Neurologic deficits after cervical laminectomy in the prone position.

New neurologic deficits are known to occur after spine surgery. We present four patients with cervical myeloradiculopathy who underwent cervical laminectomy, fusion, or both in the prone position, supported by chest rolls. Three patients were intubated and positioned while awake, whereas the fourth patient was positioned after induction. Surgeries were successfully carried out, except for transient episodes of relative hypotension intraoperatively. On recovery from anesthesia, all patients were noted to have new neurologic deficits. Immediate CT myelography or surgical reexploration was unremarkable. All patients improved gradually with administration of high-dose steroids and induction of hypertension. Use of the prone position with abdominal compression may compromise spinal cord perfusion and lead to spinal cord ischemia. The use of frames that prevent abdominal compression, as well as avoidance of perioperative arterial hypotension, is important in maintaining adequate spinal cord perfusion during and after decompressive spinal cord surgery.

Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs.

OBJECTIVE: The potent antioxidant LY231617 (2,6-bis(1,1-dimethylethyl)-4-[[(1-ethyl)amino]methyl]phenol hydrochloride) is cytoprotective in models of focal and global cerebral ischemia. We tested the hypothesis that administration of LY231617, before the insult, would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow (CBF) during the reperfusion period. DESIGN: Randomized, controlled, prospective study. SETTING: Research laboratory at a university teaching hospital. SUBJECTS: Twenty-four male beagle dogs. INTERVENTIONS: All experiments were performed under pentobarbital anesthesia and controlled conditions of normoxia, normocarbia, and normothermia. Twelve control dogs received 20 mL/kg saline (vehicle) bolus into the right atrium and 0.01 mL/kg/min i.v., beginning 20 mins before 13 mins of global cerebral ischemia (by aortic occlusion). The dogs in the drug-treated group received LY231617 as a 10-mg/kg bolus 20 mins before ischemia and 5 mg/kg/hr throughout reperfusion (n = 12). CBF was measured using radiolabeled microspheres. MEASUREMENTS AND MAIN RESULTS: Total CBF, cerebral oxygen consumption, and somatosensory evoked potentials (SEP) were measured during 240 mins of reperfusion. CBF was similar in both vehicle- and LY231617-treated animals at baseline and throughout the experimental period. In all animals, SEP became isoelectric between 60 and 100 secs after cross-clamping of the ascending aorta. SEP amplitude recovery was significantly higher in drug-treated animals compared with controls (73%+/-15% vs. 39%+/-14% [mean+/-SEM] from baseline at 120 mins [p<.05] and 86%+/-12% vs. 49%+/-14% from baseline at 240 mins [p< .05]). CONCLUSIONS: LY231617 improves recovery of cerebral electrical function after complete transient global ischemia via mechanisms unrelated to cerebral circulatory effects.

Effects of positive end-expiratory pressure ventilation on cerebral venous pressure with head elevation in dogs.

Mechanical ventilation with positive end-expiratory pressure (PEEP) may prevent venous air embolism in the sitting position because cerebral venous pressure (Pcev) could be increased by the PEEP-induced increase in right atrial pressure (Pra). Whereas it is clear that there is a linear transmission of the PEEP-induced increase in Pra to Pcev while the dog is in the prone position, the mechanism of the transmission with the dog in the head-elevated position is unclear. We tested the hypothesis that a Starling resistor-type mechanism exists in the jugular veins when the head is elevated. In one group of dogs, increasing PEEP linearly increased Pcev with the dog in the prone position (head at heart level, slope = 0.851) but did not increase Pcev when the head was elevated. In another group of dogs, an external chest binder was used to produce a larger PEEP-induced increase in Pra. Further increasing Pra increased Pcev only after Pra exceeded a pressure of 19 mmHg (break pressure). This sharp inflection in the upstream (Pcev)-downstream (Pra) relationship suggests that this may be caused by a Starling resistor-type mechanism. We conclude that jugular venous collapse serves as a significant resistance in the transmission of Pra to Pcev in the head-elevated position.

