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Biomedical subjects

A Matsuki

Publications and source records attributed to A Matsuki.

At least 145 records · Page 8Linked to original sources
PubMed1998

ONO-5046, an elastase inhibitor, attenuates liver mitochondrial dysfunction after endotoxin.

OBJECTIVE: To investigate the effect of ONO-5046, an elastase inhibitor, on liver mitochondrial dysfunction after endotoxin administration. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male Hartley guinea pigs. INTERVENTIONS: Endotoxin shock was induced by intravenous infusion of Escherichia coli lipopolysaccharide endotoxin (50 mg/kg). Six guinea pigs were treated with endotoxin and saline. Twenty-four guinea pigs received 5, 10, and 30 mg/kg/hr of ONO-5046 after endotoxin administration. Six guinea pigs received only saline. MEASUREMENTS AND MAIN RESULTS: We measured oxygen uptake in state 3 (substrate and adenosine 5'-diphosphate [ADP]) and state 4 (excess substrate, no ADP), as well as the respiratory control ratio (state 3/state 4), adenosine 5'-diphosphate/oxygen ratio (ADP/O), and arterial ketone body ratio. ONO-5046 was dose dependently effective in liver mitochondrial oxidative phosphorylation, such as oxygen uptake in stage 4, respiratory control ratio, adenosine triphosphate synthesis, ADP/O, and arterial ketone body ratio when ONO-5046 was started 30 mins after endotoxin. The administration of 30 mg/kg/hr of ONO-5046 improved mean blood pressure, which had decreased after endotoxin. CONCLUSION: ONO-5046 attenuates the endotoxin-induced liver mitochondrial dysfunctions that may be related to increased liver blood flow.

Adenosine Diphosphate↗
PubMed1998

Ketamine inhibits the tonic response to carbachol and histamine in the guinea pig trachea.

The contractile response of smooth muscles to spasmogens can be divided into two components by modifying the extracellular Ca2+ concentration. The phasic component depends on the mobilization of Ca2+ from intracellular stores whereas the tonic component depends, to a large extent, on the influx of extracellular Ca2+. The present study was designed to investigate the effect of ketamine on the tonic response to carbachol or histamine in the guinea pig trachea. Tracheal spirals from female guinea pigs were mounted in organ baths filled with aerated physiological buffer, and their isometric tension was measured. The phasic response to 10(-7) M carbachol or 10(-5) M histamine in Ca(2+)-free, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing buffer and the tonic response to each spasmogen after restoring [Ca2+] in the buffer was measured in the absence or presence of ketamine. In the presence of normal physiological buffer, ketamine decreased the contractions induced by carbachol or histamine in a dose-dependent fashion. No measurable phasic response to either carbachol or histamine was obtained in our preparation. Ketamine (5 x 10(-5) M-10(-3) M) reduced the tonic response to 10(-7) M carbachol to 79.5 +/- 2.7-4.3 +/- 0.7% of the response without ketamine. Similarly, ketamine (5 x 10(-4) M-2 x 10(-3) M) decreased the tonic response to 10(-5) M histamine to 80.7 +/- 3.9-23.0 +/- 3.2% of the response in the absence of ketamine. Our findings support the hypothesis that ketamine inhibits the paracrine agent-induced contractions of smooth muscles by interfering with the influx of extracellular Ca2+ or with an intracellular event(s) requiring extracellular Ca2+.

Anesthetics, Dissociative↗
PubMed1998

In vivo spasmolytic effect of ketamine and adrenaline on histamine-induced airway constriction. Direct visualization method with a superfine fibreoptic bronchoscope.

