The dose-dependent effects of isoflurane on outcome from severe forebrain ischemia in the rat

Isoflurane improves outcome against cerebral ischemia in the rat. However, the optimal neuroprotective concentration has not been defined. We examined the effects of different isoflurane concentrations on outcome from severe forebrain ischemia in the rat. Fasted rats were subjected to 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration (MAC) isoflurane during 10 min bilateral carotid occlusion plus systemic hypotension. Each isoflurane concentration was administered only before ischemia. Arterial blood pressure was not pharmacologically manipulated. After ischemia, the anesthetic regimen was changed to fentanyl/nitrous oxide and maintained for 2 h. Pericranial temperature was maintained normothermic during the experiment. Neuromotor score, % dead hippocampal CA1 neurons, and cortical injury were measured 5 days postischemia. Preischemic arterial blood pressure decreased as MAC was increased. Animals administered >1.0 MAC frequently exhibited postischemic seizures resulting in increased mortality. There was no difference among MAC conditions for % dead CA1 neurons (93 approximately 95%). In the cortex, neuronal necrosis was less severe with 0.5 MAC and 1.0 MAC isoflurane relative to >1.0 MAC values. The neuromotor score in the 1.0 MAC isoflurane group was superior to the 2.5 MAC group. Dose-dependent effects of preischemic administration of isoflurane on histologic and behavioral outcome after severe forebrain ischemia were observed. Isoflurane MAC values <1.5 provided superior overall outcome relative to larger isoflurane concentrations.     

Detrimental effect of high-dose prostaglandin E1 in the treatment of ischemic ulcers

Eight patients with ischemic lower extremity ulcers were entered into a randomized, controlled trial of intravenous prostaglandin E1 (PGE1) versus placebo. All ulcers had been stable or increasing in size for at least 3 weeks prior to the study. Each patient had rest pain assessment, Doppler pressure measurements, and ulcer measurements before and after infusion. Four patients received PGE1 and four received placebo. There were no significant preinfusion differences between groups. Rest pain remained stable or improved in all patients. In the placebo group the mean absolute ankle pressure decreased 5 +/- 14 mm Hg, but the mean ankle/arm pressure ratio increased 0.03 +/- 0.06. In the PGE1 group the mean absolute ankle pressure decreased 16 +/- 16 mm Hg and the mean ankle/arm pressure ratio decreased 0.05 +/- 0.06. Neither difference is statistically significant. Patients who received placebo had no change or decrease in ulcer size, but all patients who received PGE1 had an increase in ulcer size (P = 0.05, Wilcoxon rank sum test). One of the four placebo patients required extremity amputation during follow-up of 10.5 +/- 3.5 months. All four patients in the PGE1 group required amputation within 3.3 +/- 2.6 months. Despite theoretic benefits, intravenous PGE1 may be detrimental in the treatment of ischemic ulcers.     

Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat

BACKGROUND: This study examined long-term outcome from severe forebrain ischemia in the rat, as a function of anesthetic given during the ischemic injury. METHODS: Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with either 1.4% isoflurane or 70% nitrous oxide-fentanyl. Neurologic and histologic outcomes were measured at 5 days, 3 weeks, or 3 months after ischemia. RESULTS: At 5 days, isoflurane-anesthetized rats had less damage than did fentanyl-nitrous oxide-anesthetized rats (mean +/- SD, percent alive hippocampal CA1 neurons = 58+/-29 vs. 20+/-16, respectively; P = 0.011). This was accompanied by improved motor function in the isoflurane group (P = 0.002). At 3 weeks, there was no difference between groups for either outcome variable (percent alive CA1 neurons = 35+/-26 and 36+/-28 for isoflurane and fentanyl-nitrous oxide, respectively). Similarly, at 3 months, there was no difference between groups (percent alive CA1 neurons = 56+/-27 and 60+/-27 for isoflurane and fentanyl-nitrous oxide, respectively). Morris water maze performance at 3 months was similar between anesthetic groups and was also similar to sham performance. The percent alive CA1 neurons in the fentanyl-nitrous oxide group increased with duration of recovery (P = 0.004). There were no differences among isoflurane groups over time (5 days vs. 3 weeks, P = 0.26; 5 days vs. 3 months, P = 0.99; 3 week vs. 3 months, P = 0.32). CONCLUSIONS: This study found no change in the percent alive CA1 hippocampal neurons as a function of duration of recovery from severe forebrain ischemia in isoflurane anesthetized rats. In contrast, the percent alive CA1 neurons in fentanyl-nitrous oxide-anesthetized rats tripled over 3 months of recovery. The natural history of long-term responses to forebrain ischemia requires further study before conclusions can be drawn with respect to the permanence of isoflurane neuroprotection.     

