Protective Effects of the Somatostatin Analogue (Octeriotide) Versus Ischemic Preconditioning on Cardiac Dysfunction Induced by Ischemia Reperfusion Injury in Hypothyroid Rats

Abstract

Background The phenomenon of ischemic preconditioning (IPC) would protect the heart from hazards of ischemia reperfusion (IR) injury. However, IPC may lose its cardioprotective effect in the diseased states such as hypothyroidism. Octeriotide (OCT) mimics IPC in cardioprotection in normal hearts but no evidenced information in hypothyroid hearts. Hence, the present study investigated the responses of isolated hearts to IR injury after exposure to OCT in hypothyroidism induced by i.p. injection of 6-propyl 2-thouracil using a Langendorff preparation. Methods: Wister male rats were divided into four groups; Group I, normal rats, Isolated hearts were subjected to 20 min of stabilization, 20 min of zero-flow global ischemia and 45 min of reperfusion. Group II, hypothyroid group subjected to the same protocol of IR. Group III, hypothyroid rats subjected to a PC protocol (3 cycles of ischemia for 5 min and reperfusion for 5 min) prior to global ischemia. Group IV, hypothyroid rats were supplemented with OCT, 35 µg/kg S.C. in the living animal, 20 minutes before sacrifice, followed by in_vitro study of cardiac responses to IR. All rats were subjected to measurement of ABP, ECG recording, blood levels of T3, T4 and TSH, plasma total cholesterol, HDL, In_vitro study of isolated hearts to record the intrinsic activity of the heart under baseline condition, responses of the heart to IR.The levels of lactic dehydrogenase (LDH), TNFα in the coronary efflux were measured. Cardiac tissues are then stored at -80C and used for later determination of cardiac weights and cardiac tissue MDA. Results: OCT improved the post-ischemic recovery of cardiac function as evidenced by the improved isometric force developed tension (PT), PT/LV, systolic time (TPT) as well as ½ relaxation time and reduced the extent of injury, as indicated by the low LDH levels in Group IV compared to NORM hearts, which could be ascribed partly to the reducing effect of OCT on oxidative and inflammatory responses to IR as determined by the lowered MDA and TNFα consequently. On the other hand, hearts of Group II and Group III, showed significant improvement of post-ischemic recovery of cardiac inotropic parameters and LDH compared to NORM group, nevertheless, these parameters remained insignificant between both groups, suggesting that IPC didn't confer additional protection to hypothyroidism against IR injury. Conclusion Hypothyroid hearts are tolerant to IR injury. OCT administration to hypothyroid rats made their hearts more tolerant which is, partly, due to the reduced oxidative and inflammatory stresses. On the other hand, IPC failed to confer added protection in the hypothyroid hearts.