Biomedical subjects

A J Dutka

Publications and source records attributed to A J Dutka.

At least 19 recordsLinked to original sources

PubMed1992

Effect of lidocaine on somatosensory evoked response and cerebral blood flow after canine cerebral air embolism.

BACKGROUND AND PURPOSE: Victims of air embolism often recover rapidly on hyperbaric treatment then deteriorate again, even if hyperbaric treatment is continued. In previous animal experiments, lidocaine has been shown to improve recovery of somatosensory evoked response amplitude after air embolism. However, animals in these experiments rarely deteriorated. We have shown that the induction of air embolism and transient hypertension in canines produces deterioration despite hyperbaric treatment, and we decided to test the effect of lidocaine on somatosensory evoked potential recovery and cerebral blood flow in this model. METHODS: Dogs were treated with repeated doses of lidocaine or equivalent volumes of saline during hyperbaric therapy after internal carotid air embolism and transient hypertension. The investigators were unaware of treatment group assignment during the experiments. The amplitude of the median nerve somatosensory evoked potential and cerebral blood flow measured with carbon-14-labeled iodoantipyrine autoradiography were used to assess effect of therapy. RESULTS: Lidocaine-treated dogs recovered 60 +/- 10% (mean +/- 95% confidence limits) of the baseline somatosensory evoked potential amplitude 220 minutes after air embolism; saline-treated dogs recovered 32 +/- 10% (a significant difference at p less than 0.01). Lidocaine-treated dogs also had higher cerebral blood flow values than saline-treated dogs 220 minutes after air embolism. CONCLUSIONS: Lidocaine ameliorated the delayed deterioration of evoked potential associated with air embolism and hypertension in this canine model. The improved cerebral blood flow may be a mechanism of action of lidocaine or an associated effect of improved neuronal survival.

Animals↗

PubMed1992

Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia.

BACKGROUND AND PURPOSE: Delayed deterioration of neurological function after central nervous system ischemia is a well-documented clinical problem. The purpose of our study was to elucidate the role of spinal cord blood flow and spinal cord-blood barrier integrity in the evolution of delayed neurological deterioration after transient spinal cord ischemia in rabbits. METHODS: Anesthetized rabbits were subjected to lumbar spinal cord ischemia (25 minutes) and variable periods of reperfusion (30 minutes to 48 hours after ischemia). Regional spinal cord blood flow was monitored by carbon-14-labeled iodoantipyrine autoradiography; vascular permeability was assessed by quantitative microhistofluorescence of Evans blue-albumin in frozen sections of spinal cord. Hindlimb motor function was assessed by standard scoring system and tissue edema by wet/dry weight method. RESULTS: Hindlimb motor function indicated complete paralysis during ischemia and partial gradual recovery upon reperfusion (up to 8 hours), followed by progressive deterioration to severe deficits over 48 hours. Severe vascular permeability disruption was noticed early (30 minutes) after reperfusion, but almost complete recovery reestablished at 8 hours was followed by a secondary progressive increase in vascular permeability. Blood flow was reduced by 20-30% (p less than 0.01) 4 hours after ischemia in the gray matter, but hyperemia (200-300%, p less than 0.01) was observed 12-24 hours after ischemia. Spinal cord water content increased by 5.7% (p less than 0.05) 24 hours after ischemia. CONCLUSIONS: This study demonstrates that delayed neurological and motor deterioration after spinal cord ischemia is associated with severe progressive breakdown of spinal cord-blood barrier integrity that develops late (hours) after the injury. Our data suggest that no ischemic insult in early or late reperfusion is associated with delayed motor deterioration.

Animals↗

PubMed1992

Effects of an increased PO2 during recompression therapy for the treatment of experimental cerebral arterial gas embolism.

