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.
Highlights
Acute myocardial infarction (AMI), which is caused by cardiac ischemia, has become one of the leading causes of death in Western countries and is becoming increasingly more prevalent in the developing world
Incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and LET in rats treated with 1 mg/kg ruthenium red (RuR) were, respectively, 62% (p > 0.05), 25% (p < 0.005) and 25% (p < 0.05)
No further reductions were observed in VA, AVB and LET incidences in rats treated with 3 mg/kg RuR, with respective incidence of 62% (p > 0.05), 37% (p < 0.05) and 25% (p < 0.05)
Summary
Acute myocardial infarction (AMI), which is caused by cardiac ischemia, has become one of the leading causes of death in Western countries and is becoming increasingly more prevalent in the developing world. The myocardial injuries caused by AMI usually cause the patient to have severe arrhythmias that, in many cases, culminate in the patient’s death. The cardiac muscle can tolerate short periods of severe and total ischemia, such as those caused by coronary vasospasms, without myocyte cell death[1]. The greater the duration and/or severity of cardiac ischemia, the more extensive will be the myocardial damage, as well as susceptibility to further injury during reperfusion[1]. The combined damage caused by the obstruction and subsequent coronary clearing is known as a cardiac ischemia-reperfusion (CIR) injury. It is well known that these lesions compromise cardiac structure and function and are responsible for many clinical sequelae typical of AMI1
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