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.
- SourceAvailable from: Rosaria GiordanoInternational Journal of Cardiology 07/2004; 95 Suppl 1:S38-42. · 6.18 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Myocardial infarction (MI) represents an enormous clinical challenge as loss of myocardium due to ischemic injury is associated with compromised left ventricular (LV) function often leading to acute cardiac decompensation or chronic heart failure. S100A1 was recently identified as a positive inotropic regulator of myocardial contractility in vitro and in vivo. Here, we explore the strategy of myocardial S100A1 gene therapy either at the time of, or 2 h after, MI to preserve global heart function. Rats underwent cryothermia-induced MI and in vivo intracoronary delivery of adenoviral transgenes (4 x 10(10) pfu). Animals received saline (MI), the S100A1 adenovirus (MI/AdS100A1), a control adenovirus (MI/AdGFP), or a sham operation. S100A1 gene delivery preserved global in vivo LV function 1 week after MI. Preservation of LV function was due mainly to S100A1-mediated gain of contractility of the remaining, viable myocardium since contractile parameters and Ca(2+) transients of isolated MI/AdS100A1 myocytes were significantly enhanced compared to myocytes isolated from both MI/AdGFP and sham groups. Moreover, S100A1 gene therapy preserved the cardiac beta-adrenergic inotropic reserve, which was associated with the attenuation of GRK2 up-regulation. Also, S100A1 overexpression reduced cardiac hypertrophy 1 week post-MI. Overall, our data indicate that S100A1 gene therapy provides a potential novel treatment strategy to maintain contractile performance of the post-MI heart.Molecular Therapy 01/2006; 12(6):1120-9. · 7.04 Impact Factor
Article: Dipartimento Di Scienze Chirurgiche