Morning cortisol production in coronary heart disease patients.

BACKGROUND: The circadian cycle of the endogenous anti-inflammatory system (EAIS) is characterized by a morning increase in cortisol production. Circulating interleukin-6 (IL-6) activates the EAIS. A circadian variation in the onset of myocardial infarction, sudden death, stable angina (SA) and unstable angina (UA) has been reported. The aim of this study was to determine morning cortisol production in coronary heart disease (CHD) patients. MATERIALS AND METHODS: Serum cortisol and IL-6 were measured in 129 patients with either SA (n = 65) or UA (n = 64) and 40 healthy volunteers. Blood samples were taken between 9 : 00 h and 12 : 00 h. The upper normal range of cortisol (25 microg dL-1) was used as a reference to classify patients. RESULTS: Forty-eight patients had elevated cortisol levels (ECL) (32.5 +/- 5.4 microg dL-1), while 81 patients had normal cortisol levels (NCL) (15.7 +/- 5.9 microg dL-1). In NCL patients, IL-6 levels (26.6 pg mL-1, ranged from 0.2 to 183.7) were significantly higher (P < 0.004) than in ECL patients (9.70 pg mL-1, range 0.07-56.5). Forty-eight patients with UA belonged to the NCL group of patients, while only 16 UA patients belonged to the ECL group (chi(2) = 0.000). Thirty-two patients with SA belonged to the ECL group, and 33 to the NCL group (chi(2) = 0.08). CONCLUSIONS: Patients with 'inappropriately' normal morning cortisol production had high IL-6 levels. 'Inappropriately' normal cortisol, detected in 75% of UA and 50% of SA patients, may be insufficient for limiting inflammation. These findings have novel clinical implications and suggest new therapeutic approaches in the treatment of these patients.

[Effect of cAMP on the function of endothelial cells and fibromuscular proliferation after the injury of the carotid and coronary arteries in a porcine model]. / Efecto del AMPc sobre la función de las células endoteliales y la proliferación fibromuscular tras la lesión de las arterias carótida y coronaria en un modelo porcino.

INTRODUCTION AND OBJECTIVE: Reendothelization of damaged blood vessels protects against the vascular injury response. We evaluated in vivo whether a systemic increase in cAMP accelerates reendothelization and attenuates intimal hyperplasia in injured swine carotid and coronary arteries. METHODS: Both carotid arteries of 10 swines were subjected to balloon injury. Five animals had been treated with 2 ml (10 mg) of Forskolin, an activator of the adenylate cyclase, and another 5 with 2 ml of saline solution. These animals were sacrificed at day 8, and carotid artery reendothelization was evaluated. The descendent coronary (DC) artery of another 19 pigs was injured by atherotome. Nine animals had been treated with 2 ml of Forskolin, and another 10 with 2 ml of saline solution. These animals were sacrificed at day 28, with myointimal proliferation and arterial geometric remodelation being evaluated. Likewise, in these animals intracellular cAMP levels were measured at baseline and 28 and 60 minutes after saline solution or Forskolin administration and 90 min after arterial injury. RESULTS: Eight days after balloon injury, carotid artery reendothelization was greater in the Forskolin-treated group compared with the control group (p = 0.02), and the number of CD31 positive cells was statistically increased in the treated group (38 +/- 11 cells) versus controls (11 +/- 9 cells). Although the degree of vascular injury caused by atherotome was similar in all of the arteries in the control group, restenosis was only observed in 40% of these animals. Correlation analysis demonstrated that intracellular cAMP may condition arterial geometric remodeling and the diameter of the lumen after vascular injury. CONCLUSION: Our results suggest that cAMP may promote reendothelization and attenuate fibromuscular proliferation.

Endogenous anti-inflammatory response after coronary injury in a porcine model.

BACKGROUND: Corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH)/cortisol is the major anti-inflammatory system. After percutaneous translumenal angioplasty, an inflammatory process is triggered. We investigate whether CRH/ACTH/cortisol axis is activated after deep vessel wall injury (DVWI). MATERIALS AND METHODS: Plasma and leukocyte CRH and ACTH, serum cortisol and IL-1beta, and leukocyte cAMP were measured (ELISA) in 16 pigs after anaesthesia (baseline), 60 min into anaesthesia without causing vascular injury and 90 min after DVWI of the left anterior descending (LAD) coronary artery induced by percutaneous directional atherectomy (Atherocath GTO 7F; DVI, Inc., Temecula, USA). Biochemical variables were also measured at baseline, 60 and 180 min into anaesthesia in six additional pigs without coronary intervention. RESULTS: MANOVA showed that CRH/ACTH/Cortisol, cAMP and IL-1beta production was not modified during anaesthesia. Post-DVWI plasma CRH (0.077 +/- 0.046 ng mL-1), and cellular cAMP (0.14 +/- 0.067 pmol 10(-6) cells) increased significantly (P = 0.001) with respect to their baseline values (CRH = 0.036 +/- 0.013 ng mL-1; cAMP = 0.081 +/- 0.034 pmol 10-6). There was also a statistically significant increase (P = 0.02) in post-DVWI IL-1beta (from 46.6 +/- 12.8 to 64.05 +/- 13.5 pg mL-1), and in serum cortisol (P = 0.05) compared to its baseline values (8.98 +/- 3.2 microgr dL-1 vs. 6.57 +/- 2.3 microgr dL-1, respectively). CONCLUSION: In our experimental model, coronary vessel wall injury-activated CRH/ACTH/cortisol axis caused a significant increase in plasma CRH, cortisol and cellular cAMP levels, which may influence the response of coronary arteries to injury.