title: Chronic hemodynamic unloading regulates the morphologic development of newborn mouse hearts transplanted into the ear of isogeneic adult mice.
abstract: The morphologic development of newborn mouse hearts transplanted into the pinna of the ears of isogeneic adult mice was assessed in comparison to in situ ventricular myocardium of recipients. The grafted hearts became vascularized from the auricular artery at the base of the ear, and although these preparations appeared not to be intrinsically innervated, most of them showed grossly visible pulsatile activity. Since they were not subjected to hemodynamic load due to working against a pressure gradient, this technique provided an interesting experimental model for studies on the growth of chronically unloaded tissue. The ultrastructure of the myocardium from neonatal mouse hearts, which were fixed immediately after dissection, revealed no differences in comparison to previously published observations. By 2 months, there was virtually no change in the myocardial cell size as compared with newborn mouse cardiac tissue. The heterotopic hearts showed a mature ultrastructural appearance, with parallel bands of myofibrils alternating with rows of mitochondria and differentiated intercalated discs comparable to in situ myocardium. The interstitial space was widened due to fibrous tissue, with activated fibroblasts and a few mononuclear cells. In contrast, by 6 months after transplantation, the heterotopic myocardium showed a dispersion of the measured cell diameter of myocytes, with atrophy of a certain population of cells and hypertrophy in others; nevertheless, the mean cell diameter was similar to that observed in 2-month grafts. The myocytes showed significant dissociation from each other in fibrous tissue and a cellular infiltrate composed predominantly of mononuclear cells, and greater variability of the parallel arrangement of cells. They often contained myofibrils coursing in different directions rather than in parallel. Normal-sized or predominantly atrophic degenerated myocytes, characterized by a wide variety of ultrastructural alterations, were present. By 12 months after transplantation, the myocytes of heterotopic hearts were smaller in size in comparison to those after 2 or 6 months. The graft cells were separated from each other by fibrous tissue and mononuclear cells and were not aligned in parallel within the tissue; often, they appeared to have lost their connections with adjacent cells. The myofibrils within cells were strikingly disorganized, coursing in different directions. Severely degenerated myocytes were commonly seen. These results, without precluding the possible role of neural and hormonal stimuli, clearly indicate that hemodynamic work load regulates the developmental growth of newborn mouse heart transplanted into the pinna of the ear of isogeneic adult recipient mice. In other words, the mass of cardiac tissue would be adjusted to meet the prevailing hemodynamic demands.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Rossi
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001284:Atrophy; D002454:Cell Differentiation / Q000502:physiology; D004423:Ear; D005260:Female; D005838:Genotype; D006321:Heart / Q000254:growth & development / Q000502:physiology*; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology / Q000473:pathology / Q000648:ultrastructure; D016042:Transplantation, Heterotopic / Q000473:pathology; D014185:Transplantation, Isogeneic