Wangde Dai1, Sharon L Hale, Robert A Kloner. 1. University of Southern California, The Heart Institute, Good Samaritan Hospital, Los Angeles, California 90017-2395, USA.
Abstract
PURPOSE: To determine whether neonatal cardiomyocytes grafted into the aortic wall contract, develop pressure, and can be paced. METHODS AND RESULTS: Medium only (n = 9) or neonatal cardiomyocytes (n = 12, 5 x 10(6) cells each) were injected into the outer aortic wall in adult female Fischer rats. At 6 weeks after implantation, 11 out of 12 cardiomyocyte-treated aortas showed spontaneous rhythmic beating at the grafted site following excision of the heart. The spontaneous beating rate changed with pacing frequency. Five out of the 11 beating aortas had intra-aortic pressure generated by the spontaneously contracting cardiomyocytes. The pulse pressure generated by the grafted cardiomyocytes was 0.36 +/- 0.05 mmHg without pacing; during pacing it was 0.78 +/- 0.21 mmHg with systolic pressure up to 3.8 mmHg. Hematoxylin and eosin staining showed viable grafts in the outer wall of the cardiomyocyte-treated aortas in 12 out of 12 aortas. Neonatal cardiomyocytes in the graft matured with cross striations. Immunohistochemical staining of the aorta for sacromeric actin was positive in 12 out of 12 aortas. Staining of connexin 43 showed that some grafted cardiomyocytes formed gap junctions. The above examinations were negative in nine out of nine medium-treated aortas. CONCLUSION: The results show for the first time that cardiomyocytes engrafted into the foreign environment of an extracardiac vascular structure can be paced and generate measurable intravascular pressure. This study may serve as a useful model for studying the growth and response of the grafted cardiomyocytes to various stimuli in an extra-cardiac environment in vivo.
PURPOSE: To determine whether neonatal cardiomyocytes grafted into the aortic wall contract, develop pressure, and can be paced. METHODS AND RESULTS: Medium only (n = 9) or neonatal cardiomyocytes (n = 12, 5 x 10(6) cells each) were injected into the outer aortic wall in adult female Fischer rats. At 6 weeks after implantation, 11 out of 12 cardiomyocyte-treated aortas showed spontaneous rhythmic beating at the grafted site following excision of the heart. The spontaneous beating rate changed with pacing frequency. Five out of the 11 beating aortas had intra-aortic pressure generated by the spontaneously contracting cardiomyocytes. The pulse pressure generated by the grafted cardiomyocytes was 0.36 +/- 0.05 mmHg without pacing; during pacing it was 0.78 +/- 0.21 mmHg with systolic pressure up to 3.8 mmHg. Hematoxylin and eosin staining showed viable grafts in the outer wall of the cardiomyocyte-treated aortas in 12 out of 12 aortas. Neonatal cardiomyocytes in the graft matured with cross striations. Immunohistochemical staining of the aorta for sacromeric actin was positive in 12 out of 12 aortas. Staining of connexin 43 showed that some grafted cardiomyocytes formed gap junctions. The above examinations were negative in nine out of nine medium-treated aortas. CONCLUSION: The results show for the first time that cardiomyocytes engrafted into the foreign environment of an extracardiac vascular structure can be paced and generate measurable intravascular pressure. This study may serve as a useful model for studying the growth and response of the grafted cardiomyocytes to various stimuli in an extra-cardiac environment in vivo.