Toru Fujigaki

Effects of sevoflurane with and without nitrous oxide on human cerebral circulation : Transcranial Doppler study

Background This study was designed to evaluate the effects of sevoflurane with and without nitrous oxide on human middle cerebral artery (MCA) flow velocity, cerebrovascular carbon dioxide reactivity, and autoregulation compared with the awake state using transcranial Doppler ultrasonography. Methods In 14 patients, the time‐mean middle cerebral artery flow velocity (Vmca) was measured when the end‐tidal carbon dioxide level was approximately 30, 40, and 50 mmHg under the following conditions: (1) awake; (2) with 2% (1.2 MAC) sevoflurane; and (3) with 1.2 MAC sevoflurane‐60% nitrous oxide. In six other patients, the cerebrovascular autoregulation during anesthesia was determined using intravenous phenylephrine to increase blood pressure. Results Sevoflurane (1.2 MAC) significantly decreased Vmca compared with the awake value at each level of end‐tidal carbon dioxide, whereas 1.2 MAC sevoflurane‐60% nitrous oxide did not exert significant influence. The Vmca in normocapnic patients decreased from 69 cm/s to 55 cm/s with 1.2 MAC sevoflurane and then increased to 70 cm/s when nitrous oxide was added. Sevoflurane (1.2 MAC) with and without 60% nitrous oxide had a negligible effect on cerebrovascular carbon dioxide reactivity. A phenylephrine‐induced increase of mean arterial pressure did not influence Vmca during anesthesia. Conclusions Sevoflurane (1.2 MAC) reduced Vmca compared with the awake condition, whereas the addition of nitrous oxide caused Vmca to increase toward the values obtained in the awake condition. The cerebrovascular carbon dioxide reactivity and autoregulation were well maintained during 1.2 MAC sevoflurane with and without 60% nitrous oxide.

A comparison of coronary hemodynamics during isoflurane and sevoflurane anesthesia in dogs.

We studied the effects of sevoflurane and isoflurane on coronary hemodynamics in relation to myocardial oxygen supply and demand.Dogs were anesthetized with pentobarbital and fentanyl and received isoflurane or sevoflurane. An electromagnetic flow probe and a pair of piezoelectric crystals were placed on the left circumflex coronary artery (CX) to measure CX flow and diameter. The dogs were randomly assigned to receive isoflurane or sevoflurane at a dose of 0.75 and 1.5 minimum alveolar anesthetic concentration (MAC). The CX diameter decreased in parallel with the decrease in mean arterial pressure during both anesthetics. The CX blood flow decreased in parallel with the decrease in myocardial oxygen consumption (MVO2) during sevoflurane, whereas it did not change in spite of the decrease in MVO2 during isoflurane. The CX vascular resistance decreased significantly during isoflurane but not during sevoflurane. Moreover, the myocardial oxygen extraction ratio (MO2 exr) decreased at 0.75 and 1.5 MAC isoflurane and at 1.5 MAC sevoflurane, and the decrease in MO2 exr was significantly greater during isoflurane than during sevoflurane. The results suggest that sevoflurane is a less potent coronary arteriolar dilator than isoflurane, and that neither sevoflurane or isoflurane has a direct effect on the diameter of large coronary arteries. (Anesth Analg 1995;80:651-6)

Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs

AbstractPurpose. The present study was carried out to determine the direct effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility, and whether fentanyl would enhance the myocardial depression caused by propofol. Method. The anesthetics were injected directly into the circuit that supplied blood to the left circumflex coronary artery (LCX) in anesthetized open-chest dogs. Myocardial contractility was evaluated from measurements of percent segmental shortening (%SS). Results. Etomidate, ketamine, and propofol significantly reduced %SS in a dose-dependent manner. The %SS values with 1.6 and 3.2 mg of etomidate were similar to those with 3.2 and 6.4 mg of ketamine, respectively, and the %SS value with 6.4 mg of propofol was similar to those with 3.2 and 6.4 mg of ketamine. Fentanyl alone had no effects on myocardial performance and did not influence the effect of propofol on %SS. Conclusion. On the basis of clinical doses, the direct myocardial depressant effect of ketamine is more than twice as potent as that of etomidate and slightly more than that of propofol. Fentanyl has no inotropic effect and does not enhance the direct myocardial depressant effect of propofol.

Carbachol, norepinephrine, and hypocapnia stimulate phosphatidylinositol turnover in rat tracheal slices.

