Cardioprotective effects of pharmacological blockade of the mitochondrial calcium uniporter on myocardial ischemia-reperfusion injury¹

Abstract

Purpose

To evaluate whether the attenuation of mitochondrial Ca²⁺ overload produced by pharmacological blockade of mitochondrial Ca²⁺ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR).

Methods

CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion.

Results

In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively.

Conclusion

The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca²⁺ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.

Myocardial Reperfusion Injury; Ischemia; Calcium; Rats