A comparison of the effect on QT interval between thiamylal and propofol during anaesthetic induction*.

SUMMARY: The aim of this study was to determine the effect of thiamylal and propofol on heart rate-corrected QT (QTc) interval during anaesthetic induction. We studied 50 patients undergoing lumbar spine surgery. Patients were administered 3 microgxkg(-1) fentanyl and were randomly allocated to receive 5 mgxkg(-1) thiamylal or 1.5 mgxkg(-1) propofol as an induction agent. Tracheal intubation was performed after vecuronium administration. Heart rate, mean arterial pressure, bispectral index score, and 12-lead electrocardiogram were recorded at the following time points: just before (T1) and 2 min after (T2) fentanyl administration; 2 min after anaesthetic administration (T3); 2.5 min after vecuronium injection (T4); and 2 min after intubation (T5). Thiamylal prolonged (p < 0.0001), but propofol shortened (p < 0.0001), the QTc interval.

The effect of sevoflurane-induced hypotension in combination with acute hypervolaemic haemodilution on middle cerebral artery flow velocity in surgical patients.

BACKGROUND AND OBJECTIVE: This study was carried out to clarify the effect of the combination of acute hypervolaemic haemodilution and hypotensive anaesthesia induced with sevoflurane on human middle cerebral artery flow velocity using transcranial Doppler ultrasonography. METHODS: Thirty patients who were maintained with N2O-O2-sevoflurane anaesthesia undergoing hip surgery were randomly divided into two groups (no controlled hypotension group, Group A, and controlled hypotension group, Group B). Haemodilution was produced by acute preoperative infusion of 1000 mL of hydroxyethylstarch without removing blood in both groups. Mean arterial pressure was maintained at approximately 95 mmHg in Group A and at 55 mmHg for 80 min by increasing the inspired concentration of sevoflurane in Group B. Middle cerebral artery flow velocity was measured before haemodilution, after haemodilution, 80 min after starting hypotension, and 60 min after recovery from hypotension. RESULTS: Middle cerebral artery flow velocity significantly increased in both groups after haemodilution; by 28%, in Group A, P < 0.05 vs. before haemodilution and by 30% vs. before haemodilution in Group B, P < 0.05). During controlled hypotension, it decreased towards the pre-haemodilution value (P < 0.05 vs. after haemodilution). CONCLUSIONS: Sevoflurane-induced hypotension to a mean arterial pressure of 55 mmHg would reduce middle cerebral artery flow that had been increased by acute hypervolaemic haemodilution, such as haematocrit value of 26%, whereas it could preserve the flow in pre-haemodilution condition during normocapnia.

[Peripheral vascular pain].

Peripheral vascular pain consists of complex factors, and may be divided into three types, i.e., arterial pain, microvessel pain and venous pain. Among these, arterial pain requires intensive pain control because of severe ischemic pain due to arterial obstruction. Under ischemic condition, adenosine is generated, and activates unmyelinated afferents to produce pain. In addition to adenosine, acidic pH itself produces pain and sensitization to mechanical stimuli. Moreover bradykinin generated by kallikurein in acidic pH can produce pain. Nerve block is indicated to improve tissue circulation and to relieve pain. Endoscopic thoracic sympathectomy is indicated for upper extremities, and high frequency thermocoagulation is applied for lumbar sympathectomy. Spinal cord stimulation and the gene therapy with vascular endothelial growth factor have also been reported effective.

Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels.

