (LV), aortic and inferior vena cava (IVC) pressures and monitored levels of blood flow in the ascending aorta, right carotid, left anterior descending coronary and left renal arteries during acute intravenous infusions of SKA‐31 (0.1 to 5 mg/kg), followed by a single dose of SNP (5 μg/kg). SKA‐31 dose‐dependently and reversibly decreased mean aortic pressure (mPAO) to a level comparable to that produced by SNP (−23±3 vs. −28±4 mmHg). Mean IVC pressure did not change. Both SKA‐31 (1 to 5 mg/kg doses) and SNP increased systemic conductance, along with coronary and carotid artery conductances; renal conductance did not change. There was no change in LV stroke volume (SV) for any infusion, and heart rate was not altered following SKA‐31 administration (132±14 vs. 128±13 bpm). With no change in SV, the significant decrease in LV stroke work (SW) observed with either SKA‐31 or SNP was largely attributed to decreased mPAO. In summary, SKA‐31 significantly decreased mPAO by increasing systemic conductance, and did not appear to reduce cardiac contractility. Supported by the CIHR (JVT and APB) and the NIH (HW).

Effects of heparin and protamine on left ventricular performance in the dog.

The effects of protamine on left ventricular (LV) function were measured under conditions of controlled heart rate and proximal aortic pressure in eight anaesthetized, heparinised dogs. Protamine 3 mg.kg-1 produced a 21% decrease in LV dP/dt max, a 43% decrease in cardiac output, a 47% decrease in stroke work and decreases in systolic and diastolic pressures (-16%, -19% respectively). Protamine 6 mg.kg-1 resulted in a 17% decrease in LV dP/dt max, a 26% decrease in cardiac output, a 50% decrease in LV stroke work and 25 and 30% decreases in systolic and diastolic pressures. These results show that an impairment of LV function plays an important part in the circulatory depression produced by protamine.