Clonidine premedication effects on inhaled induction with sevoflurane in adults: a prospective, double-blind, randomized study.

BACKGROUND: The purpose of this study was to evaluate whether oral clonidine premedication becomes an alternative to N2O in terms of shortening the induction time and attenuation of the adrenergic response to tracheal intubation during inhalation induction with sevoflurane, and to evaluate the quality of anesthetic induction according to the patient's satisfaction. METHODS: We studied 84 female patients who were randomly allocated into four study groups: Groups I and II received a placebo orally, and Groups III and IV received clonidine at 150 and 300 microg, respectively, 90 min before induction of anaesthesia. Patients were anesthetized using a triple-deep-breath technique with 5% sevoflurane in Groups I, III and IV, and with 60% N2O-5% sevoflurane in group II. RESULTS: Induction time was significantly longer (P < 0.05) in Group I. Increases in mean blood pressure and heart rate after tracheal intubation were significantly suppressed in Groups III and IV but not in Group II compared with Group I. Comfort and impression of anesthesia was better in Groups III and IV than in Groups I and II. CONCLUSION: In volatile anesthetic induction, pre-anesthetic clonidine may become an alternative to N2O and may provide more comfort than with N2O.

Effect of re-expansion after short-period lung collapse on pulmonary capillary permeability and pro-inflammatory cytokine gene expression in isolated rabbit lungs.

BACKGROUND: Re-expansion pulmonary oedema is a rare complication caused by rapid re-expansion of a chronically collapsed lung. Several cases of pulmonary oedema associated with one-lung ventilation (OLV) have been reported recently. Elevated levels of pro-inflammatory cytokines in pulmonary oedema fluid are suggested to play important roles in its development. Activation of cytokines after re-expansion of collapsed lung during OLV has not been thoroughly investigated. Here we investigated the effects of re-expansion of the collapsed lung on pulmonary oedema formation and pro-inflammatory cytokine expression. METHODS: Lungs isolated from female white Japanese rabbits were perfused and divided into a basal (BAS) group (n=7, baseline measurement alone), a control (CONT) group (n=9, ventilated without lung collapse for 120 min) and an atelectasis (ATEL) group (n=9, lung collapsed for 55 min followed by re-expansion and ventilation for 65 min). Pulmonary vascular resistance (PVR) and the coefficient of filtration (Kfc) were measured at baseline and 60 and 120 min. At the end of perfusion, bronchoalveolar lavage fluid/plasma protein ratio (B/P), wet/dry lung weight ratio (W/D) and mRNA expressions of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and myeloperoxidase (MPO) were determined. RESULTS: TNF-alpha and IL-1beta mRNA were significantly up-regulated in lungs of the ATEL group compared with BAS and CONT, though no significant differences were noted in PVR, Kfc, B/P and W/D within and between groups. MPO increased at 120 min in CONT and ATEL groups. CONCLUSION: Pro-inflammatory cytokines were up-regulated upon re-expansion and ventilation after short-period lung collapse, though no changes were noted in pulmonary capillary permeability.

Role of potassium channels in isoflurane- and sevoflurane-induced attenuation of hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs.

BACKGROUND: Although potassium channels are thought to be responsible for the initiation of hypoxic pulmonary vasoconstriction (HPV), their role in the HPV-inhibitory effect of volatile anesthetics is unclear. The current study tested if the HPV-inhibitory effect of isoflurane and sevoflurane can be affected by changing the potassium-channel opening status with specific potassium-channel inhibitors in isolated rabbit lungs. METHODS: Isolated rabbit lungs were divided into eight groups (n = 6 each in isoflurane groups and n = 8 in sevoflurane groups): those receiving no inhibitor treatment = control-isoflurane and control-sevoflurane groups; those treated with an adenosine triphosphate-sensitive potassium (K(ATP))-channel inhibitor, glibenclamide = glibenclamide-isoflurane and glibenclamide-sevoflurane groups; those treated with a high-conductance calcium-activated potassium (K(Ca))-channel inhibitor, iberiotoxin = iberiotoxin-isoflurane and iberiotoxin-sevoflurane groups; and those treated with a voltage-sensitive potassium (Kv)-channel inhibitor, 4-aminopyridine = 4-aminopyridine-isoflurane and 4-aminopyridine-sevoflurane groups. The effect of anesthetic on HPV was tested by exposure of the lungs to isoflurane at a concentration of 0, 0.5, 1, or 2 minimum alveolar concentration, or to sevoflurane at a concentration of 0, 0.5, 1, or 1.62 minimum alveolar concentration. The relation between anesthetic concentrations and the HPV response was analyzed by the Wagner equation. RESULTS: The inhibition of Kv channels by 4-aminopyridine and K(Ca) channels by iberiotoxin augmented the HPV response. The isoflurane-induced attenuation of HPV was attenuated by voltage-sensitive potassium-channel inhibition with 4-aminopyridine, potentiated by K(Ca)-channel inhibition with iberiotoxin, but not affected by K(ATP)-channel inhibition with glibenclamide. The sevoflurane-induced attenuation of HPV was not affected by any of the potassium-channel inhibitors. CONCLUSIONS: Isoflurane may modulate the HPV response partially through K(Ca) and Kv channels, but sevoflurane may attenuate the HPV response through other pathways rather than through the currently investigated potassium channels in isolated rabbit lungs.