UNLABELLED: We sought to determine the hemodynamic and cardioprotective effects of sevoflurane in canine stunned myocardium. Forty-nine dogs were allocated to one of seven groups (n = 7 for each). In six separate groups, dogs received vehicle, glibenclamide (a nonselective adenosine triphosphate-dependent potassium [K(ATP)] channel antagonist) (0.3 mg/kg IV) or 5-hydroxydecanoic acid (a mitochondrial K(ATP) channel antagonist) (5 mg/kg IV) in the presence or absence of 1 minimum alveolar concentration (1 MAC) sevoflurane. In an additional group, dogs received 1 MAC sevoflurane with hemodynamic correction. Regional myocardial contractility was evaluated with segment shortening. Measurements were made before and during 15-min ischemia and 90-min reperfusion. Recovery of segment shortening 90 min after reperfusion was significantly improved in the dogs anesthetized with sevoflurane either with or without hemodynamic correction (70.1 +/- 4.2 and 75.9 +/- 3.1% of baseline, respectively), whereas the recovery was poor in control and glibenclamide or 5-hydroxydecanoic acid pretreated dogs (33.3 +/- 4.3, 33.8 +/- 6.8, and 45.0 +/- 5.5% of baseline, respectively). Regional myocardial perfusion showed no significant difference among groups. The results indicate that sevoflurane has a cardioprotective effect mediated through activation of mitochondrial K(ATP) channels and independent of coronary blood flow or reduction in cardiac work. IMPLICATIONS: Sevoflurane exerts a cardioprotective effect that is mediated via activation of adenosine triphosphate-sensitive potassium channels in ischemic canine hearts.

Nicotine accelerates reversal of long-term potentiation and enhances long-term depression in the rat hippocampal CA1 region.

In the hippocampal CA1 region, low-frequency stimulation (LFS; 200 pulses at 1 Hz) causes reversal of long-term potentiation (depotentiation, DP) and long-term depression (LTD), both of which are thought to be the cellular substrate of learning and memory. Because nicotine enhances learning and memory, we examined if nicotine modulates DP and LTD in the hippocampal CA1 region. Bath application of nicotine during LFS accelerated DP, that is, potentiated synaptic responses in hippocampal CA1 neurons returned to pre-tetanic control levels more rapidly in the presence of nicotine. Because a similar acceleration of DP was observed using the alpha7 nicotinic acetylcholine receptor (nAChR)-selective antagonist methyllcaconitine (MLA), the nicotine effect appeared to be at least partly mediated by nicotine-induced desensitization of alpha7 nAChRs. Delivery of LFS in the presence of nicotine or MLA also depressed synaptic responses in a naive pathway and facilitated LTD, that is, the magnitude of LTD was larger when the drug was present during LFS. Thus, these results demonstrate that nicotine facilitates DP and LTD, which may represent, at least in part, the cellular mechanism underlying nicotine-induced cognitive enhancement.

Acute and chronic nicotine exposure reverse age-related declines in the induction of long-term potentiation in the rat hippocampus.

Long-term potentiation (LTP) is widely considered to be the cellular substrate of learning and memory. The induction of LTP becomes more difficult with age in parallel with declining learning and memory ability. Because nicotine improves learning and memory in aged rats, we examined the effects of acute and chronic nicotine exposure on age-related declines in LTP induction. We found that acute nicotine exposure lowered the threshold for LTP induction in the aging hippocampus. The effect of nicotine was mimicked by the alpha7 nicotinic acetylcholine receptor (nAChR) antagonist methyllycaconitine and blocked by the non-alpha7 nAChR antagonist dihydro-beta-erythroidine, suggesting that both nicotine-mediated desensitization of alpha7 nAChRs and activation of non-alpha7 nAChRs contribute to the nicotine effect. The non-alpha7 nAChR agonist A85380 that facilitates the induction of LTP in the young hippocampus had no effect, however, suggesting that at least one pathway involving non-alpha7 nAChRs was altered by aging. Chronic nicotine treatment of aged rats also lowered the threshold for LTP induction and acute nicotine exposure lowered the threshold further in the chronic-nicotine-treated aged hippocampus. These results not only suggest that the mechanisms mediated by acute and chronic nicotine exposure are different, but also demonstrate that age-associated declines in LTP induction can be reversed with nicotine treatment.

Activation of alveolar phospholipase A2 after hydrochloric acid aspiration in rats.

