Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade.
It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta-receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D009121:Muscle Denervation; D014019:Tissue Donors
D000319:Adrenergic beta-Antagonists; D007545:Isoproterenol