Hiroaki Morooka

Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK.

Isoflurane has a pharmacological preconditioning effect against ischemia in the heart and brain, but whether this also occurs in the kidney is unclear. In this study, we investigated pharmacological preconditioning by isoflurane in the rat kidney. In the isoflurane preconditioning group (1.5% isoflurane for 20 min before renal ischemia) serum creatinine (1.2 ± 0.7 and 1.1 ± 0.2 mg/dL) and blood urea nitrogen (99 ± 29 and 187 ± 31 mg/dL) were significantly smaller at 24 and 48 h after reperfusion than in the nonpreconditioning group (creatinine; 2.4 ± 1.2 and 2.9 ± 0.9 mg/dL, urea; 62 ± 19 and 79 ± 20 mg/dL). We also investigated the intracellular signal transduction involved in isoflurane preconditioning in the kidney. The activities of the stress protein kinases, JNK and ERK but not p38, were significantly less in the kidneys of the preconditioning group than in those of the nonpreconditioning group (P < 0.05). We conclude that isoflurane has a preconditioning effect against renal ischemia/reperfusion injury when administered before ischemia. Inhibition of the protein kinases, JNK and ERK, might be involved in the mechanisms of isoflurane preconditioning.

Role of reactive oxygen in phospholipase A2 activation by ischemia/reperfusion of the rat kidney

AbstractPurpose. To investigate the role of phospholipase A2 (PLA2) in reperfusion injury of the kidney in an in vivo animal model, renal mitochondrial PLA2 activity was measured under three different conditions. Methods. Male Wistar rats (n = 72) anesthetized with pentobarbital underwent renal ischemia surgically for 45 min and were reperfused for the indicated time (renal ischemia/reperfusion). Treatments included reperfusion for various predetermined periods (phase 1), exposure to hyperbaric oxygen (phase 2), and administration of reactive oxygen species (ROS) scavenger (phase 3). Thereafter, each kidney was harvested, and mitochondrial PLA2 activity was measured by a radioisotope technique. Results. Ischemia/reperfusion resulted in time-related PLA2 activation in the renal mitochondria up to 48 h of reperfusion after renal ischemia. Renal mitochondrial PLA2 activity was further augmented by hyperbaric oxygen exposure prior to reperfusion, whereas administration of the ROS scavengers suppressed mitochondrial PLA2 activity. Conclusion. These data suggest that ROS may play an important role in the in vivo activation of PLA2 associated with renal ischemia/reperfusion.

Anticholinesterase drugs stimulate phosphatidylinositol response in rat tracheal slices

Some anticholinesterase (anti-ChE) drugs induce airway smooth muscle contraction. Whether anti-ChE drugs stimulate muscarinic receptors in airway smooth muscle as well as nicotinic receptors in neuromuscular junction is unknown. Since there is a direct relationship between phosphatidylinositol (PI) response and airway smooth muscle contraction induced by muscarinic agonists, we examined the effects of neostigmine, physostigmine, pyridostigmine, and edrophonium on PI response in the airway smooth muscle. The rat tracheal slices were incubated in Krebs-Henseleit solution containing LiCl and [(3) H]myo-inositol in the presence of carbachol, anti-ChE, or none of them. [(3) H]inositol monophosphate (IP1), which is a degradation product of PI response, was counted with a liquid scintillation counter. Inositol monophosphate accumulation was stimulated by neostigmine, physostigmine, and pyridostigmine in a dose-dependent manner, but was not affected by edrophonium. These increases were completely inhibited by atropine. The results suggest that neostigmine, physostigmine, and pyridostigmine stimulate PI response in the airway smooth muscle, which would cause bronchoconstriction, while edrophonium does not affect PI response. (Anesth Analg 1996;82:1211-4)

Effects of sevoflurane compared with those of isoflurane on arterial oxygenation and hemodynamics during one-lung ventilation

AbstractPurpose. This study was designed to compare the effects of sevoflurane and isoflurane on Pao2 and hemodynamic variables during one-lung ventilation (OLV) in surgical patients. Methods. Twelve patients undergoing an esophageal procedure with thoracotomy for which a long period of OLV was required were studied using a randomized crossover design. Group 1 received 1.2% isoflurane from the induction of anesthesia until 30 min after starting OLV, and then received 1.7% sevoflurane during the remaining period. In group 2, the order of the anesthetics was reversed. All experimental procedures were performed in the left lateral decubitus position with the chest opened. Arterial and mixed venous blood gases and cardiac outputs were analyzed immediately before OLV, during OLV, and after resumption of two-lung ventilation (TLV). Results. OLV produced lower Pao2 and higher venous admixture (Qs/Qt) values than TLV. However, there was no significant difference between sevoflurane and isoflurane in Pao2 or Qs/Qt during OLV. Other hemodynamic variables except for Pv¯o2 showed no significant differences between the anesthetics. Conclusion. The effects of sevoflurane on Pao2 and the hemodynamic variables were similar to those of isoflurane during TLV and OLV in the lateral decubitus position.

Ropivacaine inhibits neurite outgrowth in PC-12 cells.

Peripheral nerve injury often leads to neuropathic pain, which might involve sympathetic postganglionic nerve fiber sprouting in the dorsal root ganglion. Recent studies suggest the effectiveness of ropivacaine in blocking neuropathic pain. To determine if ropivacaine affects sympathetic sprouting, we used pheochromocytoma (PC-12) cells, which differentiate into neurons on exposure to nerve growth factor (NGF). PC-12 cells were precultured in the presence of 50 ng/mL of NGF for 4 days. Neurite outgrowth was quantified as neurite extension after 24-, 48-, and 72-h exposure to ropivacaine at doses ranging from 10 to 200 μg/mL. Ropivacaine inhibited the neurite outgrowth in a dose-dependent manner. The inhibitory effect of ropivacaine was completely reversible because the NGF-stimulated neurite outgrowth was recovered to control level after washing out ropivacaine. Ropivacaine, therefore, may exert its therapeutic action on neuropathic pain, at least in part, by suppressing sympathetic sprouting.

