Hostname: page-component-848d4c4894-4hhp2 Total loading time: 0 Render date: 2024-06-03T10:31:25.764Z Has data issue: false hasContentIssue false

Current issues and perspectives in hypoplasia of the left heart

Published online by Cambridge University Press:  14 April 2005

David Sedmera
Affiliation:
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, United States of America
Andrew C. Cook
Affiliation:
Cardiac Unit, Institute of Child Health, University College London, London, United Kingdom
Girish Shirali
Affiliation:
Pediatric Cardiology, Medical University of South Carolina, Charleston, South Carolina, United States of America
Tim C. McQuinn
Affiliation:
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, United States of America Pediatric Cardiology, Medical University of South Carolina, Charleston, South Carolina, United States of America

Abstract

Hypoplastic left heart syndrome is a rare but serious form of congenital cardiac disease, characterized by underdevelopment of the components of the left heart, rendering the left ventricle non-functional. Its aetiology is largely unknown, but there is certainly a genetic component. Prenatal diagnosis nowadays uncovers about half of cases. Postnatal options for treatment include comfort care, 3-stage palliative surgery, or cardiac transplantation. In this review, we discuss the morphology, possible pathogenetic mechanisms, clinical management, and perspectives of prenatal intervention based on work in animal models.

Type
Continuing Medical Education
Copyright
2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Gittenberger-de Groot AC. Het links hypoplasticsch hart als aangeboren afwijking. In: Anatomy and Embryology. Leiden: Rijksuniversiteit te Leiden, 1972, p 134.
Lev M. Pathologic anatomy and interrelationship of hypoplasia of the aortic tract complexes. Lab Invest 1952; 1: 6170.Google Scholar
Friedman S, Murphy L, Ash R. Aortic atresia with hypoplasia of the left heart and aortic arch. J Pediatr 1951; 38: 354368.Google Scholar
Noonan JA, Nadas AS. The hypoplastic left heart syndrome. An analysis of 101 cases. Pediatr Clin North Am 1958; 5: 10291056.Google Scholar
Restivo A, Ho SY, Anderson RH, Cameron H, Wilkinson JL. Absent left atrioventricular connection with right atrium connected to morphologically left ventricular chamber, rudimentary right ventricular chamber, and ventriculoarterial discordance. Problem of mitral versus tricuspid atresia. Br Heart J 1982; 48: 240248.Google Scholar
Simpson JM, Sharland GK. Natural history and outcome of aortic stenosis diagnosed prenatally. Heart 1997; 77: 205210.Google Scholar
Freedom RM, Culham JA, Moes CA, Harrington DP. Selective aortic root angiography in the hypoplastic left heart syndrome. Eur J Cardiol 1976; 4: 2529.Google Scholar
Cook AC. The anatomy of left heart hypoplasia in the human fetus. Thesis, University of London, 2003.Google Scholar
Bradley SM. Neonatal repair and dealing with a single ventricle. J S C Med Assoc 1999; 95: 335338.Google Scholar
Shokeir MH. Hypoplastic left heart. Evidence for possible autosomal recessive inheritance. Birth Defects Orig Artic Ser 1974; 10: 223227.Google Scholar
Shokeir MH. Hypoplastic left heart syndrome: an autosomal recessive disorder. Clin Genet 1971; 2: 714.Google Scholar
Brenner JI, Berg KA, Schneider DS, Clark EB, Boughman JA. Cardiac malformations in relatives of infants with hypoplastic left-heart syndrome. Am J Dis Child 1989; 143: 14921494.Google Scholar
