Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants.
To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)
Bando
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Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Md 21205.
Fraser
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CD
Chacko
V P
VP
Pillai
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Jacobus
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Cameron
D E
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Hutchins
G M
GM
Reitz
B A
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Baumgartner
W A
WA
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D004285:Dogs; D006084:Graft Rejection / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D007165:Immunosuppression Therapy; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism; D009333:Neck; D016042:Transplantation, Heterotopic / Q000502:physiology*
D007773:Lactates; D019344:Lactic Acid