Effect of cyclooxygenase-2 inhibitor pretreatment on gas exchange after hydrochloric acid aspiration in rats.

The present study was carried out to determine the effect of cyclooxygenase-2 (COX-2) inhibitor on acid aspiration-induced lung injury in rats. Rats were allocated into one of four groups. Group H received intratracheal instillation of HCl. Group S received saline intratracheally. Group HC received COX-2 inhibitor (celecoxib) 10 mg/kg intravenously 30 min before intratracheal instillation of HCl. Group C underwent bronchoalveolar lavage (BAL) only. All rats were mechanically ventilated for 30 min before BAL. Arterial blood gas analysis was done immediately before BAL. Groups H, S, and HC were subdivided to each two groups. Groups H-1, S-1, and HC-1 underwent BAL 1 h after instillation, whereas groups H-8, S-8, and HC-8 underwent BAL 8 h after instillation. The BAL fluid was used to measure the prostaglandin E2 (PGE2) concentration. Intratracheal HCl resulted in impaired oxygenation. COX-2 inhibitor attenuated the impairment of oxygenation 8 h after instillation but not after 1 h. Intratracheal HCl caused an increase in PGE2 concentration. COX-2 inhibitor attenuated an increase in PGE2 concentration 8 h after instillation but not after 1 h. The results show that COX-2 inhibitor attenuates the oxygenation impairment and the increase in alveolar PGE2 concentration during the inflammatory phase of acid aspiration-induced lung injury in rats.

Droperidol attenuates contractile and phosphatidylinositol responses of rat trachea

Droperidol attenuates airway smooth muscle contraction. However, the intracellular mechanisms involved in the droperidol-induced attenuation of airway smooth muscle contraction are not fully understood. We examined the effects of droperidol on contractile and phosphatidylinositol responses of the rat trachea. Droperidol dose dependently attenuated carbachol (CCh) induced tracheal ring contractions. The IC50 of droperidol on CCh-induced tracheal ring contraction was 13 ± 2 µmol/l. Droperidol attenuated CCh and aluminum fluoride stimulated inositol monophosphate accumulation. These results suggest that droperidol inhibits G protein coupled phospholipase C, resulting in attenuation of CCh-induced phosphatidylinositol response and subsequent attenuation of contractions of the rat trachea.

Effects of fentanyl on cardiovascular response during rapid sequence induction in hypertensive patients

This study was carried out to evaluate the effects of fentanyl on cardiovascular and catecholamine responses during rapid sequence induction (RSI) in hypertensive patients. Twenty-eight patients were allocated into one of 3 groups: group 1 (n=7) consisted of normotensive patients receiving no fentanyl, group 2 (n=10) consisted of normotensive patients receiving fentanyl, and group 3 (n=11) consisted of hypertensive patients receiving fentanyl. RSI was performed with thiamylal (4mg·kg−1) and succinylcholine (2mg·kg−1) for all groups. In groups 2 and 3, fentanyl (4 μg·kg−1) was given prior to induction. Measurements including systolic arterial pressure (SAP) and heart rate (HR) were made at preinduction (T1), preintubation (T2), 1 min after intubation (T3), and 3 min after intubation (T4). Simultaneously, plasma concentrations of epinephrine (E) and norepinephrine (NE) were measured at T1 and T3. Group 1 showed significant increases in SAP, HR, and NE at T3 as compared to T1. Group 2 showed a significant increase in HR at T3 but not in SAP or catecholamines. Group 3 showed no increase in SAP, HR, or catecholamines throughout the time course. The results suggest that fentanyl is useful to suppress sympathoadrenal and cardiovascular responses to RSI in hypertensive patients as well as normotensive patients.

Hyperbaric nitrogen prolongs breath-holding time in humans.

UNLABELLED Either an increase in PaCO(2) or a decrease in PaO(2), can affect respiratory stimulation through respiratory centers, thus influencing breath-holding time (BHT). This study was designed to determine whether and how hyperbaric air could influence BHT in comparison with hyperbaric oxygen in humans. We studied 36 healthy volunteers in a multiplace hyperbaric chamber. BHT, pulse oximeter, and transcutaneous carbon dioxide tension were measured at 1 and 2.8 atmosphere absolute (ATA) in two groups. Group A (n = 20) breathed air. Group O (n = 16) breathed oxygen with a face mask (5 L/min). BHTs were 108 +/- 28 s at 1.0 ATA and 230 +/- 71 s at 2.8 ATA in Group A, and 137 +/- 48 s at 1.0 ATA and 180 +/- 52 s at 2.8 ATA in Group O. Transcutaneous carbon dioxide tension in Group A (59 +/- 2 mm Hg) was higher than that in Group O (54 +/- 2 mm Hg) at the end of maximal breath-holding at 2.8 ATA. The prolongation of BHT in hyperbaric air is significantly greater than that in hyperbaric oxygen. IMPLICATIONS Breath-holding time is significantly prolonged in hyperbaric air than it is in hyperbaric oxygen. The mechanism involves the anesthetic effect of nitrogen suppressing the suffocating feeling during breath-holding.