Abstract
In the transplanted human heart, beta-adrenoceptor subtypes change with time after transplantation: beta1-adrenoceptors tend to decline, whereas beta2-adrenoceptors are upregulated. The aim of this study was to determine whether, in the transplanted human heart, stimulation of beta2-adrenoceptors can induce heart-rate increases. For this purpose, we assessed in eight heart-transplant recipients (mean posttransplant time: 932 days) the effects of infusion of graded doses of isoprenaline (3.5-35 ng/kg/min) 120 min after pretreatment with the beta1-adrenoceptor antagonist bisoprolol (10 mg p.o.; beta1-adrenoceptor occupancy approximately 80%; beta2-adrenoceptor occupancy <5%) on heart rate in the recipient's native (innervated) and transplanted (denervated) sinus nodes. Isoprenaline, acting under these conditions predominantly at beta2-adrenoceptors, increased heart rate both in the recipient's transplanted and native sinus nodes in a dose-dependent manner; at each dose, increases were significantly higher in the transplanted than in the native sinus node. ED20 values (dose to increase heart rate by 20 beats/min) in the transplanted sinus node were 22.2 +/- 1.8 ng/kg/min, and in the native, >35 ng/kg/min (p < 0.01). We conclude th...Continue Reading
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