Establishment of a long-surviving murine model of myocardial infarction: Qualitative and quantitative conventional microscopic findings during pathological evolution

Abstract

Ongoing basic molecular analyses are being performed in mice, and a simple long-surviving murine model of myocardial infarction (MI) would be very useful in this regard. Although a few studies have induced MI in mice by coronary artery ligation, the induction involves a complex technique and has a relatively high mortality rate. In addition, the identification of the basic pathological sequence is essential to the interpretation of experimental results. We developed a simple technique for the induction of MI in mice and examined qualitative and quantitative conventional microscopic findings during the pathological evolution over a 28-day observation period. Male BALB/c mice weighing approximately 25-30 g were anesthetized and then ventilated with a positive pressure ventilator. The heart was exposed by thoracotomy. Left coronary artery occlusion was performed by thermocoagulation using a thermocoagulation knife at the level of the tip of the left atrium. After establishing this surgical method, we used it to induce MI in 71 mice. The operative and postoperative mortality rates of this model were 5.6% (4/71) and 12.6% (9/71), respectively. In 3 (5.2%) of the 58 surviving mice, the area of infarct was not sufficient. The infarct area in the remaining 55 mice was 40 +/- 9% of the entire perimeter of the left ventricle. Conventional microscopic examinations with hematoxylin-eosin and Masson-trichrome staining disclosed that all of the characteristic histopathological features of MI occurred 1-2 days earlier than those in rats. Our surgical technique provides a sufficient infarct area, with an acceptable mortality rate. The present study clarified the histopathological sequence in this long surviving murine MI model.

Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in C57BL/6 mice

“…In the latter case, the MI is usually nontransmural. Animals with a smaller MI, unintentionally induced by ligation of the LMDA, have usually been removed from published study data analyses (7,11), or their results have been presented separately (1a, 10), because those hearts did not show significant remodeling or functional decline. For instance, Bayat et al (1a) reported that morphometric and functional indexes derived from echocardiography of mice with MI Ͻ30% of the LV (16 Ϯ 3% of the LV) were not different from those of sham-operated animals 6, 12, or 18 wk after coronary ligation.…”

Scaffold-Based Three-Dimensional Human Fibroblast Culture Provides a Structural Matrix That Supports Angiogenesis in Infarcted Heart Tissue

“…Epicardial access was achieved by a left thoracotomy. Occlusion of the first branch of the left anterior descending coronary artery was performed by thermocoagulation, 19 and vessel occlusion was confirmed by a blanching in surface color. Viable 3DFC or nonviable 3DFC patches (4-mm diameter) were sutured (10-0 Prolene suture; Ethicon Corp) onto the epicardial surface over the ischemic region.…”

“…In the literature, both large-animal (mainly canine and porcine) 8 -10 and small-animal (including lupine and rodent) [11][12][13] models have been used for both acute and chronic models of coronary vessel occlusion. In the acute model, a coronary vessel is occluded by suture ligature, cryoprobe, cautery probe, or microembolization coils, 10,[12][13][14] thereby stimulating an immediate infarction in which intrinsic collateralization of the heart is insufficient to rescue cardiac function and dead cardiomyocytes are replaced by fibrotic scar tissue. Although the infarcted region will grow and the myocardial wall will thin, hibernating cardiomyocytes surrounding the infarcted zone may be temporarily supported nutritionally.…”

Myocardial Infarction and Cardiac Remodelling in Mice

“…Although there have been studies employing a mouse model of MI (Kumashiro et al 1999;Lutgens et al 1999), they have focused mostly on the changes seen during the first few weeks post-MI. Lutgens et al (1999) recently observed LV dilatation, hypertrophy and collagen deposition at 1, 2, 3 and 5 weeks post-MI and these structural changes were associated with decreased dP/dt (maximum increase in pressure over time).…”

“…Lutgens et al (1999) recently observed LV dilatation, hypertrophy and collagen deposition at 1, 2, 3 and 5 weeks post-MI and these structural changes were associated with decreased dP/dt (maximum increase in pressure over time). Kumashiro et al (1999) also conducted a semi-quantitative analysis of total inflammatory cell infiltration, fibrosis and vascular proliferation by 4 weeks after MI. However, precise quantitative data on histopathological and morphological changes post-MI in a mouse model are lacking.…”