Regional remodeling strain and its association with myocardial apoptosis after myocardial infarction in an ovine model

ObjectiveProgressive left ventricular remodeling after myocardial infarction has been viewed as an important contributor to progressive heart failure. The objective of this study was to investigate the relationship between myocardial apoptosis and strain during progressive cardiac remodeling.MethodsBefore creation of an anterolateral left ventricular infarction by ligation of diagonal arteries, 16 sonomicrometry transducers were placed in the left ventricular free wall of 8 sheep to assess regional deformation in the infarct, adjacent, and normally perfused remote myocardial regions over 8 weeks' duration. Hemodynamic, echocardiographic and sonomicrometric data were collected before infarction and then 30 minutes and 2, 6, and 8 weeks after infarction. At the end of the study, regional myocardial tissues were collected for apoptotic signaling proteins.ResultsAt terminal study, an increase in left ventricular end-diastolic pressure of 8.1 ± 0.1 mm Hg, a decrease in ejection fraction from 54.19% ± 5.68% to 30.55% ± 2.72%, and an end-diastolic volume increase of 46.08 ± 5.02 mL as compared with the preinfarct values were observed. The fractional contraction at terminal study correlated with the relative abundance of apoptotic protein expressions: cytochrome c (r2 = 0.02, P < .05), mitochondrial Bax (r2 = 0.27, P < .05), caspase-3 (r2 = 0.31, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r2 = 0.30, P < .05). These myocardial apoptotic activities also correlated with remodeling strain: cytochrome c (r2 = 0.02, P < .05), mitochondrial Bax (r2 = 0.28, P < .05), caspase-3 (r2 = 0.43, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r2 = 0.37, P < .05).ConclusionIncrease in regional remodeling strain led to an increase in myocardial apoptosis and regional contractile dysfunction in heart failure

Strain-related regional alterations of calcium-handling proteins in myocardial remodeling

BackgroundCardiac remodeling has been shown to have deleterious effects at both the global and local levels. The objective of this study is to investigate the role of strain in the initiation of structural and functional changes of myocardial tissue and its relation to alteration of calcium-handling proteins during cardiac remodeling after myocardial infarction.MethodsSixteen sonomicrometry transducers were placed in the left ventricular free wall of 9 sheep to measure the regional strain in the infarct, adjacent, and remote myocardial regions. Hemodynamic, echocardiographic, and sonomicrometry data were collected before myocardial infarction, after infarction, and 2, 6, and 8 weeks after infarction. Regional myocardial tissues were collected for calcium-handling proteins at the end study.ResultsAt time of termination, end-systolic strains in 3 regionally distinct zones (remote, adjacent, and infarct) of myocardium were measured to be −14.65 ± 1.13, −5.11 ± 0.60 (P ≤ .05), and 0.92 ± 0.56 (P ≤ .05), respectively. The regional end-systolic strain correlated strongly with the abundance of 2 major calcium-handling proteins: sarcoplasmic reticulum Ca2+ adenosine triphosphatase subtype 2a (r2 = 0.68, P ≤ .05) and phospholamban (r2 = 0.50, P ≤ .05). A lesser degree of correlation was observed between the systolic strain and the abundance of sodium/calcium exchanger type 1 protein (r2 = 0.17, P ≤ .05).ConclusionsRegional strain differences can be defined in the different myocardial regions during postinfarction cardiac remodeling. These differences in regional strain drive regionally distinct alterations in calcium-handling protein expression