PURPOSE: The present study was carried out to determine phospholipase A2 (PLA2) activity in the bronchoalveolar lavage fluid (BALF) in rats subjected to HCI aspiration. MATERIALS AND METHODS: Rats were allocated into one of five groups. Groups H-1 and H-3 received instillation of HCI into lungs. Groups S-1 and S-3 received saline instead of HCI. Group C received no instillation. BAL was performed according to the protocol, that is, 1 hour after the instillation in groups H-1 and S-1, 3 hours after the instillation in groups H-3 and S-3, and arbitrarily in group C. Obtain BALF was analyzed for the protein concentration, PLA2 activity, and the molecular mass of PLA2. RESULTS: The protein concentration in BALF showed an increase in groups H-1 and H-3. PLA2 activity decreased in group H-1, but increased in group H-3, compared with groups S-1 and S-3, respectively. PLA2 in groups C and H-1 revealed a high molecular mass (HM), but that in group H-3 revealed a low molecular mass (LM). CONCLUSIONS: There is an increase in the alveolar LM-PLA2 at inflammatory phase after HCI aspiration, suggesting the pathophysiologic role of LM-PLA2 in the acute lung injury.

Perineural injection to nerve root and radicular blood flow: a clinical study during spinal surgery.

BACKGROUND AND OBJECTIVE: To investigate the effects of the perineural injection of lidocaine or corticosteroids on radicular blood flow during spinal surgery. METHODS: After lumbar discectomy, a probe for laser Doppler flowmetry was placed directly on the 4th or 5th lumbar nerve root. Thirty patients undergoing lumbar discectomy were randomly assigned to one of three groups. Each group received one of three protocols for a perineural injection to the nerve root: 1.0 mL 0.9% saline in group A, 1.0 mL 1% lidocaine in group B or 1.0 mL dexamethasone (4 mg) in group C. Measurements included radicular blood flow, mean arterial pressure, haemoglobin concentration, percutaneous oxygen saturation and end-tidal carbon dioxide tension. Radicular blood flow was measured by laser Doppler flowmetry before the injection and 15 min after these injections. The three groups were similar with respect to mean arterial pressure, haemoglobin concentration, percutaneous oxygen saturation and end-tidal carbon dioxide tension. RESULTS: Radicular blood flow did not change after the injection in any of the groups. CONCLUSIONS: The results suggest that the perineural injection of 1% lidocaine or dexamethasone does not affect radicular blood flow during lumbar discectomy.

A dose-response study of anticholinesterase drugs on contractile and phosphatidylinositol responses of rat trachea.

UNLABELLED: We investigated whether anticholinesterase drugs in large doses inhibit muscarinic receptors of airway smooth muscle. In vitro measurements of isometric tension and [(3)H]inositol monophosphate (IP(1)) that formed were conducted by using rat tracheal rings or slices. Neostigmine and pyridostigmine caused muscular contraction and IP(1) accumulation in small doses (10 microM and < or = 100 microM, respectively), but they attenuated muscular contraction and IP(1) accumulation in larger doses (1000 microM). Edrophonium did not affect the smooth muscle tone and IP(1) levels. Neostigmine, pyridostigmine, and edrophonium attenuated the carbachol (5.5 microM)-induced smooth muscle contraction and IP(1) accumulation, when administered in large doses (1000 microM). The attenuation of contraction by neostigmine at large doses was not affected by methoctramine, an M(2) muscarinic receptor antagonist, but was reversed by washing with fresh Krebs-Henseleit solution. The results suggest that anticholinesterase drugs have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy. IMPLICATIONS: Neostigmine and pyridostigmine, but not edrophonium, have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy.

Splanchnic perfusion during controlled hypotension combined with acute hypervolemic hemodilution: a comparison with combination of acute normovolemic hemodilution-gastric intramucosal pH study.