BACKGROUND: Ketamine (K) has been reported to produce bronchodilation in patients suffering from asthma. Although most researchers have used indirect measurements to study the effect of K in vivo, the reliability of these indirect methods are controversial. We have developed a new technique to measure the bronchial cross-sectional area (BCA) in vivo with a superfine fibreoptic bronchoscope (SFB). Employing this method, we evaluated in vivo spasmolytic effect of K and adrenaline (A). METHODS: Twenty-one mongrel dogs were anaesthetized with pentobarbitone (30 mg.kg-1) and paralyzed with pancuronium (200 micrograms.kg-1.h-1). The trachea was intubated with an endotracheal tube that has a second lumen for insertion of a SFB (OD: 2.2 mm) to measure the BCA continuously. The tip of the SFB was placed between the 2nd and 3rd bronchial bifurcation of the right lung. A videoprinter printed the BCA, which was then measured with NIH Image. Bronchoconstriction was produced with histamine (H: 10 micrograms.kg-1 + 500 micrograms.kg-1.h-1) which was administered until the end of the experiment. The BCA was assessed before and 30 min after the start of H infusion. The dogs were randomly allocated to 3 groups of 7 dogs each. In group K, K (0-10 mg.kg-1) was given i.v., and the BCA was measured 5 min after each K dose. In group A, A (0-0.4 microgram.kg-1) was given i.v., and the BCA was measured 1 min after each A dose. In group A + K, K (1 mg.kg-1 i.v. + 1 mg.kg-1.h-1 i.v.) was given followed, 30 min after, by A i.v. in the same doses as in group A. The BCA was assessed 30 min after the start of K and again 1 min after each A dose. RESULTS: K 10 mg.kg-1 reversed H-induced bronchoconstriction. A subthreshold dose of K significantly potentiated the effect of A, reversing the decrease in BCA by H. CONCLUSION: We have found that K could reverse the H-induced bronchoconstriction and potentiate the A-induced bronchial relaxation.

Animals↗
PubMed1998

Inhibited hypothalamic histamine metabolism during isoflurane and sevoflurane anesthesia in rats.

BACKGROUND: Histamine is most densely distributed in the hypothalamus and has an important effect on consciousness or wakefulness. It has been little considered whether general anesthetics could exert their effects on hypothalamic histamine metabolism. The present study was conducted to investigate the effects of isoflurane and sevoflurane anesthesia on hypothalamic histamine metabolism. METHODS: Sixty male Wistar rats were divided equally into isoflurane and sevoflurane anesthesia groups. Each group was divided into three equal sub-groups: the control, anesthesia and recovery groups. The rats of the anesthesia and recovery groups were exposed to either 2% isoflurane or 3% sevoflurane for 30 min. The recovery group was kept in air for 30 min after anesthesia. The rats were decapitated to dissect out hypothalamus which was divided into the fore and rear portion. The contents of histamine and 1-methylhistamine, which is a main histamine metabolite, were determined by high-performance liquid chromatography. The obtained data were analyzed by one-way analysis of variance followed by Bonferoni's test. RESULTS: Histamine contents of the anterior and posterior hypothalamus in both isoflurane and sevoflurane groups increased significantly during the anesthesia and 1-methylhistamine contents of the anterior and posterior hypothalamus in sevoflurane group increased remarkably after anesthesia. The increases of histamine contents supposedly reflected inhibited histamine metabolism and the increases of 1-methylhistamine would be caused by acceleration of histamine degradation. CONCLUSIONS: Histamine metabolism was inhibited during both isoflurane and sevoflurane anesthesia and accelerated only in the posterior hypothalamus during the emergence from these anesthetics.

Analysis of Variance↗
PubMed1998

Increased plasma vasopressin and atrial natriuretic peptide in chronic schizophrenic patients during abdominal surgery.

Chronic schizophrenic patients are reported to develop imbalanced water homeostasis by the pathological secretion of vasopressin and aldosterone. We measured plasma vasopressin, aldosterone and atrial natriuretic peptide in schizophrenic patients to elucidate the role of these hormones during a perioperative period. Eighteen schizophrenic patients with chronic antipsychotic drugs over 10 years and 22 as a control group who underwent elective lower abdominal surgery were the subjects of this study. In the schizophrenic patients, plasma aldosterone secretion was significantly inhibited, while plasma vasopressin and atrial natriuretic peptide were significantly increased during surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial natriuretic peptide and plasma osmolality was obtained 60 min after skin incision, but not before the induction of anesthesia. The findings suggest that chronic schizophrenic patients may develop an abnormal secretion of vasopressin, aldosterone and atrial natriuretic peptide during anesthesia.