Neuroprotective FK506 does not alter in vivo nitric oxide production during ischemia and early reperfusion in rats.

BACKGROUND AND PURPOSE: Previous studies have demonstrated that the immunosuppressant FK506 provides neuroprotection in experimental brain injury and suggest that this action may be mediated by suppression of neuronal nitric oxide synthase activation that occurs after ischemic depolarization. We sought to determine whether FK506 reduces histological injury after middle cerebral artery occlusion (MCAO) in the rat and whether the neuroprotective effect is mediated via suppression of in vivo nitric oxide (NO) production during ischemia or early reperfusion. METHODS: Under controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 hours of MCAO by the intraluminal occlusion technique in a blinded, randomized experimental trial. Ipsilateral parietal cortical laser-Doppler flowmetry was monitored throughout ischemia. Animals were randomly assigned to 4 pretreatment groups: intravenous FK506 0.3 mg/kg or 1. 0 mg/kg, vehicle (cremaphor), or an equivalent volume of saline administered 30 minutes before MCAO. Infarction volume was assessed by a triphenyltetrazolium chloride staining at 22 hours of reperfusion. In separate experiments, microdialysis probes were placed bilaterally into the striatum. Rats were perfused with artificial cerebrospinal fluid containing 3 micromol/L [14C]- L-arginine for 3 hours and then subjected to 2 hours of right MCAO. Intravenous 0.3 mg/kg FK506 or cremaphor was given 30 minutes before right MCAO. Right-left differences between [14C]-L-citrulline in the effluent were assumed to reflect differences in NO production. RESULTS: All values are mean+/-SE. FK506 at 0.3 mg/kg reduced infarction volume in cortex: 40+/-12 mm3 compared with saline (109+/-15 mm3) and cremaphor vehicle (148+/-23) (P<0.05). Striatal infarction was also reduced by low-dose FK506: 16+/-4 mm3 versus 36+/-4 mm3 and 34+/-4 mm3 in saline and vehicle groups, respectively (P<0.05). High-dose treatment reduced infarction volume in cortex (61+/-14 mm3, P<0.05 from saline and vehicle groups) and in striatum (22+/-5 mm3, P<0.05 from saline and vehicle groups). [14C]-L-citrulline recovery via microdialysis was markedly enhanced in ischemic compared with nonischemic striatum. However, ischemia-evoked [14C]-L-citrulline recovery was not different in FK506-treated rats compared with vehicle-treated animals. CONCLUSIONS: These data demonstrate that FK506 provides robust neuroprotection against transient focal cerebral ischemia in the rat. The mechanism of protection in vivo is not through attenuation of ischemia-evoked NO production during MCAO and early reperfusion.

The effect of the prone position on pulmonary mechanics is frame-dependent.

UNLABELLED: By compressing the abdomen and restricting chest wall movement, the prone position compromises pulmonary compliance. For spine surgery, placing the anesthetized patient into the prone position increases the risk of improper ventilation. In this study, we tested the hypothesis that the compromise in pulmonary compliance is related to the patient's body habitus and the surgical frame used to support the patient while in the prone position. Seventy-seven adult patients were divided into three groups according to body mass index: normal (n = 36) < or = 27 kg/m2, heavy (n = 21) 28-31 kg/m2, and obese (n = 20) > or = 32 kg/m2. Patients were placed in the prone position supported by chest rolls, a Wilson frame, or the Jackson spinal surgery table (Jackson table) according to the surgeon's preferences. Peak airway pressure (at the proximal endotracheal tube), pleural pressure (esophageal balloon), and mean arterial pressure were recorded in the supine position and prone position within 15 min of the turn. Dynamic mean (+/- SD) pulmonary compliance (mL/cm H2O) decreased when turning from the supine to the prone position in all three body mass groups when using chest rolls (normal 37+/-5 to 29+/-6; heavy 43+/-2 to 34+/-4; obese 42+/-8 to 32+/-6) or the Wilson frame (normal 39+/-6 to 32+/-7; heavy 43+/-16 to 34+/-10; obese 36+/-11 to 28+/-9). The dynamic pulmonary compliance was not altered in patients positioned on the Jackson table. Regardless of body habitus, using the Jackson table for prone positioning was not associated with a significant alteration in pulmonary or hemodynamic variables. We conclude that moving patients from the supine to the prone position during anesthesia results in a decrease in pulmonary compliance that is frame-dependent but that is not affected by body habitus. IMPLICATIONS: We hypothesized that compromise in pulmonary compliance in the prone position is related to the patient's body mass index and the surgical frame used. In this study, we demonstrated that prone positioning during anesthesia results in a decrease in pulmonary compliance that is frame-dependent but that is not affected by body mass index.

