Donald R A, Crozier I G, Foy S G, Richards A M, Livesey J H, Ellis M J, Mattioli L, Ikram H
Department of Cardiology, Princess Margaret Hospital, Christchurch, New Zealand.
Clin Endocrinol (Oxf). 1994 Apr;40(4):499-504. doi: 10.1111/j.1365-2265.1994.tb02489.x.
We assessed the magnitude and duration of the response of hypothalamic-pituitary-adrenal hormones to the stress of myocardial infarction, in the presence and absence of angiotensin converting enzyme inhibitors. In particular, we wished to analyse the interrelationships between peripheral plasma levels of corticotrophin releasing hormone (CRH), vasopressin (AVP) and adrenocorticotrophin (ACTH), and also between ACTH and cortisol, during a prolonged medical stress.
All hormones were measured within 6 hours of the onset of an acute myocardial infarction. Patients were randomly allocated to three different study groups according to a double blind procedure.
Group 1 (10 patients) received placebo treatment, Group 2 (13 patients) received a maintenance dose of captopril 25 mg three times daily, Group 3 (11 patients) received enalapril 5 mg three times daily.
Peptide hormones were measured by radioimmunoassay, and cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunteers from the electoral roll.
At the start of the study, mean +/- SEM plasma AVP (27.9 +/- 4.6 pmol/l) was significantly (P < 0.001) raised above the mean for the reference range (1.82 +/- 0.09 pmol/l), and 12 patients had values > 50 pmol/l. Mean plasma cortisol (960 +/- 89.6 nmol/l) was also raised above the reference range mean (554 +/- 28 nmol/l, P < 0.001), as was mean plasma CRH (4.97 +/- 0.5 pmol/l, reference mean 1.52 +/- 0.09 pmol/l, P < 0.001). By contrast, mean ACTH (3.88 +/- 0.66 pmol/l) was significantly less than the reference mean (10.7 +/- 0.7 pmol/l, P < 0.001). During the 72-hour observation period there was a highly significant fall (P < 0.001) in plasma CRH, AVP and cortisol. By contrast, plasma ACTH rose, and the change with time of ACTH was significantly different from the fall in plasma CRH, AVP or cortisol (P < 0.001 for each comparison). No significant differences in plasma CRH, AVP, ACTH or cortisol responses to placebo, captopril or enalapril were observed.
Within 6 hours of a myocardial infarction, mean plasma CRH, AVP and cortisol values were very significantly raised above mean control values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and cortisol fell substantially, and this pattern was not influenced by angiotensin converting enzyme inhibitors. By contrast, plasma ACTH showed a significant increase with time. This suggests that the usual relationships between CRH, AVP and ACTH, and between ACTH and cortisol are disturbed in patients admitted to hospital with myocardial infarction. Maximum levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postulated that V1 AVP receptor antagonists may have a therapeutic application in limiting infarct size.
我们评估了在存在和不存在血管紧张素转换酶抑制剂的情况下,下丘脑 - 垂体 - 肾上腺激素对心肌梗死应激反应的程度和持续时间。特别是,我们希望分析在长期医疗应激期间,外周血中促肾上腺皮质激素释放激素(CRH)、血管加压素(AVP)和促肾上腺皮质激素(ACTH)的血浆水平之间的相互关系,以及ACTH和皮质醇之间的相互关系。
在急性心肌梗死发作后6小时内测量所有激素。根据双盲程序将患者随机分配到三个不同的研究组。
第1组(10例患者)接受安慰剂治疗,第2组(13例患者)接受卡托普利25 mg每日三次的维持剂量,第3组(11例患者)接受依那普利5 mg每日三次。
肽类激素通过放射免疫测定法测量,皮质醇通过酶联免疫吸附测定法测量。所有激素的参考范围来自40名或更多来自选民名册的志愿者。
在研究开始时,平均±标准误血浆AVP(27.9±4.6 pmol / l)显著高于参考范围的平均值(1.82±0.09 pmol / l,P <0.001),12例患者的值> 50 pmol / l。平均血浆皮质醇(960±89.6 nmol / l)也高于参考范围平均值(554±28 nmol / l,P <0.001),平均血浆CRH(4.97±0.5 pmol / l,参考平均值1.52±0.09 pmol / l,P <0.001)也是如此。相比之下,平均ACTH(3.88±0.66 pmol / l)显著低于参考平均值(10.7±0.7 pmol / l,P <0.001)。在72小时观察期内,血浆CRH、AVP和皮质醇有极显著下降(P <0.001)。相比之下,血浆ACTH升高,ACTH随时间的变化与血浆CRH、AVP或皮质醇的下降显著不同(每次比较P <0.001)。未观察到血浆CRH、AVP、ACTH或皮质醇对安慰剂、卡托普利或依那普利的反应有显著差异。
在心肌梗死后6小时内,平均血浆CRH、AVP和皮质醇值非常显著高于平均对照值,而ACTH则非常显著降低。在急性心肌梗死后的3天内,血浆CRH、AVP和皮质醇大幅下降,且这种模式不受血管紧张素转换酶抑制剂的影响。相比之下血浆ACTH随时间显著增加。这表明在因心肌梗死入院的患者中,CRH、AVP和ACTH之间以及ACTH和皮质醇之间的通常关系受到干扰。12例患者中观察到的AVP最高水平超过50 pmol / l,这可能足够高以干扰组织灌注。据推测,V1 AVP受体拮抗剂在限制梗死面积方面可能具有治疗应用价值。