In this study we investigated the efficacy of an initial compression to 6 atm abs on a 53% nitrogen:47% oxygen mixture (PO2 = 2.8 atm abs) before breathing oxygen at 2.8 and 1.9 atm abs for the treatment of feline cerebral arterial gas embolism. Neurophysiologic function was determined by measuring the cortical somatosensory evoked potential (SEP) amplitude in anesthetized ventilated cats. Air was infused into the carotid artery until the SEP amplitude was reduced to less than 10% of baseline values. The animals were randomly separated into 3 groups. The first group (CONTROL) (n = 7) served as control and remained at the surface, breathing air. The second group (NITROX) (n = 10) was compressed to 6 atm abs breathing a 53:47% nitrox mixture for 30 min followed by breathing 100% oxygen at 2.8 and 1.9 atm abs. The third group (HBO) (n = 10) was compressed to 2.8 and 1.9 atm abs breathing 100% oxygen. Air infusion suppressed the SEP amplitude to the same level in all groups. The CONTROL group recovered 27.6 +/- 31.2% (mean +/- standard deviation) of the baseline SEP amplitude, whereas the NITROX group recovered 63.2 +/- 28.2%, and the HBO group recovered 66.0 +/- 19.3%. An analysis of variance with repeated measures revealed that both treatment profiles promote significant (P = 0.03) recovery of the SEP amplitude compared to no treatment. We find no additional benefit, however, by initiating treatment at 6 atm abs, even when additional oxygen is provided.

Analysis of Variance↗

PubMed1992

Management of herniated intervertebral disks during saturation dives: a case report.

During research saturation dives at 5.0 and 5.5 atm abs, 2 divers developed an acute herniation of the nucleus pulposus of the L5-S1 intervertebral disk. In both cases the pain was severe enough to require intravenous morphine or intramuscular meperidine. Although the symptoms presented by these divers are frequently considered to be an indication for immediate surgical consultation, we decided that emergency decompression posed an unacceptable risk that decompression sickness (DCS) would develop in the region of acute inflammation. In both cases strict bedrest and medical therapy were performed at depth. In the first case, 12 h was spent at depth before initiating a standard U.S. Navy saturation decompression schedule with the chamber partial pressure of oxygen elevated to 0.50 atm abs. In the second case, a conservative He-N2-O2 trimix decompression schedule was followed to the surface. In both cases, no initial upward excursion was performed. The required decompression time was 57 h 24 min from 5.5 atm abs and 55 h 38 min from 5.0 atm abs. During the course of decompression, the first diver's neurologic exam improved and he required decreasing amounts of intravenous narcotic; we considered both to be evidence against DCS. The second diver continued to have pain and muscle spasm throughout decompression, however he did not develop motor, reflex, or sphincter abnormalities. Both divers have responded well to nonsurgical therapy.

Adult↗

PubMed1992

Effects of treatment with dexamethasone on recovery from experimental cerebral arterial gas embolism.

Dexamethasone is often recommended as an adjunct to recompression in the treatment of serious central nervous system decompression accidents. We studied the effects of prophylactic and therapeutic administration of dexamethasone combined with hyperbaric treatment in anesthetized dogs that were subjected to carotid air embolism and a brief episode of arterial hypertension. To assess recovery we measured somatosensory evoked potential (SSEP) amplitude, intracranial pressure, brain water, and cerebral blood flow. Three groups were studied: pre-air treatment (dexamethasone 1 mg/kg 3-4 h before carotid air embolism, and 1 mg/kg immediately after air embolism); post-air treatment (2 mg/kg immediately after air embolism); and control (equivalent volumes of saline pre- and post-air). There was a slight improvement in SSEP early in the course of hyperbaric therapy in the pre-air treated group; the post-air group never differed from control. No differences in intracranial pressure or brain water were found among groups. No blood flows below those lethal to neurons occurred in treated animals but 4 of 7 control animals had low flows. Although prophylactic treatment with dexamethasone produces some improvement in recovery, we cannot confirm that dexamethasone is an effective adjunct to recompression when administered therapeutically.

