Hydrogen sulfide postconditioning rendered cardioprotection against myocardial ischemia-reperfusion injury is compromised in rats with diabetic cardiomyopathy.

The present study aimed to investigate the efficacy of hydrogen sulfide (H2S) post-conditioning (HPOC) against ischemia-reperfusion (I/R) challenged diabetic rat hearts with or without cardiomyopathy using the Langendorff perfusion system. Male Wistar rats were randomly divided into different groups such as normal, diabetes mellitus (DM), and diabetic cardiomyopathy (DCM). Hearts from these groups were subjected to normal perfusion, I/R, and HPOC and were analyzed for cardiac physiology, cardiomyocyte injury, mitochondrial function, oxidative stress, and H2S metabolism. The results showed that HPOC protocol reduced the cardiac injury and improved the haemodynamics in normal and DM effectively, but not in DCM (RPP in mmHg*beats/min*10(3): HPOC-32 +/- 2, DM-HPOC-19 +/- 1, DCM-HPOC-6 +/- 2, LVDP in mmHg: HPOC-96 +/- 3, DM-HPOC-73 +/- 2, DCM-HPOC-50 +/- 3). DCM rats at the basal level exhibited perturbed myocardial architecture, mitochondrial dysfunction, and impaired glycolytic flux that failed to improve by HPOC treatment after I/R. HPOC exhibited a nominal improvement in the gene expression and activities of the H2S metabolizing enzymes such as cystathionine betasynthase, rhodanese, and cystathionine-gamma-lyase in DCM hearts. Collectively, our results suggest that altered myocardial architecture along with exacerbated oxidative stress and mitochondrial dysfunction contribute towards the failure of HPOC cardioprotection against I/R-induced myocardial tissue injury in DCM.

Automated summary

The present study investigated the efficacy of hydrogen sulfide post-conditioning (HPOC) in diabetic rat hearts challenged with ischemia-reperfusion, and found that HPOC effectively reduced cardiac injury and improved hemodynamics in normal and diabetic hearts, but not in hearts with diabetic cardiomyopathy. The study also revealed that altered myocardial architecture, exacerbated oxidative stress, and mitochondrial dysfunction contributed to the failure of HPOC cardioprotection in diabetic cardiomyopathy.