[Two cases of advanced and metastatic breast cancers treated by docetaxel in combination with intra-arterial infusion of adriamycin].

Two cases of advanced and metastatic breast cancers were treated by docetaxel (TXT) in combination with intra-arterial infusion of adriamycin (ADM). Patients received 60 mg/body TXT i.v. and 30 mg/body ADM ia (AT therapy) bi-weekly. Clinical responses were observed in these two patients and the durations of responses were over 20 weeks. Critical toxicities of grade 2 leukopenia and alopecia were observed but grade 4 severe toxicities were not. Thus AT therapy can be easily and safely performed with outpatients. This therapy can improve the response rate and time to progression; therefore phase I or phase I/II clinical trials of AT therapy in Japan are recommended.

[Efficacy of simultaneous bolus injection of lidocaine with propofol on pain caused by propofol injection].

To investigate the effect of simultaneous bolus injection of 2% lidocaine 2 ml on preventing the pain on propofol injection, 80 patients were randomly assigned to one of four study groups; Group I received simultaneous bolus injection of 2% lidocaine 2 ml with infusion of propofol; Group II received bolus injection of saline 2 ml, 10 s before the start of infusion of propofol-lidocaine mixture; Groups III and IV received bolus injections of lidocaine and saline, separately 10 s before starting propofol infusion. Incidence of propofol-induced pain was significantly more frequent (P < 0.001) in Group IV (70%) than in the other groups (20% each). Number of patients who were satisfied with this anesthetic induction and requested for the same induction method in the next anesthesia was significantly larger in the groups receiving lidocaine (P < 0.05). Simultaneous bolus injection of lidocaine with propofol showed a similar clinical efficacy compared with both preadministration and premixing of lidocaine in preventing the propofol-induced pain.

Chemiluminescence underestimates nitric oxide concentration in the presence of potent inhalation anaesthetics.

We investigated the effect of potent inhalation anaesthetics on nitric oxide (NO) concentration measured by the chemiluminescence method. We found that the NO concentration was increasingly underestimated with increasing concentrations of halothane, isoflurane, enflurane and sevoflurane (r2 = 0.918-0.997, P < 0.01). Statistical analysis showed that the four inhalation agents at the same concentration produced a similar error in the measured NO concentration. In the presence of a fixed concentration of sevoflurane (5.0%), isoflurane (5.2%), enflurane (4.5%) or halothane (6.1%), the rate of reduction in the measured NO concentration increased in proportion to the NO concentration (r2 = 0.909-0.982, P < 0.01). No direct chemical interaction between the potent inhalation agents and NO was detected by gas chromatography-mass spectrometry. We conclude that NO concentration can be underestimated when measured by the chemiluminescence method in the presence of potent inhalation agents. This underestimation may result from emission absorption and/or the quenching phenomenon, but is not attributable to a chemical reaction between the inhalation agent and NO.

Isoflurane-sevoflurane adminstration before ischemia attenuates ischemia-reperfusion-induced injury in isolated rat lungs.

