Right Ventricular Cardiomyocyte Apoptosis in Patients With Acute Myocardial Infarction of the Left Ventricular Wall

Abstract

Cardiac remodeling after acute myocardial infarction (AMI) is characterized by molecular and cellular mechanisms involving both the left (LV) and right ventricular (RV) walls. Cardiomyoycte apoptosis in the peri-infarct and remote LV myocardium has a central role in cardiac remodeling. Whether apoptosis also occurs in the right ventricle of patients with ischemic heart disease has not been investigated. The aim of the present study was to investigate the presence of cardiomyocyte apoptosis in the right ventricle in patients with AMI. We assessed the number of apoptotic cardiomyocytes using multiple samplings in the LV and RV walls of 12 patients selected at autopsy who died 4 to 42 days after AMI. Five patients without cardiac disease were also selected at autopsy as controls. Apoptotic rates were calculated from the number of cardiomyocytes showing double positive staining for in situ end-labeling of DNA fragmentation (TUNEL) and for activated caspase-3. Potentially false-positive results (DNA synthesis and RNA splicing) were excluded from cell counts. The apoptotic rate in the right ventricle in patients with AMI was significantly higher than in control hearts (median 0.8%, interquartile range 0.3 to 1.0 vs median 0.01%, interquartile range 0.01 to 0.03, p <0.001). RV apoptosis significantly correlated with such parameters of global adverse remodeling as cardiac diameter to LV free wall thickness (R = +0.57, p = 0.050). RV apoptosis was significantly higher in five cases (42%) with infarct involving the ventricular septum and an adjacent small area of the RV walls (median 1.0%, interquartile range 0.8 to 2.2 vs median 0.5%, interquartile range 0.2 to 1.0, p = 0.048, p <0.001 vs controls). The association between apoptotic rate in the right ventricle and cardiac remodeling was apparent even after exclusion of cases with RV AMI involvement (R = +0.82, p = 0.023 for diameter to LV wall thickness ratio and R = -0.91, p = 0.002 for RV free wall thickness). In conclusion, patients with cardiac remodeling after AMI had a significant increase in RV apoptosis even when ischemic involvement of the RV wall was not apparent.

SERCA-2a is involved in the right ventricular function following myocardial infarction in rats

“…The occurrence of RV dysfunction and failure has been associated with a poor prognosis after MI, however only few studies have systematically addressed RV remodeling following MI [1,32]. Our study was conducted to investigate RV function following LV MI in rats that developed or not HF.…”

GS-6201, a Selective Blocker of the A2BAdenosine Receptor, Attenuates Cardiac Remodeling after Acute Myocardial Infarction in the Mouse

“…In this model of nonreperfused myocardial infarction, mortality is high, and cardiac remodeling is global and involves the infarct and border zones as well as the unaffected remote left ventricle and the right ventricle (Abbate et al, 2008a;Toldo et al, 2011). Blockade of A 2B AdoR seemed to have no effect on the infarct size, whereas A 2B AdoR blockade may have prevented thinning and stretching of the infarct and border zones (infarct expansion) and protected the border zone and the remote myocardium, as evidenced by an improvement in both left and right ventricular dimensions and, importantly, LV function.…”

Right ventricular involvement in anterior myocardial infarction: a tissue Doppler-derived strain and strain rate study

“…Finally, the findings of Abbate et al (20) may be helpful in explaining the mechanism of RV involvement. Abbate et al showed remarkable RV cardiomyocyte apoptosis in the setting of acute myocardial infarction of the left ventricular wall.…”

“…In the literature, postmortem studies mention RV involvement after left ventricular infarction (19). Abbate et al found RV cardiomyocyte apoptosis in patients with anteroseptal myocardial infarction and RV-free wall involvement upon histopathological examination (20). Bodi et al showed RV involvement after AMi in an animal model via MRI (8).…”