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细胞心肌成形术可改善受损心脏的舒张功能。

Cellular cardiomyoplasty improves diastolic properties of injured heart.

作者信息

Atkins B Z, Hueman M T, Meuchel J, Hutcheson K A, Glower D D, Taylor D A

机构信息

Department of Medicine, Duke University Medical Center, Durham, North Carolina, 27710, USA.

出版信息

J Surg Res. 1999 Aug;85(2):234-42. doi: 10.1006/jsre.1999.5681.

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 (epsilon) or between EDP and EDSL. Compliance was characterized by strain (epsilon(8)) and dynamic stiffness (dP/dL(8)) at 8 mm Hg. Creep was characterized by resting myocardial segment length (EDSL(0)) 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 (epsilon(8)) increased (0.06 +/- 0.02 CRYO vs 0.10 +/- 0.04 +ENG; P = 0.0009) while dynamic stiffness (dP/dL(8)) 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 (EDSL(0) = 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 (epsilon(8) = 0. 06 +/- 0.02 CRYO vs 0.05 +/- 0.02 -ENG; P = 0.048), but dynamic stiffness (dP/dL(8)) 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 (EDSL(0) = 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.

摘要

背景

急性心肌梗死会导致功能性心肌细胞丧失和结构完整性受损,这常常会降低舒张期顺应性并增加静息心肌节段长度(舒张期蠕变)。成功移植自体骨骼肌成肌细胞可改善顺应性,并有可能逆转蠕变。因此,我们将成肌细胞移植到冷冻损伤的兔心脏(n = 15,CRYO组),并在有移植(n = 9,+ENG组)或无移植(n = 6,-ENG组)的情况下测量局部舒张特性。

材料与方法

在冷冻损伤(CRYO组)后,通过微测压法和超声心动图测量左心室(LV)压力(P)和心肌节段长度(SL),并在成肌细胞移植后3周再次测量。根据舒张末期(ED)压力与应变(ε)或ED压力与ED节段长度(EDSL)之间的关系评估心脏功能。顺应性通过8 mmHg时的应变(ε(8))和动态弹性(dP/dL(8))来表征。蠕变通过静息心肌节段长度(EDSL(0))和8 mmHg时的静态弹性(m(stat8))来表征。

结果

通过组织学检查确定成肌细胞成功植入。在9只+ENG组动物中,舒张特性得到改善。局部应变(ε(8))增加(CRYO组为0.06±0.0?,+ENG组为0.10±0.04;P = 0.0009),而动态弹性(dP/dL(8))降低(CRYO组为43±23 mmHg/mm,+ENG组为23±14 mmHg/mm;P = 0.009)。静态弹性(m(stat8))未受影响(CRYO组为0.78±0.2 mmHg/mm,+ENG组为0.72±0.1 mmHg/mm;P = 0.08),且未发生蠕变(EDSL(0):CRYO组为10.3±2.8,+ENG组为10.4±2.3;P = 0.74)。在无成肌细胞植入的情况下(n = 6,-ENG组),应变降低(ε(8):CRYO组为0.06±0.02,-ENG组为0.05±0.02;P = 0.048),但动态弹性(dP/dL(8))未降低(CRYO组为36±19 mmHg/mm,-ENG组为28±12 mmHg/mm;P = 0.20)。此外,静态弹性降低(CRYO组为0.78±0.3 mmHg/mm,-ENG组为0.65±0.2 mmHg/mm;P = 0.05),且蠕变明显(EDSL(0):CRYO组为10.8±3.6 mm,-ENG组为13.0±4.4 mm,P = 0.04)。

结论

成肌细胞植入可能部分克服慢性心肌缺血后常出现的心肌细胞丧失和结构完整性受损。顺应性改善和舒张期蠕变逆转提示梗死心肌内有存活心肌的再生。

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