BACKGROUND: The effects of volatile anesthetics on ischemia-reperfusion (IR)-induced lung injury are not clear. The authors investigated the effects of preadministration of isoflurane and sevoflurane on IR-induced lung injury in an isolated buffer-perfused rat lung model. METHODS: Isolated rat lungs were designated into four groups: control group (n = 6): perfusion for 120 min without ischemia; IR group (n = 6): interruption of perfusion and ventilation for 60 min followed by reperfusion for 60 min; sevoflurane (SEVO)-IR (n = 6) and isoflurane (ISO)-IR (n = 6) groups: 1 minimum alveolar concentration (MAC) isoflurane or sevoflurane was administered for 30 min, followed by 60 min ischemia, then 60 min reperfusion. The authors measured the coefficient of filtration (Kfc) of the lung, lactate dehydrogenase (LDH) activity, tumor necrosis factor alpha, and nitric oxide metabolites (nitrite + nitrate) in the perfusate and the wet-to-dry lung weight ratio. RESULTS: IR caused significant increases in the coefficient of filtration (approximately sevenfold at 60 min of reperfusion compared with baseline; P < 0.01), the wet-to-dry lung weight ratio, the rate of increase of lactate dehydrogenase activity, and tumor necrosis factor a in the perfusate, and caused a significant decrease in nitric oxide metabolites in the perfusate. Administration of 1 MAC isoflurane or sevoflurane before ischemia significantly attenuated IR-induced increases in the coefficient of filtration and the wet-to-dry lung weight ratio, inhibited increases in the rate of increase of lactate dehydrogenase activity and tumor necrosis factor alpha in the perfusate, and abrogated the decrease in nitric oxide metabolites in the perfusate. No difference was found between the SEVO-IR and ISO-IR groups. CONCLUSION: Isoflurane and sevoflurane administered before ischemia can attenuate IR-induced injury in isolated rat lungs.

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients.

OBJECTIVE: To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN: Prospective, single-center, observational study. SETTING: University hospital operating room, intensive care unit. PATIENTS: Sixteen adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: None except cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. CONCLUSION: Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.

[A modified technique for insertion of the laryngeal mask airway in children].

We modified the technique for laryngeal mask airway (LMA) insertion in children. This modification involves inserting a two-thirds inflated LMA with its lumen facing laterally toward left and then rotating it 90 degrees clockwise as it passes downwards into position behind the larynx. Then the cuff is inflated fully. We conducted a survey on the use of LMA in ten consecutive children for minor superficial surgery. After slow induction, anesthesia was maintained with 3.0% of end-tidal sevoflurane concentration in 100% oxygen for 5 minutes before insertion of LMA. No muscle relaxant was used. Successful insertion was judged by the clinical integrity of the airway. The standard LMA insertion technique or another airway device was applied when three trials had failed. Traumatic insertion was observed by the attachment of blood clots to the surface of the removed LMA. A satisfactory airway was achieved in all of the children who participated in the survey. There were no significant differences in vital signs between pre- and post-insertion. Only one child was found to have attachment of blood clots on the surface of the removed LMA. We conclude that our technique would be one recommended method in pediatric practice.

Isoflurane administration before ischemia and during reperfusion attenuates ischemia/reperfusion-induced injury of isolated rabbit lungs.

UNLABELLED: To investigate the effects of isoflurane on ischemia/ reperfusion (IR)-induced lung injury, we administered isoflurane before ischemia or during reperfusion. Isolated rabbit lungs were divided into the following groups: control (n = 6), perfused and ventilated for 120 min without ischemia; ISO-control (n = 6), 1 minimum alveolar anesthetic concentration (MAC) isoflurane was administered for 30 min before 120 min continuous perfusion; IR (n = 6), ischemia for 60 min, followed by 60 min reperfusion; IR-ISO1 and IR-ISO2, ischemia followed by reperfusion and 1 MAC (n = 6) or 2 MAC (n = 6) isoflurane for 60 min; ISO-IR (n = 6), 1 MAC isoflurane was administered for 30 min before ischemia, followed by IR. During these maneuvers, we measured total pulmonary vascular resistance (Rt), coefficient of filtration (Kfc), and lung wet to dry ratio (W/D). The results indicated that administration of isoflurane during reperfusion inhibited an IR-induced increase in Kfc and W/D ratio. Furthermore, isoflurane at 2 MAC, but not 1 MAC, significantly inhibited an IR-induced increase in Rt. The administration of isoflurane before ischemia significantly attenuated the increase in IR-induced Kfc, W/D, and Rt. IMPLICATIONS: Our results suggest that the administration of isoflurane before ischemia and during reperfusion protects against ischemia-reperfusion-induced injury in isolated rabbit lungs.

Effects of hypoxic exercise conditioning on work capacity, lactate, hypoxanthine and hormonal factors in men.

