Cellular Cardiomyoplasty Improves Diastolic Properties of Injured Heart

doi:10.1006/jsre.1999.5681

Journal of Surgical Research

Volume 85, Issue 2, August 1999, Pages 234-242

https://doi.org/10.1006/jsre.1999.5681 Get rights and content

Abstract

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 (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_stat8) 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.

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Chronic 1-week cryoinjury showed similar pattern of Mn distribution kinetics (not shown). Although cryoinjury-induced MI has been previously described in other animals [8–12,18–22], this is the first report to outline the morphological and contrast-enhanced MRI features of cryoinjury-induced MI in pigs. Morphological variation of cryolesion in the present study significantly reduced as its feature depends mainly on exposure time and the cryoprobe tip-shape.
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(1) Acute cryoinjury resulted in formation of a lesion with a severely reduced rate of sub-epicardial indocyanine green (intravascular optical flow tracer) passage. In vivo late Gd-enhanced MRI showed a ∼10 mm deep hypointense area that was surrounded by a hyperintense rim while ex vivo Mn-enhanced MRI (MEMRI) detected a homogenous hypointense zone. Histological and spectroscopic examination revealed embolic erythrocytes blockages within the cryolesion with a thin necrotic rim neighboring the normal myocardium. (2) Chronic 4-week cryoinjury was characterized by uniform Gd-enhancement, whereas MEMRI revealed reduced Mn²⁺enhancement. Histological examination showed replacement of the cryoinjured myocardium by scar tissue.
Acute cryoinjury resulted in formation of a no-reflow core embolized by erythrocytes and surrounded by a rim of necrotic tissue. Upon injury progression, the no-reflow zone shrunk and was completely replaced with scar tissue by 4 weeks after injury.
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^☆: Presented at the Annual Meeting of the Association for Academic Surgery, Seattle, Washington, November 18–22, 1998.

¹: To whom correspondence should be addressed at Duke University Medical Center, Box 3327, Durham, NC 27710. Fax: (919) 684-8907.

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Journal of Surgical Research

Abstract

References (26)

Evaluation of left ventricular systolic and diastolic dysfunction during transient myocardial ischemia produced by angioplasty

J. Am. Coll. Cardiol.

The natural history of isolated left ventricular diastolic dysfunction

Am. J. Med.

Improvement of reduced left ventricular diastolic compliance in ischemic heart disease after successful coronary artery bypass surgery

Am. J. Cardiol.

Intracardiac transplantation of immature skeletal myoblasts yields two populations of striated cells in situ

Ann. Thor. Surg.

Cellular cardiomyoplasty: Myocardial regeneration with satellite cell transplantation

Ann. Thorac. Surg.

Left ventricular compliance: Mechanisms and clinical applications

Am. J. Cardiol.

Early increases in left ventricular compliance after myocardial infarction

J. Clin. Invest.

Heart Failure with normal systolic function: Update of prevalence, differential diagnosis, prognosis, and therapy [editorial]

Arch. Int. Med.

Diastolic heart failure

Curr. Probl. Cardiol.

Improved left ventricular diastolic filling in patients with coronary artery disease after percutaneous transluminal coronary angioplasty

Circulation

A load-independent in vivo model for evaluating therapeutic interventions in injured myocardium

Am. J. Physiol.

Cited by (81)

Cell therapy for cardiac repair - bench to bedside and back

Gene therapy for ischemic heart disease

Characterization of cryoinjury-induced infarction with manganese-and gadolinium-enhanced MRI and optical spectroscopy in pig hearts

A photopolymerizable hydrogel for 3-D culture of human embryonic stem cell-derived cardiomyocytes and rat neonatal cardiac cells

Strategies to promote donor cell survival: Combining preconditioning approach with stem cell transplantation

Paracrine Effects of Cell Transplantation: Strategies to Augment the Efficacy of Cell Therapies

Regular ArticleCellular Cardiomyoplasty Improves Diastolic Properties of Injured Heart☆

Abstract

J. Am. Coll. Cardiol.

Am. J. Med.

Am. J. Cardiol.

Ann. Thor. Surg.

Ann. Thorac. Surg.

Left ventricular compliance: Mechanisms and clinical applications

Am. J. Cardiol.

Early increases in left ventricular compliance after myocardial infarction

J. Clin. Invest.

Heart Failure with normal systolic function: Update of prevalence, differential diagnosis, prognosis, and therapy [editorial]

Arch. Int. Med.

Diastolic heart failure

Curr. Probl. Cardiol.

Improved left ventricular diastolic filling in patients with coronary artery disease after percutaneous transluminal coronary angioplasty

Circulation

A load-independent in vivo model for evaluating therapeutic interventions in injured myocardium

Am. J. Physiol.

Regular Article
Cellular Cardiomyoplasty Improves Diastolic Properties of Injured Heart☆