Vasodilatory Action of Propofol and the Effect of Propofol on the Contractile Response of Endotoxin Exposured Vessles in the Aortic Arteries of Rats / 대한마취과학회지

BACKGROUND: The relationship between the NO and its vasodilatory effect of propofol has been a somewhat controversial matter. And, the effects of propofol has not been evaluated in septic condition whether it is solely due to its increased iNOS activity. METHODS: First experiment is to study that the vasodilatory effect of propofol could be caused by NO. Isolated aortic rings with or without endothelium were contracted phenylephrine (10(-9)-10(-5)M) cumulatevely after porpofol (10(-5)M) administration. The effects of L-NAME (3 x 10(-4)M) and methylene blue (10(-5)M) on contractile responses for phenylephrine were evaluated. Second experiment is to study the effect of propofol on septic vesseles. the no LPS (lypopolysaccaride) and LPS treated rings with or without endothelium were contracted phenylephrine (10(-9)-10(-5)M) cumulatevely after porpofol (10(-5)M) administration. The development of sepsis was confirmed by iNOS expression using RT-PCR. RESULTS: All the aortic rings showed decreased response on phenylephrine contractile response with propofol administration. These responses were significantly less in denuded ones than in ones with intact endothelium. The endothelium dependent relaxation of propofol was inhibited by pretreatment with L-NAME and methylene blue in rat aortic rings having intact endothelium. All the aortic rings incubated with LPS showed decreased phenylephrine contractile response. The addition of propofol produced significantly more decrease in contractile response in LPS incubated rings in a greater than additive effect. The LPS induced hyporesponsiveness to phenylephrine was reversed by addition of cycloheximide. However, with the addition of propofol to LPS treated rings, complete reversal of this hyporesponsiveness to phenylephrine, failed to occur by addition of cycloheximide. CONCLUSIONS: 1) The vasodilatory effect of propofol seems to be mediatede by EDRF/NO, 2) The vasodilatory effect of propofol is increased in septic vesseles. Moreover, the inability of nitric oxide synthase inhibitior to reverse this response completely suggest that increased induction of iNOS may not be a sole responsible factor for this finding.

Effects of Inhaled Nitric Oxide on Respiratory System Mechanics in Cats with Methacholine-induced Bronchoconstriction / 대한마취과학회지

BACKGROUND: Nitric oxide (NO) is a selective pulmonary vasodilator, and inhaled NO has bronchodilatory action due to their relaxation effect on conducting airway smooth muscle. The aim of this study was to evaluate the effects of inhaled NO on respiratory system mechanics in cats. METHODS: Nineteen cats were divided into 3 groups according to the doses of NO administered; group C (control, n=7), group 20 (20 ppm of NO, n=7), and group 40 (40 ppm of NO, n=5). After measuring the baseline value, methacholine chloride 25 microgram/kg/min was infused to induce bronchoconstriction. Inhalation of NO was started for each group 15 minutes after methacholine infusion. Pressure, volume, and flow rate were monitored with Bicore CP100 pulmonary monitor and the data were transferred to a personal computer and analyzed by a processing software. Respiratory system, airway and tissue viscoelastic resistances, and dynamic and static compliances were calculated. RESULTS: Methacholine infusion increased both airway and tissue resistances. Fifteen minutes after inhaling NO, airway resistances for NO 20 ppm and 40 ppm decreased to 65.8+/-8.5% and 62.2+/-8.9% of the control value (p<0.05). The values of tissue resistances for NO 20 ppm and 40 ppm decreased to 72.4+/-10.8% and 78.2+/-10.5% of the control value respectively (p<0.05). And thirty minutes after inhaling NO, there were also decreases of airway and tissue viscoelastic resistances in both groups but had no differences compared with fifteen minutes' values. There were no significant differences between the NO 20 ppm and 40 ppm in the values of airway and tissue viscoelastic resistances. CONCLUSION: Inhaled NO of 20 ppm and 40 ppm decreased both airway and tissue viscoelastic resistances and airway resistance was decreased more markedly than tissue resistance. There were no significant differences between 20 ppm and 40 ppm of NO in respiratory system mechanics in cats.

