Influence of coronary architecture on the variability in myocardial infarction induced by coronary ligation in rats

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.

Fig 1

The left coronary artery was permanently ligated 2 mm distal to (A) or immediately below (B) the LAA. A catheter with an internal diameter of 0.89 mm was inserted from the right carotid artery into the aortic root (C). The septal artery invariably branched off either from proximal part of the LCA (n = 30, 60%) (D) or RCA (n = 20, 40%) (E). Representative histological images of left and right ventricular cavities at the level of the papillary muscles in normal rats (F). Abbreviations: LV = left ventricle, LAA = left atrial appendage, CCA = carotid coronary artery, PI = peripherally inserted, LCA = left coronary artery, RCA = right coronary artery, RV = right ventricle, LAD = left anterior descending artery, LCX = left circumflex artery, APM = anterior papillary muscle, PPM = posterior papillary muscle.

Fig 2. There are 3 branching patterns of LCX, which arose distally from a long LMCA (A, B), proximally from a short LMCA (C, D), or the septal artery (E, F).

Abbreviations, see Fig 1, LMCA = left main coronary artery.

Fig 3. The representative histological and angiographic findings of the 2 rats in which the coronary artery was ligated 2 mm distal to the LAA (A-C and D-F).

Both cases showed myocardial infarction localized to anterior territory with intact LCX and septal artery. The size of myocardial infarction was 33% (A), and 26% (C), respectively. Abbreviations, see Figs 1 and 2.

Fig 4

The representative histological and angiographic findings of the 4 rats in which the coronary artery was ligated immediately below the LAA (A-I). The former 2 rats showed myocardial infarction localized to anterior territory with intact LCX (A-C and D-F), while the latter 2 showed broad myocardial infarction involving anterior and lateral territories (G-I and J-L). The size of myocardial infarction was 35% (A), 27% (D), 51% (G), and 53% (J), respectively. The territory of the septal artery was not affected in any of the rat models of myocardial infarction. Abbreviations, see Figs 1 and 2.

Fig 5. Scatter plot showing size of myocardial infarction (A), LV end-systolic dimension (B), and LV ejection fraction (C) in the models in which the LCA was ligated distally versus proximally.

Fig 6. Relationship between the size of myocardial infarction and LV end-diastolic dimension (A), LV end-systolic dimension (B), and LV ejection fraction (C).

The black circles indicate the models in which the coronary artery was ligated 2 mm distal to the LAA and the white circles indicate the models in which the LAD was ligated immediately below LAA.