A model of hemoperfused slaughterhouse pighearts is described providing a wide range of applications which leads to a reduction in animal experiments. The size of a pigheart, heart rate, coronary perfusion, metabolism, etc. are more comparable to conditions in patients than those in hearts of small laboratory animals. Global heart function can be assessed either by measuring stroke volume, ejection fraction, Emax etc. in the working model or by measuring intraventricular pressure with balloon catheters in the isovolumetric model. Regional cardiac function can be measured by sonomicrometry and ischemic and non-ischemic areas can be compared. Local metabolic changes are measurable as well with microdialysis. Cardiac function can be kept on any given functional level by infusion of norepinephrine in spite of the fact that functional parameters are lower without adrenergic drive in vitro than in vivo. Stable heart function can be maintained for several hours with only 500 to 1000 ml of blood because the blood is permanently regenerated by a special dialysis system. This model can be applied in many research projects dealing with reperfusion injuries, inotropic, antiarrhythmic or arrhythmogenic effects of certain drugs, immunological rejection, evaluation of imaging systems (NMR, echocardiography etc.) or cardiac assist devices.

The mechanism of an indirect revascularization in ischemic myocardium by transmyocardial laser revascularization (TMLR) is not yet fully understood. An improvement of clinical symptoms caused by TMLR is reported in many clinical trials with patients in which a direct revascularization is not possible. An increase of myocardial perfusion through laser channels is doubtful, because the myocardial pressure in the wall is higher than in the cavum. Therefore we measured the local cardiac function (intramyocardial pressure, wall thickness, pressure-length curves) and acute metabolic changes (tissue lactate content, tissue pO2) in ischemic and non-ischemic regions before and after TMLR in isolated hemoperfused pig hearts. An isolated heart was chosen because it enabled us to separate coronary flow from flow through ventricular channels. The ischemia was induced by coronary occlusion or microembolization (eight hearts each). It should be noted that microembolization leads to conditions which are more comparable with those found in patients selected for TMLR. In the isolated working heart, the coronary perfusion can be controlled independently from perfusion through the ventricular cavum. Under the ischemic conditions mentioned above, we observed that the intramyocardial pressure in the ischemic region decreased below the left ventricular pressure, so one premise for indirect perfusion was met. TMLR after microembolization led to a significant improvement of regional cardiac work and the tissue oxygen pressure. These acute effects demonstrate the possibility of functional and metabolic amelioration by TMLR after ischemia induced by microembolization in an isolated hemoperfused pig heart.

The aim of this study was to characterize functional parameters in the isolated and normothermic hemoperfused porcine beating heart model after pathophysiological stimuli for extended perfusion periods. Hearts were prepared and connected to a specially developed perfusion equipment, which simultaneously allowed perfusion with warm autologous blood as well as blood dialysis. Two groups were established: group A (12 hearts: no intervention) and group B (6 hearts: occlusion of the ramus circumflexus of the left coronary artery for 2 hours). Blood gas analyses and oxymetry were performed at baseline and every 30 min during a 6 hours perfusion period. Coronary perfusion pressure (CPP) and blood flow (CBF), right and left ventricular pressure, blood and dialyzate pH-values, and temperature were monitored online by a microcontroller. A steady state regarding the CPP and the CBF was achieved after 1 hour of perfusion for both groups. In group B, CPP increased during occlusion. Comparison of both groups showed no significant differences in the bicarbonate and sodium levels in blood and dialyzate. The potassium concentration in blood and dialyzate increased in both groups constantly during the experiments. No clear alteration of the oxygen consumption was observed. Lactate levels in blood and dialyzate increased during occlusion as did the aspartataminotransferase (AST) venous levels (both determined only for group B). Four concentrations of norepinephrine were injected into the stem of the coronary arteries (10, 20, 40, 80 microg). A clear inotropic effect of this hormone on right and left ventricular pressure was observed. It was concluded that longer perfusion periods and simulation of myocardial infarction for a clinically relevant period can be performed using this model. In addition, right and left ventricular function appear to be well preserved in this model, since the isolated porcine heart responded to norepinephrine stimuli.