ИСТИНА

Introduction Thyroid hormones deficiency is one of the risk factors for cardiovascular diseases, the main cause of death in the world. Recently we showed that hypothyroid state in early ontogeny could provoke coronary endothelium dysfunction and hypercontractility of coronary arteries, which persist even after restoration of hormones level (Gaynullina et al. Nitric Oxide 2017). Such data suggest that early hypothyroidism increases coronary vascular resistance and decrease myocardial blood supply, especially under the conditions of intense heart work. In our study, we tested the hypothesis that rats exposed to the thyroid hormones deficiency in early ontogeny would demonstrate worsened cardiac performance in adult age. Methods We added antithyroid drug propylthiouracil (7 ppm) in dam’s drinking water from the 1st gestation day to 14th day after delivery. Further experiments were performed in male offspring (PTU and control groups) aged 10-12 weeks. TH levels were measured by ELISA. We recorded arterial blood pressure (BP) through an implanted catheter, lead II electrocardiogram using subcutaneous needle electrodes and left ventricular pressure by Millar transducer in urethane-anaesthetized rat. We performed β1-adrenergic agonist dobutamine injections and electrical heart pacing to simulate myocardial loading conditions. Results Chosen model of hypothyroidism resulted in the decrease of thyroid function in 2-week-old offspring which was completely improved to adulthood. The basal myocardial contractility didn’t differ between groups. However, moderate dobutamine (5 mcg/(kg*min) induced the higher inotropic response in PTU vs. control. Infusion of high-dosage dobutamine (45-105 mcg/(kg*min)) was accompanied by similar increases in heart rate and S-wave amplitude in two groups. Nevertheless, T-wave amplitude rise was more pronounced in PTU group. High-rate pacing (550 bpm) also induced the more prominent increase of T-wave amplitude in PTU rats. Elevated T-wave under myocardial loading conditions could be considered as a sign of myocardial ischemia in PTU rats. Conclusion Intense heart stimulation is accompanied by more pronounced changes in myocardial bioelectrical activity in PTU compared to control rats. Therefore, that early short-term hypothyroidism could increase the susceptibility to the myocardial ischemia in adult rats. Supported by the Russian Science Foundation (Grant N14-15-00704). Keywords Myocardial ischemia, hypothyroidism, myocardial contractility