Nobukata Urabe

Sevoflurane inhibits human platelet aggregation and thromboxane A2 formation, possibly by suppression of cyclooxygenase activity

Background Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G sub 2, and a TXA2 agonist ([+]-9,11-epithia-11,12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [sup 3 Hydrogen]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[sup 3 Hydrogen] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [sup 3 H]S145). Results Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 micro Meter) and epinephrine (1-10 micro Meter) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [sup 3 H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. Conclusions The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

Naloxone does not Antagonize the Anesthetic‐Induced Depression of Nociceptor‐Driven Spinal Cord Response in Spinal Cats

The effects of several anesthetics on spinal cord nociceptive neural mechanisms and their interactions with the opiate antagonist, naloxone, were studied in acute, spinal cord transected cats. Intra‐arterial injection of bradykinin was used as the noxious test stimulus. Spontaneous activity and the neural response induced by bradykinin were recorded by the multi‐unit activity technique in the lateral funiculus of the spinal cord. Naloxone, 0.1 or 2.0 mg/kg i.v., had little effect on the bradykinin‐induced response, but enhanced the spontaneous firing of the lateral funiculus significantly. Fentanyl, 30 μg/kg i.v., depressed both the bradykinin‐induced response and spontaneous firing. These effects of fentanyl were antagonized completely by naloxone, 0.1 mg/kg i.v. Nitrous oxide, thiamylal, halothane and ether depressed the bradykinin‐induced response considerably, but it was not antagonized by naloxone, 0.1–2.0 mg/kg i.v. Enflurane had little effect on the bradykinin‐induced response. The effects of these anesthetics on spontaneous firing were divergent: nitrous oxide enhanced it while other drugs depressed it, to various degrees. All these data suggest that the neural and/or neurochemical mechanisms of anesthetic‐induced analgesia differ from mechanisms related to opioids.

Nitrous Oxide Activates the Supraspinal Pain Inhibition System

The neurophysiological mechanism of nitrous oxide‐induced analgesia was studied in decerebrate non‐anesthetized cats. Intra‐arterial injection of bradykinin was used as the test noxious stimulus and the neural response in the lateral funiculus of the spinal cord was measured by the multi‐unit recording technique. The effects of nitrous oxide on the neural activity of spinal cord were compared before and after the spinal cord transection. Nitrous oxide activated the spontaneous firing level, but depressed the bradykinin‐induced response. These effects were more significant before the cord transection than after it. These findings indicate that nitrous oxide exerts its analgesic action through both the direct intraspinal anti‐nociceptive action and an indirect action by activating the supraspinal descending inhibition system.

Postoperative Pain Relief and Respiratory Function in ManComparison Between Intermittent Intravenous Injections of Meperidine and Continuous Lumbar Epidural Analgesia

The effect of postoperative pain relief on cardiopulmonary function was examined quantitatively in 36 patients who underwent upper abdominal surgery. Postoperative pain relief was obtained by intravenous meperidine or by mepivacaine epidurally. Expiratory volumes increased during analgesia, despite decreases in respiratory rate and minute volume, especially in the epidural group. The reduction of respiratory rate and minute volume did not result in respiratory acidosis. A reduction of 7 or 8 per cent in oxygen consumption was observed in both groups during analgesia without significant changes in metabolic factors. Differences between decreased &OV0422;s/&OV0422;T in the epidural group and increased &OV0422;s/&OV0422;Tin the meperidine group were statistically significant, After the establishment of analgesia, arterial oxygen tensoin increased in the epidural group and decreased in the meperidine group. The implications of these findings for the problems of postoperative pain relief are discussed.

Platelet aggregation is impaired during anaesthesia with sevoflurane but not with isoflurane

PurposeHalothane suppresses platelet aggregationin vitro and ex vivo, and prolongs bleeding time. In a previous invitro study we demonstrated that sevoflurane had a more suppressive effect on platelet aggregation than did halothane. The present study investigated whether the clinical use of sevoflurane affected platelet aggregationex vivo.MethodsThirty-eight patients undergoing minor elective surgery were divided randomly into sevoflurane and isoflurane groups. Anaesthesia was induced with thiopentoneiv, and was maintained with sevoflurane or isoflurane with nitrous oxide. Blood was collected to measure platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine. The first (control) blood collection was performed in the operating room before induction of anaesthesia, and the second 5–10 min after tracheal intubation but before the start of surgery, when the end-expiratory sevoflurane or isoflurane concentrations had stabilised at 1–1.5 times the minimum alveolar concentration (MAC) and mean artenal pressures were between 80–120% of preanaesthetic values.ResultsIn all samples obtained dunng sevoflurane anaesthesia (n= 15), ADP and epinephnne could not induce secondary aggregation, although they did induce pnmary aggregation. In contrast, in the isoflurane group, both primary and secondary aggregation were observed in 14 out of 15 patients, and secondary aggregation was abolished in only one of the samples obtained dunng anaesthesia.ConclusionSevoflurane, but not isoflurane, alters platelet aggregation in the clinical situation, possibly by suppression of thromboxane A2 formation.RésuméObjectifL’halothane inhibe l’agrégation plaquettairein vitro etin vivo et prolonge le temps de saignement. Nous avons anténeurement démontré que le sévoflurane avait un effet inhibiteurin vitro plus important sur l’agrégation plaquettaire que l’halothane. La présente étude a pour but de vérifier si l’usage clinique du sévoflurane affecte l’agrégation plaquettairein vivo.MéthodesTrente-huit patients soumis à une chirurgie élective mineure répartis au hasard en groupe sévoflurane et groupe isoflurane participaient à l’étude. L’anesthésie était induite au thiopentaliv, et entretenue au sévoflurane ou à l’isoflurane avec du protoxyde d’azote. Du sang était recueilli pour la mesure de l’agrégation plaquettaire induite par le diphosphate d’adénosine (ADP) et l’épinéphnne. Le premier échantillon sanguin (contrôle) était recueilli en salle d’opération avant l’induction de l’anesthésie et le second, 5–10 min après l’intubation trachéale et avant le début de l’intervention après stabilisation des concentrations télé-expiratoires de sévoflurane et d’isoflurane à 1–1,5 fois la concentration alvéolaire minimale (MAC) de même que de la pression arténelle moyenne à 80–120% des valeurs préanesthésiques.RésultatsMalgré une agrégation primaire, l’ADP et l’épinéphnne n’ont induit l’agrégation secondaire dans aucun des échantillons recueillis sous anesthésie au sévoflurane (n = 15). Par contre, on a observé dans le groupe isoflurane une aggrégation tant primaire que secondaire chez 14 des 15 patients, l’agrégation secondaire n’ayant été abolie que chez un seul des patients.ConclusionEn clinique, le sévoflurane contrairement à l’isoflurane altère l’agrégation plaquettaire possiblement par suppression de la formation de thromboxane A2.

