Cortisol dynamics and endothelin-1/nitric oxide ratio are associated with clinical vasospasme
Background: Cortisol dynamics in serum might be related to clinical vasospasm, also known as delayed ischemic neurological deficits (DIND). Two vasoactive substances that play a role in pathophysiology of DIND are endothelin-1 (ET1) and nitric oxide (NO), both are proved associated with cortisol. This study aimed to know how cortisol play a role on ET1/NO ratio and its relationship to DIND.
Methods: This was a prospective cohort study for the first 14 days after aneurysmal subarachnoid hemorrhage (SAH). Patients with inclusion criteria will be enrolled for blood test before surgery, and post-operative day 2, 4, 7, and 10 (between 8:00-9:00 AM). The blood tests were performed for cortisol, ACTH, CBG, NO, and ET1. Free cortisol is calculated with Coolens equation. Logistic regression was used to see the interaction model and its scale. Bivariate analysis (corelation) was used to see the relationship between total cortisol, free cortisol, NO, ET1, and clinical vasospasm (DIND).
Results: Forty-four patients are enrolled into this study (20 male; 24 females). Mean age is 52.02 years (52.02 ± 11.23). There were 29 patients (66%) within DIND group and 15 patients Non-DIND as the control group. The mean of cortisol level shown is significantly higher in DIND group (35.99 ± 14.24) µg/dL compared to Non-DIND group (19.57 ± 6.19) µg/dL, p < 0.001. The mean of free cortisol level was significantly higher in DIND group (2.06 ± 1.094) µg/dL compared to non-DIND group (0.838 ± 0.365 µg/dL; p < 0.001). The Scatter Plot graph show that correlation of cortisol with ET1/NO ratio started increasing on day 4 and became stronger on day 10.
Conclusion: Cortisol is associated with DIND following aneurysmal SAH, probably through its role in keeping the balance between ET1 and NO level. (Med J Indones. 2013;22:161-6. doi: 10.13181/mji.v22i3.585)
Keywords: Cortisol dynamics, delayed ischemic neurological deficits, endothelin-1, nitric oxide
Poll EM, Bostrom A, Burgel U, et al. Cortisol dynamics in the acute phase of aneurysmal subarachnoid hemorrhage: associated with disease severity and outcome. J Neurotrauma. 2010;27(1):189-195. http://dx.doi.org/10.1089/neu.2009.1014
Suhardja A. Mechanism of disease: Roles of nitric oxide and endothelin -1 in delayed cerebral vasospasm produced by aneurismal subarachnoid hemorrhage. Nature Clinical Practice Cardiovascular Medicine. 2004;1(2):110-116. http://dx.doi.org/10.1038/ncpcardio0046
Bourque SL, Davidge ST, Adams MA. The interaction between endothelin -1 and nitric oxide in the vasculature: new perspectives. AmJ Physiol Regul Integr Comp Physiol. 2011;300(6):R1288-R1295. http://dx.doi.org/10.1152/ajpregu.00397.2010
Morin C, Asselin C, Boudreau F, Provencher PH. Transcriptional regulation of pre-pro-endothelin-1 gene by glucocorticoids in vascular smooth muscle cells. Biochem Biophys Res Commun. 1998;244(2):583-7. http://dx.doi.org/10.1006/bbrc.1998.8300
Provencher PH, Villeneuve A, Morin C. Glucocorticoids increase preproendothelin-1 expression in rat aorta. Endocr Res.1998;24:737-41. http://dx.doi.org/10.3109/07435809809032679
Korhonen R, Lahti A, Hamalainen M, Kankaanranta H, Moilanen E. Dexamethasone inhibits inducible nitric-oxide synthase expression and nitric oxide production by destabilizing mRNA in lipopolysaccharide-treated macrophages. Mol Pharmacol. 2002;62(3):698-704. http://dx.doi.org/10.1124/mol.62.3.698
Wallerath T, Witte K, Schafer SC, et al. Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci U S A. 1999;96(23):13357-62. http://dx.doi.org/10.1073/pnas.96.23.13357
Rogers KM, Bonar CA, Estrella JL, Yang S. Inhibitory effect of glucocorticoid on coronary artery endothelial function. Am J Physiol Heart Circ Physiol. 2002;283(5):H1922-8.
Thony B, Auerbach G, Blau N. Tetrahydrobipterin biosynthesis, regeneration, and functions. Biochem J. 2000;347:1-26. http://dx.doi.org/10.1042/0264-6021:3470001
Drake CG. Report of World Federation of Neurological Surgeons Committee on a universal subarachnoid hemorrhage grading scale. J Neurosurg. 1988;68(6):985-6.
Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized y CT Scanning. Neurosurgery. 1980;6(1):1-9. http://dx.doi.org/10.1227/00006123-198001000-00001
Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJA, van Gijr J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604-7. http://dx.doi.org/10.1161/01.STR.19.5.604
Coolens JL, Van BH, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding Globulin. J Steroid Biochem. 1987;26(2):197-202. http://dx.doi.org/10.1016/0022-4731(87)90071-9
July J, As’ad S, Suhadi B, Islam AA. The association between cortisol dynamics and the course of aneurysmal subarachnoid hemorrhage. Asian J Neurosurg. 2011;6(2):83-87. http://dx.doi.org/10.4103/1793-5482.92166
July J, As’ad S, Suhadi FX, Islam AA. Cortisol dynamics are associated with electrocardiographic abnormalities following the aneurysmal subarachnoid hemorrhage. J Cardiovasc Dis Re. 2012;3(4):315-8. http://dx.doi.org/10.4103/0975-3583.102717
Bendel S, Koivisto T, Ruokonen E, et al. Pituitary-Adrenal function in patients with acute subarachnoid haemorrhage; A prospective cohort study. Crit Care. 2008;12:R126. http://dx.doi.org/10.1186/cc7084
Vergouwen MD, van Geloven N, de Haan RJ, Kruyt ND, Vermeulen M, Roos YB. Increased cortisol levels are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2010;12(3):342-5. http://dx.doi.org/10.1007/s12028-010-9331-8
Sarrafzadeh A, Schlenk F, Gericke C, Vajkoczy P. Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2010;13(3):339-46. http://dx.doi.org/10.1007/s12028-010-9432-4
Hanafy KA, Grobelny B, Fernandez L, et al. Brain interstitial fluid TNF-alpha after subarachnoid hemorrhage. J Neurol Sci. 2010;291(1-2):69-73. http://dx.doi.org/10.1016/j.jns.2009.12.023
Hizume T, Morikawa K, Takaki A, et al. Sustained elevation of serum kortisol level causes sensitization of coronary vasoconstricting responses in pigs in vivo. A possible link between stress and coronary vasospasme. Circ Res. 2006;99(7):767-775. http://dx.doi.org/10.1161/01.RES.0000244093.69985.2f
Pluta RM, Afshar JK, Boock RJ, Oldfield EH. Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage. J Neurosurg. 1998;88(3):557-61. http://dx.doi.org/10.3171/jns.1998.88.3.0557
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