Natowicz M, Chatten J, Clancy R, et al. Genetic disorders and major extracardiac anomalies associated with the hypoplastic left heart syndrome. Pediatrics 1988; 82: 698706.Google Scholar
Natowicz M, Kelley RI. Association of Turner syndrome with hypoplastic left-heart syndrome. Am J Dis Child 1987; 141: 218220.Google Scholar
Consevage MW, Seip JR, Belchis DA, et al. Association of a mosaic chromosomal 22q11 deletion with hypoplastic left heart syndrome. Am J Cardiol 1996; 77: 10231025.Google Scholar
Saneto RP, Applegate KE, Frankel DG. Atypical manifestations of two cases of trisomy 9 syndrome: rethinking development delay. Am J Med Genet 1998; 80: 4245.Google Scholar
Phillips HM, Renforth GL, Spalluto C, et al. Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis. Genomics 2002; 79: 475478.Google Scholar
Burton PB, Hauck A, Nehlsen-Cannarella SL, et al. Hypoplastic left heart syndrome: some clues to its aetiology. Lancet 1991; 338: 1148.Google Scholar
Sedmera D, Hu N, Weiss KM, et al. Cellular changes in experimental left heart hypoplasia. Anat Rec 2002; 267: 137145.Google Scholar
Towbin JA, Casey B, Belmont J. The molecular basis of vascular disorders. Am J Hum Genet 1999; 64: 678684.Google Scholar
Rychter Z, Rychterova V. Angio- and myoarchitecture of the heart wall under normal and experimentally changed morphogenesis. In: Pexieder T (ed.). Perspectives in Cardiovascular Research. Raven Press, New York, NY, USA, 1981, pp 431452.
Sedmera D, Pexieder T, Rychterova V, Hu N, Clark EB. Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. Anat Rec 1999; 254: 238252.Google Scholar
van der Linde-Sipman JS, Wensing CJ. The left hypoplastic heart syndrome in the minipig. Birth Defects Orig Artic Ser 1978; 14: 295314.Google Scholar
Tikkanen J, Heinonen OP. Risk factors for hypoplastic left heart syndrome. Teratology 1994; 50: 112117.Google Scholar
Oyer CE, Ongcapin EH, Ni J, Bowles NE, Towbin JA. Fatal intrauterine adenoviral endomyocarditis with aortic and pulmonary valve stenosis: diagnosis by polymerase chain reaction. Hum Pathol 2000; 31: 14331435.Google Scholar
Ni J, Bowles NE, Kim YH, et al. Viral infection of the myocardium in endocardial fibroelastosis. Molecular evidence for the role of mumps virus as an etiologic agent. Circulation 1997; 95: 133139.Google Scholar
Kohl T. Fetal echocardiography: new grounds to explore during fetal cardiac intervention. Pediatr Cardiol 2002; 23: 334346.Google Scholar
Carvalho JS. Early prenatal diagnosis of major congenital heart defects. Curr Opin Obstet Gynecol 2001; 13: 155159.Google Scholar
Allan LD, Sharland G, Tynan MJ. The natural history of the hypoplastic left heart syndrome. Int J Cardiol 1989; 25: 341343.Google Scholar
Anderson NG, Brown J. Normal size left ventricle on antenatal scan in lethal hypoplastic left heart syndrome. Pediatr Radiol 1991; 21: 436437.Google Scholar
Sharland GK, Chita SK, Fagg NL, et al. Left ventricular dysfunction in the fetus: relation to aortic valve anomalies and endocardial fibroelastosis. Br Heart J 1991; 66: 419424.Google Scholar
McCaffrey FM, Sherman FS. Prenatal diagnosis of severe aortic stenosis. Pediatr Cardiol 1997; 18: 276281.Google Scholar
van der Linde-Sipman JS. Hypoplasia of the left ventricle in four ruminants. Vet Pathol 1978; 15: 474480.Google Scholar
van Nie CJ, van Messel MA, Straatman TJ. Congenital bicuspid stenosis with left ventricular hypoplasia in a kitten. Tijdschr Diergeneeskd 1980; 105: 5862.Google Scholar
Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH. Developmental patterning of the myocardium. Anat Rec 2000; 258: 319337.Google Scholar
