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Biomedical subjects

J E Cottrell

Publications and source records attributed to J E Cottrell.

At least 55 records · Page 3Linked to original sources
PubMed1991

Midazolam improves electrophysiologic recovery after anoxia and reduces the changes in ATP levels and calcium influx during anoxia in the rat hippocampal slice.

Since blockers of excitatory transmission have been shown to reduce anoxic and ischemic neuronal damage, augmentation of inhibitory transmission by agents such as midazolam might have a similar protective effect. Rat hippocampal slices were maintained in vitro and used to determine whether and by what mechanism midazolam improves recovery of evoked responses after anoxia. The Schaffer collateral pathway in the slice was stimulated electrically, and an extracellular potential, the evoked population spike, was recorded from the CA1 pyramidal cells, which are postsynaptic. The slices were made anoxic by substituting artificial cerebrospinal fluid aerated with 95% nitrogen-5% carbon dioxide for fluid aerated with 95% oxygen-5% carbon dioxide. Percentage recovery was expressed as the amplitude of the evoked population spike 60 min after anoxia divided by its preanoxic amplitude. Protection in this model is defined as a significant (P less than 0.05) improvement in percentage recovery compared to the recovery of untreated slices. There was no recovery of the response recorded from CA1 pyramidal cells after 5 min of anoxia (4 +/- 2%) (mean +/- standard error of the mean [SEM]). Slices were treated with midazolam 10 min before, during, and 10 min after anoxia. Midazolam (1 microM) did not enhance recovery after anoxia when dissolved either in water (3 +/- 3%) or in dimethyl sulfoxide (DMSO) (1 +/- 1%). A higher concentration of midazolam (100 microM) did enhance recovery when dissolved in DMSO (27 +/- 7%) but not when dissolved in water (5 +/- 2%). To test whether prolonged pretreatment with midazolam dissolved in water would enhance recovery, slices were treated for 30 min prior to anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Paraben preservatives do not increase intracranial pressure in cats.

It has been hypothesized recently that succinylcholine-associated increases in intracranial pressure (ICP) are caused by the paraben preservatives contained in multidose vials. We tested that hypothesis in a standard feline model to determine the effects on ICP of equal-volume injections of preservative-free succinylcholine, succinylcholine with preservatives from multi-dose vials that contain both propylparaben and methylparaben, these preservatives alone at five times the dose contained in the succinylcholine, and normal saline. The preservatives alone increased ICP by 0.08 +/- 0.08 mmHg (+/- standard error; not significant). Normal saline had no effect on ICP. Preservative-free succinylcholine and succinylcholine with preservatives increased ICP by 4.2 +/- 0.10 and 3.8 +/- 0.07 mmHg respectively (P less than 0.01 compared to the preservatives alone and normal saline). The 99% upper confidence limit for the increase in ICP induced by the preservatives alone was 0.42 mmHg. This result suggests that parabens do not cause or substantially augment the ICP increase associated with succinylcholine administration.

Animals↗
PubMed1989

Treatment of intraoperative hypertensive emergencies in patients with intracranial disease.

In patients with neuropathologic processes leading to disturbed cerebrovascular autoregulation, sudden increases in arterial blood pressure may lead to a sudden elevation in cerebral blood flow and intracranial pressure. Therefore, sudden increases in arterial pressure should be assiduously avoided in the perioperative period. Hypertensive episodes may occur at any time during anesthesia, but are more likely to occur (1) during laryngoscopy and intubation, (2) at the time of skin incision, (3) at extubation, and (4) during awakening. In patients with cardiovascular disease, such hypertensive episodes may also cause deterioration of the cardiovascular situation. Catecholamines are the principal mediators of such intraoperative hypertensive reactions. There are 2 options available to the anesthesiologist: (1) attempt to suppress this response after it has occurred, or (2) prevent its occurrence at the outset. Treatment of hypertension often relies on agents that relax vascular smooth muscle. In patients with compromised intracranial compliance, however, cerebral vasodilation must be avoided because it leads to an increase in cerebral blood volume. This, in turn, may raise intracranial pressure and result either in herniation of brain contents or a decrease in cerebral perfusion pressure leading to brain ischemia. Different pharmacologic means of preventing or suppressing such intraoperative hypertensive reactions are reviewed. Many of the drugs reviewed resulted in adverse effects that could preclude their use in patients with reduced intracranial compliance. Alpha- and beta-adrenergic receptor blockers can safely be administered to such patients.

Antihypertensive Agents↗
PubMed1989

The N-methyl-D-aspartate antagonists aminophosphonovaleric acid and MK-801 reduce anoxic damage to dentate granule and CA1 pyramidal cells in the rat hippocampal slice.

The effect of the N-methyl-D-aspartate antagonists, aminophosphonovaleric acid and MK-801, on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from either the dentate granule cells or the CA1 pyramidal cells and the amplitude of this spike was compared before and 60 min following anoxia. After 10 min of anoxia the dentate granule cells recovered to 16 +/- 7% (mean +/- SE) of their preanoxic level when untreated and to 54 +/- 15% when treated with aminophosphonovaleric acid (APV). In slices treated with MK-801 the population spikes recorded from dentate granule cells recovered to 85 +/- 4% of their preanoxic level after 10 min of anoxia. Untreated CA1 pyramidal cells recovered to 8 +/- 3% of their preanoxic amplitude after 5 min of anoxia; they recovered to 59 +/- 6% when treated with MK-801 and 31 +/- 13% when treated with APV. The recovery of slices treated with the drugs was significantly different from that of untreated slices. ATP levels were measured in both the dentate and the CA1 region of slices. ATP in both regions fell less during anoxia when the slices were pretreated with either APV or MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801 in dentate tissue after 10 min of anoxia and with MK-801 in CA1 tissue after 5 min of anoxia. This reduced fall in ATP during anoxia was accompanied by better physiological recovery after anoxia. We conclude that these NMDA antagonists provide protection against anoxic damage to dentate granule and CA1 pyramidal cells in this in vitro hippocampal preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1989

Methods for studying the effect of anesthetics on anoxic damage in the rat hippocampal slice.

The rat hippocampal slice was used as a model system to study the effects of anesthetics on anoxic damage. Thiopental, but not isoflurane, allowed recovery of the postsynaptic population spike evoked from the dentate granule cells. Creatine preincubation protected both dentate granule and CA1 pyramidal cells against anoxic damage. Calcium-free, 10 mM magnesium artificial cerebrospinal fluid (ACSF) was shown to protect CA1 pyramidal cells against anoxic damage. The presynaptic population spike recovered to its preanoxic amplitude after anoxia even under conditions where the postsynaptic population spike demonstrated no recovery. Thus the hippocampal slice is a useful system for studying the effects of anesthetics and other pharmacological agents on anoxic damage.

Action Potentials↗
PubMed1989

The effect of blocking sodium influx on anoxic damage in the rat hippocampal slice.

The in vitro rat hippocampal slice was used to study the effect of tetrodotoxin, a sodium channel blocker, on anoxic damage. Tetrodotoxin improved recovery of the evoked population spike after anoxia and reduced the fall in adenosine 5'-triphosphate during anoxia. Electrophysiological responses to perforant pathway stimulation were recorded in the dentate granule cell layer before, during and after 10 min of anoxia, with and without tetrodotoxin. Preincubation with tetrodotoxin permitted recovery of the evoked population spike to 43 +/- 10% (mean +/- standard error) in the post-anoxic period; this compared to 3 +/-3% recovery in untreated tissue (P less than 0.005). Similar studies of the CA1 pyramidal cells, which are more sensitive to anoxia, showed that tetrodotoxin improved recovery of the postsynaptic response after 5 min of anoxia. The recovery was 69 +/- 15% of its pre-anoxic level when treated with tetrodotoxin. This compares to no recovery in untreated tissue (P less than 0.005). Biochemical studies demonstrated a significantly reduced fall in adenosine 5'-triphosphate levels during levels in the dentate granule cell layer fell to 1.4 nM/mg dry wt, whereas following treatment with tetrodotoxin they only fell to 2.2 nM/mg. Since it required only 5 min of anoxia to damage the CA1 pyramidal cells, adenosine 5'-triphosphate levels were measured in this region after 5 min of anoxia. Adenosine 5'-triphosphate levels in the CA1 region fell to 2.2 nM/mg in untreated tissue after 5 min of anoxia, compared to 2.9 nM/mg in the tetrodotoxin-treated tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Comparison of superoxide dismutase, thiopental, and nimodipine for maintenance of somatosensory evoked responses during aortic cross-clamping and declamping in dogs.

