Ventricular fibrillation is reduced in hypothyroid rats with enhanced myocardial alpha-adrenoceptor responsiveness

1. The severity of ventricular arrhythmias induced by coronary artery occlusion and reperfusion has been examined in control rats and animals made hypothyroid by pretreatment with 6-propylthiouracil (PTU). The maximal driving frequency and sensitivity of isolated left atria and papillary muscles to isoprenaline and to phenylephrine in the presence of propranolol, were also examined in tissues from control and hypothyroid animals. 2. Pretreatment with PTU resulted in a potentiation of responses to the alpha-adrenoceptor agonist phenylephrine in both left atria and papillary muscles, while responses to isoprenaline were depressed in left atria but unaltered in papillary muscles from hypothyroid animals. 3. In rats subject to coronary artery occlusion, PTU pretreatment reduced the incidence of ventricular fibrillation during acute myocardial ischaemia and abolished reperfusion-induced ventricular fibrillation. Mortality during myocardial ischaemia and reperfusion was also abolished. Diastolic blood pressure was similar in hypothyroid and control animals, but there was a small reduction in systolic blood pressure and a marked decrease in heart rate in PTU pretreated animals. 4. These results demonstrate that PTU-induced hypothyroidism represents a condition where cardiac alpha-adrenoceptor-mediated responses are enhanced but the severity of ischaemia- and reperfusion-induced arrhythmias is reduced.