Deleterious effect of beta-estradiol in a rat model of transient forebrain ischemia.

Estrogen has demonstrated great potential as a therapeutic agent in focal ischemic brain injury, as exogenous beta-estradiol has proven beneficial in a variety of focal stroke models. In contrast, the relatively few studies of estrogen's efficacy in transient forebrain ischemia have produced inconsistent results. The present study was therefore designed to clarify estrogen's neuroprotective potential in selective hippocampal neuronal injury resulting from four-vessel occlusion in the rat. Female Wistar rats (normal, ovariectomized, or ovariectomized and estradiol-treated) received 5 or 10 min of ischemia. No differences in hippocampal cell loss were found amongst the groups with 10 min of ischemia. Amongst the groups with 5 min of ischemia, the mildest injury was found in the ovariectomized animals, which lost only 32% of their CA1 pyramidal cells. In comparison, mean cell losses were 54% and 49%, respectively, in intact females and in ovariectomized animals with estradiol replacement. Linear regression analysis demonstrated a highly significant relationship between cell loss and plasma estradiol levels. The mechanism by which exogenous and endogenous estrogen exacerbated the injury is unclear, as estrogen has many neuroprotective effects. On the other hand, many other reported effects of estrogen in hippocampal area CA1 might confer increased sensitivity to ischemia, either by modulating the excitatory effects of glutamate or by modifying the inhibitory effects of GABA. Determining how to modulate the various competing effects of estrogen is of both theoretical and practical importance, as it is now clear that one cannot assume that estrogen administration will always improve outcome in cerebral ischemia.

Hypertonic saline worsens infarct volume after transient focal ischemia in rats.

BACKGROUND AND PURPOSE: Hypertonic saline (HS) has been advocated as a hyperosmolar agent for the treatment of cerebral edema, especially after traumatic brain injury. We tested the hypothesis that continuous intravenous HS administered during reperfusion from transient focal cerebral ischemia attenuates infarct volume. METHODS: Halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. At the onset of reperfusion, rats received a 10-mL/kg intravenous bolus of 0.9% saline (SAL, n=8) or 7.5% SAL (chloride:acetate 50:50, n=8) followed by a continuous infusion for 22 hours. In a second series of experiments, ischemic damage was determined in cohorts treated with equivolumetric 3% saline (n=8) or 20% mannitol (n=8). In a third series, regional cerebral blood flow was measured ([(14)C]iodoantipyrine autoradiography) at 6 hours of reperfusion in 7.5%-SAL-treated (n=5) or SAL-treated (n=5) animals. RESULTS: In SAL rats, serum Na(+) was 137+/-3 and 138+/-2 mEq/L (mean+/-SEM) at baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na(+) was 136+/-2 and 154+/-2 mEq/L at baseline and reperfusion, respectively. Physiological variables and reduction in laser-Doppler signal during MCAO and early reperfusion were not different between the 2 treatment groups. Cortical infarct volume was larger in 7.5%-SAL-treated rats (121+/-14 mm(3); 30+/-3% of contralateral cortex; P<0.05) than in SAL (64+/-15 mm(3); 16+/-4% of contralateral cortex). Striatal infarct volume was unchanged by HS therapy. Ipsilateral cortical tissue volume was increased relative to the contralateral side (by 26+/-5% with SAL; by 41+/-5% with 7.5% SAL). In contrast, ischemic damage was unaffected by 3%-SAL or 20%-mannitol treatment compared with SAL. Regional cerebral blood flow during reperfusion was heterogeneous in all animals, but there was no evidence of postischemic hypoperfusion or blood flow maldistribution in 7.5%-SAL-treated animals. CONCLUSIONS: These data demonstrate that hypernatremia resulting from postischemic HS infusion worsens cortical infarct volume in transient focal cerebral ischemia. The deleterious effect is not linked to exacerbation of delayed hypoperfusion during early reperfusion (6 hours); however, blood flow defects at later recovery time points remain to be excluded. These results may have implications for HS therapy in clinical ischemic stroke.

Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats.