Estrogen-mediated neuroprotection after experimental stroke in male rats.

BACKGROUND AND PURPOSE: We have previously shown that 17beta-estradiol reduces infarction volume in female rats. The present study determined whether single injection or chronic implantation of estrogen confers neuroprotection in male animals with middle cerebral artery occlusion (MCAO) and whether there is an interaction with endogenous testosterone. METHODS: Male Wistar rats were treated with 2 hours of reversible MCAO. In protocol 1, acute versus chronic estrogen administration was examined in groups receiving the following: Premarin (USP) 1 mg/kg IV, immediately before MCAO (Acute, n=13, plasma estradiol=171+/-51 pg/mL); 7 days of 25 microg (E25, n=10, 10+/-3 pg/mL) or 100 microg 17beta-estradiol (E100, n=12, 69+/-20 pg/mL) by subcutaneous implant; or saline (SAL, n=21, 3+/-1 pg/mL). Laser-Doppler flowmetry was used to monitor the ipsilateral parietal cortex throughout the ischemic period and early reperfusion. At 22 hours of reperfusion, infarction volume was determined by 0 2,3,5-triphenyltetrazolium chloride staining and image analysis. In protocol 2, rats were castrated to deplete endogenous testosterone and then treated with estradiol implants: castration only (CAST, n= 13, estradiol=5+/-2 pg/mL), sham-operated (SHAM, n= 10, 4+/-2 pg/mL), estradiol implant 25 microg (CAST+E25, n=16, 7+/-2 pg/mL) or 100 microg (CAST+E100, n=14, 77+/-14 pg/mL). RESULTS: Cortical infarct volumes were reduced in all estrogen-treated groups: Acute (21+/-4% of ipsilateral cortex), E25 (12+/-5%), and E100 (12+/-3%) relative to SAL (38+/-5%). Caudate infarction was similarly decreased: Acute (39+/-7% of ipsilateral striatum), E25 (25+/-7%), and E100 (34+/-6%) relative to SAL (63+/-4%). Castration did not alter ischemic outcome; cortical and caudate infarction (percentage of respective ipsilateral regions) were 37+/-5% and 59+/-5% in CAST and 39+/-7% and 57+/-5% in SHAM, respectively. Estrogen replacement reduced infarction volume in castrated animals in cortex (19+/-4% in CAST+E25 and 12+/-4% in CAST+E100) and in caudate (42+/-6% in CAST+25 and 20+/-7% in CAST + 100). Laser-Doppler flowmetry results during ischemia and reperfusion was not different among groups. CONCLUSIONS: Both acute and chronic 17beta-estradiol treatments protect male brain in experimental stroke. Testosterone availability does not alter estradiol-mediated tissue salvage after MCAO.

Hemodynamics of pancreatic ischemia in cardiogenic shock in pigs.

