Left ventricular remodeling after experimental myocardial cryoinjury in rats.
ABSTRACT The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation, reparation, and scarring observed in myocardial infarction with a late evolution toward heart failure. This model is therefore suitable to study myocardial repair after injury.
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ABSTRACT: We studied microvascular injury after myocardial cryothermia in rats using intravital fluorescence microscopic techniques. Cryolesions were induced to the right ventricle by freezing with -160 degrees C (probe diameter: 5 mm) for a total of 5 min. Fluorescence microscopy was performed at 15, 30, 60, 90, and 120 min as well as at 3 and 7 days after cryothermia. Analysis of the epicardial microvasculature 15 min after cryothermia revealed an area of 24.6 +/- 3.8 mm2 of nonperfused tissue, which was reduced to 5.3 +/- 1.5 mm2 (P < 0.05) after the initial 2-h observation period. Vital microscopic images of reperfused tissue characteristically demonstrated extravasation of the macromolecular fluorescent tracer FITC-dextran (21.7 +/- 3.4 mm2), suggesting substantial loss of endothelial integrity. In vivo propidium iodide staining confirmed membrane damage of microvascular endothelial cells. Three days after cryoinjury the area of nonperfused tissue was reduced further to 1.1 +/- 0.4 mm2 in the center of the lesion, while the area of perfused tissue with disruption of endothelial integrity was found significantly increased to 47.4 +/- 5.9 mm2 (P < 0.05) toward the periphery. Analysis at 7 days revealed endothelial repair at the periphery of the cryolesion, but now a central necrotic area was found demarcated (nonperfused), presenting with a size (26.0 +/- 3.5 mm2) similar to that shown during the very early (15 min) reperfusion period. Our study demonstrates recovery of microvascular perfusion during the first hours and days after myocardial cryothermia. This is, however, associated with endothelial injury, i.e., damage of plasma membrane and loss of barrier function. Infarction with capillary perfusion failure is evident at 7 days with a size which strikingly corresponds to the sizeof nonperfused tissue observed immediately after cryointervention.Journal of Surgical Research 09/1998; 79(1):1-7. · 2.02 Impact Factor
- Science 06/1970; 168(3934):939-49. · 31.03 Impact Factor
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ABSTRACT: We evaluated postinfarction myocardial function in rats and determined echocardiographic criteria for congestive heart failure (CHF) using high performance echocardiography. Extensive myocardial infarction (MI) was induced in rats by left coronary occlusion. Sham-operated animals served as controls. Five weeks later, high-frame rate ( approximately 200 Hz), fully digitized, shallow-focus (10-25 mm), two-dimensional, M-mode and Doppler echocardiography was performed. A J-tree cluster analysis was performed using parameters indicative of CHF. Reproducibility was examined. The cluster analysis joined the animals into one Sham and two MI clusters. One of the MI clusters had clinical characteristics of CHF and elevated left ventricular end diastolic pressure. Among the echocardiographic variables, only posterior wall shortening velocity separated the failing and nonfailing MI clusters. We conclude that, by high frame rate echocardiography, it is possible to obtain high- quality recordings in rats. It is feasible to distinguish MI rats with CHF due to myocardial dysfunction from those without failure and to perform longitudinal studies on myocardial function.Journal of Applied Physiology 11/2000; 89(4):1445-54. · 3.48 Impact Factor