Paraplegia is a potential complication of aortic cross-clamping. The occurrence of this devastating sequela has caused increased interest in the use of somatosensory evoked responses (SER) to monitor spinal cord ischemia during aortic cross-clamping. This study was designed to examine changes in SERs during clamping and declamping of the canine aorta after injection of superoxide dismutase (SOD), thiopental (T), and nimodipine (N). In the control group, cross-clamping the aorta produced an increase in latency and a decrease in amplitude of the SER starting at two minutes. Isoelectric SERs were obtained after 16 minutes of aortic cross-clamping, but recovered with cross-clamp removal. When the aorta was clamped for more than 16 minutes in the control group, the isoelectric SERs obtained were irreversible. After the injection of SOD and T, SER latencies and amplitudes changed to a smaller degree with aortic cross-clamping and did not become isoelectric even after 20 minutes of clamping. During aortic cross-clamp removal in the control group, SERs initially improved and then showed signs of reperfusion ischemia, which disappeared after eight minutes. There were no significant SER changes due to reperfusion when SOD or T or the combination was given prior to aortic cross-clamping. There was no difference in SER changes from the control group during aortic cross-clamping and after release of cross-clamping when N was given. Nimodipine did not alter SER changes from aortic cross-clamping alone. In summary, SOD and T, alone or in combination, protect the spinal cord against ischemia during aortic cross-clamping and declamping.

Animals↗
PubMed1988

Superoxide dismutase and hemodynamic changes following aortic crossclamp release.

Release of an aortic crossclamp usually results in hypotension which is mainly due to hypovolemia from sequestration of fluid in the tissues and the release of vasoactive substances (ie, bradykinin, free radicals) that increase capillary permeability. The purpose of this study was to evaluate superoxide dismutase (SOD), a free-radical scavenger, as a pharmacologic technique to prevent hemodynamic changes following aortic crossclamping and release. Fourteen mongrel dogs were studied and divided into two groups. The aorta was clamped for 60 minutes. Group A received NaHCO3, 3.5 mEq/kg, and SOD, 15,000 U/kg; while group B received only NaHCO3, 3.5 mEq/kg, prior to aortic crossclamp release. There was a statistically significant difference in cardiac output, systolic blood pressure, systemic and pulmonary vascular resistances, and arterial oxygen tension between the two groups following aortic crossclamp release. Cardiac output increased from 2.2 +/- .05 to 2.5 +/- .03 L/min (P < .05) after declamping, and returned toward preclamping baseline values after five minutes in group A. In group B, cardiac output decreased from 2.3 +/- .05 to 2.1 +/- .01 (P < .005) after declamping and remained unchanged five minutes later. No statistically significant changes in PaO2 occurred in group A, while there was a significant decrease in PaO2 in group B after crossclamp release. In group B, PaO2 decreased from 95 +/- 7 to 70 +/- 1 mmHg (P < .005) after crossclamp release. Bradykinin levels were almost identical in both groups studied. It is concluded that SOD significantly decreases the cardiovascular changes following aortic crossclamp release.

Animals↗
PubMed1988

Rate of induction of hypotension with trimetaphan modifies the intracranial pressure response in cats.

An infusion of 0.1% trimetaphan was administered to eight cats with artificially increased intracranial pressure (ICP) in order to decrease their mean arterial pressure (MAP) from 121 +/- 9.5 (SEM) to 58 +/- 4.6 mm Hg in less than 1 min. All cats developed an increase in intracranial pressure (ICP) (from 16 +/- 1.4 to 23 +/- 3.2 mm Hg) accompanied by a partial rebound in MAP. Eight additional cats received 0.1% trimetaphan to decrease their MAP from 128 +/- 13.4 to 52 +/- 8.1 mm Hg over more than 2 min. Four of these cats followed the same pattern, with ICP increases from 19 +/- 1.1 to 31 +/- 3.9 mm Hg, while in the other four ICP did not change. In nine of the 12 cats with an ICP increase, that increase was initiated before the partial MAP rebound. We conclude that trimetaphan causes clinically significant ICP increases in cats with increased ICP, that partial rebound in MAP frequently exacerbates these increases in ICP, and that rapid induction of hypotension tends to increase the frequency with which trimetaphan increases ICP.

Animals↗
PubMed1988

Magnesium and cobalt, not nimodipine, protect neurons against anoxic damage in the rat hippocampal slice.

Brain tissue, maintained in vitro, was used to determine whether agents that block calcium entry into neurons can improve the recovery of evoked responses after anoxia. The hippocampus was dissected from a rat brain and sliced perpendicular to its long axis such that its main neuronal circuits remain functional. A pathway in the slice was stimulated electrically, and an extracellular potential, the evoked population spike, recorded from the neurons postsynaptic to that pathway. A bipolar stimulating electrode was placed in either the perforant path or the Schaeffer collaterals and a monopolar metal microelectrode placed, respectively, in either the dentate granule cell layer or the CA1 pyramidal cell layer. The slices were maintained in vitro by superfusing them with oxygenated (95% O2, 5% CO2) artificial cerebrospinal fluid (aCSF). In order to generate anoxia, the tissue was superfused with aCSF bubbled with 95% N2, 5% CO2 for either 5 or 10 min. All drugs examined were present in the aCSF before, during, and immediately after the anoxic period. Percentage recovery was expressed as the amplitude of the evoked population spike 60 min after anoxia divided by its preanoxic amplitude. Protection in this model is defined as a significant (P less than 0.05) improvement in percentage recovery compared with the recovery of untreated slices. There was no recovery of the response recorded from untreated dentate granule cells after 10 min of anoxia (0 +/- 0%, n = 5; mean +/- SE), whereas 5 min of anoxia was sufficient to cause damage to the untreated CA1 pyramidal cells (4 +/- 3%, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Anesthetic protection against anoxic damage in the rat hippocampal slice.

