Protective effects of remote ischemic preconditioning against spinal cord ischemia-reperfusion injury in rats.

OBJECTIVES: We aimed to investigate the protective effect of remote ischemic preconditioning against spinal cord ischemia and find a clue to its mechanism by measuring glutamate concentrations in the spinal ventral horn. METHODS: Male Sprague-Dawley rats were divided into 5 groups (n = 6 in each group) as follows: sham; SCI (only spinal cord ischemia); RIPC/SCI (perform remote ischemic preconditioning before spinal cord ischemia); MK-801/RIPC/SCI (administer MK-801, N-methyl-D-aspartate receptor antagonist, before remote ischemic preconditioning); and MK-801/SCI (administer MK-801 without remote ischemic preconditioning). Remote ischemic preconditioning was achieved by brief limb ischemia 80 minutes before spinal cord ischemia. MK-801 (1 mg/kg, intravenous) was administered 60 minutes before remote ischemic preconditioning. The glutamate concentration in the ventral horn was measured by microdialysis for 130 minutes after spinal cord ischemia. Immunofluorescence was also performed to evaluate the expression of N-methyl-D-aspartate receptor 2B subunit in the ventral horn 130 minutes after spinal cord ischemia. RESULTS: The glutamate concentrations in the spinal cord ischemia group were significantly higher than in the sham group at all time points (P < .01). Remote ischemic preconditioning attenuated the spinal cord ischemia-induced glutamate increase. When MK-801 was preadministered before remote ischemic preconditioning, glutamate concentration was increased after spinal cord ischemia (P < .01). Immunofluorescence showed that remote ischemic preconditioning prevented the increase in the expression of N-methyl-D-aspartate receptor 2B subunit on the surface of motor neurons (P = .047). CONCLUSIONS: Our results showed that remote ischemic preconditioning prevented spinal cord ischemia-induced extracellular glutamate increase in ventral horn and suppressed N-methyl-D-aspartate receptor 2B subunit expression.

Protective effects of hydrogen gas against spinal cord ischemia-reperfusion injury.

OBJECTIVE: This experimental study aimed to assess the efficacy of hydrogen gas inhalation against spinal cord ischemia-reperfusion injury and reveal its mechanism by measuring glutamate concentration in the ventral horn using an in vivo microdialysis method. METHODS: Male Sprague-Dawley rats were divided into the following 6 groups: sham, only spinal ischemia, 3% hydrogen gas (spinal ischemia + 3% hydrogen gas), 2% hydrogen gas (spinal ischemia + 2% hydrogen gas), 1% hydrogen gas (spinal ischemia + 1% hydrogen gas), and hydrogen gas dihydrokainate (spinal ischemia + dihydrokainate [selective inhibitor of glutamate transporter-1] + 3% hydrogen gas). Hydrogen gas inhalation was initiated 10 minutes before the ischemia. For the hydrogen gas dihydrokainate group, glutamate transporter-1 inhibitor was administered 20 minutes before the ischemia. Immunofluorescence was performed to assess the expression of glutamate transporter-1 in the ventral horn. RESULTS: The increase in extracellular glutamate induced by spinal ischemia was significantly suppressed by 3% hydrogen gas inhalation (P < .05). This effect was produced in increasing order: 1%, 2%, and 3%. Conversely, the preadministration of glutamate transporter-1 inhibitor diminished the suppression of spinal ischemia-induced glutamate increase observed during the inhalation of 3% hydrogen gas. Immunofluorescence indicated the expression of glutamate transporter-1 in the spinal ischemia group was significantly decreased compared with the sham group, which was attenuated by 3% hydrogen gas inhalation (P < .05). CONCLUSIONS: Our study demonstrated hydrogen gas inhalation exhibits a protective and concentration-dependent effect against spinal ischemic injury, and glutamate transporter-1 has an important role in the protective effects against spinal cord injury.

The Sum of Early Diastolic Annulus Velocities in the Mitral and Tricuspid Valve Can Predict Adverse Events After Cardiac Surgery.