Animals↗

PubMed1992

Comparison of two recompression profiles in treating experimental cerebral air embolism.

The standard treatment for cerebral arterial gas embolism (CAGE) is an initial recompression to 6 atm abs on air for 30 min followed by oxygen breathing at 2.8 and 1.9 atm abs. It has been suggested that initial recompression to 2.8 atm abs on O2 may be as beneficial, thus avoiding potential treatment complications associated with the deeper depth. To test this hypothesis, we measured the recovery of the somatosensory evoked potential (SEP) following air embolism in anesthetized, ventilated cats. Air was infused into the carotid artery in increments of 0.08 ml until the SEP amplitude was reduced to less than 10% of the baseline value for 15 min. Three groups were studied. A control group (n = 10) received no further treatment after SEP suppression. The second group (6 atm abs/HBO] (n = 8) was compressed to 6 atm abs on air for 30 min followed by O2 breathing at 2.8 atm abs for 100 min. The third group (HBO) (n = 8) was compressed to 2.8 atm abs on O2 for 130 min. The control group recovered 28.8 +/- 18.2% (mean +/- SD) of the baseline amplitude, whereas the 6 atm abs/HBO group recovered 48.6 +/- 22.6%, and the HBO group recovered 62.0 +/- 20.3%. An analysis of variance revealed that only the HBO group had significantly (P less than 0.01) better recovery than the control group. There was no significant difference in SEP recovery between the 2 treatment groups. These results suggest that treating CAGE at 2.8 atm abs with O2 is a viable alternative to the current therapy.

Animals↗

PubMed1992

Morphologic and electrophysiologic effects of cochlear implantation and electrical stimulation.

The nondeafened guinea pig model was utilized in this study to assess the functional and morphologic effects of cochlear implantation and electrical stimulation. Auditory brainstem responses (ABRs) were recorded prior to and following intrascalar implantation of a 3M-House cochlear electrode (n = 41 ears), as well as after electrical stimulation (n = 23 ears). The experimental population was divided into the following groups according to implantation and stimulation parameters: 200 microA for 3 hours (group I); 200 microA for 24 hours (group II); 400 microA for 3 hours (group III); implanted, but not stimulated (group IV); and nonimplanted, not stimulated ears (group V). Of those cochleae that sustained the trauma of implantation, 32 percent had no detectable ABR to 110 dB SPL clicks, while only 7 percent additionally failed to respond to 130 dB SPL clicks. No significant difference (one-way ANOVA with repeated measures at the 95 percent confidence limit) could be detected when comparing those ears that retained ABRs according to experimental grouping. Morphologic analysis was performed on 29 cochleae. Spiral ganglion "packing densities" were not found to be significantly different among the groups (ANOVA). The status of the organ of Corti was significantly better in groups II and V in comparison to the other groups (Kruskal-Wallis test with pairwise comparisons, p less than 0.05); there was no discernible dose-response relationship. Morphologic and electrophysiologic changes correlated with insertion trauma and infection rather than with electrical stimulation at the levels tested in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1991

Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke.

Rats produced more TNF activity in cerebrospinal fluid (CSF) than in blood after intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). After intravenous (i.v.) LPS, blood TNF levels exceeded CSF levels. Thus, brain cells appear to produce TNF in response to LPS. Rats with the stroke-risk factors hypertension or combined hypertension and genetic stroke-proneness produce more TNF in response to a provocative dose of LPS i.v. than control animals free of these risk factors. The possible relevance to stroke vulnerability is discussed.

Animals↗

PubMed1991

Allopurinol pretreatment improves evoked response recovery following global cerebral ischemia in dogs.