Fishman NH, Hof RB, Rudolph AM, Heymann MA. Models of congenital heart disease in fetal lambs. Circulation 1978; 58: 354364.Google Scholar
Rychter Z, Rychterova V, Lemez L. Formation of the heart loop and proliferation structure of its wall as a base for ventricular septation. Herz 1979; 4: 8690.Google Scholar
Tobita K, Keller BB. Right and left ventricular wall deformation patterns in normal and left heart hypoplasia chick embryos. Am J Physiol Heart Circ Physiol 2000; 279: H959H969.Google Scholar
Harh JY, Paul MH, Gallen WJ, Friedberg DZ, Kaplan S. Experimental production of hypoplastic left heart syndrome in the chick embryo. Am J Cardiol 1973; 31: 5156.Google Scholar
Clark EB, Hu N, Dummett JL, et al. Ventricular function and morphology in chick embryo from stages 18 to 29. Am J Physiol 1986; 250: H407H413.Google Scholar
Harh JY, Paul MH. Experimental cardiac morphogenesis. I. Development of the ventricular septum in the chick. J Embryol Exp Morphol 1975; 33: 1328.Google Scholar
Ben-Shachar G, Arcilla RA, Lucas RV, Manasek FJ. Ventricular trabeculations in the chick embryo heart and their contribution to ventricular and muscular septal development. Circ Res 1985; 57: 759766.Google Scholar
Icardo JM, Fernandez-Teran A. Morphologic study of ventricular trabeculation in the embryonic chick heart. Acta Anat 1987; 130: 264274.Google Scholar
Pexieder T. Development of the outflow tract of the embryonic heart. Birth Defects Orig Artic Ser 1978; 14: 2968.Google Scholar
Sedmera D, Pexieder T, Hu N, Clark EB. Developmental changes in the myocardial architecture of the chick. Anat Rec 1997; 248: 421432.Google Scholar
Tobita K, Schroder EA, Tinney JP, Garrison JB, Keller BB. Regional passive ventricular stress-strain relations during development of altered loads in chick embryo. Am J Physiol Heart Circ Physiol 2002; 282: H2386H2396.Google Scholar
Jay PJ, Berul CI, Tanaka M, et al. Cardiac conduction and arrhythmia: insights from Nkx2.5 mutations in mouse and humans. In: Chadwick DJ, Goode J (eds). Development of the Cardiac Conduction System. Wiley, Chichester, 2003, pp 227241.
Riordan CJ, Randsbaek F, Storey JH, et al. Inotropes in the hypoplastic left heart syndrome: effects in an animal model. Ann Thorac Surg 1996; 62: 8390.Google Scholar
Halnon NJ, Wetzel GT. Implications of improving survival in the management of life-threatening congenital heart disease: new challenges in pediatric cardiology. Curr Opin Cardiol 2002; 17: 271273.Google Scholar
Allan LD, Maxwell DJ, Carminati M, Tynan MJ. Survival after fetal aortic balloon valvoplasty. Ultrasound Obstet Gynecol 1995; 5: 9091.Google Scholar
Kohl T, Sharland G, Allan LD, et al. World experience of percutaneous ultrasound-guided balloon valvuloplasty in human fetuses with severe aortic valve obstruction. Am J Cardiol 2000; 85: 12301233.Google Scholar
Marshall AC, van der Velde ME, Tworetzky W, et al. Creation of an atrial septal defect in utero for fetuses with hypoplastic left heart syndrome and intact or highly restrictive atrial septum. Circulation 2004; 110: 253258.Google Scholar
Tchervenkov CI, Jacobs ML, Tahta SA. Congenital Heart Surgery Nomenclature and Database Project: hypoplastic left heart syndrome. Ann Thorac Surg 2000; 69: S170S179.Google Scholar
Glauser TA, Rorke LB, Weinberg PM, Clancy RR. Congenital brain anomalies associated with the hypoplastic left heart syndrome. Pediatrics 1990; 85: 984990.Google Scholar
Meacham LR, Winn KJ, Culler FL, Parks JS. Double vagina, cardiac, pulmonary, and other genital malformations with 46,XY karyotype. Am J Med Genet 1991; 41: 478481.Google Scholar