Effect of NG-nitro-L-arginine Methyl Ester Pretreatment on Spinal Cord Damage by Aortic Occlusion in Rabbits / 대한마취과학회지

BACKGROUND: Production of nitric oxide (NO) radicals may contribute to neuronal injury. We examined that the inhibition of NO synthase (NOS) could improve postischemic neurologic outcome after spinal cord ischemia in rabbits. Also, we measured cGMP as a marker of NOS activation in control and experimental groups. METHODS: Spinal cord ischemia in rabbits was induced by aortic occlusion with aneurysm clip at the level just below branching of left renal artery. Five minutes before aortic occlusion, saline (control group, n=10) or a NOS inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg, L-NAME group, n=10) was injected intravenously. After 15 min ischemia and 1 hour reperfusion, animals were sacrified and the spinal cords were extruded for the measurement of cGMP by enzymeimmunoassay. For neurologic examination, the same procedures of ischemia/reperfusion and drug injection were done, except that rabbits were perfused for 4 hours (control-4 and L-NAME-4, n=8 at each group) or 48 hours (control-48 and L-NAME-48, n=8 at each group) after aortic occlusion. RESULTS: L-NAME (10 mg/kg) increased mean systemic arterial pressure accompanied by bradycardia, and reduced cGMP significantly. Control-4 animals showed better neurologic function than L-NAME-4 animals (p<0.05), however, there was no significant difference of neurologic outcome between control-48 and L-NAME-48 groups. CONCLUSION: Intravenous administration of L-NAME prior to spinal cord ischemia/reperfusion diminishes the extent of postischemic neuronal spinal cord damage at the early postreperfusion period.

Effect of NG-nitro-L-arginine Methyl Ester Pretreatment on Spinal Cord Damage by Aortic Occlusion in Rabbits / 대한마취과학회지

BACKGROUND: Production of nitric oxide (NO) radicals may contribute to neuronal injury. We examined that the inhibition of NO synthase (NOS) could improve postischemic neurologic outcome after spinal cord ischemia in rabbits. Also, we measured cGMP as a marker of NOS activation in control and experimental groups. METHODS: Spinal cord ischemia in rabbits was induced by aortic occlusion with aneurysm clip at the level just below branching of left renal artery. Five minutes before aortic occlusion, saline (control group, n=10) or a NOS inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg, L-NAME group, n=10) was injected intravenously. After 15 min ischemia and 1 hour reperfusion, animals were sacrified and the spinal cords were extruded for the measurement of cGMP by enzymeimmunoassay. For neurologic examination, the same procedures of ischemia/reperfusion and drug injection were done, except that rabbits were perfused for 4 hours (control-4 and L-NAME-4, n=8 at each group) or 48 hours (control-48 and L-NAME-48, n=8 at each group) after aortic occlusion. RESULTS: L-NAME (10 mg/kg) increased mean systemic arterial pressure accompanied by bradycardia, and reduced cGMP significantly. Control-4 animals showed better neurologic function than L-NAME-4 animals (p<0.05), however, there was no significant difference of neurologic outcome between control-48 and L-NAME-48 groups. CONCLUSION: Intravenous administration of L-NAME prior to spinal cord ischemia/reperfusion diminishes the extent of postischemic neuronal spinal cord damage at the early postreperfusion period.

The Effect of Nitric Oxide on Edema Formation in Cryogenic Brain Injury Model of the Rat / 대한마취과학회지

BACKGROUND: Nitric oxide (NO) is a simple molecule with a complex involvement in a wide variety of biologic functions. However, whether NO protects or aggravates brain injury is still controversial. This study was conducted to determine the effect of nitric oxide on the formation of brain edema resulting from a focal cryogenic injury in rats. METHODS: Thirty nine Sprague-Dawley rats (200~250 gm) were allowed food and water ad libitum. Anesthesia was induced in a specially designed plastic box with 5% halothane in oxygen. In experiment I (24 rats), animals were divided randomly into eight group (3 rats in each group) according to the decapitation time in control, 15, 30, 45, 60, 90, 120, and 180 min. Cryogenic injury was made by pouring liquid nitrogen to exposed temporo-parietal area through metal funnel for 60 seconds. After cryogenic injury, brain was quickly removed and cerebral hemispheres were seperated. Separated cerebral hemispheres were dried in a drying oven for 7 days at 60 degrees C. Cerebral water content was assessed by dry-weight method. In experiment II (15 rats), one subgroup (n=8) was control group, normal saline 0.5 ml was injected intraperitoneally 30 minutes before injury. the other (n=7) was experimental group, and a competitive nitiric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), was given intraperitoneally 30 minutes before injury in a dose of 20 mg/kg. Body temperature was monitored during whole experiment. Ninety minutes after injury, brain was quickly removed and cerebral hemispheres were seperated. The cerebral water content of separated cerebral hemisphere was assessed by dry-weight method. RESULTS: In time courses of cryogenic brain edema of experiment I, the amount of brain edema was increased till 90 minutes after cryogenic brain injury and then decreased. In L-NAME group of ex-periment II, the amount of cerebral edema was not changed significantly (p<0.05). But, there was a tendency of decrease in brain edema formation in L-NAME group than control group. CONCLUSION: It was not proved that nitric oxide had a major role in the edema formation aftercryogenic brain injury, but it still seems that nitric oxide has at least partly involved in the pathogenesis of cerebral edema resulting from traumatic brain injury.