OBJECTIVES: To assess whether a tissue Doppler imaging (TDI)-based parameter consisting of the sum of early diastolic velocities of the mitral annulus (Me') and tricuspid annulus (Te') can serve as a predictor of adverse outcomes after cardiac surgery. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 100 patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After anesthetic induction, transesophageal echocardiography was performed to obtain the values of the early transmitral flow velocity (E), Me', and Te'. The primary endpoint was the incidence of postoperative major organ morbidity and mortality (MOMM) events, including death, redo surgery, prolonged ventilation, stroke, sternal infection, and dialysis. Receiver operating characteristic and multivariate logistic analyses were used to examine the prognostic performance of TDI-based parameters for predicting MOMM incidence. The secondary endpoint was the incidence of death or rehospitalization for cardiovascular disease within 1 year post-discharge. TDI-based parameters were measured in 87 of the 100 patients enrolled. Me' plus Te' had better prognostic ability (area under the curve 0.771; threshold 13 cm/s; sensitivity 86.7%; specificity 64.9%) than that of Me' or E to Me' (E/Me')% and was an independent predictor of MOMM (odds ratio 0.45; 95% confidence interval 0.28-0.74, p = 0.001), whereas Me' was not. Lower Me' plus Te' (≤13 cm/s) was associated with a significantly higher incidence and earlier onset of cardiovascular events within 1 year post-discharge (p = 0.012). CONCLUSIONS: Compared with Me' and E/Me', which traditionally are used for assessing diastolic function, Me' plus Te' showed better prognostic ability for both short- and long-term outcomes of cardiac surgery.

Neuropathic pain attenuates ischemia reperfusion injury through ß2-adrenergic pathway.

AIMS: The relationship between neuropathic pain and myocardial infarction (MI) was uncertain because of some medication or underlying diseases. This study investigated the impact of neuropathic pain on ischemia reperfusion injury using isolated rat hearts and cardiomyocytes. MAIN METHODS: Male Sprague-Dawley rats were assigned to the control and allodynia (AL) groups, with the latter subjected to the fifth lumbar spinal-nerve ligation. First, isolated hearts underwent 25-min ischemia and 90-min reperfusion to assess hemodynamic changes and MI area. Second, isolated cardiomyocytes underwent 10-min laser illumination to assess the opening of mitochondrial permeability transition pore (mPTP) and cellular hypercontraction. Lastly, expression of pro-survival kinases was measured in another cardiomyocytes using flow cytometry. AL-treated hearts were concomitantly examined regarding the involvement of ß-adrenergic pathways by esmolol (ESM), ß1-blocker (100µM, AL+ESM), and ICI118551 (ICI), ß2-blocker (50nM, AL+ICI). KEY FINDINGS: All hemodynamic variables did not change significantly in between-group comparisons except at 30min of reperfusion. MI area decreased remarkably in the AL and AL+ESM groups after 90-min reperfusion. The AL+ICI group significantly increased it as compared with the AL and AL+ESM groups. Similarly, the AL and AL+ESM groups significantly inhibited mPTP opening and cellular hypercontraction, whereas the AL+ICI group reversed these effects. Enhanced expression of pro-survival kinases was observed in the AL and AL+ESM groups, but the AL+ICI group abolished this enhancement. SIGNIFICANCE: Our findings suggested that neuropathic pain possessed cardioprotective effects through inhibiting mPTP opening. The underlying mechanisms were possibly regulated by ß2-adrenergic activation and pro-survival kinase expression in cardiomyocytes.

Transcutaneous near-infrared spectroscopy for monitoring spinal cord ischemia: an experimental study in swine.

We aimed to assess the ability of near-infrared spectroscopy (NIRS) to detect spinal cord ischemia, and to evaluate changes in regional oxygen saturation (rSO2) following recovery of spinal cord circulation and cerebrospinal fluid drainage. Four 12-month-old female swine weighing 28.7-29.5 kg were acquired for this study. NIRS probes were placed along the midline of the upper (T6/7) and lower (T9/T10) thoracic vertebrae. The thoracic aorta was clamped distal of the left subclavian artery to induce spinal ischemia. Aortic cross-clamping was maintained for 30 min. Fifteen minutes after aortic de-clamping, the cerebrospinal fluid drainage catheter was opened to air, and cerebrospinal fluid drainage was initiated. Following aortic clamping, rSO2 in both upper and lower regions of the spinal cord decreased by 15 % within 5 min and by 20 % within 10 min (relative change). After aortic de-clamping, rSO2 values in both regions returned to baseline within 5 min. No changes in rSO2 in either the upper or lower vertebrae were observed following initiation of cerebrospinal fluid drainage. Histological analysis revealed that ischemic changes had occurred in all spinal levels. NIRS may be used to detect decreases in and recovery of spinal cord circulation following aortic clamping and de-clamping, whereas it may not reflect minor changes in spinal cord circulation due to cerebrospinal fluid drainage. Further clinical studies are required to investigate the potential for NIRS as an index of spinal cord circulation.