Scheurer M, Shirali GS. Hypoplastic left heart syndrome: native and post-norwood. Pediatric Ultrasound Today 2003; 8: 6584.Google Scholar
Vlahos AP, Lock JE, McElhinney DB, van der Velde ME. Hypoplastic left heart syndrome with intact or highly restrictive atrial septum: outcome after neonatal transcatheter atrial septostomy. Circulation 2004; 109: 23262330.Google Scholar
Bove EL, Lloyd TR. Staged reconstruction for hypoplastic left heart syndrome. Contemporary results. Ann Surg 1996; 224: 387394; discussion 394–385.Google Scholar
Malec E, Januszewska K, Kolcz J, Mroczek T. Right ventricle-to-pulmonary artery shunt versus modified Blalock-Taussig shunt in the Norwood procedure for hypoplastic left heart syndrome – influence on early and late haemodynamic status. Eur J Cardiothorac Surg 2003; 23: 728734.Google Scholar
Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: lessons learned from 115 consecutive patients. Circulation 2002; 106: I82I89.Google Scholar
Poirier NC, Drummond-Webb JJ, Hisamochi K, et al. Modified Norwood procedure with a high-flow cardiopulmonary bypass strategy results in low mortality without late arch obstruction. J Thorac Cardiovasc Surg 2000; 120: 875884.Google Scholar
Reddy VM, McElhinney DB, Moore P, Haas GS, Hanley FL. Outcomes after bidirectional cavopulmonary shunt in infants less than 6 months old. J Am Coll Cardiol 1997; 29: 13651370.Google Scholar
Fraisse A, Colan SD, Jonas RA, Gauvreau K, Geva T. Accuracy of echocardiography for detection of aortic arch obstruction after stage I Norwood procedure. Am Heart J 1998; 135: 230236.Google Scholar
Gutgesell HP, Gibson J. Management of hypoplastic left heart syndrome in the 1990s. Am J Cardiol 2002; 89: 842846.Google Scholar
Chang RK, Chen AY, Klitzner TS. Clinical management of infants with hypoplastic left heart syndrome in the United States, 1988–1997. Pediatrics 2002; 110: 292298.Google Scholar
Morrow WR, Naftel D, Chinnock R, et al. Outcome of listing for heart transplantation in infants younger than six months: predictors of death and interval to transplantation. The Pediatric Heart Transplantation Study Group. J Heart Lung Transplant 1997; 16: 12551266.Google Scholar
Silverman NH, McElhinney DB. Which two ventricles cannot be used for a biventricular repair? Echocardiographic assessment. Ann Thorac Surg 1998; 66: 634640.Google Scholar
Mahle WT, Gaynor JW, Spray TL. Atrioventricular valve replacement in patients with a single ventricle. Ann Thorac Surg 2001; 72: 182186.Google Scholar
Harrison MR. Fetal surgery. Am J Obstet Gynecol 1996; 174: 12551264.Google Scholar
Sydorak RM, Nijagal A, Albanese CT. Endoscopic techniques in fetal surgery. Yonsei Med J 2001; 42: 695710.Google Scholar
Maxwell D, Allan L, Tynan MJ. Balloon dilatation of the aortic valve in the fetus: a report of two cases. Br Heart J 1991; 65: 256258.Google Scholar
Hornberger LK, Sanders SP, Rein AJ, et al. Left heart obstructive lesions and left ventricular growth in the midtrimester fetus. A longitudinal study. Circulation 1995; 92: 15311538.Google Scholar
Clark EB, Hu N, Frommelt P, et al. Effect of increased pressure on ventricular growth in stage 21 chick embryos. Am J Physiol 1989; 257: H55H61.Google Scholar
Sedmera D, Thompson RP, Kolar F. Effect of increased pressure loading on heart growth in neonatal rats. J Mol Cell Cardiol 2003; 35: 301309.Google Scholar
Grohmann D. Mitotische Wachstumsintensitat des embryonalen und fetalen Hunchenherzens und ihre Bedeutung fur die entstehung von Herzmissbildungen. Z f Zellforschung 1961; 55: 104122.Google Scholar