BACKGROUND & AIMS: Previous studies have shown that the renin-angiotensin axis plays a pivotal role in vasoconstriction of the gastric, intestinal, and hepatic circulations during cardiogenic shock. The aim of this study was to evaluate the fundamental hemodynamic mechanism of pancreatic ischemia during cardiogenic shock induced by pericardial tamponade. METHODS: Cardiogenic shock was induced by pericardial tamponade. Cardiac output (and total peripheral vascular resistance) was determined by thermodilution. Pancreatic blood flow (and vascular resistance) was determined with radiolabeled microspheres. RESULTS: Graded increases in pericardial pressure produced corresponding decreases in cardiac output to 42% +/- 1% and arterial pressure to 67% +/- 3% of baseline and increases in total peripheral vascular resistance to 146% +/- 5% of baseline. Pancreatic blood flow decreased disproportionately to 30% +/- 3% of baseline, because of a disproportionate increase in pancreatic vascular resistance to 220% +/- 19% of baseline. Previously confirmed blockade of the renin-angiotensin axis ablated this response, whereas confirmed blockade of the alpha-adrenergic system or vasopressin system had no significant effect. Without shock, central intravenous infusions of angiotensin II closely mimicked this selective vasoconstriction. CONCLUSIONS: Angiotensin-mediated selective pancreatic vasoconstriction results in significant pancreatic ischemia during cardiogenic shock.

Enhanced recovery of brain electrical activity by adenosine 3',5'-cyclic monophosphate following complete global cerebral ischemia in dogs.

OBJECTIVE: To test the hypothesis that adenosine 3',5'-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: Twenty-five male beagle dogs. INTERVENTIONS: Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60, 90, and 120 mins of reperfusion, n = 9). MEASUREMENTS AND MAIN RESULTS: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 +/- 6; cAMP 56 +/- 9; dibutyl-cAMP 67 +/- 10 mL/min/100 g [mean +/- SEM, p < .05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 +/- 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 +/- 4% of preischemic baseline value in the cAMP-pretreated group (p < .05), and to 70 +/- 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p < .05). CONCLUSIONS: cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP- and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circulatory effects.

Effects of pentoxifylline on cerebral blood flow, metabolism, and evoked response after total cerebral ischemia in dogs.

OBJECTIVE: To test the hypothesis that pentoxifylline improves recovery of cerebral electrical activity and metabolic function after a transient cerebral global ischemia by improving cerebral blood flow during the reperfusion period. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: Forty male beagle dogs. INTERVENTIONS: Six control dogs received pentoxifylline (40 mg/kg bolus followed by infusion at 0.2 mg/kg/hr) without ischemia. Thirteen dogs received Ringer's lactate solution with 12 mins of cerebral global ischemia (by aortic occlusion). Nine dogs received pentoxifylline before ischemic insult. Six dogs received pentoxifylline on reperfusion, and six dogs received pentoxifylline 30 mins after reperfusion. MEASUREMENTS AND MAIN RESULTS: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pentoxifylline did not affect cerebral blood flow, oxygen consumption, or somatosensory evoked potentials without ischemia. Pretreatment with pentoxifylline resulted in attenuated postischemic hyperemia at 10 mins of reperfusion (94 +/- 15 vs. 133 +/- 11 [SEM] mL/min/100 g; p < .05), but there was no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. Pentoxifylline treatment during reperfusion resulted in no recovery of cerebral blood flow or oxygen consumption. All ischemic groups demonstrated a rapid ablation of somatosensory evoked potential amplitude and there were no differences in the decrement of the amplitude on ischemia. At 180 mins of reperfusion, somatosensory evoked potentials recovered to the following percentages of the baseline control values: 28 +/- 4% in dogs treated with Ringer's lactate solution; 58 +/- 4% in the pentoxifylline pretreated group (p < .05); 40 +/- 5% in dogs receiving pentoxifylline at reperfusion (p > .05); and 53 +/- 8% in dogs receiving pentoxifylline at 30 mins of reperfusion (p < .05). CONCLUSIONS: Pentoxifylline treatment improves recovery of cerebral electrical function after complete transient cerebral global ischemia by a mechanism that does not involve improvement in cerebral blood flow or global oxygen consumption.

Incidence and perioperative management of tension pneumocephalus following craniofacial resection.