Effects of tramadol on substantia gelatinosa neurons in the rat spinal cord: an in vivo patch-clamp analysis.

Tramadol is thought to modulate synaptic transmissions in the spinal dorsal horn mainly by activating µ-opioid receptors and by inhibiting the reuptake of monoamines in the CNS. However, the precise mode of modulation remains unclear. We used an in vivo patch clamp technique in urethane-anesthetized rats to determine the antinociceptive mechanism of tramadol. In vivo whole-cell recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) were made from substantia gelatinosa (SG) neurons (lamina II) at holding potentials of 0 mV and -70 mV, respectively. The effects of intravenous administration (0.5, 5, 15 mg/kg) of tramadol were evaluated. The effects of superfusion of tramadol on the surface of the spinal cord and of a tramadol metabolite (M1) were further analyzed. Intravenous administration of tramadol at doses >5 mg/kg decreased the sEPSCs and increased the sIPSCs in SG neurons. These effects were not observed following naloxone pretreatment. Tramadol superfusion at a clinically relevant concentration (10 µM) had no effect, but when administered at a very high concentration (100 µM), tramadol decreased sEPSCs, produced outward currents, and enhanced sIPSCs. The effects of M1 (1, 5 mg/kg intravenously) on sEPSCs and sIPSCs were similar to those of tramadol at a corresponding dose (5, 15 mg/kg). The present study demonstrated that systemically administered tramadol indirectly inhibited glutamatergic transmission, and enhanced GABAergic and glycinergic transmissions in SG neurons. These effects were mediated primarily by the activation of µ-opioid receptors. M1 may play a key role in the antinociceptive mechanisms of tramadol.

Improved Performance of the Fourth-Generation FloTrac/Vigileo System for Tracking Cardiac Output Changes.

OBJECTIVES: The aims of this study were to compare cardiac output (CO) measured by the new fourth-generation FloTrac™/Vigileo™ system (Version 4.00) (COFVS) with that measured by a pulmonary artery catheter (COREF), and to investigate the ability of COFVS to track CO changes induced by increased peripheral resistance. DESIGN: Prospective study. SETTING: University Hospital. PARTICIPANTS: Twenty-three patients undergoing cardiac surgery. INTERVENTIONS: Phenylephrine (100 µg) was administered. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, including CO(REF) and CO(FVS), were measured before and after phenylephrine administration. Bland-Altman analysis was used to assess the discrepancy between CO(REF) and CO(FVS). Four-quadrant plot and polar-plot analyses were utilized to evaluate the trending ability of CO(FVS) against CO(REF) after phenylephrine boluses. One hundred thirty-six hemodynamic interventions were performed. The bias shown by the Bland-Altman analysis was-0.66 L/min, and the percentage error was 55.4%. The bias was significantly correlated with the systemic vascular resistance index (SVRI) before phenylephrine administration (p<0.001, r(2) = 0.420). The concordance rate determined by four-quadrant plot analysis and the angular concordance rate calculated using polar-plot analysis were 87.0% and 83.0%, respectively. Additionally, this trending ability was not affected by SVRI state. CONCLUSIONS: The trending ability of the new fourth-generation FloTrac™/Vigileo™ system after increased vasomotor tone was greatly improved compared with previous versions; however, the discrepancy of the new system in CO measurement was not clinically acceptable, as in previous versions. For clinical application in critically ill patients, this vasomotor tone-dependent disagreement must be decreased.

Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

BACKGROUND: Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. METHODS: Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). RESULTS: Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P < 0.01), while intracerebroventricular methysergide lowered the seizure threshold (P < 0.05 vs. saline). CONCLUSIONS: The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

The ability of the Vigileo-FloTrac system to measure cardiac output and track cardiac output changes during one-lung ventilation.

