The influence of age on the wound healing of experimental myocardial infarction in rats

Kranz, D; Hecht, A; Fuhrmann, Irene

doi:10.1016/s0014-4908(75)80050-0

Cited by 4 publications

(6 citation statements)

References 21 publications

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“…This may provide the MRL an advantage in resolving the wound tissue. The remodeling response to injury in the MRL is also quite different from that seen in the C57BL͞6, where little movement of myocardial cells, little cell proliferation, and the formation of scar tissue at the injury site as part of the myocardial wound repair process is predominant (13,38,39). In the MRL, on the other hand, there seems to be early movement of cardiomyocytes into the wound site and DNA synthesis and proliferation of these cells.…”

Section: Discussionmentioning

confidence: 84%

Heart regeneration in adult MRL mice

Leferovich

Bedelbaeva

Samulewicz

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

230

190

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The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL͞6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10 -20% for the MRL compared with 1-3% for the C57BL͞6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.

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Section: Discussionmentioning

confidence: 84%

Heart regeneration in adult MRL mice

Leferovich

Bedelbaeva

Samulewicz

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

230

190

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“…In autoradiographic studies of myocardial infarction induced by coronary ligation in rats, a proliferation of DNA-synthesizing connective tissue cells at the infarction border was demonstrated by 12 hours after ligation, and maximum proliferation of connective tissue cells was reached on the 2nd day post-MI (Kranz et al, 1971;Kranz, 1975). Studies of [ 14 C]glycine incorporation into subcellular fractions of cardiac protein and nucleic acids following coronary ligation in dogs demonstrated that the healing process started as early as 24 hours after infarction and reached a maximum on the 4th day post-MI (Gudbjarnason et al, 1964).…”

Section: Discussionmentioning

confidence: 99%

Myocardial healing and repair after experimental infarction in the rabbit.

Lerman¹,

Apstein²,

Kagan³

et al. 1983

Circulation Research

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Adequacy of healing after acute myocardial infarction may determine the incidence of postmyocardial infarction rupture and ventricular aneurysm. Accordingly, in 36 rabbits, from 1 to 8 days after coronary ligation, and in 18 shams, we measured collagen formation and mechanical resistance of the infarcted left ventricle to stretch and rupture. Prolyl hydroxylase, an intracellular enzyme of collagen synthesis, increased from control activity of 3970 ± 431 to 9224 ± 643 counts/min per mg (cpm/mg) extractable protein (P < 0.01) at 48 hours and was nearly maximal at 3 days postmyocardial infarction (14,518 ± 2,030 cpm/mg, P < 0.01). Lysyl oxidase, an extracellular collagen cross-linkage enzyme, increased from control activity of 29.6 ± 4.8 to 74.7 ± 18.8 cpm/mg extractable protein (P < 0.01) at 72 hours and peaked at 121.5 ± 7.3 (P < 0.01) 4-6 days postmyocardial infarction. Hydroxyproline, a measure of collagen content, increased from control of 2.8 ± 0.2 to 5.3 ± 0.6 mg/g dry weight (P < 0.05) at 72 hours and continued to increase at 8 days postmyocardial infarction (14.5 ±1.7 mg/g dry weight; P < 0.01). When enzyme activities and hydroxyproline content were expressed relative to other reference bases, including DNA, tissue protein, dry weight, and total left ventricle, similar results were obtained. The mechanical properties of the infarcted left ventricle were determined by filling a balloon in the excised left ventricle until rupture. The rupture threshold in the normal left ventricle, [664 ± 43 mm Hg (n = 16)], was not significantly different from that of the infarcted left ventricle on days 1-8 postmyocardial infarction. However, left ventricular rupture occurred more often through the myocardial infarction on days 1-4 postmyocardial infarction (59%) than on days 6 and 8 (18%; P = 0.03) when collagen content had significantly increased. Wall stress at the point of rupture in left ventricles from shams and normals was 30 ± 2 g/mm 2 ; tensile strength in isolated left ventricle muscle strips was 25 ± 4 g/mm 2 and in isolated scar strips at 7 days postmyocardial infarction was 59 ± 7 g/mm 2. The passive stiffness of the infarcted left ventricle increased from control of 61 ± 5 to 94 ± 6 mm Hg/100 fi\ (P < 0.05) at 4 days and 100 ± 7 mm Hg/100 pi (P < 0.01) at 6 days postmyocardial infarction. Stiffness correlated with hydroxyproline content over the 8 days postmyocardial infarction (r = 0.599; P < 0.001). Thus, the acutely infarcted ventricle was highly resistant to rupture during the initial 48 hours postmyocardial infarction, before any increase in collagen occurred. This result suggests that the preinfarction collagen content has an important role in preventing rupture. After 72 hours postmyocardial infarction, collagen synthesis appeared to be a determinant of infarct stiffness and resistance of the infarcted ventricle to rupture. (Circ Res 53: 378-388, 1983)