Postischemic treatment with hypothermia improves outcome from incomplete cerebral ischemia in rats

It is known that hypothermia can improve outcome when induced during ischemia. We evaluated whether hypothermia can decrease ischemic injury if it is induced after incomplete ischemia. Rats were anesthetized with 1.4% inspired isoflurane, and ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 min. Hypothermia (31 degrees C) was induced or normothermia (37 degrees C) was maintained for 1 h after completion of the ischemic challenge. Isoflurane anesthesia was maintained during this period. Five of 15 normothermic rats and 3 of 15 hypothermic rats died of stroke after ischemia. For all rats tested, hypothermic-treated animals had a significantly better neurologic outcome than normothermic rats (p less than 0.05). Histopathology showed a correlation of r = 0.67 (p less than 0.05) with neurologic outcome, and neuronal damage was significantly worse in normothermic compared with hypothermic rats (p less than 0.05). These results show that postischemic hypothermia will decrease neuronal injury and improve neurologic outcome associated with incomplete ischemia.     

Low-dose clonidine enhances pregnancy-induced analgesia to visceral but not somatic stimuli in rats

This is one of a series of experiments designed to examine the possible pharmacologic basis for analgesia normally associated with pregnancy. The antinociceptive effects of low-dose (0.1 mg/kg) subcutaneous clonidine on analgesia associated with pregnancy were evaluated in rats. Colorectal distention thresholds and tail-flick latencies were determined in timed pregnant rats (n = 27) before mating, on days 7 and 21 of gestation, and on postpartum day 7. Immediately after baseline testing on each of those days, animals received 0.1 mg/kg clonidine subcutaneously and were retested 30 min later. On day 21 of gestation, 20 micrograms/kg naloxone (n = 9) and 0.2 mg/kg yohimbine (n = 5) were intravenously administered after clonidine testing, and animals were retested 15 min later. In the absence of clonidine, pregnant animals demonstrated a statistically significant increase in their tolerance of colorectal distention pressures and longer latencies to tail-flick withdrawal on day 21 of gestation. Clonidine produced a further significant increase in distention thresholds on day 21 of gestation but did not change these thresholds on any other day, nor did it change tail-flick latencies. Naloxone and yohimbine reversed the effect of clonidine on the distention thresholds on day 21. Systemic clonidine, at a dose lower than that required to produce antinociception in nonpregnant rats, enhanced pregnancy-induced analgesia to visceral stimulation late in pregnancy, an effect that was reversed by naloxone and yohimbine. These results suggest a synergistic antinociceptive effect of clonidine due to an interaction with an endogenous opiate system that is only activated late in pregnancy.     

Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats

BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide. METHODS: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25 microgram. kg-1. h-1. 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. RESULTS: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. CONCLUSIONS: The results indicate that improved histologic-behavioral outcome provided by isoflurane anesthesia cannot be explained by differential vasodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypoperfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on periischemic CBF must be responsible for beneficial effects of isoflurane in this model.     

Protective effects of prostaglandin E1 on normothermic liver ischemia.

Effects of treatment with prostaglandin E1 (PgE1) on normothermic liver ischemia were studied in male Lewis rats. Animals were subjected to 90 min of warm liver ischemia. Two groups of rats were constituted: group A (no treatment) and group B (PgE1 treatment). PgE1 (100 micrograms/kg) was given as a bolus 2 min before induction of ischemia and 2 min before the end of ischemia. Survival rates were assessed and, 6 h after the end of ischemia, serum transaminases, histology of the liver, Kupffer cell activity were evaluated. PgE1 treatment significantly improved survival rate (80%) in comparison with the nontreated group (40%). A significant reduction in transaminase levels was observed after PgE1 The extent of necrosis and congestion was improved by PgE1 treatment. Sheep red blood cell 51Cr liver uptake was deeply depressed 6 h after the end of ischemia in group A (6 +/- 2.3%/g tissue), and was significantly higher (p less than 0.001) after PgE1 administration in group B (32.98 +/- 11.7%/g tissue). Our results demonstrate that PgE1 is able to protect the liver from ischemic insult. The mechanism by which prostaglandins exert this beneficial effect on normothermic liver ischemia may be related to their action on hepatic macrophages.     

High-dose S(+)- ketamine improves neurological outcome following incomplete cerebral ischemia in rats

PURPOSE: To determine the effects of the non-competitive NMDA-receptor antagonist S(+)-ketamine on neurological outcome in a rat model of incomplete cerebral ischemia. METHODS: Thirty rats were anesthetized, intubated and mechanically ventilated with isoflurane, O2 30% and nitrous oxide 70%. Following surgery animals were randomly assigned to one of the following treatment groups: Rats in group 1 (n = 10,OFF control) received fentanyl (bolus: 10 microg x kg(-1) i.v.; infusion 25 microg x kg(-1) x h(-1)) and N2O 70% / O2. Rats in group 2 (n = 10) received O2 30% in air and low-dose S(+)-ketamine (infusion: 0.25 mg x kg(-1) x min(-1)). Rats in group 3 (n = 10) received O2 30% in air and high-dose S(+)-ketamine (infusion: 1.0 mg x kg(-1) min(-1)). Following 30 min equilibration period ischemia was induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mm Hg for 30 min. Plasma catecholamines were assayed before and at the end of ischemia. Neurological deficit was evaluated for three postischemic days. RESULTS: Neurological outcome was improved with high-dose S(+)-ketamine when compared to fentanyl / N2O -anesthetized controls (9 vs. 1 stroke related deaths, P<0.05). Increases in plasma catecholamine concentrations were higher in fentanyl / N2O -anesthetized (adrenaline baseline 105.5+/-92.1 pg x ml(-1), during ischemia 948+/-602.8 pg x ml(-1), P<0.05; noradrenaline baseline 407+/-120.2 pg x ml(-1), ischemia 1267+/-422.2 pg x ml(-1), P <0.05) than in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71+/-79.5 pg x ml(-1), ischemia 237 +/-131.9; noradrenaline baseline 317.9+/-310.5 pg x ml(-1), ischemia 310.5+/-85.7 pg x ml(-1)). CONCLUSION: Neurological outcome is improved following incomplete cerebral ischemia with S(+)-ketamine. Decreases in neuronal injury may be related to suppression of sympathetic discharge.     

Ketamine decreases plasma catecholamines and improves outcome from incomplete cerebral ischemia in rats.

Central neuroexcitatory receptors (N-methyl-D-aspartate [NMDA], non-NMDA) may affect outcome from cerebral ischemia by altering sympathetic nervous system activity. We tested whether ketamine, an NMDA antagonist, and NBQX, a non-NMDA antagonist, improve outcome from incomplete cerebral ischemia in the rat and whether a change in outcome is related to changes in plasma catecholamines. There were five treatment groups: group 1 (control, n = 10) received a fentanyl infusion at a rate of 25 microgram.kg-1.h-1 and ventilation with 70% N2O in O2. Group 2 (n = 10) received the same anesthetic treatment and were given an intraperitoneal injection of 30 mg/kg NBQX 15 min prior to ischemia. Group 3 (n = 10) received a ketamine infusion of 1.0 mg.kg-1.min-1 and ventilation with room air. Group 4 (n = 10) received a ketamine infusion of 1.5 mg.kg-1.min-1. Group 5 received a ketamine infusion of 1 mg.kg-1.min-1 plus a 6 ml/kg intraperitoneal injection of 40% glucose solution 15 min before the start of ischemia. Ischemia was produced by right common carotid ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Blood gases, pH, and skull temperature were controlled during ischemia. Plasma glucose increased during ischemia in all groups but was lower in ketamine-anesthetized rats (groups 3 and 4). Glucose-loaded ketamine-anesthetized rats (group 5) had plasma glucose concentrations similar to the control group. Plasma epinephrine and norepinephrine concentrations were significantly less in ketamine-anesthetized rats (groups 3, 4, and 5) during ischemia compared to controls (P less than 0.05). Neurologic outcome was significantly better (P less than 0.05) in all ketamine-treated rats (groups 3, 4, and 5) compared to the control group, regardless of plasma glucose concentration during ischemia. NBQX did not improve neurologic outcome. These results suggest that ketamine improves neurologic outcome from incomplete cerebral ischemia by a mechanism related to a decrease in plasma catecholamine activity.     