This study was aimed at comparing the cardiac output (CO) measured by the Vigileo™-FloTrac™ system with that estimated by the thermodilution pulmonary artery catheter (PAC) during one-lung ventilation (OLV) and determining the reliability of this system in tracking phenylephrine-induced CO changes during OLV. Sixteen patients scheduled for descending aorta replacement were enrolled. The study was performed 30 min after starting OLV under stable hemodynamic conditions. We recorded hemodynamic variables, CO measured by PAC thermodilution (ICO), CO measured by Vigileo™-FloTrac™ system (Version 3.02, Edwards Lifesciences, Irvine, CA, USA) (APCO), and systemic vascular resistance index (SVRI) before (T0) and after (T1) phenylephrine (100 µg) administration. We used Bland-Altman analysis to compare ICO and APCO. Polar plot and four-quadrant plot were used to assess the tracking ability of the Vigileo™-FloTrac™ system against ICO after administration of phenylephrine. Ninety hemodynamic interventions were performed. Bland-Altman analysis revealed that the mean bias between APCO and ICO was 0.05 L/min and the percentage error, 46.9 %. Four-quadrant plot analysis showed a concordance rate of 24.7 %, while polar plot analysis showed that the concordance rate was 13.3 %; the angular bias, -45.9°; radial limit of agreement, 85.3°. The bias between APCO and ICO was significantly correlated with the SVRI value (p < 0.001, r(2) = 0.822). The reliability of the Vigileo™-FloTrac™ system during OLV to estimate CO and track phenylephrine-induced CO changes was not acceptable.

Use of tricyclic antidepressants as analgesic adjuvants results in nonhazardous prolongation of the QTc interval.

BACKGROUND: Tricyclic antidepressants (TCAs) are known to prolong QTc interval. However, little is known about the QTc lengthening effect of TCAs at analgesic dosages and the predictive factors for abnormal QTc prolongation. METHODS: We conducted a single-center, retrospective observational study, and evaluated 87 patients (65 amitriptyline, 22 nortriptyline) who underwent 12-lead electrocardiogram (ECG) examinations both before and after receiving TCAs for herpes zoster pain or postherpetic neuralgia from May 2007 to January 2012. Data on QTc interval, age, gender, the type and daily dosage of TCAs, the medication period until the second ECG examination, and ECG findings were obtained from electronic medical charts. RESULTS: The median daily dosages were 25 mg/day for amitriptyline and 10 mg/day for nortriptyline. The median medication period for all participants was 62 days. TCAs significantly prolonged the QTc interval (before, 413.2 +/-17.0 ms; after, 419.9 +/- 18.9 ms, p < 0.01). Three patients showed marked QTc prolongation, but it did not exceed 500 ms, or deltaQTc of 60 ms, and none had an episode of fatal arrhythmia. Univariate logistic regression analysis revealed left ventricular hypertrophy (LVH) to be the sole risk factor for abnormal QTc prolongation. The adjusted odds ratio was 4.09 (95% CI, 1.01-16.55, p < 0.05) by multivariate logistic regression analysis. CONCLUSIONS: TCAs as analgesic adjuvant significantly prolonged the QTc interval, but within an acceptable range. LVH was a significant predictor of abnormal QTc prolongation.

A delayed case of tension pneumopericardium after total gastrectomy.

A case of tension pneumopericardium that occurred after total gastrectomy in an 80 year old woman is presented. There have been some prior case reports of pneumopericardium that occurred during positive pressure ventilation; in this patient hypotension due to tension pneumopericardium occurred after extubation. Return of spontaneous ventilation with negative-pressure breathing may have induced air aspiration into the pericardial sac from the abdominal cavity.

Detection of left ventricular dysfunction using early diastolic mitral annular velocity in patients undergoing mitral valve repair for mitral regurgitation.