1. Hypoxanthine is a purine degradation product and exercise plasma hypoxanthine can be an index of ATP supply-demand imbalance during exercise. The present study determined the effects of hypoxic exercise conditioning on work capacity, blood lactate, plasma hypoxanthine and various neurohormonal factors. 2. Blood lactate, plasma hypoxanthine and neurohormonal factors (catecholamines, renin-angiotensin system activity and natriuretic peptides) were measured at rest and after maximal cardiopulmonary exercise testing (at sea level) both at pre- and post-hypoxic exercise conditioning in six males (40 +/- 2 years). The training protocol consisted of ergometer exercise twice weekly for 40 min in a hypobaric chamber (61.7-47.2 kPa) for 3 weeks. 3. Pulmonary function and haematological and echocardiographic parameters were not altered after hypoxic exercise conditioning. Work rate at peak exercise (264 +/- 10 vs 321 +/- 31 W; P = 0.10) tended to be increased and peak O2 pulse (15.0 +/- 1.0 vs 18.4 +/- 1.4 mL/beat; P < 0.05) increased after exercise conditioning. The double product during submaximal exercise decreased and systolic blood pressure at peak exercise increased after exercise conditioning. Resting and exercise neurohormonal factors were unchanged, except for reduced resting plasma adrenaline levels. Blood lactate at peak exercise (7.4 +/- 0.7 vs 4.8 +/- 0.5 mmol/L; P < 0.05) became lower and peak plasma hypoxanthine (43.2 +/- 5.7 vs 26.4 +/- 5.0 mumol/L; P < 0.1) tended to be decreased after exercise conditioning. 4. Hypoxic exercise conditioning tended to increase maximal power output with a decrease in exercise blood lactate and a trend towards a decrease in exercise plasma hypoxanthine. These data suggest that exercise conditioning under simulated altitude may improve ATP supply-demand imbalance during exercise with less anaerobiosis, which could contribute to enhanced endurance performance.

Role of inhaled nitric oxide in ischaemia-reperfusion injury in the perfused rabbit lung.

We have tested if inhaled nitric oxide (NO) is beneficial in ischaemia-reperfusion (IR) lung injury using an isolated perfused rabbit lung model. Ischaemia for 60 min was followed by reperfusion and ventilation with nitric oxide 40 ppm (n = 6) or without nitric oxide ventilation (n = 6) for 60 min. In the control group (n = 6), the lungs were perfused continuously for 120 min. Permeability coefficient (Kfc) and vascular resistance (PVR) were measured serially for 60 min after reperfusion. We also determined the left lung W/D ratio and measured nitric oxide metabolites (NOx) and cGMP concentrations in bronchoalveolar lavage (BAL) fluid from the right lung. IR increased Kfc, PVR and W/D followed by decreased cGMP. Ventilation with nitric oxide restored these changes by preventing the decrease in cGMP. Differences in NOx concentrations in BAL fluid between the control and IR groups were not statistically significant. Our results indicate that IR impaired pulmonary vascular function and resulted in microvascular constriction and leakage. Ventilation with nitric oxide from the beginning of the reperfusion period improved pulmonary dysfunction such as vasoconstriction and capillary leak by restoring cGMP concentrations.

Prostaglandin E1 antagonizes hypoxic pulmonary vasoconstriction but reduces systemic blood pressure in dogs.

