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心脏内人工补片瘢痕挛缩的药理学抑制

Pharmacologic inhibition of scar contracture of intracardiac prosthetic patches.

作者信息

Richards W O, Doolin E J, Miginsky M P, Moulton A L

出版信息

J Surg Res. 1984 Jul;37(1):33-42. doi: 10.1016/0022-4804(84)90158-6.

Abstract

Significant fibrosis and contracture often cause complications of pericardial and Dacron grafts within the heart. Both continue to be utilized because more suitable materials are unavailable. Newer prosthetic materials and the administration of drugs that might minimize intracardiac fibrosis and contracture after implantation were studied. Measured patches of three prosthetic materials were implanted into the right atrium of 18 dogs: 6 with expanded polytetrafluoroethylene (PTFE or Gore-Tex--W. L. Gore & Associates, Elkton, Md.), 6 with glutaraldehyde-preserved bovine pericardium, and 6 with Dacron patches. The animals were sacrificed after 8 weeks and gross and microscopic pathologic examinations were performed. The patch materials did not intrinsically shrink but all demonstrated marked distortion from the growth of surrounding scar tissue. In a fourth group of eight dogs with intraatrial Dacron patches, four were treated for 8 weeks with oral 3-aminopropionitrile fumarate, and four were not treated. A blinded observed evaluated the adhesions on a scale of 0 = no adhesions or patch distortion, to 4 = dense adhesions with marked distortion of the patches. The untreated dogs had dense adhesions of the lung and pericardium and the patches were encased in scar tissue with marked distortion. The average score was 3.5. The treated dogs had only minimal pleural adhesions and only a thin neointimal covering of the patch with virtually no distortion. The average score was 1.0 (P = 0.0032). The tensile strength of the healed atriotomies was evaluated with stress testing. The intact atrial wall ruptured at a force of 2.60 +/- 0.37 kg/m/sec2, the untreated atriotomy wound at 2.38 +/- 0.18 kg/m/sec2, and the treated atriotomy wound at 2.60 +/- 0.17 kg/m/sec2. There was no statistically significant difference among these groups. No other side effects of the 3-aminopropionitrile fumarate were noted, with only a single superficial wound infection caused by early postoperative trauma. Pharmacologic inhibition of scar formation minimized distortion and contracture of intracardiac prosthetic patches and decreased adhesions. Though further experimental evaluations are necessary, prolonged low-dose oral administration of beta-aminoproprionitrile (BAPN) may be beneficial in preventing complications of prosthetic implants and reoperative cardiac surgery in children.

摘要

显著的纤维化和挛缩常常导致心脏内心包和涤纶移植物出现并发症。由于没有更合适的材料,这两种材料仍在继续使用。对新型人工合成材料以及可能使植入后心内纤维化和挛缩减至最小的药物进行了研究。将三种人工合成材料的测量片植入18只狗的右心房:6只植入膨体聚四氟乙烯(PTFE或戈尔特斯——W.L.戈尔联合公司,马里兰州埃尔克顿),6只植入戊二醛保存的牛心包,6只植入涤纶片。8周后处死动物并进行大体和显微镜病理检查。补片材料本身不会收缩,但由于周围瘢痕组织生长,均出现明显变形。在第四组8只植入心内涤纶片的狗中,4只用口服富马酸3 -氨基丙腈治疗8周,4只未治疗。一位不知情的观察者按0(无粘连或补片变形)至4(有致密粘连且补片明显变形)的标准对粘连情况进行评估。未治疗的狗有肺和心包的致密粘连,补片被瘢痕组织包裹且明显变形。平均评分为3.5。治疗的狗只有轻微的胸膜粘连,补片仅有一层薄的新生内膜覆盖,几乎没有变形。平均评分为1.0(P = 0.0032)。通过应力测试评估愈合心房切开术的抗张强度。完整心房壁在2.60±0.37 kg/m/sec²的力作用下破裂,未治疗的心房切开术伤口在2.38±0.18 kg/m/sec²的力作用下破裂,治疗的心房切开术伤口在2.60±0.17 kg/m/sec²的力作用下破裂。这些组之间无统计学显著差异。未观察到富马酸3 -氨基丙腈的其他副作用,仅术后早期创伤导致1例表浅伤口感染。瘢痕形成的药物抑制使心内人工补片的变形和挛缩减至最小,并减少了粘连。尽管需要进一步的实验评估,但长期低剂量口服β -氨基丙腈(BAPN)可能有助于预防儿童人工植入物和再次心脏手术的并发症。

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