OBJECTIVES: Ejection fraction (EF) is considered an unreliable index in patients with mitral regurgitation (MR). Left ventricular dysfunction (LVD) frequently occurs after mitral valve repair (MVR), with the incidence being 15% to 34%. This study aimed at investigating whether preoperative early diastolic mitral annular velocity (E') is associated with LVD after MVR. DESIGN: Retrospective study. SETTING: University hospital. PARTICIPANTS: Sixty-three patients undergoing MVR for severe MR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LVD was defined by a postoperative EF of<50%. Receiver operating characteristic (ROC) analysis and separate multivariate logistic regression models were used to examine the independent effects of echocardiographic variables on LVD risk. LVD occurred in 20 patients (31.7%). E' was correlated significantly with perioperative EF change (p = 0.019, r = 0.293). The area under the ROC curve was 0.777 (95% confidence interval [CI]: 0.644-0.911) for E', and the optimal threshold value of E' for predicting LVD was 6.5 cm/s (sensitivity, 80%; specificity, 67.4%). The frequency of LVD was 33.3% for a preoperative EF< 65%; 44.4% for preoperative EF< 65% and left ventricular end-systolic diameter>32 mm; and 88.9% for preoperative EF< 65%, left ventricular end-systolic diameter>32 mm, and E'< 6.5 cm/s (p = 0.006). Multivariate logistic regression models analysis revealed that E' was an independent risk factor for LVD (odds ratio: 1.98, 95% CI: 1.22-3.22). CONCLUSIONS: Preoperative E' value was an independent risk factor of LVD after mitral valve repair in patients with severe MR.

Discrepancy between superior vena cava oxygen saturation and mixed venous oxygen saturation can predict postoperative complications in cardiac surgery patients.

OBJECTIVE: To determine if increases in discrepancy between ScvO2 and SvO2 (ScvO2 - SvO2 = ΔSO2) during surgery in cardiac surgery patients can predict postoperative complications. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: One hundred two patients undergoing cardiac surgery were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Central venous oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) values during surgery automatically were collected. The average value of ΔSO2 for every minute was calculated. The area under the receiver operating characteristic curve for prolonged postoperative ICU stay (≥3 days) was 0.745 for ΔSO2, which was significantly different from those of ScvO2 and SvO2 (p<0.05) (ScvO2; 0.584, SvO2; 0.598). The optimal threshold value of ΔSO2 to predict prolonged ICU stay (≥3 days) was 12% (sensitivity: 72.0%, specificity: 76.9%). Postoperative ICU duration, ventilation time, and hospital stay were significantly longer in Group D patients (intraoperative maximum ΔSO2 ≥12%) than those in Group N patients (intraoperative maximum ΔSO2<12%). As for postoperative complications, the number of patients with postoperative use of intra-aortic balloon pumping, delirium, respiratory failure requiring tracheotomy, and severe complications was significantly higher in Group D patients. Multivariate logistic regression models were used to evaluate the independent effects of perioperative variables on the risk of developing prolonged ventilation (>24 hours) and prolonged ICU stay (≥3 days). A discrepancy in intraoperative ΔSO2 was an independent risk factor for prolonged postoperative ventilation and ICU stay. CONCLUSION: The discrepancy between ScvO2 and SvO2 during cardiac surgery is an independent risk factor of postoperative complications such as prolonged ICU stay and ventilation time.

Relationship between noradrenaline release in the locus coeruleus and antiallodynic efficacy of analgesics in rats with painful diabetic neuropathy.

AIMS: In animal models of neuropathic pain, the noradrenergic descending pain inhibitory pathways from the locus coeruleus (LC) may be suppressed. However, no study has investigated the correlation between noradrenaline (NA) release in the LC and efficacy of analgesics in rats with painful diabetic neuropathy. Using microdialysis and analysis of mechanical hypersensitivity, we investigated the correlation between NA release in the LC and efficacy of morphine, tramadol, and clomipramine in rats with diabetic mellitus (DM). MAIN METHODS: In freely moving rats, basal NA concentrations in LC perfusate were quantitated 72 to 96 h after microdialysis probe implantation. Following intravenous administration of each drug, NA concentrations were expressed as a percentage of basal values. We concurrently measured the threshold to elicit a paw withdrawal response every 20 min for 80 min. KEY FINDINGS: NA concentrations in the LC perfusate were significantly higher in the tramadol and clomipramine groups compared to the morphine group. Naloxone administration did not significantly affect NA concentrations. In the morphine group, NA release in the LC was not significantly correlated with the pain threshold. In contrast, in the tramadol and clomipramine groups, NA release in the LC was significantly correlated with the pain threshold. The correlation coefficient was higher in the clomipramine group than in the tramadol group. SIGNIFICANCE: Our results suggest that the descending noradrenergic pathway can play an important role in analgesia for DM neuropathy and that there is a significant correlation between NA release in the LC and the efficacy of tramadol and clomipramine.

