Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

Abstract

Original ArticleCardiac remodeling following myocardial infarction (MI) is characterized by scar formation with wall thinning at the site of myocyte fiber loss and progressive left ventricular (LV) dilatation with collagen deposition within noninfarcted myocardium (non-MI) 1 . Ventricular dilatation is a primary consequence of MI location and size 2 , but other factors influence fibrosis accumulation, such as the cardiac renin-angiotensin system, endothelins, catecholamines, and inflammatory mediators 3,4 . However, the role of hemodynamic changes occurring during ongoing infarction have not been investigated 5 . It is still also unclear where fibrosis deposition actually takes place, because subendocardial (SE) regions of non-MI have rarely been contemplated in post-MI morphometric studies 6,7 . The aim of this study was to investigate, using the experimental MI model in the rat, the role of hemodynamic changes taking place acutely after left coronary artery ligature in subsequent fibrosis accumulation within non-MI. MethodsTwenty-one male Wistar rats weighing 275±5g were used for the experiments. All procedures were carried out in accordance with the norms of the Brazilian College of Animal Experiments and conformed to the "Guide for the Care and Use of Laboratory Animals." Our Institutional Ethical Committee approved the protocol.Animals were anesthetized with Ketamine chloride, 50 mg.kg -1 i.p. and Pentobarbital sodium, 25 mg.kg -1 i.p. and put under mechanical ventilation with a rodent ventilator (Model 683, Harvard Apparatus Inc., MA USA). Systemic and LV blood pressures were obtained from femoral and carotid arteries, respectively. The catheters were connected to pressure transducers and coupled to a calibrated preamplifier (General Purpose Amplifier 4 -model 2, Stemtech Inc. WI, USA). The pressure tracings were recorded by using a computerized system processor (AT/Codas, Dataq Instruments Inc., OH, USA). Objective -To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. Methods -By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. Results -

Borage oil attenuates progression of cardiac remodeling in rats after myocardial infarction

“…The remote subendocardium was the region most susceptible to inflammation, as previously demonstrated by our studies 14,17 . In present study, the attenuation of the inflammatory response was most evident in remote subendocardium after Borage oil treatment.…”

“…Tissue sections were stained with haematoxylin-eosin (HE) and Pircro-Sirius red to morphometric measurements using a digital image analysis system (Leica Imaging Systems Ltd., Cambridge, UK) The ratio between endocardial infarct surface length and total left ventricular endocardial circumference and the ratio between epicardial infarct surface length and total left ventricular epicardial circumference were averaged to calculate infarct size 17 .…”

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

“…10,11,27,28 In infarction, the development of interstitial and subendocardial (SE) fibrosis within noninfarcted myocardium has been recognized. 12,29,30 In this case, SE fibrosis appears to represent a repair process in response to persistent ischemia in this region, since the coronary driving pressure (CDP) has been documented to be low during the early phases after infarction 12 .…”

“…9,10,11 Recurrent ischemic episodes predictably result in myocyte necrosis and scar formation. 12,13,14 In different animal models of car-diac hypertrophy, it has been repeatedly documented that the collagen volume fraction (CVF) increases. 15,16,17,18 Two main forms of fibrillar collagen accumulation are currently acknowledged: reactive and reparative fibrosis.…”

“…16,23 Reparative fibrosis results from myocyte loss and represents wound healing scarring, such as occurs following myocardial infarction. 12,15 In eccentric hypertrophic response to volume overload, myocyte growth and fibrillar collagen accumulation appear to develop in a proportional manner. [24][25][26] However, increased fibrosis has recently been reported in cases of volume overload.…”