Characterization of the structural and functional changes in the myocardium following focal ischemia-reperfusion injury

Abstract

Kuppusamy P, Sen CK. Characterization of the structural and functional changes in the myocardium following focal ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 294: H2435-H2443, 2008. First published March 28, 2008 doi:10.1152 doi:10. /ajpheart.01190.2007 cardiac magnetic resonance imaging (MRI) and histological approaches have been employed in tandem to characterize the secondary damage suffered by the murine myocardium following the initial insult caused by ischemia-reperfusion (I/R). I/R-induced changes in the myocardium were examined in five separate groups at the following time points after I/R: 1 h, day 1, day 3, day 7, and day 14. The infarct volume increased from 1 h to day 1 post-I/R. Over time, the loss of myocardial function was observed to be associated with increased infarct volume and worsened regional wall motion. In the infarct region, I/R caused a decrease in end-systolic thickness coupled with small changes in end-diastolic thickness, leading to massive wall thickening abnormalities. In addition, compromised wall thickening was also observed in left ventricular regions adjacent to the infarct region. A tight correlation (r 2 ϭ 0.85) between measured MRI and triphenyltetrazolium chloride (TTC) infarct volumes was noted. Our observation that until day 3 post-I/R the infarct size as measured by TTC staining and MRI was much larger than that of the myocytesilent regions in trichrome-or hematoxylin-eosin-stained sections is consistent with the literature and leads to the conclusion that at such an early phase, the infarct site contains structurally intact myocytes that are functionally compromised. Over time, such affected myocytes were noted to structurally disappear, resulting in consistent infarct sizes obtained from MRI and TTC as well as trichrome and hematoxylin-eosin analyses on day 7 following I/R. Myocardial remodeling following I/R includes secondary myocyte death followed by the loss of cardiac function over time. redox ACUTE MYOCARDIAL DAMAGE caused by a surge in reactive oxygen species following ischemia-reperfusion (I/R) has been demonstrated and extensively studied (25,26,39). The secondary loss of myocytes subsequent to the initial insult is a progressive phase reported by numerous laboratories (2,3,12,15,18,31,32) and remains poorly understood. In addition, the functional significance of this secondary death process remains to be characterized.The current state of magnetic resonance (MR) imaging (MRI) represents a versatile noninvasive tool for measuring cardiac function and structure (7,8,24,28,34,37). Cardiac MRI has been applied to study I/R injury (8 -11, 23, 24, 35-37), left ventricular (LV) remodeling (13), and myocardial metabolism (5, 19, 33) in canine as well as rodent models. Contrast-enhanced MRI monitors infarct damage after myocardial infarction (9,10,21,30,34). Because these observations are obtained from rodent as well as canine models, it is important to recognize that the rodent and canine models do have some contrasting features, primarily because o...

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