OBJECTIVES: We tested the following hypotheses: a) spontaneously hypertensive stroke-prone rats (SHR-SP) have more brain injury than spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) when exposed to transient focal ischemia; b) infarction size is not correlated with baseline blood pressure; and c) infarction size is inversely related to the cerebral hyperemic response to oxotremorine, a muscarinic agonist that increases cerebral blood flow (CBF) by stimulating endothelial nitric oxide synthase. DESIGN: In vivo study. SETTING: Animal laboratory in a university teaching hospital. SUBJECTS: Adult age-matched male WKY, SHR, and SHR-SP. INTERVENTIONS: Rats were instrumented under halothane anesthesia. Transient focal cerebral ischemia was produced for 2 hrs with the intravascular suture technique. Cerebral perfusion, estimated with laser Doppler flowmetry (LD-CBF), in response to intravenous oxotremorine, was measured in one cohort of rats to estimate endothelial nitric oxide synthase function. Infarction volume was measured at 22 hrs of reperfusion with 2,3,5-triphenyltetrazolium chloride staining. MEASUREMENTS AND MAIN RESULTS: Infarction volume in the striatum of SHR-SP (42+/-4 mm3) was greater than in SHR (29+/-6 mm3) or WKY (1+/-1 mm3) (n = 9 rats/strain). Resting (unanesthetized) mean arterial blood pressure was similar in SHR-SP (177+/-5 mm Hg) and SHR (170+/-5 mm Hg) despite a greater infarction volume in SHR-SP (n = 4) compared with SHR (n = 5). The percentage increase in LD-CBF signal in response to oxotremorine was similar for both groups (SHR, 64%+/-22% [n = 10]; SHR-SP, 69%+/-22% [n = 8]). However, in this cohort, cortical infarction volume was less in SHR (30%+/-4% of ipsilateral cortex) than in SHR-SP (49%+/-2% of ipsilateral cortex). CONCLUSIONS: Although SHR-SP have greater infarction volume than SHR, the mechanism of injury does not appear to be related to a difference in unanesthetized baseline mean arterial blood pressure or to an alteration in endothelium-produced nitric oxide.

sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion.

BACKGROUND AND PURPOSE: We previously showed that the intravenous administration of the potent final sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine (PPBP) provides neuroprotection against transient focal cerebral ischemia and that the protection depends on treatment duration. We tested the hypothesis that PPBP would provide neuroprotection in a model of transient focal ischemia and 7 days of reperfusion in the rat as assessed with neurobehavioral outcome and infarction volume. METHODS: Under the controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) with the intraluminal suture occlusion technique. We used laser Doppler flowmetry to assess MCAO. At 60 minutes after the onset of ischemia, rats were randomly assigned to 1 of 4 treatment groups in a blinded fashion and received a continuous intravenous infusion of control saline or 0.1, 1, or 10 micromol. kg(-1). h(-1) PPBP for 24 hours. Neurobehavioral evaluation was performed at baseline (3 to 4 days before MCAO) and at 3 and 7 days of reperfusion. Infarction volume was assessed with triphenyltetrazolium chloride staining on day 7 of reperfusion in all rats. RESULTS: Triphenyltetrazolium chloride-determined infarction volume of ipsilateral cortex was smaller in rats treated with 10 micromol. kg(-1). h(-1) PPBP (n=15, 68+/-12 mm(3), 18+/-3% of contralateral structure, P<0.05) (mean+/-SEM) compared with corresponding rats treated with saline (n=15, 114+/-11 mm(3), 31+/-3% of contralateral structure). PPBP did not provide significant neuroprotection in the caudoputamen complex. Although MCAO was associated with several alterations in behavior, the treatment with PPBP had no effect on behavioral outcomes. CONCLUSIONS: The data demonstrate that the potent final sigma(1)-receptor ligand PPBP decreases cortical infarction volume without altering neurobehavior after transient focal ischemia and prolonged reperfusion in the rat.

Effect of AR-R 17477, a potent neuronal nitric oxide synthase inhibitor, on infarction volume resulting from permanent focal ischemia in rats.

