Role Of High Epidural Block On The Perioperative Heart Rate Variability Of Eldly Patients With Hypertensive Left Ventricular Hypertrophy

【AIM】1. To observe the effect of high epidural block (HEB) on the perioperative heart rate variability(HRV) of eldly patients with hypertensive left ventricular hypertrophy who undergoing the upper abdominal surgery, and elucidate the possible mechanism.2. To observe the role of HEB on beta1-adrenorecept-mediated signal transduction via G-protein coupled receptor kinase-1 dependent pathway in the peripheral lymphocytic of eldly patient with hypertensive left ventricular hypertrophy, and provide a novel theory of HEB on the perioperative myocardial protection.【Methods】1. Twenty ASAⅡ～Ⅲgrade eldly patients with hypertensive left ventricular hypertrophy who underwent subtotal gastrectomy in Fuzhou General Hospital from May to December 2007 were recruited to the study. The written informed consent was obtained from the subjects, and the experiment was permitted by Hospital Ethics Committee.2. According the anaesthesia method, the patients were classified into two groups: HEB combined with general anaesthesia group (GEA group, n=10), and single general anaesthesia group(GA group, n=10).3. While changes of each component of HRV analysis in the frequency domain in five minutes were observed, the venous blood samples were drawn out to isolated peripheral lymphocytes during the different perioperative periods, i.e. before operation, at the waking time and 1, 3, 5 days post-operation. Isoproterenol-stimulated cAMP product in lymphocytes was measured with radioimmunoassay. The protein expression of beta1-adrenergic receptor in cytoplasm,cytomembrane and total cells of lymphocytes were detected with western bolt respectively. At the same time , the mRNA expression of beta-adrenergic receptor,G-protein coupled receptor kinase-1 and beta-arrestin-1 were detected with fluorescent quantitative real-time polymerase chain reaction respectively.【Results】1. Compared with the baselines before the surgery, total power(TP) of HRV, together with high-frequency(HF) power and low-frequency(LF) power, decreased significantly after the general anaesthesia and surgery. All of them did not recover untill 5 days after the surgery. TP, HF, LF and LF/HF in GA group were decreased more significantly than those in GEA group during the perioperative periods.2. The isoproterenol-stimulated cAMP product in lymphocytes had significantly reduced immediately after extubation,and yet not return to the baseline in 5 days after the operation in both groups. But, in generally , cAMP product in GA group was decreased more significantly than that in GEA group during the most of perioperative time.3. The expression of beta1-adrenergic receptor mRNA in lymphocytes was down-regulated during the perioprative periods. but that ofβ1-ARK mRNA was up-regulated .Both of them changed in different degrees in all the subjects. In generally, there was less fluctuation in the GEA group than in the GA one. It was interesting that the expression of beta-arrestin -1 in lymphocytes didn't change much during the same time.4. During the perioprative periods, the level of beta1-adrenergic receptor protein in different lymphocytes component i.e. membrane, cytoplasm and total cell changed differently. As a matter of fact ,the internalization, externalization and reduced of protein expression complicated. Compared with the GA group , the change tendency was more steady in the GEA group during the perioperative periods.5 As shown by the Pearson liner correlate analysis, TP positively correlated well with isoproterenol-stimulated cAMP (r=0.577,P<0.01), but inversely correlated with the expression ofβ1-ARK mRNA in the lymphocytes during the perioperative periods(r=-0.520,P<0.01). Meanwhile, the expression ofβ1-ARK mRNA inversely correlated with the isoproterenol-stimulated cAMP in the lymphocytes(r=-0.440,P<0.01)。【Conclusion】1. After general anaesthesia and upper abdominal surgery, the function of autonomic nervous system is badly damaged in the eldly patients with hypertensive left ventricular hypertrophy. Compared with the GEA group, the damage in the GA group is usually more serious.2. The desensitization of beta1- adrenergic receptor in lymphocytes is common during the perioperative periods, which may be concerned with the up-regulation of expression ofβ1-ARK gene mRNA as a result of stress reaction.3. The change ofβ1-ARK gene mRNA could be a major contributory factor in the decrease of HRV in the eldly patients with hypertensive left ventricular hypertrophy4. High epidural block could partially inhibit the up-regulation ofβ1-ARK mRNA, and alleviate the desensitizaiton of beta1-adrenergic receptor, thus keep the balance of autonomic nervous system, which could promote the early rehabilitation.