TY - JOUR
T1 - Cellular cardiomyoplasty improves diastolic properties of injured heart
AU - Atkins, B. Zane
AU - Hueman, Matthew T.
AU - Meuchel, Jennifer
AU - Hutcheson, Kelley A.
AU - Glower, Donald D.
AU - Taylor, Doris A.
N1 - Funding Information:
This investigation was supported in part by the National Institutes of Health, R-01 Grant HL57988-01, awarded to D.A.T. from the National Heart Lung and Blood Institute.
PY - 1999/8
Y1 - 1999/8
N2 - 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 (ε(g)) 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 (m(stat8)). 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 (m(stat6)) 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.
AB - 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 (ε(g)) 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 (m(stat8)). 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 (m(stat6)) 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.
KW - Cellular cardiomyoplasty
KW - Cryoinjury
KW - Diastolic function
KW - Histology
KW - Intracardiac grafts
KW - Myoblast
KW - Myocardial infarction
KW - Regional function
UR - http://www.scopus.com/inward/record.url?scp=0032809114&partnerID=8YFLogxK
U2 - 10.1006/jsre.1999.5681
DO - 10.1006/jsre.1999.5681
M3 - Article
C2 - 10423324
AN - SCOPUS:0032809114
SN - 0022-4804
VL - 85
SP - 234
EP - 242
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -