Akitoshi Ohara

A comparative study of the antinociceptive action of xenon and nitrous oxide in rats

We attempted to clarify the mechanism of antinociceptive action induced by xenon and nitrous oxide.Eighty percent of nitrous oxide or 80% xenon was applied to rats inside enclosed clear plastic glass cylinders with their tails protruding for assessment of the tail-flick response to radiant heat. With repeated testing, there was a rapid reduction to nitrous oxide antinociception within 90 min, which was interpreted as development of tolerance, but not to xenon antinociception. Nitrous oxide antinociception was blocked by the intraperitoneal administration of 0.1 or 1.0 mg/kg yohimbine, but not by 1.0 or 5.0 mg/kg L659-066 or by 5.0 or 10 mg/kg naloxone. Xenon antinociception was not affected by any of these drugs. Yohimbine and L659-066 are characterized as alpha2-adrenoceptor antagonists. Although yohimbine penetrates the blood-brain barrier after systemic administration, L659-066 does not penetrate it and act peripherally. Therefore, the results indicate that alpha2-adrenoceptors, but not opioid receptors, may play a key role in antinociception induced by nitrous oxide in the central nervous system. Furthermore, the mechanism of xenon antinociception differs from that of nitrous oxide because it does not involve either alpha2 or opioid receptors. Implications: The precise mechanism of antinociceptive action of nitrous oxide and xenon remains unknown. It is still controversial whether an opioid system plays a role in antinociception induced by nitrous oxide. The results of the study showed that antagonism of central alpha2-adrenoceptors, but not opioid receptors, reverses the antinociception induced by nitrous oxide but not by xenon, which indicates that alpha2-adrenoceptors may play a key role in nitrous oxide antinociception. (Anesth Analg 1997;85:931-6)

Intracerebroventricular administration of a nitric oxide-releasing compound, NOC-18, produces thermal hyperalgesia in rats

This study was undertaken to define the role of nitric oxide (NO) in central nociceptive mechanisms by intracerebroventricular injection of an NO-releasing compound, NOC-18, in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. Sixty-nine rats were divided into the seven groups, and the following drugs were injected intracerebroventricularly in 5 microliters of saline: no drug (control) (n = 13), 15 micrograms of NOC-18 (n = 15); 150 micrograms of NOC-18 (n = 9); 100 micrograms of N-nitro-L-arginine methyl ester (L-NAME) (n = 8); 15 micrograms of NOC-18 + 100 micrograms of L-NAME (n = 8); 10 micrograms of methylene blue (MB) (n = 8); 15 micrograms of NOC-18 + 10 micrograms of MB (n = 8). NOC-18 caused a dose-dependent curtailment (7% and 23% decreases for 15 micrograms and 150 micrograms of NOC-18, respectively) of the tail-flick latency during the period from 15 to 120 min. L-NAME caused prolongation (15% maximum) of the tail-flick latency during the period from 15 to 150 min. However, NOC-18-induced hyperalgesia was not influenced by L-NAME. MB also caused prolongation (9% maximum) of the tail-flick latency during the period from 15 to 150 min, and completely blocked the hyperalgesia induced by 15 micrograms of NOC-18. These findings indicate that the NO-cGMP pathway is directly involved in thermal hyperalgesia in the brain.

Pulmonary resistance in dogs: a comparison of xenon with nitrous oxide

Xenon (Xe) may cause an increase in airway resistance due to its high density and viscosity. The object of this study was to examine the effects of Xe on pulmonary resistance using dog models with normal and methacholine-treated airways. During anaesthesia 22 mongrel dogs’ tracheas were intubated and the lungs were mechanically ventilated with 70% N2/30% O2 as a control gas. The gases 70% nitrous oxide (N2O), 50% N2O, 70% Xe and 50% Xe were administered in a random order for 25 min. Bronchoconstriction was produced by a continuous infusion of methacholine, 0.22 mg · kg−1 · hr−1. Pulmonary resistance (Rl) was calculated by the isovolume method using flow at the airway opening, volume and transpulmonary pressure. In normal dogs,Rl breathing 70% Xe (mean ± SEM, 0.84 ± 0.12 cm H2O · L−1 · sec−1) was greater (P < 0.05) than with 70% N2O, 50% N2O or control gas (0.61 ± 0.08, 0.59 ± 0.06 and 0.62 ± 0.06 cm H2O · L−1 sec−1). Breathing 50% Xe theRL (0.77 ± 0.10 cm H2O · L−1 · sec−1) was not different from 50% N2O or control. Methacholine infusion increasedRL 3.92 ± 1.98 (mean ± SD) times. TheRL breathing 50% Xe (2.55 ± 0.44 cm H2O · L−1 · sec−1) was not greater than during 50% N2O or control (2.08 ± 0.33 and 2.13 ± 0.33 cm H2O · L−1 · sec−1) in methacholine-treated dogs. The data suggest that inhalation of high concentrations of Xe increases airway resistance, but only to a modest extent in dogs with normal or methacholine-treated airways.RésuméA cause de sa densité et de sa viscosité élevées, le Xénon (Xe) peut augmenter la résistance des voies aériennes. Le but de ce travail consiste à étudier les effets du Xe sur la résistance pulmonaire de chiens aux voies aériennes normales ou traitées à la méthacholine. Pendant l’anesthésie, la trachée de 22 chiens batards est intubée et les chiens sont ventilés mécaniquement avec le gaz contrôle (70% N2/30% O2). Du protoxyde d’azote (N2O) 70%, 50% N2O, 70% Xe et 50% Xe sont administrés aléatoirement pour 25 min. La bronchoconstriction est produite par une perfusion continue de méthacholine, 0,22 mg · kg−1 · hr−1. La résistance pulmonaire (Rl) est calculée selon la méthode de lïsovolume avec la mesure du débit à l’entrée des voies aériennes, du volume et de la pression transpulmonaire. Chez les chiens normaux, laRl sous 70% Xe (moyenne ± SEM, 0,84 ± 0,12 cm H2O · L−1 · sec−1) est plus élevée (P < 0,05) qu’avec 70% N2O, 50% N2O et qu’avec le gaz contrôle (0,61 ± 0,08, 0,59 ± 0,06 et 0,62 ± 0,06 cm H2O · L−1 · sec−1). Sous 50% Xe, laRl (0,77 ± 0,10 cm H2O · L−1 · sec−1) ne diffère pas du 50% N2O ou du contrôle. La perfusion de méthacholine augmente laRl 3,92 ± 1,98 (moyenne ± SD) fois. Sous 50% Xe, laRl (2,55 ± 0,44 cmH2O · L−1 · sec−1) n’est pas plus élevée que sous 50% N2O ou que sous le gaz contrôle (2,08 ± 0,33 et 2,13 ± 0,33 cmH2O · L−1 · sec−1) chez les chiens traités à la méthacholine. Ces données suggèrent que l’inhalation de hautes concentrations de Xe augmente la résistance des voies aériennes, mais modérément seulement, chez les chiens aux des voies aériennes normales ou traitées à la méthacholine.

Cardiovascular Effects of an Ultra–Short-Acting Nitric Oxide–Releasing Compound, Zwitterionic Diamine/NO Adduct, in Dogs

