Comparison of myocardial remodeling between cryoinfarction and reperfused infarction in mice.

Myocardial infarction is associated with inflammatory reaction leading to tissue remodeling. We compared tissue remodeling between cryoinfarction (cMI) and reperfused myocardial infarction (MI) in order to better understand the local environment where we apply cell therapies. Models of closed-chest one-hour ischemia/reperfusion MI and cMI were used in C57/Bl6-mice. The reperfused MI showed rapid development of granulation tissue and compacted scar formation after 7 days. In contrast, cMI hearts showed persistent cardiomyocyte debris and cellular infiltration after 7 days and partially compacted scar formation accompanied by persistent macrophages and myofibroblasts after 14 days. The mRNA of proinflammatory mediators was transiently induced in MI and persistently upregulated in cMI. Tenascin C and osteopontin-1 showed delayed induction in cMI. In conclusion, the cryoinfarction was associated with prolonged inflammation and active myocardial remodeling when compared to the reperfused MI. These substantial differences in remodeling may influence cellular engraftment and should be considered in cell therapy studies.

Quantitation of myocardial borderzone using reconstructive 3-D echocardiography after chronic infarction in rats: incremental value of low-dose dobutamine.

Myocardial remodeling determines the degree of left ventricular dysfunction and mortality after transmural chronic myocardial infarction (CMI). Noninvasive characterization and quantitation of myocardial borderzone and collagenous scar are therefore parameters of clinical interest. The aims of this study were (i) to measure accuracy of reconstructive 3-D echocardiography (3DE) in scar and myocardial borderzone size assessment and (ii) to investigate the incremental value of low-dose dobutamine stress. 3DE was performed in 14 immunodeficient rats (rnu-rnu, 180-200 g) with anterior CMI 25 d after coronary ligation. Briefly, consecutive parallel short-axis cineloops were obtained electrocardiogram-gated starting from base to the apex. Morphology (mass, surface) and function (contractility, contractile reserve) of different compartments were assessed and correlated with 3-D histomorphometry. Histology was done using picrosirius red for collagen staining. 3DE left ventricular mass correlated closely with histomorphometry (y = 0.89x + 155, p < 0.0001, r = 0.80). Hypo- and akinetic myocardial surface correlated well with borderzone myocardium (y = 0.34x + 17, p = 0.009, r = 0.62) and collagenous scar (y = 1.9x + 4.4, p < 0.0001, r = 0.79), respectively. Extent of abnormal wall motion was closely related to borderzone and scar tissue area (y = 0.82x + 7, p < 0.0001, r = 0.77). 3DE quantitation of borderzone myocardium, but not collagenous scar, was more closely correlated to histomorphometry during inotropic stimulation. Global contractile reserve is positively associated with the size of myocardial borderzone. Regional contractile reserve of borderzone myocardium is not negatively associated with its collagen content. 3DE allows precise quantitation of myocardial borderzone and identification of transmural scar tissue noninvasively. Assessment of contractile reserve improves characterization and estimation of myocardial borderzone after CMI.