OBJECTIVE: We tested whether AR-R 17477, a selective inhibitor of neuronal nitric oxide synthase, reduces brain injury in rats subjected to permanent focal ischemia. DESIGN: Randomized within cohort; nonblinded study. SETTING: University basic science laboratory. SUBJECTS: Halothane-anesthetized male Wistar rats (n = 53). INTERVENTIONS: Rats were treated with either intravenous saline (diluent) or AR-R 17477 (1 or 3 mg/kg) 30 mins before or 60 mins after the onset of permanent focal cerebral ischemia. Infarction volume was determined at 18 or 48 hrs of ischemia. MEASUREMENTS AND MAIN RESULTS: Pretreatment with 1 mg/kg AR-R 17477 was associated with a decreased infarct volume (2,3,5-triphenyltetrazolium chloride staining) in the striatum (saline, 81+/-7 mm3; AR-R 17477, 55+/-3 mm3) but not in the cortex at 18 hrs of occlusion (saline, 302+/-29 mm3; AR-R 17477, 237+/-36 mm3). However, this therapeutic effect of AR-R 17477 was no longer evident if the rats were allowed to survive for 48 hrs before analysis of infarction volume. In fact, in this separate cohort of animals, three of eight AR-R 17477-treated and five of eight saline-treated rats died before completing 48 hrs of ischemia. Efficacy of AR-R 17477 was completely absent (even at 18 hrs of ischemia) when drug treatment was delayed until 1 hr after the onset of ischemia. Infarction volume at 18 hrs of ischemia was similar between rats treated with saline, 1 mg/kg (cortex, 229+/-43 mm3; striatum, 67+/-8 mm3) or 3 mg/kg AR-R 17477 (cortex, 284+/-34 mm3; striatum, 75+/-5 mm3). In addition, only one of eight rats treated with 3 mg/kg AR-R 17477 at 1 hr of ischemia survived 48 hrs of occlusion, compared with three of eight rats treated with saline. CONCLUSIONS: Neuronally generated nitric oxide is a mediator of brain injury during permanent focal ischemia in rats. However, severity of the ischemic insult appears to limit the therapeutic efficacy of the specific neuronal nitric oxide synthase inhibitor, AR-R 17477.

Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury.

We describe here a new strategy for the treatment of stroke, through the inhibition of NAALADase (N-acetylated-alpha-linked-acidic dipeptidase), an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. We demonstrate that the newly described NAALADase inhibitor 2-PMPA (2-(phosphonomethyl)pentanedioic acid) robustly protects against ischemic injury in a neuronal culture model of stroke and in rats after transient middle cerebral artery occlusion. Consistent with inhibition of NAALADase, we show that 2-PMPA increases NAAG and attenuates the ischemia-induced rise in glutamate. Both effects could contribute to neuroprotection. These data indicate that NAALADase inhibition may have use in neurological disorders in which excessive excitatory amino acid transmission is pathogenic.

Halothane minimum alveolar anesthetic concentration and neuronal nitric oxide synthase activity of the dorsal horn and the locus ceruleus in rats.

UNLABELLED: There is some evidence of a relationship between nitric oxide and pain control pathways. However, it is still controversial whether nitric oxide synthase (NOS) inhibitors affect minimum alveolar anesthetic concentration (MAC). We examined the effects of 7-nitro indazole (7-NI), a selective neuronal NOS (nNOS) inhibitor, on halothane MAC. With nicotinamide adenine dinucleotide phosphate diaphorase histochemistry, we also investigated the nNOS activity of the dorsal horn and the locus ceruleus in 26 Sprague-Dawley rats. 7-NI (100, 500, 1000 mg/kg intraperitoneally) reduced halothane MAC to 0.34% +/- 0.12%, 0.1% +/- 0.03%, and 0.05% +/- 0.12%, dose dependently (P < 0.01). 7-NI also reduced the number of nicotinamide adenine dinucleotide phosphate diaphorase-positive cells by 20% to 65% (P < 0.05 or 0.01) and the staining intensity of the axons in the locus ceruleus and lumbar and thoracic spinal cord as compared with the control group. 7-NI reduced the MAC observed with halothane anesthesia, which was accompanied by nNOS activity suppression in the spinal cord and the locus ceruleus. Our results support the hypothesis that the nitric oxide signaling pathway is related to MAC. IMPLICATIONS: We examined the effects of a selective neuronal nitric oxide synthase inhibitor, 7-nitro indazole, on halothane minimum alveolar anesthetic concentration and measured the nitric oxide synthase activity in the spinal cord and the locus ceruleus of Sprague-Dawley rats using nicotinamide adenine dinucleotide phosphate diaphorase staining method. 7-Nitro indazole decreased both the minimum alveolar anesthetic concentration and neuronal nitric oxide synthase activity.

