A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Abstract

The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore, we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2-or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional shortening as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point, in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, coneshaped infarcts with reperfusion at the macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice. heart function; cardiac remodeling; echocardiography WITH THE ACCUMULATING AVAILABILITY of various models of genetically modified mice, there is a growing interest in murine models of myocardial infarction (MI) for the study of cardiac remodeling (18). The most widely studied model of murine MI is permanent ligation of the left anterior descending coronary artery (LAD) (12, 16). Although highly representative of ischemic cell death as occurs in humans, the ligation model is inherently associated with infarcts of variable size, requiring large group numbers of mice in studies that evaluate antiremodeling therapies. Even more importantly, LAD ligation in the mouse heart typically leads to apical infarcts with large aneurysm formation causing a particular ventricular geometry. Ligation-induced infarcts in the mouse heart appear therefore less representative for infarcts encountered in clinical practice, where acute LAD occlusion followed by aggressive reperfusion therapy often leads to moderately sized infarcts of the anterior free wall.Several alternative models of MI have been proposed and studied over the years in various animal models, including infarction by freeze-thaw injury, or cryoinjury (2, 20). In the last years, cryoinjury has been mainly applied in studies on intracardiac cell transplantation (9,14,1...

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

“…However, the possible mechanisms for the cardioprotective effects of the three natriuretic peptides on I/R seem to be controversial. NPRC activation is thought to be responsible for the cardioprotective role of CNP as mentioned above, and the selective agonist of NPRC (cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ) also reduces infarct size and maintains coronary perfusion pressure [12]. Studies of ANP and BNP effects show the involvement of cGMP generated via the NPRA receptor in the reduction of infarct size [24,25].…”

“…Surgical techniques were employed according to Tarnavski et al [18] with some minor revisions. Briefly, mice were anaesthetized and artificially ventilated with a mixture of oxygen and N 2 O [1:2 (vol/vol)] using a rodent ventilator, to which 2-2.5% isoflurane was added for anaesthesia [19]. The ventilation rate was set at 80 strokes/min, a peak inspiration pressure of 18 cm H 2 O and a positive end expiration pressure of 4 cm H 2 O.…”

“…Three weeks after MI, echocardiographic and haemodynamic measurements were performed as previously described [19]. M-mode echocardiograms of the LV with simultaneous electrocardiograph (ECG) (ProSound SSD-4000, Aloka, Tokyo, Japan) were obtained using a 13-MHz probe.…”

“…Subsequently, baseline recordings were obtained for MAP, HR and LV systolic pressure. In addition, we measured the contractility parameter LV dP / dt max , the afterload independent LV dP / dt P30 (positive LV dP / dt at LV pressure of 30 mm Hg) and the relaxation parameters Tau (τ) and LV dP / dt min [19].…”

Ligating LAD with Its Whole Length Rather than Diagonal Branches as Coordinates Is More Advisable in Establishing Stable Myocardial Infarction Model of Swine

“…For instance, intracoronary autologous bone-marrow cell transfer after acute MI can improve LVEF as little as 5% [20]. Under such circumstances, a stable MI model is imperative to minimize the possible confounding effect [1,17].…”