Chronic myocardial infarction in the mouse: Cardiac structural and functional changes

Objectives: We studied the effects of chronic left coronary artery ligation on cardiac structure and function in the mouse. Methods: Morphometric studies of the left ventricle were performed in coronary artery- ligated and sham-operated animals at one, two, three and five weeks after surgery. The fraction of DNA-synthesizing cells was determined as the fraction of cells incorporating 5'-bromo-2'-deoxyuridine, which was infused by osmotic minipumps one week before sacrifice. Collagen content of the septum was determined morphometrically. Left ventricular pressure and its derivatives were measured in separate groups of animals at one and three weeks after surgery. Results: Ligation of the main left coronary artery resulted in antero-apical infarction of the left ventricular wall, involving ~40% of left ventricular circumference. Infarction resulted in thinning of the infarcted area and left ventricular dilatation. DNA synthesis increased, peaking between one and two weeks in the border-zone of the infarct (22- fold), septum (ten-fold) and right ventricle (five-fold). At five weeks, DNA synthesis was still increased in the border zone of the infarct. Septal collagen content increased ~eight-fold in infarcted mice at two weeks, and decreased thereafter; it was still significantly elevated at five weeks. Left ventricular systolic pressure, and maximal positive and negative dP/dt decreased following infarction; left ventricular end-diastolic pressure was elevated at three weeks, but this effect was not statistically significant. Conclusion: These data provide basic information on changes in cardiac structure and function in mice following chronic coronary artery ligation. They indicate the feasibility of induction of chronic myocardial infarction in this species. Furthermore, they show the similarity of cardiac structural and functional consequences of chronic myocardial infarction in mice to those previously described in rats.