Neuroprotection from focal ischemia by 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) is dependent on treatment duration in rats.

UNLABELLED: The IV administration of the potent sigma1-receptor ligand 4-phenyl-1-(4-phenylbutyl)piperidine (PPBP) provides neuroprotection against focal cerebral ischemia. We tested the hypothesis that prolonged, continuous administration of PPBP would provide further neuroprotection in a rat model of transient focal ischemia and reperfusion. Under controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 h of middle cerebral artery occlusion by the intraluminal occlusion technique. Sixty minutes after the onset of ischemia, rats were randomly assigned to six treatment groups to receive a continuous IV infusion of PPBP (1 micromol . kg(-1). h(-1) for 1, 2, 3, or 4 days or saline for 1 or 4 days. The infarction volume was assessed by triphenyltetrazolium chloride (TFC) staining on Day 4 after ischemia in all rats. The TTC-determined infarction volume of the ipsilateral cerebral cortex was smaller in rats treated with PPBP for 1 day (42+/-13 mm3; 10%+/-3% of ipsilateral hemisphere; P < 0.05) (mean+/-SEM) compared with that in corresponding 1-day control rats (124+/-22 mm; 29%+/-5% of ipsilateral hemisphere; P < 0.05) or 4-day control rats (112+/-10 mm; 26%+/-2% of ipsilateral hemisphere; P < 0.05). Cortical infarction volumes in 2-, 3-, and 4-day PPBP-treated rats were not different compared with 1- and 4-day saline-treated controls. These data demonstrate that the sigma1(-receptor ligand PPBP attenuates ischemic injury when administration is initiated 60 min after the onset of focal ischemia but that prolonged continuous treatment with PPBP beyond 24 h provides no neuroprotection. IMPLICATIONS: sigma-Ligands decrease infarction size in various animal models when given after the onset of stroke. Prolonged treatment with a potent sigma-ligand is associated with loss of therapeutic efficacy for this compound.

Intravenous basic fibroblast growth factor does not ameliorate brain injury resulting from transient focal ischemia in cats.

This study sought to test the hypothesis that intravenous basic fibroblast growth factor (bFGF) inhibits the development of brain injury during transient focal ischemia. Halothane-anesthetized cats (n=39) underwent left middle cerebral artery occlusion for 60 minutes. After the onset of reperfusion, wounds were closed and the cats were allowed to emerge from anesthesia. Experimental cats were treated with intravenous bFGF at a dose of either 2 or 5 microg/kg per hour, beginning 45 minutes after initiation of ischemia and continuing until 24 hours of reperfusion, when neurologic function and infarction volume were evaluated. The cats in the control group received diluent. Three of thirteen cats treated with bFGF 2 microg/kg/hour and six of sixteen cats treated with bFGF 5 microg/kg/hour died during the 24 hour reperfusion period. There was no difference in injury volume or neurologic evaluation score in the control group (n=10; hemisphere injury, 1301+/-306 mm3, mean+/-SE; score 53+/-3), and cats treated with either 2 microg/kg/hour (n=10; hemisphere injury, 1170+/-292 mm3; score 50+/-3) or 5 microg/kg/hour bFGF (n=10; hemisphere injury, 1343+/-374 mm3; score 50+/-2). The data collected do not support the hypothesis that intravenous bFGF is neuroprotective in a cat model of transient focal ischemia.

Gender-linked brain injury in experimental stroke.