Adult↗
PubMed1998

[Perioperative management of a patient with cryoglobulinemia for open heart surgery].

A 57-year-old male with cryoglobulinemia underwent an aortic valve replacement for aortic regurgitation under total intravenous anesthesia with droperidol, fentanyl and ketamine in combination with mild hypothermic cardiopulmonary bypass (esophageal temperature = 34 degrees C). Preoperative steroid therapy with prednisolone of daily dose from 40 to 7.5 mg for six months and plasma exchange (3200 ml) on the day before the operation were performed to attenuate the degree of cryoglobulinemia. He showed an uneventful intraoperative course and there was no postoperative complication associated with cryoglobulinemia.

Anesthesia, Intravenous↗
PubMed1998

[Preanesthetic assessment of a patient with giant negative T waves on ECG following subarachnoid hemorrhage].

Giant negative T waves on ECG are associated with intracranial hemorrhage such as subarachnoid hemorrhage, ischemic heart disease such as subendocardial infarction, myocardial disease and others. They embarrass us in anesthetic management of urgent neurosurgical patients because of the requirement of making differential diagnosis among these diseases accompanying the ECG abnormality. An 80 year old woman undergoing radical clipping for cerebral artery aneurysm showed giant negative T waves on ECG. Although the ECG taken on admission to the hospital had been normal, huge giant negative T waves of 2 mV and QTc prolongation were detected on arrival in the operating room. Therefore, her cardiac function was evaluated by echocardiography to rule out subendocardial infarction. The echocardiogram revealed that wall motion of the left ventricle was mildly depressed, but her cardiac function was well maintained since the cardiac output was 4.1 l.min-1 and the ejection fraction was 59%. We thought that giant negative T waves were caused by subarachnoid hemorrhage and decided to perform anesthesia and surgery. Circulation during anesthesia and surgery was stable except a transient decrease in blood pressure due to massive hemorrhage during rupture of the aneurysm. We conclude that preanesthetic assessment of cardiac function by echocardiography is useful for anesthetic management of patients with giant negative T waves on ECG undergoing urgent radical operation for cerebral aneurysm.

Aged↗
PubMed1998

[Pharmacokinetics of propofol and ketamine during and after total intravenous anesthesia with propofol, fentanyl and ketamine for pediatric patients].

Pharmacokinetics of propofol and ketamine during propofol-fentanyl-ketamine (PFK) anesthesia for pediatric surgery was studied. Plasma levels of propofol (Pp) were maintained approximately at 2.5 micrograms.ml-1 during surgery. Fifteen minutes after the cessation of propofol infusion, Pp decreased to 1.5 micrograms.ml-1. Plasma levels of ketamine (Pk) were maintained at 150-200 ng.ml-1 during the surgery. After the cessation of ketamine infusion, Pk decreased as quickly as Pp. Pk values at 15 minutes and 120 minutes after the cessation of the infusion were 93 ng.ml-1, 24 ng.ml-1, respectively. On the other hand, plasma norketamine (Pn) levels increased gradually during surgery and stayed at 100-150 ng.ml-1 after the end of ketamine infusion to play an important role in post-operative sedation and pain relief. In conclusion, pharmacokinetics of propofol and ketamine in pediatric patients was similar to that in adult patients. PFK anesthesia can be used safely for pediatric as well as for adult patients.

Anesthesia, Intravenous↗
PubMed1998

[Clinical indication of propofol for pediatric patients--pharmacokinetics of propofol and ketamine during and after total intravenous anesthesia with propofol, fentanyl and ketamine (PFK) in a neonate].

A 60-day-old neonate boy received hepatic portojejunostomy for biliary atresia under PFK. Pharmacokinetics of propofol and ketamine during and after PFK was also studied. Plasma levels of propofol (Cp) and ketamine (Ck) were maintained at 2 to 3 micrograms ml-1 and at 200 to 300 ng ml-1 during surgery, respectively. Both Cp and Ck decreased quickly after the end of infusions. From the pharmacokinetic point of view, PFK may be safely applied even for neonates.