Jeter Jr JR, Cameron IL. Cell proliferation patterns during cytodifferentiation in embryonic chick tissues: liver, heart and erythrocytes. J Embryol Exp Morphol 1971; 25: 405422.Google Scholar
Mikawa T, Borisov A, Brown AM, Fischman DA. Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus: I. Formation of the ventricular myocardium. Dev Dyn 1992; 193: 1123.Google Scholar
Sedmera D, Reckova M, DeAlmeida A, et al. Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system. Anat Rec 2003; 274A: 773777.Google Scholar
Meilhac SM, Kelly RG, Rocancourt D, et al. A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart. Development 2003; 130: 38773889.Google Scholar
Miller CE, Donlon KJ, Toia L, Wong CL, Chess PR. Cyclic strain induces proliferation of cultured embryonic heart cells. In Vitro Cell Dev Biol Anim 2000; 36: 633639.Google Scholar
Clark EB, Hu N, Turner DR, Litter JE, Hansen J. Effect of chronic verapamil treatment on ventricular function and growth in chick embryos. Am J Physiol 1991; 261: H166H171.Google Scholar
Sedmera D, Pexieder T, Hu N, Clark EB. A quantitative study of the ventricular myoarchitecture in the stage 21–29 chick embryo following decreased loading. Eur J Morphol 1998; 36: 105119.Google Scholar
Hefti MA, Harder BA, Eppenberger HM, Schaub MC. Signaling pathways in cardiac myocyte hypertrophy. J Mol Cell Cardiol 1997; 29: 28732892.Google Scholar
Pasumarthi KB, Field LJ. Cardiomyocyte cell cycle regulation. Circ Res 2002; 90: 10441054.Google Scholar
Mima T, Ueno H, Fischman DA, Williams LT, Mikawa T. Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development. Proc Natl Acad Sci USA 1995; 92: 467471.Google Scholar
Jedlicka S, Finkelstein JN, Paulhamus LA, Clark EB. Increased PDGF-like protein in banded embryonic ventricle. Pediatr Res 1991; 29: 19A.Google Scholar
Pexieder T, Jedlicka S, Sugimara K, Tatimatsu A, Sato H. Immunohistochemical localization of platelet derived growth factor (PDGF) during cardiac morphogenesis in chick and mouse embryos and fetuses. In: Clark EB, et al. (eds). Developmental Mechanisms of Heart Disease. Futura Publishing, Armonk, NY, USA, 1995, pp 207212.
Parlow MH, Bolender DL, Kokan-Moore NP, Lough J. Localization of bFGF-like proteins as punctate inclusions in the preseptation myocardium of the chicken embryo. Dev Biol 1991; 146: 139147.Google Scholar
Sedmera D, Grobety M, Reymond C, Baehler P, Kucera P, Kappenberger L. Pacing-induced ventricular remodeling in the chick embryonic heart. Pediatr Res 1999; 45: 845852.Google Scholar
Sugi Y, Sasse J, Lough J. Inhibition of precardiac mesoderm cell proliferation by antisense oligodeoxynucleotide complementary to fibroblast growth factor-2 (FGF-2). Dev Biol 1993; 157: 2837.Google Scholar
Franciosi JP, Bolender DL, Lough J, Kolesari GL. FGF-2-induced imbalance in early embryonic heart cell proliferation: a potential cause of late cardiovascular anomalies. Teratology 2000; 62: 189194.Google Scholar
Leveen P, Pekny M, Gebre-Medhin S, et al. Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev 1994; 8: 18751887.Google Scholar
Schatteman GC, Motley ST, Effmann EL, Bowen-Pope DF. Platelet-derived growth factor receptor alpha subunit deleted Patch mouse exhibits severe cardiovascular dysmorphogenesis. Teratology 1995; 51: 351366.Google Scholar
Li X, Ponten A, Aase K, et al. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol 2000; 2: 302309.Google Scholar
Simm A, Nestler M, Hoppe V. PDGF-AA, a potent mitogen for cardiac fibroblasts from adult rats. J Mol Cell Cardiol 1997; 29: 357368.Google Scholar
