Multiple Progressive Thermopreconditioning Improves Cardiac Ischemia/Reperfusion Induced Left Ventricular Contractile Dysfunction and Structural Abnormality in Rat.

BACKGROUND: Triple progressive thermopreconditioning (3PTP) may induce high Hsp-70 expression to maintain cardiac function. We suggest that 3PTP may reduce myocardial ischemia/reperfusion (I/R) injury during organ transplantation through Bag3/Hsp-70 mediated defense mechanisms.

METHODS: Male Wistar rats were divided into sham control group and 72 hours after 3PTP in a 42°C water bath (3PTP) group. Rats underwent 60 minutes of ischemia by occlusion of the left anterior descending coronary artery followed by 240 minutes reperfusion. Hemodynamic parameters, including the electrocardiogram, microcirculation, heart rate, left ventricular end-diastolic pressure (LVEDP), maximal rate of rise (+dp/dt) and fall (-dp/dt) in the left ventricular pressure for index of contraction and relaxation were determined. Myocardial infarct size was evaluated by the Evans blue-2,3,5-triphenyltetrazolium chloride method. 3PTP-induced protective mechanisms were determined by western blot and immunohistochemistry.

RESULTS: Cardiac I/R depressed cardiac microcirculation, induced S-T segment elevation and R-R and P-R interval elongation, increased infarct size associated with erythrocyte extravasation, leukocytes and macrophage/monocyte infiltration, granulocyte colony-stimulating factor (G-CSF), poly(ADP-ribose) polymerase 1 stain and TUNEL positive cells. However, 3PTP evoked significant cardio-protections against I/R injury, characterized by the increased +dp/dt value and the decreased elevated LVEDP, erythrocyte extravasation, leukocyte and macrophage/monocyte infiltration, G-CSF expression, poly(ADP-ribose) polymerase 1 expression, TUNEL-positive cells, fragmentation and infarct area. In addition, 3PTP increased Hsp-70 and Bag3 expression and decreased Bax/Bcl-2 ratio, but did not affect Beclin-1 and LC3-II/LC3-I ratio in the heart with I/R injury.

CONCLUSIONS: 3PTP therapies may through Bag3 upregulation alleviate I/R injury-induced left ventricular structural deterioration and dysfunction.