Functional role of beta2-adrenoceptors in the transplanted human heart.
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 that in the transplanted human heart, beta2-adrenoceptor stimulation does evoke increases in heart rate. The enhanced response to isoprenaline in the transplanted sinus node could be caused by the upregulated beta2-adrenoceptors or by the fact that during isoprenaline infusion, vagal activity increases, thus blunting the response in the native (innervated) but not in the transplanted (denervated) sinus node.
Hakim
K
K
Clinic for Cardio-Thoracic Surgery, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany.
Fischer
M
M
Günnicker
M
M
Poenicke
K
K
Zerkowski
H R
HR
Brodde
O E
OE
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D017298:Bisoprolol / Q000008:administration & dosage / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011859:Radiography; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*; D012849:Sinoatrial Node / Q000187:drug effects / Q000294:innervation
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol; D017298:Bisoprolol