Abstract
It has been shown that the size of myocardial infarction in rats created by coronary ligation technique is not uniform, varying from 4% to 65%. We hypothesized that infarct size variability induced by coronary artery ligation might be caused by coronary artery branching pattern. Coronary artery angiography was performed in 50 normal Lewis rats and in chronic myocardial infarction models in which coronary artery was ligated immediately below the left atrial appendage or 2mm distal to the left atrial appendage (n = 25 for each), followed by histological analysis. Unlike the human, the rats had a single major septal artery arising from the proximal part of the left coronary artery (n = 30) or right coronary artery (n = 20). There were three branching patterns of left circumflex artery (LCX): 33 (66%) had LCX branching peripherally from a long left main coronary artery (LMCA), while the remainder 17 (34%) had the LCX branching from the proximal part of the septal artery or a short LMCA. The rats with distal coronary ligation presented myocardial infarction localized to an anterior territory irrespective of LCX branching pattern. In the rats with proximal coronary ligation, 64% (n = 16) had broad myocardial infarction involving the anterior and lateral territories, while the remainder (36%, n = 9) had myocardial infarction localized to an anterior territory with the intact LCX arising proximally from a short LMCA. The interventricular septum was spared from infarction in all rats because of its anatomical location. Infarct size variations were caused not only by ligation site but also by varying LCX branching patterns. There are potential risks to create different sizes of myocardial infarction, particularly when targeting a broad range of myocardial infarction. The territory of the septal artery always appears to be spared from myocardial infarction induced by the coronary ligation technique.
Highlights
Rat myocardial infarction models have been widely used, for studying the pathophysiology of post-infarct remodeling process, and for testing the efficacy of pharmacological and/or therapeutic strategies for adverse sequelae [1,2,3]
We aimed to characterize the distribution of the coronary arteries in a rat strain that is routinely used in studies of regenerative therapies and investigated the factors involved in the varying size and location of myocardial infarction that is created by coronary artery ligation
The septal artery invariably branched off either from the proximal part of the left coronary artery (n = 30, 60%) or the right coronary artery (n = 20, 40%) (Fig 1D and 1E). It descended along the right surface of the interventricular septum toward the apex of the left ventricle (LV) (Fig 1D–1F)
Summary
Rat myocardial infarction models have been widely used, for studying the pathophysiology of post-infarct remodeling process, and for testing the efficacy of pharmacological and/or therapeutic strategies for adverse sequelae [1,2,3]. It is reported that the size of myocardial infarction induced by the coronary ligation technique is not uniform, varying from 4% to 65% in rat models [7] This varying size of myocardial infarction inherent in the coronary ligation model is attributed at least partly to being unable to occlude the coronary artery exactly at the same point in all animals as the left coronary artery is usually intramyocardial in its proximal region, returning to the surface epicardially at approximately 3 to 4 mm from its origin [8,9,10,11]. We aimed to characterize the distribution of the coronary arteries in a rat strain that is routinely used in studies of regenerative therapies and investigated the factors involved in the varying size and location of myocardial infarction that is created by coronary artery ligation
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