This study is a retrospective review to evaluate factors associated with the risk of pneumocephalus following craniofacial resection and the management of tension pneumocephalus. Twenty-two craniofacial operative procedures were reviewed in 18 patients entered into the Neurosciences Critical Care Unit, Johns Hopkins Hospital, during a 54 month period, from 1986-1991. Pneumocephalus developed after 7 of 22 operations; of these seven, two developed tension pneumocephalus. The use of lumbar cerebral spinal fluid (CSF) drainage during the operation correlated most strongly with the development of pneumocephalus. The diagnosis of esthesioblastoma also correlated significantly. Both episodes of tension pneumocephalus occurred after craniofacial resection in which lumbar drainage of CSF was performed. Tension pneumocephalus was successfully treated in these two patients with a combination of air evacuation and medical management of raised intracranial pressure. Transient diabetes insipidus developed in both patients. The risk of pneumocephalus following craniofacial procedures is significant, and may be increased by the use of lumbar drainage of CSF intraoperatively. Rapid neurologic deterioration following craniofacial resection may be caused by the development of tension pneumocephalus. Early diagnosis of tension pneumocephalus and aggressive management of raised intracranial pressure may be important in preventing serious neurological complications.

Sucralfate does not reduce the risk of acid aspiration pneumonitis.

OBJECTIVE: To study the pulmonary effects of aspirating a mixture of sucralfate in water and sucralfate in hydrochloric acid in an animal model of aspiration pneumonia. DESIGN: Prospective, randomized, controlled study with repeated measures. SETTING: University research laboratory. SUBJECTS: Thirty-two in situ, isolated, blood perfused porcine lung preparations. INTERVENTIONS: Five control preparations received no aspiration. Twenty-seven preparations received a standard aspiration of 1.5 mL/kg body of a) distilled water (n = 5), b) sucralfate in distilled water (n = 8), c) 1/10 normal hydrochloric acid (n = 6), and d) mixture of sucralfate in distilled water and hydrochloric acid (n = 8). MEASUREMENTS: The pH measurements were made of all aspirates. Lung weight, airway pressures, and pulmonary artery pressures were continuously monitored before and for 4 hrs after aspiration. Lung wet/dry weight ratio was measured at the completion of the study. RESULTS: The pH of sucralfate mixed with distilled water was 4.9, pH of 1/10 normal hydrochloric acid was 1.0, and pH of equal volumes of a sucralfate-water suspension mixed with hydrochloric acid was 1.5. Airway pressures and pulmonary arterial pressures increased in all aspirate groups over time compared with those values of control lungs. Control lungs gained 18 +/- 3 (SEM) g over 4 hrs and the wet/dry ratio was 4.951 +/- 0.310. Lungs aspirating distilled water gained 147 +/- 49 g and the wet/dry ratio was 5.198 +/- 0.120. Lungs aspirating sucralfate and distilled water increased their weight by 109 +/- 30 g and the wet/dry ratio was 5.380 +/- 0.076. Lungs aspirating a suspension of sucralfate and water and hydrochloric acid were similar to lungs aspirating hydrochloric acid alone with weight increases of 265 +/- 30 g and 346 +/- 81 g, and the wet/dry ratio of 7.011 +/- 0.273 and 7.230 +/- 0.390, respectively. CONCLUSIONS: Sucralfate has minimal acid buffering effect. Aspiration of sucralfate mixed with distilled water causes lung edema similar to aspiration of water alone. Aspiration of a sucralfate-water suspension mixed with hydrochloric acid causes severe lung edema. These results suggest that patients given sucralfate prophylaxis for stress ulceration are at risk for acid aspiration.

Lung injury produced by pancreatic proteases in dogs.

With an isolated, blood-perfused canine lung-lobe preparation, the potential role of reactive oxygen metabolites and neutrophils in pancreatic protease (alpha-chymotrypsin)-induced acute lung injury was studied. Administration of alpha-chymotrypsin caused a low-pressure pulmonary edema (mean lung lobe weight increased from 71 to 197 gm). Pretreatment with superoxide dismutase alone did not attenuate the injury (58 to 166 gm), but when combined with catalase, the injury was significantly ameliorated (64 to 107 gm). However, depletion of circulating leukocytes did not attenuate the injury (69 to 200 gm). These findings suggest that circulatory proteases can cause lung injury by a mechanism that is mediated, at least in part, by toxic oxygen metabolites that are not of neutrophil origin.

