Arrhythmogenesis in isolated rat hearts with enhanced alpha-adrenoceptor-mediated responsiveness.
1. It has been postulated that stimulation of myocardial alpha-adrenoceptors is one of the primary mediators of the dysrhythmias which occur during periods of myocardial ischaemia and reperfusion. This study examines arrhythmogenesis during coronary artery occlusion and reperfusion in isolated perfused rat hearts from control animals and from rats with enhanced myocardial alpha-adrenoceptor responsiveness. 2. Rats were administered propylthiouracil (PTU) in their drinking water for 8 weeks. This treatment resulted in an enhanced responsiveness of isolated left atria to the alpha-adrenoceptor agonist phenylephrine compared with atria from control animals. 3. In Langendorff-perfused isolated hearts, the spontaneous rate of contraction was significantly lower in the PTU-pretreated group than in either age-matched or weight-matched controls. Occlusion of the left anterior descending artery (LAD) for 25 min resulted in ventricular tachycardia (VT) of similar incidence and duration in all groups and ventricular fibrillation (VF) in both control groups but not the PTU-pretreated group. 4. Following the 25-min ischaemic period the myocardium was reperfused for 10 min. The incidence and duration of VT and VF during this period was similar in all groups except that the duration of VF in the PTU-pretreated group was significantly lower than in controls. 5. In perfused hearts paced at 4 Hz, the incidence and duration of dysrhythmias during ischaemia and reperfusion was again similar in all groups, only the duration of VF being affected (reduced) by PTU-pretreatment. 6. In conclusion, this study does not lend support to the hypothesis that myocardial alpha-adrenoceptors have a primary role in arrhythmogenesis, but the data would support a role for these receptors in myocardial protection.
Chess-Williams
R
R
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Milton
H L
HL
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism; D016279:Atrial Function, Left / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011441:Propylthiouracil / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011441:Propylthiouracil