Hydrogen sulfide preconditioning could ameliorate reperfusion associated injury in diabetic cardiomyopathy rat heart through preservation of mitochondria

Abstract

Evidence suggests that hydrogen sulfide precondition (HIPC) is an effective protocol in the management of ischemia reperfusion (I/R) by attenuating free radical and calcium overload in mitochondria. However the efficacy of HIPC is largely unknown in diabetic cardiomyopathy (DCM) hearts subjected to I/R procedure.Male Wistar rats were randomly divided into three groups: i) normal, ii) diabetes mellitus (DM), and iii) diabetic cardiomyopathy (DCM). DM and DCM animals were prepared by using streptozotocin injection at the age of 4 week (35 mg/kg, i.p). DCM animals were additionally administered with high fat diet for 3 months. Isolated rat hearts were perfused by using Langendorff apparatus with continuous hemodynamic monitoring.Following reperfusion, cardiac physiological efficiency was highly compromised in DCM heart (high infarct size by 94% and low relative pressure product by 65%) as compared to normal rat heart. HIPC effectively improved cardiac physiology of I/R challenged normal rat hearts by 62.5% (RPP), reduced injury by 60% (Infarct size) and subsequently preserved mitochondrial electron transport chain enzyme activities NQR by 57%, membrane potential, swelling behaviour, ATP content, ATP producing capacity and oxidative defence system by reducing lipid peroxidation by 55% compared with I/R. But in DM and DCM animals, isolated hearts conditioned with HIPC substantially improved cardiac physiology (RPP) by 44% in DM and 58% in DCM, arrest tissue injury (Infarct size) by 72% in DM and 79% in DCM and preserved mitochondrial activity only to its own sham control, primarily due to the basal level defect. Furthermore, we found that SSM fraction of diabetic heart mitochondria showed overall better improvement in their function than IFM by HIPC. However, mitochondrion experienced I/R associated oxidative stress was not improved by HIPC.