STUDY OBJECTIVE: To evaluate the effect of controlled hypotension combined with acute hypervolemic or normovolemic hemodilution on the splanchnic perfusion in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 28 ASA physical status I and II patients scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly divided into two groups. Group A (n = 14) received controlled hypotension with acute normovolemic hemodilution (ANH). Group B (n = 14) received controlled hypotension with acute hypervolemic hemodilution (HHD). ANH was produced by drawing approximately 1000 mL of blood and replacing it with the same amount of 6% hydroxyethyl starch solution (HES). HHD was produced by preoperative infusion of 1000 mL of 6% HES without removing blood. The final hematocrit values were 24+/-2% (mean +/- SD) in Group A and 25+/-3% in Group B. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS: Measurements included the gastric pH (pHi), the arterial blood pH (pHa), and plasma lactate. These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, 60 minutes after recovery from hypotension, and on the first postoperative day. The value of pHi was measured by tonometric method. MAIN RESULTS: The pHa and lactate values showed no change in either group A or group B throughout the time course. Gastric pHi values in group A showed a significant decrease from 7.424+/-0.033 to 7.335+/-0.038 (p<0.05) after hemodilution, whereas it showed no further decrease at 80 minutes after starting hypotension and 60 minutes after recovery from hypotension. The pHi values in group B showed no significant decrease after hemodilution and no further change at 80 minutes after starting hypotension. CONCLUSIONS: HHD does not impair splanchnic perfusion, whereas ANH might cause impairment. Controlled hypotension with prostaglandin E1 would not impair splanchnic perfusion in combination with either HHD or ANH.

Interaction of isoflurane and cromakalim, a KATP channel opener, on coronary and systemic haemodynamics in chronically instrumented dogs.

BACKGROUND: Although isoflurane has been shown to cause coronary and systemic vasodilation through KATP channel activation, the interaction of KATP channel openers and isoflurane has not been fully investigated. The present study was carried out to determine the haemodynamic actions of cromakalim, a KATP channel opener, under the conscious state and during isoflurane anaesthesia in chronically instrumented dogs. METHODS: Fourteen dogs were chronically instrumented to measure systemic and coronary haemodynamics. Each dog was randomly assigned to receive doses of either cromakalim, 4 and 10 microg x kg(-1) i.v., or isoflurane, 2.1% end-tidal (1.5 MAC), plus cromakalim, 4 and 10 microg x kg(-1) i.v. RESULTS: Cromakalim dose-relatedly decreased mean arterial pressure and systemic vascular resistance and increased coronary blood flow in both conscious and anaesthetized states. With isoflurane, the duration of effects of cromakalim were prolonged. Isoflurane exerted an additive effect on the increase in coronary blood flow induced by a low-dose cromakalim, whereas it did not influence the effect of a high-dose cromakalim. The maximum rate of increase in left ventricular pressure and segment shortening were increased by cromakalim in the conscious state but unchanged during isoflurane anaesthesia. CONCLUSION: The results suggest that the coronary vasodilating effects of isoflurane and cromakalim are basically additive until cromakalim exerts the maximal effect, and that the action of cromakalim on the coronary vasculature is prolonged by isoflurane.

The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors.

Nefiracetam, a pyrrolidone derivative developed as an anti-dementia drug, persistently potentiated currents through neuronal nicotinic acetylcholine (ACh) receptors (alpha7, alpha4beta2) expressed in Xenopus oocytes, and the potentiation was blocked by either the selective protein kinase C (PKC) inhibitors, GF109203X and staurosporine, or co-expressed active PKC inhibitor peptide. In primary cultures of rat hippocampal neurons, nefiracetam increased the rate of nicotine-sensitive miniature excitatory postsynaptic currents, without affecting the amplitude, and the increase was inhibited by GF109203X. In addition, the drug caused a marked increase in the glutamate release from electrically stimulated guinea pig hippocampal slices, and the effect was abolished by the nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. Nefiracetam induced a long-lasting facilitation of synaptic transmission in both the CA1 area and the dentate gyrus of rat hippocampal slices, and the facilitation was inhibited by alpha-bungarotoxin and mecamylamine. Such facilitatory action was still found in the hippocampus with selective cholinergic denervation. The results of the present study, thus, suggest that nefiracetam enhances activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to a sustained facilitation of hippocampal neurotransmission. This may represent a cellular mechanism underlying the cognition-enhancing action of nefiracetam. The results also provide the possibility that nefiracetam could be developed as a promising therapeutic drug for senile dementia or Alzheimer's disease.