前列地尔促进移植肝功能早期恢复的临床研究

目的　探讨前列地尔对术后早期移植肝功能恢复的影响。方法　对 6例肝移植患者从术中开始通过中心深静脉用微量泵给予前列地尔 (治疗组 ) ,术后同法持续 2 4h给予 ,拔除中心静脉插管后通过外周静脉缓慢输注 ,直至术后 2 0d ;另有 4例除不用前列地尔外 (对照组 ) ,其余处理同治疗组。观察两组患者术后 2 1d内的血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)、总胆红素 (TBil)和直接胆红素 (DBil)水平 ,记录胆汁引流量 ;记录各例术后在重症监护病房的留置时间。结果　术后第 1d两组患者的ALT和AST水平均显著升高 ,但治疗组显著低于对照组 (P <0 .0 1) ,3～ 5d后前述指标均迅速恢复至正常水平 ;两个组术后血清TBil和DBil均开始缓慢升高 ,但治疗组的水平明显低于对照组 (P <0 .0 5 ) ,且升高持续时间也短于对照组 (P <0 .0 5 ) ;治疗组的胆汁引流量显著多于对照组 (P <0 .0 5 ) ,需要重症监护的时间显著短于对照组 (P <0 .0 1)。结论　术后早期应用前列地尔对促进移植肝功能的早期恢复有积极意义。     

Intravenous infusion of prostaglandin E1 (PGE1) in management of limb ischemia

Twenty-three patients who had advanced arteriosclerotic disease of the lower extremities as manifested by rest pain, nonhealing ischemic ulcers, or impending gangrene and who were not candidates for direct arterial revascularization procedure underwent intravenous infusion of prostaglandin E1 (PGE1). Thirty-nine per cent of the patients showed subjective and/or objective improvement in the blood supply, and in 22 per cent (5 patients) amputation was avoided. Complications were minor and disappeared once the infusion was discontinued. PGE1 in prescribed dosages can be safely infused intravenously. Even though the results are not as encouraging as when PGE1 is given by the intra-arterial route, IV therapy improves the ischemic symptoms and avoids the necessity of amputation in some patients.     

Albumin or hetastarch improves neurological outcome and decreases volume of brain tissue necrosis but not brain edema following closed-head trauma in rats.

The present study examined whether hemodilution with 20% human serum albumin (HSA) or 10% hydroxyethyl starch (HES) improved the outcome from closed-head trauma (CHT) in rats. Rats anesthetized with halothane were given one of three hemodilution solutions (i.e., 20% HSA, 10% HES, or control [0.9% saline]) after CHT or sham surgery. CHT was delivered using a weight drop impact of 0.5 J onto the closed cranium. The hemodilution solution (volume = 1% of body weight) was given just after determining the neurological severity score (NSS) at 1 hour following CHT. The NSS was determined again at 24, 48, and 72 hours following CHT. At 72 hours, brains were removed, and brain edema and brain tissue necrosis volume were determined. Solutions of 20% HSA and 10% HES significantly improved brain tissue necrosis volume (143 +/- 72 mm3 and 104 +/- 53 mm3 as compared to 271 +/- 65 mm3 in controls, mean +/- SD) and NSS (12 +/- 2 and 9 +/- 2 as compared to 15 +/- 2 in controls at 72 hours, median +/- range) but not brain edema. The hematocrit decreased similarly in all groups during hemodilution. Hemodilution with 20% HSA and 10% HES following CHT in rats did not decrease brain edema but did decrease brain tissue necrosis volume and NSS (improved neurological function), suggesting that the beneficial effect of hemodilution resulted not from decreased edema formation but rather from effects not measured in this study such as improved perfusion of the salvageable brain tissue surrounding the core injury.     

Survival in nonocclusive mesenteric ischemia: early diagnosis by multidetector row computed tomography and early treatment with continuous intravenous high-dose prostaglandin E(1)

OBJECTIVES: The aim of the study was to establish a procedure for early diagnosis and treatment of nonocclusive mesenteric ischemia (NOMI). BACKGROUND: NOMI has a high mortality rate, and early diagnosis and treatment are important for improving survival in patients with this condition. METHODS: The subjects were 22 patients treated at our hospital over 13 years. Diagnostic criteria for NOMI were established based on the first 13 cases. In the 9 more recent cases, we performed abdominal contrast multidetector row computed tomography (MDCT) upon suspicion of NOMI based on these criteria. Imaging allowed definite diagnosis of NOMI, and continuous intravenous high-dose PGE1 administration was initiated immediately after diagnosis (dose, 0.01-0.03 microg/kg per min; mean administration period, 4.8 days). RESULTS: Nine of the first 13 patients died of multiple organ failure associated with multiple intestinal necrosis. These cases suggested that NOMI may develop when 3 of the following 4 criteria are met after cardiovascular surgery or maintenance dialysis in elderly patients: symptoms of the ileus develop slowly from abdominal symptoms, such as an unpleasant abdominal feeling or pain; a requirement for catecholamine treatment; an episode of hypotension; and slow elevation of the serum transaminase level. In the 9 recent cases, definite diagnosis was made from spasm of the principal arteries in arterial volume rendering and curved planar reformation MDCT images. Early treatment with PGE1 prevented acute-stage NOMI in 8 of the 9 cases. CONCLUSIONS: Early diagnosis of NOMI is possible using the above criteria and MDCT, and initiation of PGE1 treatment may increase survival in patients with NOMI.     