Shimizu T, Kinugawa K, Yao A, et al. Platelet-derived growth factor induces cellular growth in cultured chick ventricular myocytes. Cardiovasc Res 1999; 41: 641653.Google Scholar
Mikawa T. Retroviral targeting of FGF and FGFR in cardiomyocytes and coronary vascular cells during heart development. Ann NY Acad Sci 1995; 752: 506516.Google Scholar
Kardami E, Liu L, Kishore S, et al. Regulation of basic fibroblast growth factor (bFGF) and FGF receptors in the heart. Ann NY Acad Sci 1995; 752: 353369.Google Scholar
Sheikh F, Fandrich RR, Kardami E, Cattini PA. Overexpression of long or short FGFR-1 results in FGF-2-mediated proliferation in neonatal cardiac myocyte cultures. Cardiovasc Res 1999; 42: 696705.Google Scholar
Velez C, Aranega AE, Melguizo C, et al. Modulation of contractile protein troponin-T in chick myocardial cells by basic fibroblast growth factor and platelet-derived growth factor during development. J Cardiovasc Pharmacol 1994; 24: 906913.Google Scholar
Bohlmeyer TJ, Helmke S, Ge S, et al. Hypoplastic left heart syndrome myocytes are differentiated but possess a unique phenotype. Cardiovasc Pathol 2003; 12: 2331.Google Scholar
Cheng W, Reiss K, Kajstura J, et al. Down-regulation of the IGF-1 system parallels the attenuation in the proliferative capacity of rat ventricular myocytes during postnatal development. Lab Invest 1995; 72: 646655.Google Scholar
Ludwig T, Eggenschwiler J, Fisher P, et al. Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds. Dev Biol 1996; 177: 517535.Google Scholar
Hornberger LK, Singhroy S, Cavalle-Garrido T, et al. Synthesis of extracellular matrix and adhesion through beta(1) integrins are critical for fetal ventricular myocyte proliferation. Circ Res 2000; 87: 508515.Google Scholar
Donahue JK, Heldman AW, Fraser H, et al. Focal modification of electrical conduction in the heart by viral gene transfer. Nat Med 2000; 6: 13951398.Google Scholar
Christensen G, Minamisawa S, Gruber PJ, Wang Y, Chien KR. High-efficiency, long-term cardiac expression of foreign genes in living mouse embryos and neonates. Circulation 2000; 101: 178184.Google Scholar
Hassink RJ, Brutel de la Riviere A, Mummery CL, Doevendans PA. Transplantation of cells for cardiac repair. J Am Coll Cardiol 2003; 41: 711717.Google Scholar
Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106: 19131918.Google Scholar
Stamm C, Westphal B, Kleine HD, et al. Autologous bone- marrow stem-cell transplantation for myocardial regeneration. Lancet 2003; 361: 4546.Google Scholar
Orlic D, Kajstura J, Chimenti S, et al. Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann NY Acad Sci 2001; 938: 221229; discussion 229–230.Google Scholar
Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701705.Google Scholar
Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 2001; 98: 1034410349.Google Scholar
Rangappa S, Entwistle JW, Wechsler AS, Kresh JY. Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype. J Thorac Cardiovasc Surg 2003; 126: 124132.Google Scholar
Rangappa S, Fen C, Lee EH, Bongso A, Wei ES. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg 2003; 75: 775779.Google Scholar
Bittner RE, Schofer C, Weipoltshammer K, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl) 1999; 199: 391396.Google Scholar
Gussoni E, Soneoka Y, Strickland CD, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401: 390394.Google Scholar
Eisenberg LM, Burns L, Eisenberg CA. Hematopoietic cells from bone marrow have the potential to differentiate into cardiomyocytes in vitro. Anat Rec 2003; 274A: 870882.Google Scholar