OBJECTIVE: To investigate whether prostaglandin E1 (PGE1) directly inhibits hypoxic pulmonary vasoconstriction in dogs. DESIGN: Prospective, longitudinal study. SETTING: University research laboratory. SUBJECTS: Six mongrel dogs in vivo. INTERVENTIONS: The left thorax of anesthetized and ventilated dogs was opened and the left lower lobe was separately ventilated. The tip of the thermodilution pulmonary artery catheter was introduced into the left lower lobe pulmonary artery. The left lower lobe was ventilated with hyperoxic (95% oxygen and 5% CO2) or hypoxic (95% nitrogen and 5% CO2) gas. By manipulating the occluders placed on both pulmonary arteries, blood flow in the left lower lobe was regulated. Continuous pressure-flow plots for the left lower lobe were then obtained. MEASUREMENTS AND MAIN RESULTS: Measurements included continuous pressure-flow plot generation, thermodilution cardiac output and blood flow in the left lower lobe, and blood gas analysis. Alveolar hypoxia of the left lower lobe caused blood flow in the left lower lobe to decrease from 371.8 +/- 63.4 to 95.0 +/- 23.4 mL/min and shifted the pressure-flow plot to the right, with a decreased slope and with an increase in the pressure-axis intercept. Subsequently, systemic venous infusion of PGE1 at a rate of 0.3 microg/kg/min had no effect on the pressure-flow plot configuration, blood flow in the left lower lobe, pulmonary vascular resistance, systemic vascular resistance, and PaO2. However, there was a decrease in the pressure-axis intercept of the pressure-flow plot. Infusion of PGE1 at a rate of 3.0 microg/kg/min (high-dose) during hypoxia reduced pulmonary vascular resistance and systemic vascular resistance by 19% and 25%, respectively, and returned the pressure-flow plot toward normal while blood flow in the left lower lobe increased to 122.6 +/- 21.0 mL/min. Consequently, PaO2 decreased from 270 +/- 31 to 144 +/- 32 torr (36.0 +/- 4.1 to 19.2 +/- 4.3 kPa). CONCLUSION: High-dose PGE1 essentially inhibits hypoxic pulmonary vasoconstriction, at the expense of a deterioration in pulmonary gas exchange and systemic blood pressure in dogs.

Isoflurane inhibits endothelium-mediated nitric oxide relaxing pathways in the isolated perfused rabbit lung.

PURPOSE: The role of volatile anaesthetics on nitric oxide (NO)-dependent relaxation is unclear in the pulmonary circulation. We examined the effects of isoflurane on NO-dependent relaxation in isolated perfused rabbit lungs. METHODS: Eighteen rabbit lungs were perfused in a constant-flow recirculation manner. In study 1 (n = 12), acetylcholine (ACh, 4 x 10(-10)-10(-8) M) or nitroglycerine (NTG, 6 x 10(-10)-10(-8) M) was cumulatively injected into the pulmonary artery in the absence or presence of isoflurane (1, 2 MAC). In study 2 (n = 6), ACh was injected as in study 1 in the presence or absence of N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), an NO synthesis blocker. In all experiments, indomethacin was administered to prevent formation of vasoactive prostanoid metabolites, and the pulmonary vessels were preconstricted with prostaglandin F2 alpha (PGF2 alpha) infused before ACh or NTG injection. The ACh- or NTG-induced relaxation was expressed as % decrease in PGF2 alpha preconstriction. RESULTS: Isoflurane at 2 MAC attenuated the dose-dependent relaxation to ACh at doses of 4 x 10(-9) M and 4 x 10(-8) M from 27.8 +/- 4.3% and 38.8 +/- 5.3% to 17.0 +/- 3.5% and 25.5 +/- 4.9%, respectively (P < 0.05). Isoflurane did not change the dose-dependent relaxation to NTG and L-NAME abolished the ACh-induced relaxation. CONCLUSION: Isoflurane inhibited NO-dependent relaxation in the pulmonary circulation at a site distal to the endothelial cell receptor-mediated responses but proximal to guanylate cyclase activation of vascular smooth muscle. Acetylcholine-induced relaxation in isolated perfused rabbit lungs was regulated primarily by NO.

[A case of crush syndrome resulting from continuous compression of the upper arm by automatically cycled blood pressure cuff].

We report a case of crush syndrome (rhabdomyolysis) resulting from the prolonged compression of the inadvertently inflated blood pressure cuff around her upper arm. A 61-yr-old woman had undergone total gastrectomy, splenectomy and cholecystectomy for gastric cancer. At the end of the surgery lasting for 5 hrs 40 mins, we found the right upper arm extremely swollen with cyanotic petechiae beyond the inflated cuff. Failure of deflation of the automatically cycled blood pressure cuff was strongly suspected as a cause. She complained numbness and ardor on her hand with motor nerve disturbance and plasma CPK level was elevated. Diuretics were given and fluids were infused vigorously to prevent the renal failure, and continuous cervical epidural block was instituted to increase the blood flow to the injured arm. Prostaglandin E1 and ulinastatin (a protease inhibitor) were also effective for recovery from the crush syndrome. One month later she was discharged home accompanied with a slight numbness on the arm. Attention should be paid to deflation of the automatically cycled blood pressure cuff during anesthesia.

The effect of thoracic epidural anesthesia on hypoxic pulmonary vasoconstriction in dogs: an analysis of the pressure-flow curve.