Evoked population spikes were recorded from the dentate granule cell layer of hippocampal slices obtained from adult rats. These slices were subjected to short periods of anoxia in the presence of different anesthetics. The recovery of the population spike after anoxia was compared across treatments. Little or no recovery was found after 10 min of anoxia when no anesthetic (4 +/- 4%), 1.5% isoflurane (5 +/- 5%), or 15% isoflurane (0 +/- 0%) was present during the anoxic periods. However, the population spike did recover to 81 +/- 7% of its preanoxic amplitude within 1 h after the anoxia if thiopental 160 mg/liter was present in the perfusate during the anoxia. Fifteen percent isoflurane and 160 mg/liter thiopental were equipotent in reducing the amplitude of the evoked population spike before anoxia but only thiopental protected against the damage after 10 min of anoxia. Our results suggest that the blocking of the evoked population spike by thiopental is not the sole mechanism of its protection against anoxic damage. Isoflurane (1.5%) was able to provide a small degree of protection against shorter periods (7 min) of anoxia.

Animals↗
PubMed1987

Effect of alpha-tocopherol and free radicals on anoxic damage in the rat hippocampal slice.

The effect of alpha-tocopherol on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from the dentate granule cell layer after stimulation of the perforant path. The amplitude of the population spike was compared before and after anoxia. Control slices recovered to 22 +/- 7% of their preanoxic amplitude after 7 min of anoxia. Slices treated with alpha-tocopherol showed significantly greater recovery after anoxia (P less than 0.001). The population spike recovered to 64 +/- 15% of its preanoxic amplitude. As alpha-tocopherol is a free radical scavenger, our results provide evidence that free radicals are partly responsible for irreversible anoxic damage. alpha-Tocopherol is not toxic and may prove efficacious in protecting the brain against anoxic damage.

Animals↗
PubMed1987

Nitrous oxide reduces thiopental-induced prolongation of survival in hypoxic and anoxic mice.

Arnfred's mouse model was used to test the effect of thiopental during hypoxia (5% O2) and anoxia, with and without simultaneous administration of nitrous oxide. As found by Arnfred and others, thiopental without N2O more than doubled survival time during hypoxia (from 5.2 +/- 0.6 to 13.9 +/- 2.6 min). This effect was completely offset by simultaneous use of N2O (from 13.9 +/- 2.6 to 4.8 +/- 0.7 min). Thiopental without N2O also increased survival time during complete anoxia (from 26 +/- 1 to 59 +/- 1 sec). This effect was diminished by 58% when N2O was added (from 59 +/- 1 to 40 +/- 1 sec). We conclude that nitrous oxide diminishes the effect of barbiturates upon survival time in hypoxic and anoxic mice.

Animals↗
PubMed1986

In vitro induction of somatic cell hybridization by the local anesthetic chloroprocaine.

Chloroprocaine, an aminoester local anesthetic commonly used for epidural block, has been found to induce interspecies somatic cell hybrids in vitro. Mixed cultures of human amniocytes and mouse hepatoma cells, deficient in hypoxanthine phosphoribosyl transferase, were exposed to 1.6, 0.8, or 0.4 X 10(-3)M chloroprocaine for 3 hr at 37 degrees C, then maintained for 3 weeks in a double-selective medium of hypoxanthine, aminopterin, and thymidine (HAT) and ouabain to eliminate the unfused parental cells. Clones of actively multiplying cells appeared in cultures exposed to 1.6 and 0.8 X 10(-3)M chloroprocaine. Chromosome analysis confirmed they were hybrids. Cultures treated with 0.8 X 10(-3)M chloroprocaine exhibited the highest frequency of cell hybridization (8.8 X 10(-5). The hybrid clones bore the morphologic characteristics of both parents although their growth pattern closely resembled the mouse parent. Procaine, sodium bisulfite (the antioxidant present in the commercial solutions of chloroprocaine), and the two chloroprocaine metabolites, chloroaminobenzoic acid and diethylaminoethanol, were nonfusogenic. The hybridogenic effect of chloroprocaine has not been previously described with other local anesthetics.

Animals↗