The reperfusion of previously ischemic tissue may lead to the formation of highly reactive free radicals that promote tissue injury. Xanthine oxidase has been implicated as one source of these free radicals. We examined the role of xanthine oxidase in brain injury using a cerebrospinal fluid compression model of global cerebral ischemia with 15 minutes of ischemia and 4 hours of reperfusion. Seven dogs were pretreated with the xanthine oxidase inhibitor allopurinol (50 mg/kg for 5 days). Neurophysiological recovery was monitored with cortical somatosensory evoked potentials. As an attempt to correlate brain recovery with the mechanism of protection, free brain malondialdehyde was measured at the end of reperfusion by high-performance liquid chromatography. Brain water content was measured by wet-dry weights. Compared with seven untreated control dogs, allopurinol pretreatment significantly improved recovery of somatosensory evoked potentials after 4 hours of reperfusion. However, the amount of free malondialdehyde in the allopurinol-treated dogs was 32% greater than that in the controls. Brain water content was similar in the two groups. These results suggest that xanthine oxidase contributes to brain injury after ischemia and reperfusion. However, tissue damage caused by xanthine oxidase may be mediated through mechanisms other than free radical production.

Allopurinol↗

PubMed1991

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.

Adult↗

PubMed1990

Background review and current concepts of reperfusion injury.

We define the concept of reperfusion injury, and we present a background chronology of experimental work supporting and questioning this concept. We identify several new influences, such as current clinical interest in thrombolytic therapy for acute ischemia of heart and brain and the growing recognition of endothelium as a regulator of homeostasis. We propose that these influences will encourage a reexamination of reperfusion injury as a factor in the ultimate outcome of tissue exposed to reversible ischemia. We briefly discuss the major mechanisms presently implicated in reperfusion injury--loss of calcium homeostasis, free radical generation, leukocyte-mediated injury, and acute hypercholesterolemia.

Calcium↗

PubMed1990

Influence of cerebral ischemia and post-ischemic reperfusion on mitochondrial oxidative phosphorylation.

Unilateral ischemia in the right cerebral hemisphere of the rat was induced by ligation of the right common carotid artery coupled with controlled hemorrhage to produce hypotension (25 +/- 8 mm/Hg). Where indicated after 30 min of ischemia, the withdrawn blood was reinfused to restore arterial pressure to normal. Mitochondria isolated from the ipsilateral hemisphere after 30 min of ischemia showed significantly lower respiratory rates than the organelles isolated from the contralateral side. Oxidation of NAD(+)-linked substrates was more sensitive to inhibition in ischemia (30%) than was of ferrocytochrome c (12%), succinate oxidation being intermediate. The activities of membrane-bound dehydrogenases (both NADH and succinate-linked) were also significantly lowered. Ischemia did not affect the cytochrome content of mitochondria. Respiratory activity (NAD(+)-linked) of mitochondria isolated from the ipsilateral hemisphere was twice as sensitive to inhibition by fatty acid as was of preparations from the contralateral side. Mitochondria isolated from cerebral cortex after 90 min of post-ischemic reperfusion showed no significant improvement in the rate of substrate oxidation. Adenine nucleotide translocase activity and energy-dependent Ca2+ uptake, both of which decreased significantly in mitochondria isolated from the ischemic brain, showed little recovery, on reperfusion. These observations suggested the strong possibility that the deleterious effects of ischemia on mitochondrial respiratory function might be mediated by free fatty acids that are known to accumulate in large amounts in ischemic tissues. The pattern of inhibition of ATPase activity was consistent with this view.

Animals↗

PubMed1990

No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia.

Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia.

Animals↗

PubMed1990

Bubble-induced dysfunction in acute spinal cord decompression sickness.