BACKGROUND This study was conducted to clarify the cardiovascular effects of a new NO-releasing compound, NOC-7, and to compare it with other nitrovasodilators, sodium nitroprusside (SNP) and nitroglycerin, in dogs anesthetized with pentobarbital. METHODS AND RESULTS A bolus injection of NOC-7 decreased mean aortic blood pressure in a dose-dependent manner. The onset was rapid and the recovery quick. Continuous infusion of NOC-7 decreased mean aortic pressure from 115 +/- 3.9 to 84 +/- 2.9 mm Hg and infusion of SNP, from 118 +/- 3.8 to 87 +/- 3.1 mm Hg. The optimum doses of NOC-7 and SNP were determined to be 2.73 +/- 0.77 and 11.5 +/- 6.1 micrograms.kg-1.min-1, respectively. During infusion of NOC-7, heart rate and cardiac output were increased (P < .05), pulmonary artery pressure was not changed, and systemic and pulmonary vascular resistances were decreased (P < .05). Electromagnetic flowmetry showed that portal venous and internal carotid arterial blood flow were increased (P < .05) and that hepatic and renal arterial blood flows were not changed. These hemodynamic changes during NOC-7 infusion were similar to those with SNP. The plasma level of NO2-/NO3 did not change, but methemoglobin increased slightly (P < .05). Comparison between hypotensive responses before and after a 3.5-hour infusion of NOC-7 or nitroglycerin showed that acute tolerance developed to nitroglycerin but not to NOC-7. CONCLUSIONS The results indicate that NOC-7 may be useful as an ultra-short-acting nitrovasodilator that has no major adverse effect or tolerance.

A new nitric oxide donor, NOC-18, exhibits a nociceptive effect in the rat formalin model

The utility of a new nitric oxide (NO) donor, NOC-18, and the contribution of the neurotransmitter NO to nociception in response to tissue injury in rats, were examined following the subcutaneous injection of formalin into the hindpaw. This model induces biphasic responses in pain-related behavior, such that C-fiber activation during the first phase triggers a state of central sensitization characterized by the second phase. Formalin-induced nociceptive behavior was facilitated by intracerebroventricular administration of NOC-18 in the second phase, but not the first phase. This enhancement was completely abolished by the soluble guanylate cyclase inhibitor, methylene blue. These findings indicate that NO causes nociception via the NO-cGMP pathway in the central nervous system and NOC-18 proved to be a convenient and useful tool for the investigation of nociception-related NO.

Laser Doppler skin blood flow and sympathetic nervous responses to surgical incision during halothane and isoflurane anesthesia

The aim of the present study was to evaluate whether a sudden decrease in skin blood flow measured using a laser Doppler velocimeter reflects sympathetic nervous response to surgical skin incision during halothane (n = 17) and isoflurane (n = 16) anesthesia in 33 ASA physical status I or II patients scheduled for laparotomy.Plasma norepinephrine concentrations in the responding patients who showed a sudden decrease in the skin blood flow after surgical incision increased significantly and continued to increase 1-10 min after skin incision under halothane and isoflurane anesthesia. Although plasma norepinephrine concentrations in the nonresponders did not increase after surgical incision with halothane, the concentrations increased significantly at 1 min, but not at 3 and 10 min, after skin incision with isoflurane. The results indicate that the sudden decrease in laser Doppler flow reflects the sympathetic response to surgical incision. However, these also suggest that the factors that control the skin blood flow may not be simply sympathetic but may reflect other modulators as well. Plasma epinephrine concentration increased during skin incision, but the concentrations did not differ between the patients with and without a sudden decrease in skin blood flow. Increases in systolic blood pressure and rate-pressure product on skin incision were also significantly more in patients with skin blood flow response compared with those without the response. The magnitude of changes in plasma norepinephrine concentration and hemodynamic variables with skin incision was greater with isoflurane than with halothane at the same minimum alveolar anesthetic concentration level. (Anesth Analg 1997;85:291-8)

Percutaneous coronary intervention of a single coronary artery arising from the right sinus of Valsalva

We describe a 67-year-old woman who presented with acute lateral myocardial infarction. Coronary angiography demonstrated a single coronary artery along with the left anterior descending and left circumflex arteries that originated from proximal branches of the right coronary artery, which arose from a normal ostium in the right sinus of Valsalva. Percutaneous coronary intervention (PCI) was performed to treat 99% stenosis with a filling defect in the midportion of the left circumflex artery. This extremely rare coronary anomaly was successfully treated by PCI.