Acute Intravenous Infusion of Immunoglobulins Protects Against Myocardial Ischemia-Reperfusion Injury Through Inhibition of Caspase-3.

BACKGROUND/AIMS: To investigate the cardioprotective effects of intravenous immunoglobulins (IVIG) in rats subjected to regional myocardial ischemia reperfusion (I/R).

METHODS

Langendorff-perfused rat hearts were used in this study. Hearts subjected to regional ischemia served as a negative untreated control. The effects of IVIG pre- and post-ischemic treatment on left ventricular function, coronary vascular dynamics and contractility were assessed. IVIG were administered in either a low or high dose. The infarct size was determined using triphenyltetrazolium chloride and through biochemical assays using the measured creatine kinase and lactate dehydrogenase levels. Apoptosis was evaluated by the TUNEL assay, and the caspase-3 expression level was assessed by immunoblotting. The cytokine levels were measured by ELISA.

RESULTS

Low and high doses of immunoglobulins administered 2 hours before sacrifice, before the ischemic insult or at reperfusion resulted in a significant improvement in cardiac hemodynamics, coronary vascular dynamics and heart contractility. A significant decrease in the infarct size and cardiac enzymes was also evident compared to those in the control. IVIG administered as an infusion at reperfusion or pre-treatment resulted in a marked decrease in myocyte apoptosis, which was associated with decreased levels of caspase-3 expression in the supernatants of homogenized left ventricles. Infusion of IVIG both pre-ischemia and at reperfusion did not show the same protective effects.

CONCLUSIONS

This study demonstrates a novel protection to the heart by low and high doses of IVIG given either pre- or post-ischemia.