Repair and reorganization of minced cardiac muscle in the adult newt (Notophthalmus viridescens)

Abstract

Studies of the response of adult mammalian and amphibian ventricle t o injury have indicated the formation of a connective tissue scar in the place of the wounded or amputated muscle. I t has been demonstrated that amphibian myocytes adjacent to a wound surface, unlike mammalian myocytes, have a proliferative capacity. In the present study, a minced cardiac muscle graft was placed into the adult newt ventricle in order to increase the number of myocytes near a wound surface. With such a n increased number of reactive myocytes, it was thought a new wall consisting primarily of muscle might be formed. Onesixteenth to one-eighth of the ventricular apex was removed, minced and returned to the amputation surface of the ventricle. General histological and autoradiographic studies were conducted on two sham-operated animals and on five experimental animals which were killed at 5, 10, 20,30,50 and 70 days after surgery. Major events of the repair and reorganization of minced cardiac muscle included blood clot formation followed by necrosis of the blood clot and much of the muscle graft. By ten days, an apparent coalescence of muscle fragments and continuity of ventricular and graft lumina were observed, although the graft area never formed a n integrated unit with the wounded ventricular wall. The peak of mitotic activity (3.19%) and thymidine labeling (28.1%) of graft cells, including many cells which resembled cardiac myocytes, was observed at 20 days. At 30 days, the graft was observed a s a continuous wall composed primarily of muscle fibers. Several 30-, 50-and 70-day grafts had rhythmic contractions. These results suggest that amphibian cardiac muscle has histogenetic and proliferative capacities not attributable to mammalian cardiac muscle.The response to adult amphibian and mammalian cardiac muscle to injury has been reviewed by several investigators (Bing, '71; Polezhaev, '72; Rumyantsev, '73; Zak, '74). Two important aspects of this response are the formation of a connective tissue scar in the place of the injured muscle and the proliferation of new cells within the injured area Oberpriller and Oberpriller ('74) reported that 30 days after amputation of one-eighth of the adult newt ventricle, a connective tissue scar spanned the injured area of the ventricle. Only scattered myocytes were observed throughout the connective tissue scar. Scar tissue formation has been reported for the injured mammalian ventricular myocardium but few, if any, myocytes reside within the scar tissue. Though little DNA synthetic activity has been observed in injured mammalian ventricular myocytes (Bing, '71; Zak, '74), DNA synthesis in amphibian ventricular myocytes adjacent to the injury has been observed. Rumyantsev ('66) reported that in injured frog ventricle up to 17% of the cells in the area adjacent to the injury underwent DNA synthesis after a single injection of tritiated thymidine. Oberpriller and Oberpriller ('74) reported that in the injured newt ventricle, approximately 10% of the cells in a n area adjacent to i...

Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes

“…A block to entry into S phase is evident upon expression of p16. Details of the plasmids can be found in Materials and Methods. that observed after injury to the newt ventricle (Bader and Oberpriller, 1979;Bader and Oberpriller, 1978). Second, 19% of the cells go through more than one round of cell division in culture which may account for the 2.5 fold increase in the number of cardiomyocytes described in vivo, after injury (Bader and Oberpriller, 1979).…”

Building and re-building the heart by cardiomyocyte proliferation

“…Yet, cardiomyocytes proliferate avidly during fetal development and in the first days of postnatal life, enabling massive cardiac growth (Soonpaa et al, 1996). Moreover, zebrafish and other teleost fish regenerate portions of their hearts after injury via cardiomyocyte division, and some urodele amphibians have also been reported to regenerate to varying degrees (Bader and Oberpriller, 1978;Flink, 2002;Poss et al, 2002;Witman et al, 2011). Even neonatal mice exhibit some cardiac regenerative capacity (Porrello et al, 2011).…”

Re-programming of newt cardiomyocytes is induced by tissue regeneration

“…In zebrafish up to 20% of the ventricular myocardium can be replaced after resection over a two-month period (Poss et al, 2002). The repair process is associated with the proliferation of cardiomyocytes, which are characterized by a partial disassembly of sarcomeric structures -as monitored by electron microscopy (Bader and Oberpriller, 1978;Tate and Oberpriller, 1989). Although previous studies uncovered differences between the proliferative capabilities of subpopulations of cultured adult newt cardiomyocytes (Bettencourt-Dias et al, 2003), it is not clear whether different subsets of cardomyocyte or cardiomyocyte progenitor cells contribute to heart repair in vivo and whether all cardiomyocytes own an inherent plasticity that might enable them to contribute to regenerative processes.…”