Increases in inotropic state without change in heart rate: Combined use of dobutamine and zatebradine in conscious dogs

The cardiovascular and left ventricular functional effects of dobutamine (5, 10 and 20 mu g kg(-1) min(-1)) were examined in conscious, chronically instrumented dogs in the presence and absence of control of heart rate with the specific bradycardic agent, zatebradine. Dobutamine increased heart rate, cardiac output, stroke volume, diastolic coronary blood flow velocity and pressure-work index (calculated myocardial oxygen consumption) and decreased systemic vascular resistance and diastolic coronary vascular resistance. Mean arterial pressure and left ventricular systolic and end-diastolic pressures were unchanged. Dobutamine-induced increases in heart rate and pressure-work index were attenuated by zatebradine. Dobutamine alone increased preload recruitable stroke work slope (63 +/- 6 to 116 +/- 11 mmHg) and + dP/dt. These positive inotropic effects were unaffected by zatebradine. Dobutamine decreased the time constant of isovolumic relaxation (30 +/- 3 to 25 +/- 2 ms). Dobutamine-induced decreases in the time constant of isovolumic relaxation were nor altered by zatebradine, indicating that changes in the time constant occurred independent of heart rate. Dobutamine also increased the maximal segment lengthening velocity to a similar degree in zatebradine-treated versus untreated dogs. Control of dobutamine-induced tachycardia by zatebradine decreases myocardial oxygen consumption but does not alter the positive inotropic and lusitropic effects of dobutamine.