BACKGROUND AND PURPOSE: Premenopausal women are at lower risk than men for stroke, but the comparative vulnerability to tissue injury once a cerebrovascular incident occurs is unknown. We hypothesized that female rats sustain less brain damage than males during experimental focal ischemia and that the gender difference in ischemic outcome can be eliminated by ovariectomy. METHODS: Age-matched male (M), intact female (F), and ovariectomized female (O; plasma estradiol: 4.1+/-1.6 pg/mL compared with 7.4+/-1.5 in F and 4.0+/-1.1 in M) rats from two different strains, normotensive Wistar and stroke-prone spontaneously hypertensive rats, were subjected to 2 hours of intraluminal middle cerebral artery occlusion, followed by 22 hours of reperfusion. Cerebral blood flow (CBF) was monitored throughout the ischemic period by laser-Doppler flowmetry. Infarction volume in the cerebral cortex (Ctx) and caudoputamen (CP) was determined by 2,3,5-triphenyltetrazolium chloride staining. In a separate cohort of M, F, and O Wistar rats, absolute rates of regional CBF were measured at the end of the ischemic period by quantitative autoradiography using [14C]iodoantipyrine. RESULTS: F rats of either strain had a smaller infarct size in Ctx and CP and a higher laser-Doppler flow during ischemia compared with respective M and O rats. Mean end-ischemic CBF was higher in F compared with M and O rats in CP, but not in Ctx. Cerebrocortical tissue volume with end-ischemic CBF < 10 mL/100 g/min was smaller in F than M rats, but not different from O rats. CONCLUSIONS: We conclude that endogenous estrogen improves stroke outcome during vascular occlusion by exerting both neuroprotective and flow-preserving effects.

Intraoperative cardiovascular collapse in an infant with Arnold-Chiari malformation.

We report a case of an infant with a diagnosis of Arnold-Chiari malformation who developed acute cardiovascular collapse during posterior fossa decompression surgery. Haemodynamic manifestations were hypotension and bigeminy characterized by resistance to conventional resuscitation. The aetiology was considered to be due to brainstem compression exerted to control surgical bleeding from an inadvertently lacerated sinus at an unusual site, the rim of the foramen magnum. Restoration of blood pressure and disappearance of arrhythmia immediately followed removal of the brainstem compression rather than volume or pharmacological resuscitation.

The comparison of epidural fentanyl, epidural lidocaine, and intravenous fentanyl in patients undergoing gastrectomy.

This study was conducted prospectively to compare the effect of epidural fentanyl (EP-F), epidural lidocaine (EP-L), and intravenous fentanyl (IV-F) on hemodynamic and hormonal responses to surgery and postoperative analgesic requirement in 30 patients undergoing gastrectomy during isoflurane anesthesia. An epidural catheter was placed via the T8-9 interspace. Group EP-F received fentanyl 2 micrograms/kg in 10 mL saline, and Group EP-L, 10 mL 1.5% lidocaine, epidurally; Group IV-F was given fentanyl, 2 micrograms/kg, IV. Fifty percent of the original dose was repeated every hour. Hemodynamic data and plasma hormonal levels were compared between those before and those at 1 h after skin incision. The total number of analgesic administrations within the first 48 h postoperatively were compared. Group EP-L developed more frequent episodes of hypotension. Group IV-F required higher isoflurane concentrations and the plasma epinephrine levels increased more than in Groups EP-F and EP-L. In Groups EP-L and IV-F, the plasma antidiuretic hormone (ADH) level increased more than in Group EP-F. In Groups EP-F and IV-F, the plasma cortisol and adrenocorticotropic hormone (ACTH) levels increased more than in Group EP-L. The use of postoperative analgesics was significantly less in Group EP-F. In conclusion, in Group EP-F, attenuated hormonal responses to surgery was accompanied with less hypotension and postoperative analgesic requirements were reduced.

[Comparison of airway complications on tracheal extubation in deeply sevoflurane anesthetized versus awake children].