Intrathecal gabapentin and clonidine synergistically inhibit allodynia in spinal nerve-ligated rats.

AIMS: The objective of this study was to elucidate the interaction between intrathecally administered gabapentin and clonidine on neuropathic pain associated with allodynia in the spinal nerve ligation model in the rat. MAIN METHODS: Thresholds for hind paw responses to mechanical stimuli were determined by delivering von Frey filaments to the plantar surface. The left L5 spinal nerve was ligated and a fine catheter was intrathecally implanted at the L3-4 interspace under sevoflurane anesthesia. After confirmation of the established allodynia, gabapentin at 10, 30, 60 and 100µg or clonidine at 5, 15, 30 and 50µg was injected as a monotherapy in conscious rats through the intrathecal catheter to obtain the dose-response curve of %MPE (maximum possible effect) of the antiallodynic effect and its ED(50). Gabapentin and clonidine were concomitantly administered in a fixed-dose ratio proportional to the predetermined ED(50) of these drugs, thereby obtaining a dose-response curve for the drug combination and its ED(50). The profile of the interaction between these drugs was analyzed using an isobolographic analysis. KEY FINDINGS: The ED(50) for gabapentin and clonidine were 57.3±4.0 and 20.2±1.0µg, respectively (mean±SEM). However, the co-administration of gabapentin and clonidine at a ratio of 20:7 contributed to a much smaller experimental ED(50) values (gabapentin 10.1±1.1µg, and clonidine 3.6±0.3µg) compared with their theoretical ED(50)s on the additive line in the isobologram. SIGNIFICANCE: In the L5 spinal nerve-ligated rats, the intrathecal co-administration of gabapentin and clonidine exerted a synergistic action on the mechanical antiallodynic effect.

[Case of chronic trifascicular block resulting in cardiac arrest during operation].

An 82-year-old man underwent thoracoscopic upper lobectomy of the left lung for the treatment of the lung cancer. The major complication was asymptomatic chronic trifascicular block. During the surgery, after the upper lobe had been resected, second degree atrioventricular block (Morbitz type II) occurred unexpectedly, soon evolving in complete AV block, with pulse wave disappearing, indicating pulseless electrical activity. Immediately, we used an epicardial pacing wire, and spontaneous circulation returned. Postoperatively, a permanent pacemaker was implanted. Asymptomatic chronic bifascicular block and trifascicular block rarely progress into complete AV block during operation, which we should be prepared in advance. Accordingly in some cases, preoperative insertion of a temporary pacemaker should be considered as a preventive measure.

[Prolonged pain after left hepatectomy].

We have experienced a patient complaining of the prolonged pain after left hepatectomy. The patient was a 53-year-old man. He underwent left hepatectomy for cholangiocellular carcinoma, and complained of prolonged abdominal pain for more than 10 days after the operation. After detailed examinations, we noticed duodenal perforation. After the conservative treatment, his pain was improved. In this case, the causes of the prolonged pain might be peritoneal irritation caused by gastric contents and duodenal perforation. The peritoneal irritation was caused by bile leakage and the deformity of the stomach that might be due to the enlarged dead space after left hepatectomy. We should be cautious of possible pyloric obstruction as the cause of prolonged pain after left hepatectomy.

Dexmedetomidine decreases the convulsive potency of bupivacaine and levobupivacaine in rats: involvement of alpha2-adrenoceptor for controlling convulsions.

Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is used in combination with local anesthetics for sedation and analgesia. We tested the hypothesis that dexmedetomidine used for sedation alters the convulsive potency of racemic bupivacaine and levobupivacaine in awake, spontaneously breathing rats. In the first experiments, male Sprague-Dawley rats were randomly divided into six groups: bupivacaine with no dexmedetomidine (bupivacaine control; BC), bupivacaine with small-dose dexmedetomidine (BS), bupivacaine with large-dose dexmedetomidine (BL), levobupivacaine with no dexmedetomidine (levobupivacaine control; LC), levobupivacaine with small-dose dexmedetomidine (LS), and levobupivacaine with large-dose dexmedetomidine (LL) (n = 10 for each group). Continuous infusion of dexmedetomidine (Groups BC and LC, 0 microg x kg(-1) x h(-1); Groups BS and LS, 3.6 microg x kg(-1) x h(-1); and Groups BL and LL, 10.8 microg x kg(-1) x h(-1)) was started after bolus injection (Groups BC and LC, 0 microg/kg; Groups BS and LS, 0.5 microg/kg; and Groups BL and LL, 1.5 microg/kg). Fifteen minutes after the start of the dexmedetomidine infusion, continuous infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC, LS, and LL) at 1 mg x kg(-1) x min(-1) was started and continued until tonic/clonic convulsions occurred. Dexmedetomidine achieved significantly different sedation levels both in Groups BC, BS, and BL and in Groups LC, LS, and LL (P < 0.05). Convulsive doses of bupivacaine and levobupivacaine were significantly larger in Groups BL and LL than in Groups BC and LC, respectively (P < 0.01 for both). Concentrations of bupivacaine and levobupivacaine in plasma and in brain at the onset of convulsions were also larger in Groups BL and LL than in Groups BC and LC (P < 0.01 for both). In the second experiment, yohimbine (1 mg/kg) administered 10 min before and 5 min after the start of dexmedetomidine infusion completely reversed the sedative effect of dexmedetomidine (bolus 1.5 microg/kg, followed by 10.8 microg x kg(-1) x h(-1)). Convulsive doses and plasma and brain concentrations of bupivacaine and levobupivacaine at the onset of convulsions in rats receiving yohimbine and dexmedetomidine were significantly smaller than in those receiving only dexmedetomidine (P < 0.05 for all) and were similar to those without dexmedetomidine or yohimbine. We conclude that dexmedetomidine used for sedation decreases the convulsive potency of both bupivacaine and levobupivacaine in rats. Alpha(2)-adrenoceptor agonism may be involved in this anticonvulsant potency.

Vasodilation increases the threshold for bupivacaine-induced convulsions in rats.

UNLABELLED: Bupivacaine affects the vascular resistance by peripheral and central nervous system (CNS) mechanisms. As vasoconstrictors increase the CNS toxicity of IV bupivacaine, vasodilators may decrease its CNS toxicity. We examined the hypothesis that vasodilators decrease the CNS toxicity of bupivacaine in awake, spontaneously breathing rats. Male Sprague-Dawley rats were randomly divided into control (C), nicardipine (N), and phentolamine (P) groups (n = 12 in each group). Racemic bupivacaine was administered IV at 1 mg/kg/min until tonic/clonic convulsions occurred. Saline, nicardipine (0.4 microg/min), and phentolamine (10 microg/min within 5 min, 50 microg/min thereafter) were simultaneously administered with bupivacaine in groups C, N, and P, respectively. Mean arterial blood pressure was significantly increased by infusion of bupivacaine in group C and was maintained at baseline levels before the onset of convulsions in groups N and P. The convulsive dose of bupivacaine in group C was 5.8 +/- 1.5 mg/kg, but was significantly larger in groups N and P (7.6 +/- 1.5 and 8.1 +/- 1.1 mg/kg, P = 0.02 and 0.001, respectively). However, there were no differences in total or protein-unbound plasma concentration of bupivacaine or in concentration of bupivacaine in the brain at the onset of convulsions among the 3 groups. We conclude that nicardipine and phentolamine increase the cumulative dose but do not affect the threshold plasma or brain concentrations required for bupivacaine-induced convulsions. IMPLICATIONS: Bupivacaine, a long-acting local anesthetic, induces central nervous system toxicity when its plasma concentration is increased. Nicardipine and phentolamine increased the cumulative dose but did not affect the threshold plasma concentrations, required for bupivacaine-induced convulsions, suggesting that both nicardipine and phentolamine inhibited the increase in the plasma concentration of bupivacaine by inducing peripheral vasodilation.