de Belder A J, Radomski M W, Why H J, Richardson P J, Martin J F
Department of Cardiology, King's College Hospital, London.
Br Heart J. 1995 Oct;74(4):426-30. doi: 10.1136/hrt.74.4.426.
To determine the activity of the calcium-dependent constitutive (cNOS) and calcium-independent inducible nitric oxide (iNOS) synthases in heart tissue from patients with different cardiac diseases.
Endomyocardial biopsy specimens were obtained from patients with dilated hearts (by echocardiography and ventriculography) and normal coronary arteries (by selective angiography). Recognised clinical, radiological, and histopathological criteria were used to diagnose non-inflammatory dilated cardiomyopathy (DCM) (n = 6), inflammatory cardiomyopathy (ICM) (n = 5), and peripartum cardiomyopathy (PPCM) (n = 3). Comparative groups were chosen with similarly dilated hearts caused by ischaemic (n = 5) or valvar disease (n = 4), and, in addition, non-dilated hearts with ischaemic (n = 5) and valvar (n = 3) disease. Venous blood was taken at the time of myocardial biopsy for assay of plasma tumour necrosis factor alpha (TNF alpha).
Myocardial tissue from patients with DCM, ICM, and PPCM showed considerable iNOS activity (16.8 (2.7) pmol citrulline/mg protein/min) with little or no cNOS activity (1.3 (0.9) pmol citrulline/mg protein/min). In contrast, myocardial tissue from patients with both dilated and non-dilated hearts of ischaemic or valvar aetiology showed cNOS and little, if any, iNOS activity (dilated--cNOS 11.7 (2.4) and iNOS 0.8 (0.6) pmol citrulline/mg protein/min; non-dilated--cNOS 12.1 (1.8) and iNOS 1.4 (0.8) pmol citrulline/mg protein/min). Plasma TNF alpha was detectable only in patients with inflammatory DCM.
These results support the hypothesis the generation of nitric oxide by iNOS accounts for some of the dilatation and impaired contractility associated with inflammatory and non-inflammatory dilated cardiomyopathy and peripartum cardiomyopathy.
测定不同心脏疾病患者心脏组织中钙依赖性组成型(cNOS)和钙非依赖性诱导型一氧化氮(iNOS)合酶的活性。
通过超声心动图和心室造影确诊心脏扩大,通过选择性血管造影确诊冠状动脉正常,获取心内膜活检标本。采用公认的临床、放射学和组织病理学标准诊断非炎性扩张型心肌病(DCM)(n = 6)、炎性心肌病(ICM)(n = 5)和围产期心肌病(PPCM)(n = 3)。选择由缺血性(n = 5)或瓣膜病(n = 4)导致心脏同样扩大的患者作为比较组,此外,还选择有缺血性(n = 5)和瓣膜病(n = 3)的非扩大心脏患者作为比较组。在心肌活检时采集静脉血检测血浆肿瘤坏死因子α(TNFα)。
DCM、ICM和PPCM患者的心肌组织显示出相当高的iNOS活性(16.8(2.7)pmol瓜氨酸/毫克蛋白/分钟),而cNOS活性很低或无活性(1.3(0.9)pmol瓜氨酸/毫克蛋白/分钟)。相比之下,缺血性或瓣膜性病因导致的心脏扩大和非扩大患者的心肌组织显示出cNOS活性,而iNOS活性很低或无活性(扩大心脏——cNOS 11.7(2.4)和iNOS 0.8(0.6)pmol瓜氨酸/毫克蛋白/分钟;非扩大心脏——cNOS 12.1(1.8)和iNOS 1.4(0.8)pmol瓜氨酸/毫克蛋白/分钟)。仅在炎性DCM患者中可检测到血浆TNFα。
这些结果支持以下假说,即iNOS产生的一氧化氮是导致炎性和非炎性扩张型心肌病以及围产期心肌病相关的一些心脏扩张和收缩功能受损的原因。