We investigated the incidence of respiratory complications and oxygen saturation level during emergence from sevoflurane anesthesia in children whose tracheas were extubated while they were anesthetized or after they became awake. Thirty children, aged 1-10 years, were studied. Anesthesia was induced with sevoflurane or thiopental and maintained with nitrous oxide, oxygen and sevoflurane. After nitrous oxide was discontinued at the end of surgery, the patients were randomly assigned to two groups: deeply anesthetized extubation group (anesthetized group) and awake extubation group (awake group). In anesthetized group, the patients were extubated while they were administered 1.5% or higher sevoflurane in 100% oxygen. In awake group, extubation was performed while the patients were awake. The incidence of respiratory complications such as apnea, laryngospasm, bronchospasm and arrythmias was not significantly different between the two groups. There was a significantly higher incidence of the airway obstruction but less incidence of cough and breath-holding in anesthetized group. Oxygen saturation level before and after tracheal extubation was not different between the two groups. In conclusion, with proper attention to airway obstruction, it may be possible to extubate while children are deeply anesthetized with sevoflurane.

Haemodynamic, diuretic and hormonal responses to prostaglandin E1 infusion in halothane anaesthetized dogs: comparison among epidural lidocaine, epidural fentanyl and epidural saline.

Deliberate hypotension decreases blood loss and transfusion but it may be accompanied by adverse effects due either to the hypotensive agents themselves or to haemodynamic alterations. Prostaglandin E1 (PGE1) has the advantage of a diuretic effect coupled with systemic hypotension. To elucidate the mechanisms by which PGE1 induces diuresis we compared the haemodynamic, diuretic and hormonal responses to PGE1 infusion simultaneously with epidural lidocaine (EP-L n = 7), epidural fentanyl (EP-F n = 8) or epidural saline (CONT n = 7) in halothane anaesthetized mongrel dogs. All groups developed a decrease in mean arterial pressure during PGE1 infusion (from 105 +/- 24 to 77 +/- 18 mmHg in EP-L; 106 +/- 19 to 79 +/- 13 mmHg in the EP-F; and 129 +/- 14 to 106 +/- 18 mmHg in the CONT groups (mean +/- SD)) (P < 0.05). In the EP-F and CONT groups urinary output increased during PGE1 infusion (from 4.31 +/- 1.89 to 6.15 +/- 2.03 ml.min-1 and 2.71 +/- 1.23 to 4.48 +/- 1.66 ml.min-1 (P < 0.05), respectively) and was accompanied by increases in renal blood flow (from 87.0 +/- 40.7 to 111.0 +/- 42.8 ml.min-1 and from 121.6 +/- 46.6 to 158.4 +/- 64.9 ml.min-1 (P < 0.05), respectively) and in fractional excretion of sodium (FENa) (from 4.78 +/- 3.88 to 7.63 +/- 5.20% in CONT group).(ABSTRACT TRUNCATED AT 250 WORDS)

[Culture of the irrigating fluid of the epidural space obtained during chronic epidural catheterization].

The most serious complication during long-term epidural catheterization is epidural infection. Bacterial culture of the irrigating fluid of epidural space was carried out periodically in 39 patients in whom epidural catheters were inserted for a long period of time. Eight (17%) of 47 samples of epidural irrigating fluid were contaminated by the normal skin flora. All of these cases were accompanied with epidural contamination by the same organisms. No significant correlation was found between clinical signs of infection (low grade fever, leucocytosis and localized infective signs at the puncture site) and the contamination of the epidural irrigating fluid or that of the epidural catheter. When epidural irrigating fluid was contaminated, the epidural catheter was removed immediately and the patient was treated by antibiotics. None of the patients had epidural abscess or neurological deficit. In conclusion, bacterial culture of epidural irrigating fluid is valuable for the early diagnosis of epidural infection during long-term epidural catheterization.

Lumbar epidural anaesthesia prevented prostaglandin E1-induced diuretic effect in enflurane anaesthetized patients.