Preoperative risks predict neurological outcome of carotid endarterectomy related stroke.

The aim of this study was to determine if preoperative risk factors are predictors of poor stroke outcome after carotid endarterectomy. In addition, the effect of other stroke risk factors on stroke severity was determined. A retrospective review of carotid endarterectomy results spanning 10 years, encompassing 561 patients, and reporting the combined results of all surgeons at our institution was performed. Patients were assigned to one of four groups. There were 227 patients with no preoperative risks (Group 1), 61 with angiographic risks (Group 2), 196 with medical risks with or without angiographic risks (Group 3), and 77 with neurological risks with or without medical/angiographic risks (Group 4). Other risks associated with stroke occurrence were recorded including: intraoperative risks (cross-clamp time, use of shunt, use of glucose solutions), surgical complications (carotid occlusion/thrombus or ligation), and medical complications (hypoxia, myocardial infarct). Stroke incidence was 5% with 2% (11 patients) and 3.4% (19 patients) having good and poor outcomes, respectively. Stroke incidence was highest in Groups 2 and 4 (10 and 14%, respectively), and Group 4 had the highest incidence of poor-outcome stroke (12%). Cross-clamp time, intraoperative shunt placement, and intraoperative glucose administration were similar among preoperative risk groups and were not primary determinants of stroke severity. The most common medical complication was myocardial infarction, which had the highest incidence in Groups 3 and 4 (6.1 and 5%, respectively). The highest incidence of surgical complications occurred in Groups 2 and 4, carotid thrombosis being the most common event (16 patients). Surgical complications were more commonly associated with stroke than were medical complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cyclosporine on cerebral blood flow and metabolism in dogs.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Pentoxifylline attenuates edema formation in proteolytic enzyme-induced lung injury.

Ex vivo canine lung lobes were exposed to a pancreatic proteolytic enzyme (chymotrypsin) alone or chymotrypsin after pretreatment with a continuous infusion with pentoxifylline. The lobes exposed to chymotrypsin gained 133 g, while the pentoxifylline-treated lobes gained only 65 g (p less than .05) over the 3-h experimental period. These results suggest that pentoxifylline significantly attenuates the lung weight gain associated with chymotrypsin.

Age-related cerebrovascular response to global ischemia in pigs.

We tested the hypothesis that 1- to 2-wk-old pigs (piglet) have improved recovery of cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and somatosensory-evoked potentials (SEP) compared with 6- to 8-mo-old pigs (pig) after transient global cerebral ischemia. All animals were anesthetized with pentobarbital sodium. After tracheostomy ventilation was adjusted to maintain normoxia (arterial oxygen pressure, 100-150 mmHg) and normocarbia (arterial carbon dioxide pressure, 35-40 mmHg). Arterial blood gases, blood pressure, and hemoglobin concentration remained within physiological limits throughout the experiment. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta. During ischemia the electroencephalogram and SEP became isoelectric within 40 and 120 s, respectively. At 10 min of reperfusion hyperemia occurred in most brain regions (e.g., whole brain: piglet, 270 +/- 45%; pig, 316 +/- 48%). In pigs delayed hypoperfusion occurred in all regions except white matter. In contrast, piglets only had delayed hyperperfusion to the brain stem and caudate nucleus. Throughout reperfusion CMRO2 was decreased in pigs (3.3 +/- 0.4 to 1.9 +/- 0.2 ml.min-1.100 g-1) but was not different from control (2.7 +/- 0.3 ml.min-1.100 g-1) in piglets. By the end of reperfusion SEP amplitude was closer to control in piglets than pigs (55 +/- 9 vs. 32 +/- 4% of control). We conclude that 1- to 2-wk-old piglets have quicker return of CBF, CMRO2, and SEP to control values after global ischemia, which mechanistically may explain previous reports of improved neurological recovery in young animals after transient ischemia.