Cellular Cardiomyoplasty Improves Diastolic Properties of Injured Heart

• Published in: The Journal of surgical research Vol. 85; no. 2; pp. 234 - 242
• Main Authors: Atkins, B.Zane, Hueman, Matthew T., Meuchel, Jennifer, Hutcheson, Kelley A., Glower, Donald D., Taylor, Doris A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01-08-1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Cardiomyoplasty - methods; Catheterization; cellular cardiomyoplasty; cryoinjury; Cryosurgery; Diastole - physiology; diastolic function; Disease Models, Animal; Heart Injuries - diagnostic imaging; Heart Injuries - physiopathology; Heart Injuries - therapy; histology; Injuries of the thorax. Foreign bodies. Diseases due to physical agents; intracardiac grafts; Manometry; Medical sciences; Muscle, Skeletal - cytology; Muscle, Skeletal - transplantation; myoblast; myocardial infarction; Myocardium - cytology; Rabbits; regional function; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Traumas. Diseases due to physical agents; Ultrasonography; Ventricular Function, Left - physiology; Ventricular Pressure - physiology; cryoinjury; diastolic function; histology; myoblast; myocardial infarction; intracardiac grafts; cellular cardiomyoplasty; regional function; Heart; Diastole; Infarct; Rabbit; Cardiovascular disease; Myocardial disease; Myocyte; Result; Improvement; Autograft; Heart disease; Surgery; Graft; Acute; Lagomorpha; Experimental study; Coronary heart disease; Trauma; Plasty; Vertebrata; Mammalia; Treatment; Animal; Myocardium; Technique; Cold induced disorder
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1999.5681

Background. Acute myocardial infarction leads to loss of functional myocytes and structural integrity that often decreases diastolic compliance and increases resting myocardial segment length (diastolic creep). Successfully engrafting autologous skeletal myoblasts could improve compliance and potentially reverse creep. Thus, we transplanted myoblasts into cryoinjured rabbit heart (n = 15, CRYO) and measured regional diastolic properties in the presence (n = 9, +ENG) or absence (n = 6, −ENG) of engraftment.
Materials and methods. Left ventricular (LV) pressures (P) and myocardial segment lengths (SL) were measured in vivo by micromanometry and sonomicrometry after cryoinjury (CRYO) and again 3 weeks following transplantation of myoblasts. Performance was estimated from the relationships between end-diastolic (ED) P and strain (ϵ) or between EDP and EDSL. Compliance was characterized by strain (ϵ8) and dynamic stiffness (dP/dL8) at 8 mm Hg. Creep was characterized by resting myocardial segment length (EDSL0) and static stiffness at 8 mm Hg (mstat8).
Results. Successful myoblast engraftment was determined via histologic examination. In nine +ENG animals, diastolic properties improved. Regional strain (ϵ8) increased (0.06 ± 0.02 CRYO vs 0.10 ± 0.04 +ENG; P = 0.0009) while dynamic stiffness (dP/dL8) decreased (43 ± 23 mm Hg/mm CRYO vs 23 ± 14 mm Hg/mm +ENG; P = 0.009). Static stiffness (mstat8) was unaffected (0.78 ± 0.2 mm Hg/mm CRYO vs 0.72 ± 0.1 mm Hg/mm +ENG; P = 0.08), and creep did not occur (EDSL0 = 10.3 ± 2.8 CRYO vs 10.4 ± 2.3 +ENG; P = 0.74). In the absence of myoblast engraftment (n = 6, −ENG), strain decreased (ϵ8 = 0.06 ± 0.02 CRYO vs 0.05 ± 0.02 −ENG; P = 0.048), but dynamic stiffness (dP/dL8) did not (36 ± 19 mm Hg/mm CRYO vs 28 ± 12 mm Hg/mm −ENG; P = 0.20). Furthermore, static stiffness decreased (0.78 ± 0.3 mm Hg/mm CRYO vs 0.65 ± 0.2 mm Hg/mm −ENG; P = 0.05) and creep was obvious (EDSL0 = 10.8 ± 3.6 mm CRYO vs 13.0 ± 4.4 mm −ENG, P = 0.04).
Conclusions. Myoblast engraftment may partially overcome the loss of myocytes and structural integrity that often follow chronic myocardial ischemia. Improved compliance and reversal of diastolic creep suggest regeneration of viable muscle within once infarcted myocardium.