Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants

K. Bando, C. D. Fraser, V. P. Chacko, R. Pillai, W. E. Jacobus, D. E. Cameron, G. M. Hutchins, B. A. Reitz, William A Baumgartner

Research output: Contribution to journalArticle

Abstract

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 methyl prednisolone (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 <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. Mean coronary flow did not decline during the rejection; nor did lactate production change significantly during any stage of the experiment. Peak coronary flow decreased during rejection and recovered after augmented immunotherapy, however, indicating impairment and recovery of coronary reserve, respectively. These results suggest that ischemia, as assessed by coronary blood flow and lactate production, is not a significant component of early rejection in this model. Furthermore, these experiments support use of 31P NMR spectroscopy as a reliable technique in the noninvasive assessment of rejection.

Original languageEnglish (US)
Pages (from-to)251-257
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume10
Issue number2
StatePublished - 1991

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Allografts
Immunotherapy
Transplants
Biopsy
Lactic Acid
Prednisone
Immunosuppression
Energy Metabolism
Cyclosporine
Magnetic Resonance Spectroscopy
Ischemia
Dogs
Phosphocreatine
Metabolome
Prednisolone
Weaning
Phosphorus
Coronary Vessels
Phosphates
Blood Pressure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Bando, K., Fraser, C. D., Chacko, V. P., Pillai, R., Jacobus, W. E., Cameron, D. E., ... Baumgartner, W. A. (1991). Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants. Journal of Heart and Lung Transplantation, 10(2), 251-257.

Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants. / Bando, K.; Fraser, C. D.; Chacko, V. P.; Pillai, R.; Jacobus, W. E.; Cameron, D. E.; Hutchins, G. M.; Reitz, B. A.; Baumgartner, William A.

In: Journal of Heart and Lung Transplantation, Vol. 10, No. 2, 1991, p. 251-257.

Research output: Contribution to journalArticle

Bando, K, Fraser, CD, Chacko, VP, Pillai, R, Jacobus, WE, Cameron, DE, Hutchins, GM, Reitz, BA & Baumgartner, WA 1991, 'Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants', Journal of Heart and Lung Transplantation, vol. 10, no. 2, pp. 251-257.
Bando K, Fraser CD, Chacko VP, Pillai R, Jacobus WE, Cameron DE et al. Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants. Journal of Heart and Lung Transplantation. 1991;10(2):251-257.
Bando, K. ; Fraser, C. D. ; Chacko, V. P. ; Pillai, R. ; Jacobus, W. E. ; Cameron, D. E. ; Hutchins, G. M. ; Reitz, B. A. ; Baumgartner, William A. / Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants. In: Journal of Heart and Lung Transplantation. 1991 ; Vol. 10, No. 2. pp. 251-257.
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abstract = "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 methyl prednisolone (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 <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. Mean coronary flow did not decline during the rejection; nor did lactate production change significantly during any stage of the experiment. Peak coronary flow decreased during rejection and recovered after augmented immunotherapy, however, indicating impairment and recovery of coronary reserve, respectively. These results suggest that ischemia, as assessed by coronary blood flow and lactate production, is not a significant component of early rejection in this model. Furthermore, these experiments support use of 31P NMR spectroscopy as a reliable technique in the noninvasive assessment of rejection.",
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AU - Fraser, C. D.

AU - Chacko, V. P.

AU - Pillai, R.

AU - Jacobus, W. E.

AU - Cameron, D. E.

AU - Hutchins, G. M.

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N2 - 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 methyl prednisolone (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 <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. Mean coronary flow did not decline during the rejection; nor did lactate production change significantly during any stage of the experiment. Peak coronary flow decreased during rejection and recovered after augmented immunotherapy, however, indicating impairment and recovery of coronary reserve, respectively. These results suggest that ischemia, as assessed by coronary blood flow and lactate production, is not a significant component of early rejection in this model. Furthermore, these experiments support use of 31P NMR spectroscopy as a reliable technique in the noninvasive assessment of rejection.

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