[Analysis of cardiac function of discordant heart xenografts using a blood-perfused, isolated, supported heart model].
Changes in cardiac function during hyperacute rejection are not fully understood because of lack of appropriate models. In this study, a blood-perfused, isolated, supported heart model was employed for the analysis of cardiac function in discordant heart xenografts.


METHODS
Experiment 1: Changes in left ventricular end-systolic pressure (LVESP) and coronary perfusion pressure (CPP) were measured for 120 min. Dry heart weight after perfusion was measured in the following 4 groups: group A; isolated rat heart perfused with blood from support rat, group B; guinea pig heart, support guinea pig, group C; guinea pig heart, support rat, and group D; guinea pig heart, support rat with cobra venom factor (CVF) pretreatment. Complement C3 of support rat serum in group C and group D was measured by single radial immunodiffusion (SRID). Experiment 2: Fifteen guinea pig hearts perfused with blood from untreated support rats were analyzed for correlation between survival time and LVESP, and CPP as well.


RESULTS
In groups A and B, LVESP and CPP was stable up to 120 min. In group C, 4 out of 6 hearts were stopped beating within 120 min. The difference between LVESP at 10 min in group C and that in group B was not obtained, possibly due to high variation of values in group C, whereas CPP in group C was higher than that in group B (p < 0.05). In group D, CVF was shown to deplete complement C3. Group D showed constant LVESP and CPP, similar to non-xenograft groups. Dry heart weight of group C was larger than those of group B and D. There were positive correlations between survival time and LVESP at 10 min, and increasing rate of LVESP after 10 min as well. A negative correlation between survival time and CPP at 10 min was observed, while no correlation was obtained between survival time and increasing rate of CPP after 10 min.


CONCLUSIONS
1) Decreases in LVESP and increases in CPP in xenograft group are considered to be due to hyperacute rejection. 2) These changes can be abolished by depletion of C3. 3) Guinea pig hearts can work well in xenograft condition as in allograft condition in certain circumstances, i.e. depletion of C3. 4) The blood-perfused, isolated, supported heart model is useful for the analysis of cardiac function in discordant xenografts.
Miyatake
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Second Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D004546:Elapid Venoms / Q000494:pharmacology; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008955:Models, Cardiovascular; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left / Q000502:physiology
D004546:Elapid Venoms