Background The intracellular mechanisms involved in the alpha‐adrenoceptor‐ or hyperventilation‐induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol (PI) metabolism and airway smooth muscle contraction induced by muscarinic agonists, the authors examined the effects of carbachol (CCh), norepinephrine (NE), and hypocapnia on PI turnover in the airway smooth muscle. Methods Rat tracheal slices were incubated in Krebs‐Henseleit solution containing LiCl and [sup 3 Hydrogen]myo‐inositol in the presence of NE, CCh, or neither. The PCO2 in the solution was 36 plus/minus 3 mmHg (normocapnia), 19 plus/minus 2 mmHg (moderate hypocapnia), or 5 plus/minus 2 mmHg (severe hypocapnia), respectively. [sup 3 Hydrogen]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter. Results Basal IP1 formed was greater at severe hypocapnia than at normocapnia. Norepinephrine‐ and CCh‐induced IP1 formation were also greater at hypocapnia than at normocapnia. Conclusions These results indicate that CCh, NE, and hypocapnia stimulate PI turnover in the airway smooth muscle, which would cause bronchoconstriction, and hypocapnia also augments NE‐ and CCh‐induced PI turnover, which could cause worsening of exercise‐induced asthma and vagotonic asthma, respectively.

Effect of ONO-1101, a novel short-acting β-blocker on hemodynamic responses to isoflurane inhalation and tracheal intubation

PurposeWe investigated the effect of a new ultrashort-acting β-blocker, ONO-1101, on hemodynamic responses to isoflurane inhalation and tracheal intubation.MethodsFifty-four ASA PS 1 or 2 patients were randomly allocated to receive either ONO-1101, 0.04 mg·kg−1·min−1, or saline prior to tracheal intubation. Anesthesia was induced with thiamylal, 4 mg·kg−1, and vecuronium, 0.15 mg·kg−1. Tracheal intubation was carried out after 3 min controlled mask ventilation with 66% N2O and 3% inspired isoflurane in oxygen. Heart rate and blood pressure were continuously recorded from the start of induction until 5 min after intubation. Plasma concentrations of catecholamines were measured before induction, 3 min after initiating inhalation of isoflurane, and 1 min after tracheal intubation.ResultsSignificant increases in heart rate occurred in both groups in response to isoflurane inhalation and tracheal intubation, but the magnitude of the increase was significantly less in the ONO-1101 group. Blood pressure increased after tracheal intubation in the saline group but remained unchanged in the ONO-1101 group. Plasma concentrations of norepinephrine increased after induction and intubation in both groups, with no significant difference between the groups.ConclusionONO-1101 infusion is effective for the attenuation of hemodynamic responses to isoflurane inhalation and tracheal intubation.

Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl

Although thiobarbiturates potentiate, and fentanyl attenuates peripheral vasoconstriction, the intracellular mechanism involved in this phenomenon is not clear. Because smooth muscle contraction induced by α1-adrenoceptor agonists is mediated by the phosphatidylinositol (PI) response, this study was carried out to clarify if thiamylal and fentanyl affect the norepinephrineinduced PI response in rat aortic slices. Rat aortic slices were incubated in Krebs-Henseleit solution containing 5 mM LiCl, [3H]myo-inositol, and varying concentrations of thiamylal or fentanyl. The PI response was stimulated by 0.09 μM (ED50) norepinephrine (NE). The [3H]inositoI monophosphate (IP1) was separated from [3H]myo-inositol by column chromatography and counted with a liquid scintillation counter. The basal IP1, accumulation was not affected by thiamylal and fentanyl. Norepinephrine-induced IP1 accumulation was potentiated by thiamylal at concentrations of 10 μM and 100 μM. Norepinephrine-induced IP1 accumulation was attentuated by 1 μM and 10 μM fentanyl. The results suggest that thiamylal stimulates the NE-induced PI response, which potentiates the vasoconstriction, and fentanyl attentuates NE-induced PI response, which would attenuate the vasoconstriction.RésuméOn connaît mal le mécanisme intracellulaire qui fait que le thiamylal potentialise la vasoconstriction périphérique et que le fentanyl l’atténue. Comme la constriction du muscle lisse induite par les agonistes α1-adrénergiques dépend de la réponse du phosphatidylinositol (PI), cette étude vise à vérifier sur des tranches d’aorte de rat si le thiamylal et le fentanyl affectent la réponse du PI induite par la norépinéphrine (NE). Cellesci sont incubées dans une solution de Krebs-Henseleit contenant 5 mM de LiCl, du [3H] myo-inositol et différentes concentrations de thiamylal ou de fentanyl. La réponse du PI est provoquée par 0,09 μM (ED50) de NE. Le [3H] inositol monophosphate (IP1) est séparé du [3H] myo-inositol par Chromatographie sur colonne anionique et mesuré avec un compteur à scintillation liquide. L’accumulation d’IP1 initiale n’est pas affectée par le thiamylal et le fentanyl. L’accumulation d’IP1 induite par la NE est potentialisée par le thiamylal à des concentrations de 10 μM et de 100 μM. L’accumulation d’IP1 induite par la NE est atténuée par 1 μM et 10 μM de fentanyl. Ces résultats suggèrent que le thiamylal stimule la réponse induite par la NE, laquelle potentialise la vasoconstriction, et que le fentanyl atténue la réponse de l’IP1 induite par la NE, laquelle pourrait atténuer la vasoconstriction.

The effects of prolonged controlled hypotension induced by prostaglandin E1 on renal tubular function.

The effects of the prolonged 3-hour and 6-hour controlled hypotension induced by prostaglandin E1 (PGE1) on renal tubular function have been comparatively studied with trimethaphan (TMP; 3-hour hypotensive anesthesia) and enflurane deep anesthesia (6-hour hypotensive anesthesia), using the urine N-acetyl-β-D-glucosaminidase (NAG index) and the serum and urine N-acetyl-β-D-glucosaminidase (fractional clearance ofβ2-m; Fc-β2-m) as markers. During 3-hour and 6-hour controlled hypotension PGE1 , NAG index and Fc-β2-m and urine volume could be maintained without remarkable changes. In the group with TPM, NAG index and Fc-β2-m significantly increased. The increasing trend was also noted over time in deep anesthesia with enflurane. On 1st postoperative day, Fc-β2-m significantly increased in PGE1 group in both 3-hour and 6-hour hypotensive anesthesia, whereas it restored to normal on 2nd postoperative day. Also, in TMP and enflurane deep anesthesia, Fc-β2-m significantly increased on 1st postoperative day. With the latter, significant increase was also observed on 2nd postoperative day. These results suggest that, in 3-hour and 6-hour controlled hypotension induced by PGE1 , renal tubular function is normally maintained and that it is useful for prolonged controlled hypotensive anesthesia. However, further study is necessary because tubular dysfunction might appear on 1st postoperative day.

Comparison of the effects of amrinone and dobutamine on hemodynamics and myocardial oxygen balance in dogs with experimental left ventricular failure

The purpose of the present study was to induce left ventricular failure in anesthetized dogs by repeated ventricular fibrillation and then to determine if amrinone is effective in circulatory support by comparing the effects of amrinone and dobutamine. After the repetitive ventricular fibrillation, mean arterial pressure and stroke volume index decreased, pulmonary capillary wedge pressure (PCWP) increased, and acute left ventricular failure occurred. Thereafter, dogs were divided into the following four groups. In Group C (n = 6), normal saline was administered; in Group D (n = 6), dobutamine was administered at 7 micrograms/kg/min; and in Groups A40 (n = 6) and A80 (n = 7), amrinone was administered at 40 micrograms/kg/min and 80 micrograms/kg/min, respectively. Stroke volume index increased by 78% in Group D and 46% in both Groups A40 and A80. Pulmonary capillary wedge pressure decreased by 44% in Group A40 and 38% in Group A80, but remained unchanged in Group D. Similarly, total peripheral resistance decreased by 32% in Group A40, 29% in Group A80, but remained unchanged in Group D. These results suggest that amrinone increased cardiac output and decreased both preload and afterload. In the coronary circulation, both drugs caused direct coronary vasodilation since they increased myocardial oxygen supply in excess of the increase in myocardial oxygen demand. Neither drug produced signs of myocardial ischemia, as indicated by myocardial lactate metabolism. Amrinone should be a useful drug after open heart surgery, especially in cases where significant adverse effects of catecholamines occur or where a low-output state with increased preload and afterload exists.

Effects of intravenous anesthetics on phosphatidylinositol turnover in rat cerebral cortical prisms

Noradrenergic pathways in the brain have been thought to be related to the site of anesthetic action. Norepinephrine (NE) in the central nervous system stimulates phosphatidylinositol (PI) turnover through alpha 1-adrenergic receptors. The present study was designed to examine the effects of intravenous anesthetics on NE-induced PI turnover in rat cerebral cortical prisms. NE-induced inositol monophosphate (IP1) formation was inhibited by droperidol (dose for 50% inhibition [ID50], 0.0258 +/- 0.00023 microM [mean +/- SE]), fentanyl (2.36 +/- 0.0017), diazepam (201 +/- 2.12), and thiamylal (231 +/- 1.94) in a dose-dependent manner, but was not affected by ketamine. Naloxone or flumazenil did not attenuate the inhibitory effect of fentanyl or diazepam on NE-induced IP1 formation. The results suggest that these effects on the PI turnover in the cortex may be related to their pharmacologic properties including the anesthetic action.

Combined effects of adrenergic and intravenous anesthetic agents on inositol monophosphate levels in rat liver prisms

Combined effects of adrenergic and intravenous anesthetic agents on phosphatidylinositol (PI) turnover were studied using rat liver prisms incubated with [3H]myo‐inositol. Rat liver prisms responded to epinephrine, norepinephrine and phenylephrine dose‐dependently with an increase in inositol monophosphate (IP1) formation but they did not respond to ephedrine. Dopamine‐induced effects were seen only at concentrations as high as 10‐4 mol 1‐1. The enhancement of IP1 formation induced by epinephrine was potentiated by thiamylal at concentrations of 10‐5 mol. 1‐1 and 10‐4 mol. 1‐1, remained unaffected by ketamine, fentanyl or midazolam, but was dose‐dependently inhibited by droperidol. The present results from in vitro studies of liver cell metabolism suggest that α‐adrenergic agents in combination with barbiturates may potentiate liver cell damage by activation of PI turnover and interrelated intracellular Ca++ accumulation.