Propofol has both enhancing and suppressing effects on human platelet aggregation in vitro.

BACKGROUND Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects. METHODS Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G2 (PGG2), or STA2 (a thromboxane A2 [TXA2] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG2-induced TXA2 formation was measured using a commercially available radioimmunoassay kit. To estimate TXA2 receptor-binding affinity, 3H-S145, a specific TXA2 receptor antagonist, was added, and the radioactivity of receptor-bound 3H-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA2-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit. RESULTS Propofol (40 microM) enhanced, whereas 100 microM suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 microM) also enhanced, but 100 microM suppressed, AA-induced aggregation. Propofol (100 microM) enhanced PGG2- and STA2-induced aggregation. Propofol (100 microM) suppressed AA-induced TXA2 formation but did not alter that induced by PGG2. Propofol (30-100 microM) suppressed AA-induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA2 receptor-binding affinity. Propofol (30 and 100 microM) augmented inositol 1,4,5-triphosphate formation in STA2-stimulated platelets. CONCLUSIONS The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG2. Furthermore, propofol also enhanced STA2-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.

Activation of the Supraspinal Pain Inhibition System by Ketamine Hydrochloride

The neurophysiologic mechanism of ketamine‐induced analgesia was studied in cats under conditions of electrolytic decerebration or pentobarbital anesthesia. Injection of bradykinin into the femoral artery served as the noxious stimulus and the neural response in the lateral funiculus of the spinal cord was recorded by the multi‐unit activity technique. Ketamine depressed the bradykinin‐induced response more markedly in decerebrate, non‐anesthetized cats than in pentobarbital‐anesthetized cats. The depressant action disappeared following cervical cord transection at C1, in both decerebrate non‐anesthetized and pentobarbital‐anesthetized cats. Thus, the analgesic action of ketamine is probably exerted mainly through activation of the supraspinal pain inhibition system and a direct action on the spinal cord nociceptive neural mechanism, if any, is slight. The excitatory action of ketamine on the supraspinal pain inhibition system is susceptible to the depressant action of pentobarbital.

Pentobarbital-Anesthetized and Decerebrate Cats Reveal Different Neurophysiological Responses in Anesthetic-Induced Analgesia

Cats were used to assess the significance of differences in animal preparations in the study of anesthetic‐induced analgesia. Comparison was made between pentobarbital‐anesthetized and decerebrate non‐anesthetized cats. Bradykinin dissolved in normal saline was injected into the femoral artery as a noxious stimulus, and the neural response in the spinal cord lateral funiculus was recorded using the multi‐unit activity technique. The magnitude of the neural response and the changes in spontaneous firing were compared before and after cervical cord transection at C1. Before the transection, the response was greater in anesthetized than in decerebrate cats. The cord transection potentiated the response in both preparations, but the degree of potentiation was greater in decerebrate than in anesthetized cats.

Antianalgesic Action of Thiamylal Sodium in Cats

The effects of thiamylal on the nociceptor‐driven neural activity in the spinal cord were studied in decerebrate, non‐anesthetized cats. Noxious stimulation was induced by the injection of bradykinin into the femoral artery and the neural response in the lateral funiculus was measured by the multi‐unit activity technique. The effects of thiamylal on the bradykinin‐induced response were compared before and after the spinal cord transection, above the recording site. Thiamylal, 5 mg/kg i.v., potentiated the response significantly before the cord transection and depressed it after the transection. These findings indicate that the antianalgesic action of thiamylal is induced at the spinal cord level: although this anesthetic agent does have a direct intraspinal depressant action, the multisynaptic neural network of the supraspinal pain inhibition system is more susceptible to the actions of anesthetics, and the depression of this descending system by thiamylal results in a release of spinal cord nociceptive neural mechanisms from the supraspinal control.

Selective bronchial suctioning in the adult using a curve-tipped catheter with a guide mark

Our results of previous and successive studies indicate that torque control of curve-tipped catheters is easily accomplished by placing a guide mark on the catheter. Thus, a guide mark was made on a curve-tipped 14 FG Portex suction catheter using a felt pen. The efficacy of selective bronchial suctioning using this catheter was studied in 50 patients. Directed suctioning of the left and right bronchial passages was performed in each patient 3 times and once, respectively, with the head in the midline position. The success rate of left bronchial suctioning was 92% (138/150 attempts) and success in right bronchial suctioning 98% (49/50 attempts). The curve-tipped catheter with a guide mark significantly improved the success rate of left bronchial entry over the previous rate from 50% to 92%.