PLASMA CORTICOTROPIN-RELEASING HORMONE, VASOPRESSIN, ACTH AND CORTISOL RESPONSES TO ACUTE MYOCARDIAL-INFARCTION

OBJECTIVES We assessed the magnitude and duration of the response of h ypothalamic-pituitary-adrenal hormones to the stress of myocardial inf arction, 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 bet ween ACTH and cortisol, during a prolonged medical stress. DESIGN All hormones were measured within 6 hours of the onset of an acute myocard ial Infarction. Patients were randomly allocated to three different st udy groups according to a double blind procedure. PATIENTS 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 p atients) received enalapril 5 mg three times daily. MEASUREMENTS Pepti de hormones were measured by radioimmunoassay, and cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunt eers from the electoral roll. RESULTS At the start of the study, mean/-SEM plasma AVP (27.9+/-4.6 pmol/l) was significantly (P<0.001) raise d 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 signif icant fall (P<0.001) in plasma CRH, AVP and cortisol. By contrast, pla sma ACTH rose, and the change with time of ACTH was significantly diff erent from the fall in plasma CRH, AVP or cortisol (P<0.001 far each c omparison). No significant differences in plasma CRH, AVP, ACTH or cor tisol responses to placebo, captopril or enalapril were observed. CONC LUSIONS Within 6 hours of a myocardial infarction, mean plasma CRH, AV P and cortisol values were very significantly raised above mean contro l values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and cortiso l fell substantially, and this pattern was not influenced by angiotens in converting enzyme inhibitors. By contrast, plasma ACTH showed a sig nificant increase with time. This suggests that the usual relationship s between CRH, AVP and ACTH, and between ACTH and cortisol are disturb ed in patients admitted to hospital with myocardial infarction. Maximu m levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postula ted that V, AVP receptor antagonists may have a therapeutic applicatio n in limiting infarct size.