Anesthesia, Intravenous↗
PubMed1998

[Two cases of circulatory failure after local infiltration of epinephrine during tonsillectomy].

We experienced two cases of circulatory failure after local infiltration of 0.0005% epinephrine solution for the purpose of prophylactic hemostasis during tonsillectomy under sevoflurane anesthesia. Case 1: A 14 year-old girl developed ventricular bigeminy, tachycardia and hypertension following infiltration of the epinephrine solution 6ml around the tonsil. Sinus rhythm returned with intravenous lidocaine 40 mg and propranolol 0.4 mg. However, the patient showed gradually decreasing heart rate, depressed ST segments and inverted T waves and poor peripheral circulation. Her blood pressure decreased abruptly at the same time and finally the pulsation of the radial and femoral arteries was not palpable. She was treated with intravenous ephedrine in vain. Therefore, she received intravenous epinephrine and cardiac massage, and then recovered from the circulatory failure with her ECG showing normal sinus rhythms. Emergence from the anesthesia was smooth. Her cardiac failure may have been caused by the decreasing cardiac contraction and the increasing afterload due to the vasoconstriction after the intravenous beta-blocker. Case 2: An eleven year-old boy showed ventricular tachycardia and hypertension after infiltration of the epinephrine solution 11.5 ml around the tonsil. Lidocaine was given intravenously. This restored sinus rhythm but the ST segments on his ECG were elevated. ST segments became normalized after intravenous nitroglycerin. However, pulmonary edema developed suddenly, and it was cured by intensive treatment. His ventricular tachycardia and hypertension after the local administration of epinephrine were presumably responsible for the acute heart failure causing the pulmonary edema. Our experience suggests that the maintenance of cardiac function and the reduction of afterload are important to overcome the circulatory disaster following the local infiltration of epinephrine.

Adolescent↗
PubMed1998

[Electroconvulsive therapy decreased bispectral index--a case report].

A 28-year old female schizophrenic patient underwent electroconvulsive therapy (ECT) under propofol anesthesia. She received ECT five times, and Bispectral Index (BIS) was recorded four times out of the five ECT. BIS values (mean +/- SD) were 95.3 +/- 1.3 before anesthesia, 38.0 +/- 13.1 after loss of consciousness, 45.3 +/- 12.7 immediately after ECT and 27.3 +/- 11.6 about two minutes after ECT. In conclusion, ECT may decrease BIS during continuous propofol infusion.

Adult↗
PubMed1998

[Effect of propofol as an agent for anesthetic induction on pituitary-adrenocortical function during anesthesia and surgery].

Effect of propofol as an agent for anesthetic induction on plasma levels of cortisol, beta-endorphin-like immunoreactivity (beta-ELI), growth hormone (GH) and prolactin were evaluated in 20 non-abdominal surgical patients ranged in ages from 19 to 64 years. Anesthesia was induced with either intravenous propofol 2-2.5 mg in ten patients or intravenous thiopental 4-5 mg in the remaining 10 patients as the control group, and succinylcholine was administered intravenously to facilitate tracheal intubation. Enflurane-nitrous oxide-oxygen was then given to maintain anesthesia in all the patients of both groups. Plasma cortisol levels decreased slightly with anesthesia in the propofol group, but they increased slightly after anesthetic induction in the control group. Therefore they were significantly lower in the propofol group than those in the control group. They tended to increase gradually during surgery and reached the peak value after the emergence from anesthesia in both groups. Plasma beta-ELI levels were unchanged with anesthesia alone in the patients of both groups. They tended to increase gradually during surgery and reached the peak value after the emergence from anesthesia in both groups. Plasma GH levels were not affected with anesthesia, but they increased slightly during surgery in both groups. Plasma prolactin levels increased significantly during anesthesia and surgery in both groups, and they decreased after the emergence from anesthesia but were still significantly higher than the preanesthetic values in both groups. The authors' findings suggest that effects of propofol as an agent for anesthetic induction on pituitary-adrenocortical function during anesthesia and surgery are comparable to those of thiopental, and that propofol does not exert inhibitory effect on pituitary-adrenocortical function during anesthesia and surgery.

