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

Abstract

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.

Stroke promotes survival of nearby transplanted neural stem cells by decreasing their activation of caspase 3 while not affecting their differentiation

“…Casp3 is involved in differentiation of cells [26,27] and elimination of synapses, thus its downregulation might be the mechanism involved in adaptation on ischemia needed for cell survival. Indeed, there is a growing list of evidences that decreased activity of Casp3 is an important mechanism involved in protection against ischemia [28,29]. Further analyses will be needed to understand molecular pathways behind observed increase of expression of Casp3 in the brain affected by ischemia and decreased expression of Casp3 in the transplanted neural stem cells.…”

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

“…In a meta-analysis by Bice et al [121], NO interventions also limited infarct size during the early reperfusion period. In myocardial injury, inhaled gaseous NO inhibited cardiomyocyte apoptosis and reduced infarct size [122-125]. The concentration of creatine kinase also decreased [122-124, 126, 127].…”

The effects of simvastatin preconditioning on the expression of caspase-3 after myocardial ischemia reperfusion injury in rats

“…Four types of cardiac dysfunction occurred after myocardial ischemia reperfusion injury, including reflux, myocardial stunning, fatal reperfusion injury and reperfusion arrhythmia (7,8). At present, there are different explanations for the mechanism of myocardial ischemia-reperfusion injury, such as oxygen free radical theory (9), calcium overload theory (10) and inflammatory response theory (11). Kocak et al (12) suggested that apoptosis would occur during myocardial ischemia-reperfusion injury, and apoptosis plays a decisive role in the final infarct area of myocardium.…”