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.

Inactivation of alpha7 ACh receptors and activation of non-alpha7 ACh receptors both contribute to long term potentiation induction in the hippocampal CA1 region.

Acute and chronic nicotine exposure differentially facilitate the induction of long-term potentiation (LTP), a synaptic model of learning and memory, in the hippocampal CA1 region. The mechanisms underlying these effects of nicotine, however, are unknown. In the present study, both nicotinic acetylcholine receptor (nAChR) agonists and an alpha7 nAChR antagonist facilitated the induction LTP in the hippocampal CA1 region of naive rat. Furthermore, chronic nicotine treatment lowered the threshold for induction of LTP, and acute application of nicotinic agonists, but not an alpha7 antagonist, further facilitated LTP induction in the chronic-nicotine-treated hippocampus. These results suggest not only that both activation of non-alpha7 nAChRs and inactivation of alpha7 nAChRs contribute to LTP induction, but also that chronic-nicotine-mediated facilitation of LTP induction is due to chronic-nicotine-induced desensitization of alpha7 nAChRs.

Nicotine reverses GABAergic inhibition of long-term potentiation induction in the hippocampal CA1 region.

Nicotine is known to enhance cognitive function but the mechanism is unknown. The present study examined the modulatory effect of nicotine on the induction of long-term potentiation (LTP), a synaptic model of learning and memory. A weak tetanic stimulation consisting of 20 pulses at 100 Hz induced stable LTP in the hippocampal CA1. The induction of LTP was completely blocked if the tetanus was delivered in the presence of muscimol (2.5 microM), a gamma-aminobutyric acid (GABA) receptor agonist. This inhibition was sensitive to, and reversed by, not only nicotinic acetylcholine receptor (nAChR) agonists (nicotine and epibatidine), but also the alpha7 nAChR-selective antagonist methyllycaconitine (MLA). Furthermore, ACh-puff activation of alpha7 nAChRs on feedforward interneurons induced inhibitory postsynaptic currents in pyramidal cells that were blocked by nicotine or MLA. In addition, nicotine reduced field monosynaptic inhibitory postsynaptic potentials in the presence of MLA. These results suggest not only two pathways of nicotine-induced disinhibition of pyramidal cells, one involving desensitization of alpha7 nAChRs and the other involving non-alpha7 nAChRs, but also two potential mechanisms underlying the modulatory effect of nicotine on LTP induction, both reducing GABAergic inhibition, thereby indirectly increasing the excitability of pyramidal cells.

The effects of propofol with and without ketamine on human cerebral blood flow velocity and CO(2) response.

UNLABELLED: The combination of propofol and ketamine has been used for total IV anesthesia. This study was designed to clarify the effects of propofol-ketamine anesthesia on cerebral circulation by using transcranial Doppler ultrasonography. In Study 1, we examined the time course of time-mean middle cerebral artery blood flow velocity (Vmca) after ketamine (n = 10) or saline (n = 6) administration during propofol anesthesia. In Study 2, CO(2) responses were measured under the following conditions: awake (Group C, n = 7), propofol anesthesia (Group D, n = 7), and propofol-ketamine anesthesia (Group E, n = 8). Ketamine administration during propofol anesthesia administration did not affect Vmca, mean arterial pressure, or heart rate. Vmca under normocapnia in Groups D and E were 36 +/- 3 and 37 +/- 3 cm/s (mean +/- SE), respectively. The values were significantly lower than that of Group C (70 +/- 3 cm/s). The CO(2) response slopes of Groups D and E were significantly lower than that of Group C, although there was no significant difference between Groups D and E. These results suggest that ketamine does not influence Vmca or the cerebrovascular CO(2) response during propofol anesthesia administration, although the sample size in each group was small. IMPLICATIONS: Our study suggests that ketamine does not influence middle cerebral artery blood flow velocity or the cerebrovascular CO(2) response assessed by transcranial Doppler ultrasonography during propofol anesthesia administration in patients without neurological complications.