An Analysis of the Hypothalamic-Pituitary-Adrenal Axis Functions in Cirrhotic Rats in Response to Surgical Stress.

Introduction: The activation of hypothalamic-pituitary-adrenal (HPA) axis through severe diseases and stress courses leads to a rise in circulatory cortisol for an adequate response to stress. This axis is one of the important systems that involve in neuroendocrine response to the surgical stress. Hepatoadrenal syndrome that is a manifestation of adrenal insufficiency (AI) in the course of liver disease is described as insufficient production of steroid hormones mainly cortisol due to primary dysfunction of the adrenal gland or secondary malfunction of the HPA axis to provoke the adrenal gland leading to severe illness and increased mortality. Through this evidence, we presented this question as to whether cirrhotic patients have a greater mortality rate than other patients after surgery and if the HPA axis is partly responsible for this phenomenon. Also how the adrenal gland functions during surgery in cirrhotic rats. We conducted this study to assess the effect of cirrhosis on the HPA axis through surgery in cirrhotic rats by evaluating the changes in serum corticosterone level and blood sugar before, immediately, and 30 minutes after surgery.

Method: This study was performed in the animal lab approved by the Ethics Committee of Tehran University of Medical Sciences in 2014, on 25 male Wistar rats. Thioacetamide was used for induction of cirrhosis in rats with new method of monitoring weekly changes of rats' weight which had 100% success in procedure and reduction in mortality rate. Laparotomy was performed on all of the rats during 9-12 in the morning within 10-15 minutes. Laparotomy was chosen as surgical stress because of its simplicity and feasibility. Three blood samples were obtained from each rat immediately after inducing anesthesia, immediately after the conclusion of surgery, and 30 minutes after surgery. The plasma concentration of corticosterone was measured with enzyme-linked immunosorbent assay test. P value of 0.05 or less was considered as statistical significance.

Result: Cirrhotic rat group consisted of 15 rats and control group consisted of 10 rats. There was a significant difference in the mean level of corticosterone and blood sugar between the cirrhotic rat group and control group in the 3 time levels ( P =0.044/ P < 0.001). Pairwise comparison of mean corticosterone and blood sugar levels between case (mean: 249.359 ± 3.90) and control (mean: 262.40 ± 4.69) showed a significant difference ( P =0.04, 95% CI = 0.30-25.79/ P < 0.001, 95% CI = 129.62-233.96). Unlike the control group, the level of serum corticosterone was compared in the cirrhotic rat group (group 1) before, immediately, and 30 minutes after surgery, which showed a significant difference in our study ( P value  = 0.005). However, this result was also significant in comparing the blood sugar in 3 time levels of surgery in the control group ( P value < 0.001) but not in the cirrhotic rat group ( P value = 0.233).

Conclusion: There was a significant rise in corticosterone levels during 3 time levels of surgery in cirrhotic rats; nevertheless, this elevation was significantly lower than the control group. Also the mean level of blood sugar was higher in the control group than in cirrhotic rats. However, this difference was significant in comparison with the same times of surgery between the two groups. These results approximately can substantiate our hypothesis that AI in the field of cirrhosis would also affect the response of HPA axis to stress during and after surgery that can be concomitant with higher rate of cardiovascular unsteadiness incidences, deteriorating the severity of illness and rise in mortality rate.