Inhibition of tumor necrosis factor and amelioration of brain infarction in mice.

Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MCAO. TNFbp produced a significant reduction in the cortical infarct volume of vehicle-treated animals (p < 0.001). The reduction in the volume of brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further analysis of TNF-alpha inhibition following acute brain ischemia is indicated.

Cerebral air embolism treated by pressure and hyperbaric oxygen.

We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air embolism, occurring as the result of invasive medical procedures, and neither suffered any permanent damage detectable by clinical examination and MRI. This outcome contrasts with reports of infarct and disability among untreated victims of air embolism.

Barotraumatic cerebral air embolism and the mental status examination: a report of four cases.

Barotraumatic cerebral air embolism is described as sudden loss of consciousness accompanied by major motor disturbances. However, arterial gas embolism can have disturbances of cortical function that are much more subtle. Four patients presented with significant abnormalities of mental status. In two patients, the findings were subtle enough that the patients were initially regarded as normal. In the other two, cortical dysfunction was relatively resistant to therapy and might have gone unrecognized without careful examination. In order to detect disturbances in cortical function the neurologic examination should include testing beyond the usual emergency evaluation of consciousness and degree of orientation.

Spinal cord decompression sickness: a comparison of recompression therapies in an animal model.

Somatosensory evoked potentials (SEP) were used in an animal model to measure spinal cord electrophysiological function. Animals were submitted to a dive profile resulting in spinal cord decompression sickness (DCS). The animals were treated after a delay allowing the lesion to consolidate. Serial measurements of SEP documented the onset, duration, and outcome of treatment. Physiological data were recorded throughout each experiment. Group A (n = 10) was recompressed to 60 fsw (feet of sea water) breathing 100% oxygen (2.8 ATA) and Group B (n = 8) was treated at 66 fsw breathing 66% oxygen (2.0 ATA). No differences were found between groups in the severity, surface interval before treatment, or the maximum effect of treatment. The maximum effect of treatment was seen by 25 min of treatment. Animals were regrouped into responders and nonresponders. The latter displayed a more rapid onset, a more severe insult, and more adverse physiological effects than the responders. The possibility of a different etiology was considered together with the failure to differentiate between the treatment groups. It was concluded that treatment B was safer but the problems of introducing a new therapeutic table outweighed the safety advantage.

Oxygen in the treatment of spinal cord decompression sickness.

Twenty-five anesthetized dogs were used to find the optimum Po2 for the delayed treatment of spinal cord decompression sickness (DCS). They were instrumented for the measurement of physiological variables and somatosensory spinal evoked potentials (SEP) given an air dive of 15 min at 10 bar (300 ft) and decompressed in under 6 min. At the surface SEP were observed for signs of DCS. Fifteen minutes after cord DCS was observed in the SEP, the dogs were compressed to 5.0 bar breathing one of 5 gas mixtures giving a Po2 of 1.0, 1.5, 2.0, 2.5, or 3.0 bar. At the start of therapy all groups were in a similar physiological state with a similar loss of SEP. Between 40 and 120 min, recovery was significantly different (P less than 0.05) between the groups, most SEP recovery having occurred within 15 min. The treatments ended with 22, 32, 70, 66, and 42% recovery, respectively. It would appear that the optimum Po2 is around 2.0 bar.

Pressure in the treatment of spinal cord decompression sickness.

Previous work had shown that a Po2 of about 2.0 bar was the optimal Po2 for the treatment of spinal cord decompression sickness (DCS). With 20 anesthetized dogs the hypothesis was tested that pressures in excess of a threshold, taken as 3 bar, did not enhance recovery of spinal cord DCS. Dogs were subjected to a 15-min air dive at 10 bar (300 ft) and decompressed over 5.5 min. At the surface, spinal cord evoked potentials (SEP) were observed for changes indicating DCS. Fifteen minutes after DCS was first detected the dogs were recompressed to 3, 5, 7, or 2.8 bar breathing 66, 40, 29, or 100% oxygen which gave a Po2 of 2.0 bar except in the 2.8 bar group. The recovery of the SEP over 2 h was observed. Group mean recoveries at 67, 62, 29, and 42% were not significantly different after 120 min. As the hypothesis was supported, a tentative proposal for changing current therapy was made.

Cerebral arterial air embolism: I. Is there benefit in beginning HBO treatment at 6 bar?

