A maintained afterload model of ischemia in erythrocyte-perfused isolated working hearts

The aim of this study was to develop an erythrocyte-perfused isolated working heart model of global ischemia that would allow controllable reductions in coronary perfusion pressure but with maintained afterload to facilitate the temporal association of myocardial ischemia with ventricular contractile or metabolic dysfunction. Isolated working rat hearts were perfused at 37 degrees C with a washed, resuspended porcine erythrocyte perfusate (40% hematocrit) at a preload of 10 mmHg and afterload of 75 mmHg, paced at 300 beats per min. A bifurcation above the aorta permitted imposition of two one-way valves, one opened by ventricular ejection in systole and closed by aortic afterload in diastole, the other closed by aortic pressure from ventricular ejection but opened to allow coronary perfusion in diastole according to an adjustable pressure head (75 mmHg initially). Ischemia was imposed by lowering the coronary perfusion pressure to 35 mmHg while maintaining diastolic afterload at 75 mmHg. The presence of erythrocytes provides oxygen delivery in the normal physiological range. This model permits the severity of ischemia to be graded by any specified level. The maintained afterload model of ischemia is a simple enhancement of the isolated working heart permitting a separation of workload and coronary perfusion pressure variables. This provides greater control over and direct monitoring of experimental ischemic events in progress.