The aim of the present study was to examine whether hypoxic pulmonary vasoconstriction (HPV) is preserved during one-lung ventilation combined with thoracic epidural anesthesia (TEA) in dogs. Using a separately ventilated left lower lobe (LLL) in situ, the pressure-flow (P-Q) curve was obtained. The HPV response was assessed by the shift of the P-Q curve, changes in blood flow diversion rate (FDR) and decrease in PaO2 during hypoxic gas ventilation of LLL. In the control group (n = 7), the shift of P-Q curve, changes in FDR, and decrease in PaO2 remained constant during four consecutive hypoxic stimulations. In the TEA group (n = 6), the P-Q curve shifted to the left during hyperoxia, but the magnitude of the shift during hypoxia was unchanged. FDR and decrease in PaO2 were significantly reduced compared with baseline values (P < 0.05 with analysis of variance). TEA reduced heart rate, cardiac output, mean arterial pressure, mean pulmonary arterial pressure, and mixed venous oxygen tension. Our results suggest that TEA did not affect the primary pulmonary vascular tone at baseline or during lobar hypoxia, but enhanced the diversion of blood flow and arterial blood oxygenation during lobar hypoxia. This enhanced HPV response probably reflects hemodynamic changes, such as decreased cardiac tension, due to sympathetic nerve activity blockade by TEA.

[Effects of temperature and humidity on the stability of nitric oxide, and efficacy of soda lime as a selective absorber of nitrogen dioxide].

Although inhaled nitric oxide (NO) has attracted attention as a pulmonary vasodilator, little heed has been given to its potential toxicity. Nitric oxide is known to be rapidly oxidized to nitrogen dioxide (NO2), which may damage pulmonary tissue. We examined the effects of temperature and humidity on the production of NO2 from NO. We also evaluated the amount of NO2 absorbed by soda lime, which is usually placed in the inspiratory line. For this purpose, we measured changes over time in the concentrations of NO and NO2 in mixtures that included NO, oxygen, and nitrogen in various concentrations, and at different temperatures and humidities. We confirmed that the formation of NO2 from NO follows the equation: -d[NO]/dt = 2 k[NO]2 [O2], where k is the rate constant. We found that k was significantly smaller at 37 degrees C than at 25 degrees C but was not influenced by humidity (0%, 40% or 90%). Although soda lime was very effective in absorbing NO2 from the inspiratory line, NO was simultaneously absorbed at the same molar ratio when the two gases existed together in the line. We thus conclude that inhalation of NO at 37 degrees C is more desirable than inhalation at room temperature, to suppress the production of NO2. When soda lime is used in the inspiratory line, attention should be paid to the reduction in the concentration of NO in the line.

[Inhibition of pulmonary vasoconstriction by inhaled nitric oxide].

We examined effects of inhaled NO gas on pulmonary vasoconstriction induced with hypoxic gas or PGF2 alpha utilizing the isolated perfused rabbit lung. While NO 180 ppm did not change the basal pulmonary artery pressure, the pressure response to hypoxia or PGF2 alpha was completely inhibited by pretreatment with NO inhalation. Inhaled NO during maximal pressor response also depressed the elevated pressure to the basal level. These findings suggest that NO inhaled to the alveoli diffuses directly into the pulmonary vascular smooth muscle and then causes nonspecific vasodilation, and its effect is more potent than that of constitutive type of EDRF/NO.

Properties and kinetics of membrane-bound enzymes when both the enzyme and substrate are components of the same microsomal membrane. Studies on lathosterol 5-desaturase.

Microsomes isolated from rat liver contain an NADH-dependent lathosterol 5-desaturation system that catalyzes the introduction of a delta 5 bond into lathosterol to form 7-dehydrocholesterol. Microsomes were preloaded in vitro with liposomes composed of lathosterol and phosphatidylcholine in the presence of a high-speed supernatant (S105) protein prior to enzyme assay. The desaturation led to a reaction that occurred in two distinct phases. That is, there was an initial burst of product formation over an approximate time scale of 5 min that fell off, thereafter to a steady state rate for over 30 min. The latter steady state phase was slower than the burst phase, because lateral diffusion of the lathosterol substrate must occur before the next reaction can take place. The total amount of the burst, which may be obtained by extrapolating the linear part of the curve in the steady state phase back to zero time, provides a means of obtaining the enzyme concentration in terms of functional active sites. It was found that the kinetics between enzyme and substrate within the same membrane also followed the usual kinetic formalism of a Michaelis-Menten type reaction as in nonaggregated homogenous solution.