| Summary: | 博士 === 國立臺灣大學 === 生理學研究所 === 90 === Anesthetic managements can greatly affect the regulatory system to maintain homeostasis. Surgical stress induces the activation of sympathetic nervous system and humeral responses and release of free radicals. Anesthetic management deals with mainly the stress responses. Different anesthetic managements interacting with different surgical techniques bring different effects on regulatory system. The purpose of this study is to determine the effect of different anesthetic managements on the release of free radicals and explore the functional change of kidney. The study was divided into two parts according to the method performed. Two experiments dealing with free radical production and lipid peroxidation during total knee replacement using tourniquet under intrathecal anesthesia were included in the first part. Release of tourniquet produces reactive oxygen species (ROS) and induces ischemia-reperfusion injury. The first experiment was designed to compare the effects of low dose propofol infusion and intravenous midazolam on ROS production. Patients undergoing elective total knee replacement under intrathecal anesthesia was allocated randomly to one of two groups. In the propofol group, sedation was performed with propofol 0.2 mg kg-1 followed by infusion at a rate of 2 mg kg-1 h-1. In the control group, intravenous midazolam 5 mg was given. ROS production was measured by lucigenin chemiluminescence analysis. Blood samples were obtained from the radial artery after spinal anesthesia, 1-min. before release of tourniquet, 5-min and 20 min. after reperfusion. ROS production was significantly increased 5 and 20 min. after reperfusion in midazolam group. In the propofol group, no significant increase on ROS production was found. We conclude that low dose propofol sedation attenuates ROS production in tourniquet-induced ischemia-reperfusion injury.
The goal of the second experiment in the first part is to testify if sequential tourniquet release has the ischemic preconditioning (IPC) effect on ROS production and lipid peroxidation, patients undergoing elective bilateral total knee replacement (TKR) under intrathecal anesthesia were studied. Blood samples were obtained after spinal anesthesia, 1-min. before release of tourniquet, 5 min. and 20 min. after each tourniquet release. Lucigenin chemiluminescence analysis and phosphatidylcholine hydroperoxide (PCOOH) assay were used to measure ROS production and lipid peroxidation. Our results showed that ROS production significantly increases in 5 and 20 min. after the first tourniquet and 5 min. after the second tourniquet release. The peak ROS production lays on 20 min. after the first reperfusion but the second peak was attenuated. PCOOH changed non-significantly throughout this study. We concluded that in spite of significant ROS production after release of tourniquet, IPC phenomenon stands in bilateral TKR. Based on these two experiments, the choice of anesthetic sedatives and the methods of tourniquet application affects the production of oxidative free radicals. It can be concluded that anesthetic management can affect the complications following ischemic-reperfusion injury.
The second part of our study dealed with the effects of anesthetic managements on kidney. There were two experiments in this part. The goal of the first experiment was to investigate the effects of incremental doses of ketamine on renal sympathetic nervous activity (RSNA), renal blood flow (RBF) and renal vascular resistance (RVR). A biphasic pattern on the effects of increasing dose of ketamine on renal sympathetic nerve activities (RSNA) was shown in previous study. We hypothesized that if RVR and RBF are mainly controlled by RSNA, they will show a similar biphasic pattern under increasing doses of ketamine. Rats anesthetized with urethane were studied with ketamine 0.5, 1, 2 mg/kg i.v. in 30 minute intervals. Multifiber RSNA recording, mean arterial pressure (MBP) were studied and RBF (by electromagnetic flowmeter), RVR were calculated by dividing MBP with RBF. Our results showed that although incremental doses of ketamine brings a biphasic pattern on MBP and RSNA, the decrease on RBF and the increase on RVR goes a dose-dependent way.
Hypotension deteriorates renal functions. Fluid administration is frequently used to prevent hypotension following high level spinal anesthesia. We designed the second experiment in the second part to evaluate the effects of fluid loading on renal hemodynamics and cortical microvascular blood flow (CMBF) as well as electrolytes excretion and urine production under high level (above T4) spinal anesthesia. Intravenous normal saline infusion started (5 ml/kg/hr) in control group and fluid loading (15 ml/kg/hr) group 30 min. before spinal anesthesia. CMBF was measured by laser flowmetry. Glomerular filtration rates (GFR) by inulin clearance, effective renal plasma flow (ERPF) by P-aminohippurate clearance, urine production and electrolytes excretion were measured in every 30 min. interval after spinal anesthesia. Severe hypotension was notable within 5-10 min. after intrathecal anesthesia and recovered within 30 min. The changes in blood pressure, heart rate were comparable in both groups. In control group, GFR and ERPF decreased significantly in the first 30 min by 51.9 ± 19.8% and 44.3 ± 13.7% (p<0.05) and recovered comparably in the 30-60 min. interval. UFR and CMBF deteriorate longer than 60 min. In fluid loading group, only GFR was affected in the first 30 min. GFR, ERPF and UFR were slightly increased in the second 30 min. interval. CMBF maintained well throughout the experiment. We concluded that in spite of severe hypotension, fluid loading prevents the deteriorations on renal circulation and filtration especially cortical blood flow and urine production.
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