Adult↗
PubMed1997

Midazolam reverses histamine-induced bronchoconstriction in dogs.

PURPOSE: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. METHODS: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. RESULTS: Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. CONCLUSION: Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.

Anesthetics, Intravenous↗
PubMed1997

Uneventful total intravenous anaesthesia with ketamine for schizophrenic surgical patients.

Ketamine has been considered to be contraindicated for schizophrenic patients because it may induce psychological emergence reactions and psychiatric deterioration. Total intravenous anaesthesia (TIVA) with ketamine combined with droperidol and fentanyl (DFK) has been used in 14 schizophrenic patients undergoing various surgical procedures. Two patients died post-operatively of concomitant severe disease rather than from schizophrenia related pathophysiology or anaesthetic complication. One patient showed transient mild anxiety in the early post-operative period soon relieved by the patient's routine medication. However, no patient developed exacerbations of psychosis or psychological emergence reactions during the first post-operative month. The cardiovascular state during and after DFK remained stable in all cases. It is concluded that ketamine when combined with droperidol and fentanyl is a satisfactory anaesthetic for patients with schizophrenia.

Adjuvants, Anesthesia↗
PubMed1997

Increase in serum creatine phosphokinase concentrations after suxamethonium during sevoflurane or isoflurane anaesthesia in children.

We have studied whether sevoflurane or isoflurane anaesthesia modulates the effect of suxamethonium on serum concentrations of enzyme markers of skeletal muscle function in paediatric patients. Eighty patients undergoing bilateral tonsillectomy, aged 5-12 yr, were allocated randomly to receive anaesthesia with either sevoflurane and nitrous oxide or isoflurane and nitrous oxide. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) concentrations were measured before, and at 30 min and 20 h after induction of anaesthesia. Mean CK concentrations increased from 97.0 (SD 17.3) to 478 (170) iu litre-1 in the sevoflurane group and from 86.9 (22.4) to 628 (223) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum CK concentration in the sevoflurane group (478 (170) iu litre-1) was significantly less (P < 0.05) than that in the isoflurane group (628 (223) iu litre-1). Mean serum AST concentration increased from 17.5 (4.9) to 31.7 (3.5) iu litre-1 in the sevoflurane group and from 17.3 (2.4) to 34.8 (5.7) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum AST concentrations in the sevoflurane group were significantly lower (P < 0.05) than those in the isoflurane group. There were no significant differences in serum ALT or LDH concentrations between the groups either before or after anaesthesia. We conclude that administration of suxamethonium during either sevoflurane or isoflurane anaesthesia caused a marked increase in serum CK concentrations in paediatric patients. The clinical significance of this finding is uncertain.

Anesthetics, Inhalation↗
PubMed1997

Measurement of bronchodilatation using a superfine fibreoptic bronchoscope.

In this study, we report the development and accuracy of a direct technique to measure airway calibre using a superfine fibreoptic bronchoscope. Ten mongrel dogs were anaesthetized with pentobarbitone and the trachea intubated with a tracheal tube; the small lumen of the tube allowed passage of a superfine fibreoptic bronchoscope (od 2.2 mm). Bronchial cross-sectional area and airway pressure were recorded continuously and dynamic pulmonary compliance and airway resistance calculated. The dogs were allocated to one of two groups. In the first group (six dogs), bronchoconstriction was induced with histamine 10 micrograms kg-1 i.v. and 500 micrograms kg-1 h-1 c.i.v. Thirty minutes later, adrenaline 0-0.4 mg kg-1 was given i.v. Bronchial cross-sectional area, dynamic pulmonary compliance and airway resistance were assessed simultaneously. In the second group, 0.9% saline was given 30 min after placement of the superfine fibreoptic bronchoscope and 10 min later atropine 0.1 microgram kg-1 was administered. In the first group, histamine decreased mean percentage bronchial cross-sectional area by 49.2 (SD 11.5) %, reduced dynamic pulmonary compliance from 32.1 (12.6) to 22.3 (5.2) ml cm H2O-1 and increased airway resistance from 39.1 (11.6) to 57.2 (10.2) cm H2O litre-1 s-1. Adrenaline produced a dose-dependent increase in percentage bronchial cross-sectional area and dynamic pulmonary compliance to 119.4 (31.3)% and 27.4 (5.5) ml cm H2O-1, respectively, and a decrease in airway resistance to 43.9 (7.2) cm H2O litre-1 s-1. There were significant correlations between percentage bronchial cross-sectional area and dynamic pulmonary compliance (r = 0.720, P < 0.0001) and airway resistance (r = 0.727, P < 0.0001). Atropine 0.1 mg kg-1 increased basal bronchial cross-sectional area to 137.5 (16.9) %. These data indicate that adrenaline reversed histamine- and pentobarbitone-induced bronchoconstriction.