A method for studying treatment of cerebral arterial gas embolism in dogs is described. The model produces severe cortical dysfunction and cerebral blood flow deficits. The efficacy of treatment was assessed using median nerve somatosensory cortical evoked potentials (CEP), [14C]iodoantipyrene autoradiographic cerebral blood flow studies, brain water content, and various physiological parameters. A direct comparison of modified U.S. Navy Treatment Tables 6 and 6A is reported. Complete recovery of CEP was not seen after 90 min of treatment. The maximum rate of CEP recovery occurred in the first 15 min of treatment. Recovery continued out to 60 min. Thereafter, some dogs on treatment 6A showed signs of deterioration. The cerebral blood flow studies were the same in both groups and showed no sign of pathologically low levels of flow. It appeared that there was no advantage in preceding 2.8-bar (60-ft) oxygen treatments with compression to 6 bar (165 ft) on air for the treatment of arterial air embolism in this model.

Cerebral arterial air embolism: II. Effect of pressure and time on cortical evoked potential recovery.

In a dog model of cerebral arterial gas embolism we studied the relative merits of several different treatments: air breathing at 2.8, 6, 8, and 10 bar (60, 165, 230, and 300 ft), and oxygen breathing at 2.8 bar. The study was confined to the recovery of cortical evoked potentials (CEP) while at pressure. It was confirmed that this was a very severe model; few dogs achieved full recovery and three failed to show any recovery. Injecting 0.4 ml of air into the right internal carotid artery was seen to be as effective in suppressing function in the left hemisphere as in the right. The level of recovery with compression treatment as a percentage of control was directly related to the level to which CEP was suppressed. No other physiological correlates were found with either the degree of CEP suppression or the degree of recovery. Nor was any improvement observed in the rate or maximum amount of recovery at any time out to 20 min as a result of pressures greater than 2.8 bar. Overall, no treatment surpassed oxygen at 2.8 bar.

Cerebral arterial air embolism: III. Cerebral blood flow after decompression from various pressure treatments.

The effect of various combinations of time between 2 and 20 min and between pressures of 2.8 and 10 bar (60 and 300 ft) breathing air or oxygen at 2.8 bar (60 ft), on the continued recovery of cortical evoked potentials (CEP), cerebral blood flow (CBF), and water content of the brain were studied in the dog cerebral arterial air embolism model. It was found that the compression-decompression cycle alone resulted in a rise in cerebrospinal fluid pressure sustained for at least 20 min. The CBF study at 30 min showed an increased flow in dived, nonembolized animals. Water content of the brain was also significantly increased in these animals. The data suggest that the clearance of air is probably independent of pressure once past a threshold of 2.8 bar and is certainly hastened by oxygen. A time of around 8 min is probably required to clear the embolism. The evidence of gas bubble redistribution with recurrence and development of new sites of vascular obstruction in dogs exposed to significant inert gas uptake, however, suggests that a second problem of the clearance of recirculating gas exists. An incidental observation suggests that recently dived dogs may have been more prone to secondary deterioration. The results of these studies again suggest that there may be advantages to confining the treatment of arterial gas embolism to 2.8 bar breathing oxygen.

Cerebral arterial air embolism: IV. Failure to recover with treatment, and secondary deterioration.

Cerebral arterial gas embolism was induced in 23 dogs that were then treated using one of six routines: no treatment; air at 2.8 bar (60 ft) for 2 min; air at 10 bar (300 ft) for 5 min; oxygen at 2.8 bar for 10 or 20 min; and air at 6 bar (165 ft) for 10 min. After decompression they were monitored for a total of 90 min after the time of embolization. The dogs then underwent an autoradiographic study of cerebral blood flow (CBF). A number of the air-treated dogs experienced a reduction in cortical evoked potential after decompression. Dogs in all groups, except the untreated group and the dog at 10 bar for 5 min, showed an improved CBF compared with their short-study counterparts. After compression treatment, CBF improved with time. Function in 7 dogs deteriorated to a variable small degree in the air-treated groups, while only 3 dogs in the group on oxygen for 10 min deteriorated by around 10%. The CBF of the oxygen groups was close to the undived control values, and their cerebrospinal fluid (CSF) pressures had returned to control levels. There was a dissociation between improving CBF and deteriorating function. It is evident that secondary deterioration is a random affair and therefore not easily studied. The results of the four-part series are summarized and discussed.

A model of spinal cord dysbarism to study delayed treatment: II. Effects of treatment.

Using the spinal cord decompression sickness model described in Part I, we explored the effects of delay to treatment on the recovery of spinal evoked potentials (SEP). The primary treatments of oxygen at 60 fsw (2.8 bar) and air at 165 fsw (6.0 bar) were studied. In this exploratory study the results were surprisingly poor in all treatments applied. There is evidence that in this model a delay of 15-18 min between diagnosis and start of therapy would generally allow some recovery of SEP, which would rarely be complete. Supporting experiments involving cord ischemia are described. The results from this study enabled us to design a set of practicable experimental criteria for the purpose of discovering the optimal combinations of oxygen and pressure for the treatment of spinal cord decompression sickness.