Ganglionic blockade improves neurologic outcome from incomplete ischemia in rats: partial reversal by exogenous catecholamines

The authors investigated the effects of nitrous oxide (N2O), ganglionic blockade, and combined infusion of epinephrine and norepinephrine (0.1 microgram.kg-1.min-1 each) on neurologic outcome and brain histopathology in a model of incomplete cerebral ischemia in the rat. Thirty-eight Sprague-Dawley rats were assigned to one of four groups: group 1 (n = 10) received 70% N2O in O2; group 2 (n = 12) received 70% N2O in O2, plus ganglionic blockade; and group 3 (n = 10) received 70% N2O in O2, plus ganglionic blockade and catecholamine infusion. In groups 1-3, ischemia was produced by right carotid occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Group 4 (n = 6) received 70% N2O in O2 and hemorrhagic hypotension without carotid occlusion for 30 min. At the end of ischemic and nonischemic hypotension, the carotid artery was unclamped and the blood slowly reinfused. Neurologic outcome was evaluated for a 5-day period with a graded deficit score (0 = normal to 39 = stroke-related death). Brain histopathology was evaluated in coronal section at the level of the caudate nucleus according to a 6-point scale, from 0 = normal to 5 = total hemispheric infarction. Arterial blood gases, pH, and body temperature were kept constant in all groups. Compared to N2O alone (group 1), treatment with ganglionic blockade (group 2) decreased plasma catecholamines by 75% and significantly improved neurologic outcome from incomplete cerebral ischemia (P less than 0.05). Administration of exogenous epinephrine and norepinephrine in the presence of N2O and ganglionic blockade (group 3) worsened neurologic outcome compared to group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats

Background  

Blood–brain barrier (BBB) disruption mediated by matrix metalloproteinase (MMPs) activation is a critical event during cerebral ischemia. The inhibition of MMP might be a potential approach to protect against secondary injury. The present study was designed to determine the effects of quercetin on BBB disruption and MMP activity, in a focal ischemia model induced by photothrombosis, in rats.     

Isoflurane delays but does not prevent cerebral infarction in rats subjected to focal ischemia

BACKGROUND: Several investigations have shown that volatile anesthetics can reduce ischemic cerebral injury. In these studies, however, neurologic injury was evaluated only after a short recovery period. Recent data suggest that injury caused by ischemia is a dynamic process characterized by continual neuronal loss for a prolonged period. Whether isoflurane-mediated neuroprotection is sustained after a longer recovery period is not known. The current study was conducted to compare the effect of isoflurane on brain injury after short (2-day) and long (14-day) recovery periods in rats subjected to focal ischemia. METHODS: Fasted Wistar-Kyoto rats were anesthetized with isoflurane and randomly allocated to an awake (n = 36) or an isoflurane (n = 34) group. Animals in both groups were subjected to focal ischemia by filament occlusion of the middle cerebral artery. Pericranial temperature was servocontrolled at 37 degrees C throughout the experiment. In the awake group, isoflurane was discontinued and the animals were allowed to awaken. In the isoflurane group, isoflurane anesthesia was maintained at 1.5 times the minimum alveolar concentration. After 70 min of focal ischemia, the filament was removed. Animals were killed 2 days (awake, n = 18; isoflurane, n = 17) and 14 days (awake, n = 18; isoflurane, n = 17) after ischemia. The volumes of cerebral infarction and selective neuronal necrosis in the animals were determined by image analysis of hematoxylin and eosin-stained coronal brain sections. RESULTS: Cortical and subcortical volumes of infarction were significantly less in the isoflurane 2-day group (26 +/- 23 mm3 and 17 +/- 6 mm3, respectively) than in the awake 2-day group (58 +/- 35 mm3, P < 0. 01; and 28 +/- 12 mm3, P < 0.01, respectively). By contrast, cortical and subcortical volumes of infarction in the awake (41 +/- 31 mm3 and 28 +/- 16 mm3, respectively) and isoflurane (41 +/- 35 mm3 and 19 +/- 8 mm3, respectively) 14-day groups were not different (cortex, P = 0.99; subcortex, P = 0.08). The volume of cortical tissue in which selective neuronal necrosis was observed, however, was significantly less in the isoflurane 14-day group (5 +/- 4 mm3) than in the awake 14-day group (17 +/- 9 mm3, P < 0.01). The total number of necrotic neurons in the region of selective neuronal necrosis was significantly smaller in the isoflurane 14-day group than in the awake 14-day group (P < 0.01). CONCLUSION: Compared with the awake state, isoflurane reduced the extent of infarction assessed 2 days after focal ischemia in rats. At 14 days, however, only selective neuronal necrosis, but not infarction, was reduced by isoflurane. These results suggest that isoflurane delays but does not prevent cerebral infarction caused by focal ischemia. Isoflurane may attenuate the delayed development of selective neuronal necrosis in periinfarct areas in this animal model.     