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“…However, young or even adult rodents are not suitable as models of myocardial infarction in humans, because myocardial infarctions occur primarily in middle-aged and older individuals (Bairey Merz et al 2006). The importance of using older animals in MI experiments, especially in the case of small rodents, has been compelled by the findings of studies published earlier by our group (Christensen et al 2009;Dedkov et al 2005;Dedkov, Zheng, et al 2007;Zhang et al 2010) and other laboratories (Kranz et al 1975;Wexler 1978;Raya et al 1997;Bujak et al 2008;Yang et al 2008), which In all scars, densely packed collagen fibers were noticed along the endocardial and epicardial surfaces, including subendocardial and subepicardial regions with surviving cardiac myocytes (CM) (arrows), in areas around the residual coronary arteries (A), and in the midwall layer where they occasionally embedded the remnants of mummified dead CM (arrowheads). On the other hand, loosely packed collagen fibers were dispersed through the rest of the scar.…”

Section: Sex-related Differences In LV Remodeling and Scar Formationmentioning

confidence: 99%

“…Furthermore, despite the well-established fact that advanced age results in delay of infarct healing in post-MI rats (Kranz et al 1975;Wexler 1978) and significantly increases a risk of post-MI cardiac rupture (Yang et al 2008) as well as exaggerates adverse LV remodeling (Bujak et al 2008) in mice, most MI experiments were done in young or young-adult animals. However, our previous studies have demonstrated that the adaptive changes in post-MI hearts of middle-aged rats (Dedkov et al 2006;Dedkov, Zheng, et al 2007) may provide a better correlation to the human population in which the occurrence of MI is more prevalent among middle-aged and elderly individuals of both sexes (Bairey Merz et al 2006;Vaccarino et al 2011).…”

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confidence: 99%

Structural Composition of Myocardial Infarction Scar in Middle-aged Male and Female Rats

Bogatyryov

Tomanek

Dedkov

2013

J Histochem Cytochem.

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ArticleSudden obstruction of coronary blood flow causes ischemic death of cardiomyocytes followed by a universal cascade of reparative events (Frangogiannis 2006) leading to infarct healing and scar formation in the heart. Nevertheless, a growing body of evidence from animal studies suggests that females exhibit a different pattern of myocardial infarction (MI) healing and left ventricular (LV) remodeling than males. For instance, post-MI female mice reveal less exaggerated inflammation and enhanced reparative fibrotic response during infarct healing, contributing to a lower rate of cardiac rupture and a lesser degree of LV remodeling in comparison with males (Cavasin et al. 2004;Gao et al. 2005;Fang et al. 2007;Wang F et al. 2007). In addition, despite comparable infarct size and LV cavity dilatation, the thickness of noninfarcted myocardium is less in post-MI female than male rats (Litwin et al. 1999), indicating a smaller increase in compensatory hypertrophy in response to post-MI cardiac remodeling in the females.Although most of these studies were focused on earlier reparative events taking place in male and female hearts during the overlapping phases of MI healing (i.e., inflammatory, proliferative and maturation phases), surprisingly little attention has been paid to providing a comparative assessment of the structural components in a mature scar. However, it has been previously shown that the tissue composition of a mature scar is an important determinant of its mechanical properties (Connelly et al. 1985) and, thereby, can drastically influence overall ventricular performance SummaryThe present study was designed to determine whether the structural composition of the scar in middle-aged post-myocardial infraction (MI) rats is affected by the biological sex of the animals. A large MI was induced in 12-month-old male (M-MI) and female (F-MI) Sprague-Dawley rats by ligation of the left coronary artery. Four weeks after the MI, rats with transmural infarctions, greater than 50% of the left ventricular (LV) free wall, were evaluated. The extent of LV remodeling and fractional volumes of fibrillar collagen (FC), myofibroblasts, vascular smooth muscle (SM) cells, and surviving cardiac myocytes (CM) in the scars were compared between the two sexes. The left ventricle of post-MI male and female rats underwent a similar degree of remodeling as evidenced by the analogous scar thinning ratio (0.46 ± 0.02 vs. 0.42 ± 0.05) and infarct expansion index (1.06 ± 0.07 vs. 1.12 ± 0.08), respectively. Most important, the contents of major structural components of the scar revealed no evident difference between M-MI and F-MI rats (interstitial FC, 80.74 ± 2.08 vs. 82.57 ± 4.53; myofibroblasts, 9.59 ± 1.68 vs. 9.56 ± 1.15; vascular SM cells, 2.27 ± 0.51 vs. 3.38 ± 0.47; and surviving CM, 3.26 ± 0.39 vs. 3.05 ± 0.38, respectively). Our data are the first to demonstrate that biological sex does not influence the structural composition of a mature scar in middleaged post-MI rats. (J Histochem Cytochem 61:833-848, 2013)

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The influence of age on the wound healing of experimental myocardial infarction in rats

Cited by 4 publications

References 21 publications

Heart regeneration in adult MRL mice

Heart regeneration in adult MRL mice

Myocardial healing and repair after experimental infarction in the rabbit.

Structural Composition of Myocardial Infarction Scar in Middle-aged Male and Female Rats

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