Autoregulation of coronary blood flow in the isolated beating pig heart

The isolated beating pig heart model is an accessible platform to investigate the coronary circulation in its truly morphological and physiological state, whereas its use is beneficial from a time, cost, and ethical perspective. However, whether the coronary autoregulation is still intact is not known. Here, we study the autoregulation of coronary blood flow in the working isolated pig heart in response to brief occlusions of the coronary artery, to step-wise changes in left ventricular loading conditions and contractile states, and to pharmacologic vasodilating stimuli. Six slaughterhouse pig hearts (473 ± 40 g) were isolated, prepared, and connected to an external circulatory system. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved. After release of a coronary occlusion, coronary blood flow rose rapidly to an equal (maximum) level as the flow during control beats, independent of the duration of occlusion. Moreover, a linear relation was found between coronary blood flow and coronary driving pressure for a wide variation of preload, afterload, and contractility. In addition, intracoronary administration of papaverine did not yield a transient increase in blood flow indicating the presence of maximum coronary hyperemia. Together, this indicates that the coronary circulation in the isolated beating pig heart is in a permanent state of maximum hyperemia. This makes the model excellently suitable for testing and validating cardiovascular devices (i.e., heart valves, stent grafts, and ventricular assist devices) under well-controlled circumstances, whereas it decreases the necessity of sacrificing large mammalians for performing classical animal experiments.