Five anesthetized dogs undertook a chamber dive, on air, to 300 feet of seawater for 15 min. After the dive, spinal cord decompression sickness was detected by recording a reduced amplitude of the somatosensory evoked potential compared with predive base-line values. After the diagnosis of decompression sickness and rapid perfusion fixation of the animal, the spinal cord was removed and examined histologically. Numerous space-occupying lesions (SOL) that disrupted the tissue architecture were found in each cord, mainly in the white matter. The size and distribution of the SOL were determined using computerized morphometry. Although SOL occupied less than 0.5% of the white matter volume, we tested a number of algorithms to assess whether the SOL may have been directly involved in the loss of spinal cord function that followed the dive. We determined that the loss of somatosensory evoked potential amplitude may be attributed to the SOL if 30-100% of the spinal cord fibers that they displaced were rendered nonconducting. A number of possible mechanisms by which SOL may interfere with spinal nerve conduction are discussed.

Animals↗

PubMed1990

Pharmacologic therapy for ischemic cerebrovascular disease.

This article considers pharmacologic therapy for the prevention and treatment of ischemic cerebrovascular disease. The emphasis is on prevention of stroke, since current pharmacologic treatments do not reliably reduce morbidity or mortality once a stroke has occurred. Antihypertensive treatment, anticoagulants, and antiplatelet agents are discussed along with general guidelines for poststroke therapy.

Anticoagulants↗

PubMed1990

Treatment of experimental cerebral air embolism with lidocaine and hyperbaric oxygen.

Experiments were performed to assess the combined therapeutic effects of hyperbaric oxygen (HBO) and i.v. lidocaine on neural function after ischemia induced by cerebral air embolism in anesthetized cats. Neural function was determined by measuring the somatosensory evoked potential (SEP) amplitude. Air was infused into the carotid artery in increments of 0.08 ml to maintain the SEP amplitude at 10% or less of baseline values for 15 min. Three groups were studied. A control group (n = 9) received no further treatment after SEP suppression. An HBO group (n = 8) was treated with oxygen at 2.8 atm abs for 130 min. A third group (n = 8) received an i.v. lidocaine infusion in addition to HBO. Air infusion suppressed the SEP amplitude to the same level in all groups. The control group recovered 27.4 +/- 5.5% (mean +/- SEM) of the baseline SEP amplitude, whereas the HBO group recovered 62.0% +/- 7.2%, and the HBO plus lidocaine group recovered 75.3 +/- 5.7%. The results show that both HBO and the combination of HBO and lidocaine promote a significant recovery of the SEP amplitude compared to no treatment. However, lidocaine therapy adds no benefit to HBO therapy alone.

Analysis of Variance↗

PubMed1989

Alterations in brain monoamine neurotransmitter release at high pressure.

High pressure exposure produces neurological changes which manifest as tremors, EEG changes and convulsions. Since previous studies have implicated the involvement of the monoaminergic system in these symptoms, it was of interest to study monoamine release at high pressure. Synaptosomes isolated from guinea pig brain were used to follow monoamine efflux at 68 ATA. The major observation was a decrease in the initial calcium dependent release of all three monoamines in response to K+ induced depolarization. This response is similar to that previously observed for GABA, glycine and glutamate. This generalized pressure induced depression of initial transmitter release suggests a mechanism common to the release process for both excitatory and inhibitory neurotransmission.

Animals↗

PubMed1989

Influence of granulocytopenia on canine cerebral ischemia induced by air embolism.

We subjected nine dogs with severe granulocytopenia 4 days after the administration of mechlorethamine to 1 hour of cerebral ischemia induced by the controlled, incremental injection of air into the internal carotid artery. Cortical somatosensory evoked responses and cerebral blood flow determined by [14C]iodoantipyrine autoradiography were compared with those of six control dogs that had received mechlorethamine 1 day previously and were not yet granulocytopenic. Eleven additional control dogs received no mechlorethamine but had identical ischemic insults and were followed for 4 hours after ischemia. Both control groups had identical evoked response outcomes after 1 hour of recovery from ischemia. Granulocytopenic dogs had improved evoked response recoveries compared with either control group after 1 hour of recovery. No areas of very low blood flow were observed 1 hour after ischemia in the granulocytopenic dogs, but three of five dogs in the control group receiving mechlorethamine had such areas.

Agranulocytosis↗