Prevention of spinal cord ischemia by selective intercostal arterial infusion of prostaglandin E1

Purpose: A new protective method against the spinal cord ischemia that occurs during aortic clamping was investigated in dogs. Oxygenated blood containing prostaglandin E₁ (PGE₁) was administered at the clamped aortic segment, and the effect was evaluated by measurement of the sensory evoked spinal potential (SESP). Methods: In 30 dogs, a thoracotomy was made with dissection of the thoracic aorta. After intravenous heparin (100 units/kg) was administered, the proximal and distal descending thoracic aortas were cross-clamped for 60 minutes. Group A (n = 10) received oxygenated blood at the rate of 1.0 ml/kg/min. Groups B (n = 10) and C (n = 10) received oxygenated blood at the same rate, with PGE₁ at the dosage of 25 and 50 ng/kg/min, respectively. The infusion was continuously administered throughout the entire period of ischemia. SESP was measured with epidural electrodes before clamping, 10 and 60 minutes after clamping, and 10 and 60 minutes after declamping. Neurologic outcome was assessed at 24 hours after the operation and graded according to the method of Tarlov. Results: There was no significant hemodynamic change in any group. At 60 minutes after clamping and at 10 and 60 minutes after declamping, the amplitude of SESP was lower than that at preclamping in groups A and B (p < 0.05). At 60 minutes after clamping and at 10 and 60 minutes after declamping, the SESP was more markedly decreased in group A compared with groups B and C. Regarding postoperative neurologic outcome, the dogs with SESP amplitude of more than 50% of the preclamping control value at 60 minutes after clamping showed neither paralysis nor paraplegia. Seven of nine dogs with less than 50% SESP amplitude showed neurogenic deficit. In a comparison of groups A, B, and C, the Tarlov score for group A dogs was significantly lower than that for group C dogs (p < 0.05). Conclusion: In this model, PGE₁ administration at the rate of 50 ng/kg/min showed sufficient spinal cord protection against ischemia without a decrease in the blood pressure. Further studies are needed to determine the dose that will provide the maximal protective effect and to determine the maximum duration of ischemia against which PGE₁ shows protective effects. (J Vasc Surg 1998;28:301-7.)     

Parathyroid hormone, but not prostaglandin E2, changes the shape of osteoblasts maintained on bone in vitro

Parietal bones from 2-week-old rats were dissected free from the sutural regions, dura mater, and periosteum, leaving the surface covered with osteoblasts and some osteoclasts. Prostaglandin (PG) production by these "stripped" bones under basal conditions and after exposure to parathyroid hormone (PTH) was measured by radioimmunoassay of the culture medium (minimum essential medium with or without added 10% heat-inactivated fetal calf serum). Cultured specimens were examined by scanning electron microscopy for changes in osteoblast length, orientation, ruffling, and overlap. As demonstrated previously, PTH caused the osteoblasts to elongate, align, and show fewer ruffles compared to controls. PTH increased PG synthesis by the stripped bones. Indomethacin inhibited PG formation but did not affect the osteoblast shape change. PGE2, indomethacin, or both drugs together had no discernible effect on any morphologic features. These findings indicate that PGE2 does not change osteoblast shape and that the cell shape change with PTH is not mediated by endogenous prostanoids.