Progressive thermopreconditioning attenuates rat cardiac ischemia/reperfusion injury by mitochondria-mediated antioxidant and antiapoptotic mechanisms

Objectives: Progressive thermal preconditioning (PTP) provides vascular protection with less hemodynamic fluctuations, endoplasmic reticulum (ER), and oxidative stress compared with whole body hyperthermia. We suggest PTP might efficiently diminish cardiac ischemia/reperfusion-induced apoptosis and autophagy injury. Methods: A total of 67 male Wistar rats were divided into a non-PTP control group, 24 or 72 hours after a single cycle or 3 consecutive cycles of PTP in a 42 degrees C water bath (1-24, 1-72, 3-24, and 3-72 groups). We measured the cardiac O-2(-) amount in vivo in response to left anterior descending coronary artery ligation for 2 hours and re-perfusion for 3 hours. Cardiac function and injury were determined by microcirculation, electrocardiography, and infarct size. The PTP-induced protective effects on nicotinamide adenine dinucleotide phosphate oxidase gp91-mediated oxidative stress, ER stress, and apoptosis-and autophagy-related mechanisms were examined using Western blot and immunohistochemistry. Results: Coronary arterial ischemia/reperfusion depressed cardiac microcirculation, induced ST-segment elevation and increased infarct size in non-PTP and PTP rats. Ischemia/reperfusion enhanced the cardiac O-2(-) levels by enhanced nicotinamide adenine dinucleotide phosphate oxidase gp91 expression, cytosolic cytochrome C release, and decreased mitochondrial Bcl-2 expression. Cardiac injury activated ER stress-78-kDa glucose-regulated protein expression, increased the Bax/Bcl-2 ratio, cleaved caspase 3 expression and poly( ADP-ribose)-polymerase fragments, leading to apoptosis formation, and promoted LC3-II expression, resulting in autophagy formation. PTP treatment elevated heat shock protein 70, heat shock protein 32, Bcl-2, Bcl-xL, and manganese superoxide dismutase in the rat heart, especially in the 3-72 group. PTP treatment significantly restored cardiac microcirculation, decreased oxidative stress, ER stress, apoptosis, autophagy, and infarct size. Conclusions: PTP significantly reduced cardiac ischemia/reperfusion injury by upregulating antioxidant, antiapoptotic, and antiautophagic mechanisms.