Prostaglandin E1 (PGE1) is used to induce deliberate hypotension during anaesthesia. The purpose of this study was to compare the PGE1-induced diuretic effect in anaesthetized patients with and without lumbar epidural anaesthesia. The changes in haemodynamic variables, urinary flow, one-hour creatinine clearance (Ccr), and fractional excretion of sodium (FENa) during injection of PGE1 or a vehicle were compared in 42 surgical patients during enflurane anaesthesia with lumbar epidural anaesthesia (EPI group) with those in 44 surgical patients during enflurane anaesthesia alone (GA group). Patients in the GA group demonstrated increases in urinary flow (114 +/- 46%) (mean +/- SE), Ccr (74 +/- 26%), and FENa (54 +/- 23%) during PGE1 infusion, which were not observed in the patients in the EPI group. Mean arterial pressure decreased during PGE1 infusion from 92 +/- 3 to 70 +/- 2 mmHg in the GA group (P < 0.01) and from 85 +/- 2 to 65 +/- 1 mmHg in the EPI group (P < 0.01). Plasma antidiuretic hormone concentration during surgery was 12.5 +/- 2.6 U.L-1 in the GA group and 2.3 +/- 0.8 U.L-1 in the EPI group (P < 0.001). It is concluded that PGE1-induced diuresis was prevented by lumbar epidural anaesthesia.

Coronary artery spasm with ventricular tachycardia after administration of methoxamine during cervical epidural anesthesia--a case report.

Coronary artery spasm occurred during thoracotomy under cervical epidural anesthesia in a 60-year-old male patient who had no prior history of myocardial ischemia. It is most likely that the administration of methoxamine induced the spasm. Hypotension and venodilatation induced by the epidural anesthesia and increased vagal tone might also contribute to the spasm.

[Anaphylactic shock with ventricular fibrillation induced by chlorhexidine].

We experienced a case in which a 66 year-old male patient developed anaphylactic shock followed by ventricular fibrillation, possibly due to intravenous aspiration of chlorhexidine used for topical application when right internal jugular vein was punctured. He was successfully resuscitated without any sequelae. Although lymphocyte transformation test failed to identify the specific allergen, IgE antibodies against chlorhexidine in the patient's serum were detected by radioallergosorbent technique. Chlorhexidine is an extensively used antiseptic, but there have been many reports regarding severe adverse reactions associated with its use. Chlorhexidine does not seem to be a safe antiseptic.

[Effects of epidural clonidine added to lidocaine solution upon the requirements of sedatives during epidural anesthesia].

The authors studied 34 patients undergoing abdominal total hysterectomy in order to evaluate whether epidural clonidine added to lidocaine solution could alter the requirements of sedatives during epidural anesthesia. Patients were randomly assigned to one of four groups; 18 ml of 2% lidocaine with 1:200,000 clonidine (n = 6), 1:100,000 clonidine (n = 7), 1:200,000 epinephrine (n = 13), or neither (plain, n = 8). The requirements of sedatives (diazepam, thiamylal) and analgesic (butorphanol) prior to the second epidural injection were compared among the four groups. The dose of intravenous diazepam or thiamylal required for sedation in the patients receiving lidocaine with 1:100,000 clonidine had a tendency to be smaller as compared with those in other three groups. There was a significant difference (P less than 0.05) in the requirement of diazepam between the patients given lidocaine with 1:100,000 clonidine and those given plain lidocaine. The present results suggest that the addition of clonidine to lidocaine solution could reduce the requirements of sedatives in epidural anesthesia.

Effective doses of epidural morphine for relief of postcholecystectomy pain.

Having previously established the effective dose of intrathecal morphine for relief of postcholecystectomy pain, we determined in this study the effective dose of epidural morphine for relief of postcholecystectomy pain in 154 patients given epidural injections of a placebo (group 1, n = 49), 2 mg morphine (group 2, n = 54), or 4 mg morphine (group 3, n = 51) intraoperatively mixed in 1.5% lidocaine. The percentage of patients who did not request an analgesic, 30 mg IM pentazocine, for relief of pain during the first 24 postoperative hours was significantly greater in groups 2 and 3 than in group 1. In patients who did need 30 mg IM pentazocine postoperatively, the number of times pentazocine was administered was also significantly greater in group 1 than in groups 2 and 3. The percentage of patients developing respiratory depression or vomiting in the first 48 postoperative hours was similar in the three groups. Based on the present data and those we previously reported for intrathecal morphine, we conclude that an epidural morphine dose of 2-4 mg and an intrathecal morphine dose of 0.06-0.12 mg are equipotent for relief of postcholecystectomy pain.