Airway Resistance↗
PubMed1997

The relaxant effect of ketamine on guinea pig airway smooth muscle is epithelium-independent.

Airway epithelial cells and vascular endothelial cells modulate the tone of the underlying smooth muscle by releasing relaxing factors such as prostanoids and nitric oxide (NO). In the present study, we investigated whether the relaxant effect of ketamine depends on any of the epithelium-derived relaxing factors. Tracheae of female guinea pigs were cut spirally into strips (15 x 3 mm) and mounted in water-jacketed organ baths filled with Krebs-bicarbonate buffer aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. Changes in the tension of the strips were measured isometrically with a force displacement transducer and recorded with a polygraph. In the first set of experiments, we examined the effect of ketamine on the concentration-response curves for histamine and carbachol in strips in which the epithelium was kept intact and in strips with denuded epithelium. In the second and third set of experiments, we studied the effect of indomethacin, a cyclooxygenase inhibitor, and N-omega-nitro-L-arginine methylester(L-NAME), a NO synthase inhibitor, on the relaxant activity of ketamine on tracheal strips contracted by histamine or carbachol. The following results were obtained: 1. Mechanical denudation of the tracheal epithelium shifted the concentration-response curve for histamine to the left (the 50% effective concentration [EC50] value of histamine decreased from 3.5 +/- 0.02 x 10(-6) M in the intact strips to 0.98 +/- 0.01 x 10(-6) M in denuded strips, P < 0.001). However, removal of the tracheal epithelium did not change the response to carbachol (the EC50 for carbachol was 1.1 +/- 0.02 x 10(-7) M in intact strips versus 0.88 +/- 0.01 x 10(-7) M after epithelial removal, P > 0.05). 2. Ketamine shifted to the right the concentration-response curves for histamine and carbachol in both intact and denuded tracheae. 3. Indomethacin did not alter the relaxant effect of ketamine on the tracheae contracted by either histamine (the concentration that inhibits 50% [IC50] of ketamine = 1.5 +/- 0.01 x 10(-3) M in control strips and 1.3 +/- 0.04 x 10(-3) M in strips pretreated with indomethacin, P > 0.05) or carbachol (the IC50 of ketamine was 2.5 +/- 0.02 x 10(-4) M in control strips and 2.4 +/- 0.01 x 10(-4) M in strips pretreated with indomethacin, P > 0.05). 4. L-NAME did not influence the relaxant effect of ketamine on tracheae contracted by either histamine (the IC50 of ketamine = 1.6 +/- 0.05 x 10(-3) M in control strips and 1.6 +/- 0.05 x 10(-3) M in strips pretreated with L-NAME, P > 0.05) or carbachol (the IC50 of ketamine = 2.6 +/- 0.04 x 10(-4) M in control strips and 2.3 +/- 0.01 x 10(-4) M in trips pretreated with L-NAME, P > 0.05). These results indicate that neither the mechanical removal of the tracheal epithelium nor the blockade of the release of potent mediators from tracheal epithelial cells influence the relaxant effect of ketamine on guinea pig tracheal strips contracted by histamine or carbachol. We conclude that ketamine relaxes the airway smooth muscle by an epithelium-independent mechanism.

Airway Resistance↗