Intrinsic autoregulation of cardiac output in rainbow trout (Oncorhynchus mykiss) at different heart rates.

Intrinsic regulation of the heart in teleosts is partly driven by central venous pressure, which exerts a modulatory role on stroke volume according to the well-known Frank-Starling mechanism. Although this mechanism is well understood from heart perfusion studies, less is known about how this mechanism operates in vivo, where heart rate varies markedly. We used zatebradine, a bradycardic agent, to attain resting heart rates in surgically instrumented animals. A dose of zatebradine of 2.79+/-0.47 mg l(-1) decreased heart rate by half, from 44.4+/-4.19 beats min(-1) to 22.1+/-1.9 beats min(-1). Zatebradine had no significant effect on the peripheral vasculature and no inotropic effects, so was a suitable pharmacological agent with which to manipulate heart rate. When heart rate halved, cardiac output dropped to 87.5+/-4.6% of the control value, due to the concomitant increase in stroke volume to 165+/-13%. In vivo recordings of venous pressure at varying heart rates indicated that the partial compensation in cardiac output was possible through an increase in pressure in the sinus venosus, from -0.06+/-0.04 kPa at a control heart rate of 58.3+/-3.5 beats min(-1) (N=10) to 0.07+/-0.05 kPa after injection of zatebradine (4 mg kg(-1)). The operation of the so-called time-dependent autoregulatory mechanism was further demonstrated in perfused hearts. The positive pressures recorded in the sinus venosus at low heart rates coincident with non-invasive measurements in trout suggest that atrial filling in trout is more dependent on the build-up of pressure in the venous circulation (vis-à-tergo filling) than a suction mechanism during ventricular contraction (vis-à-fronte filling).