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Biomedical subjects

E D Hall

Publications and source records attributed to E D Hall.

At least 163 records · Page 9Linked to original sources
PubMed1985

Suloctidil treatment prevents the development of post-traumatic feline spinal cord ischemia.

The effects of suloctidil (1.0 mg/kg i.v.) on white matter spinal cord blood flow (SCBF) and somatosensory evoked potential (SEP) conduction were assessed in a feline lumbar spinal cord contusion model. SEP conduction ceased immediately after a 500 g-cm injury and did not recover. SCBF following suloctidil declined by only 12% from pre-injury levels over the 4 hr experiment as compared to a 42% decline observed following vehicle injection. Accordingly, 7/8 vehicle cats, but only 1/5 suloctidil-treated cats, had 4 hr SCBF values of less than 10 ml/100 g/min. Bradycardiac and hypotensive effects of suloctidil were also noted. The ability of suloctidil to prevent post-traumatic ischemia may be useful in the acute treatment of spinal cord injury.

Animals↗
PubMed1984

Methylprednisolone preservation of motor nerve function during early degeneration.

Intensive pretreatment of cats with methylprednisolone acetate (8 mg/kg, i.m. once daily for 7 days) was found to significantly preserve the functional capabilities of degenerating soleus motor nerve terminals, as measured at 48 h after motor axon section in the in vivo soleus nerve-muscle preparation. This effect is similar to that reported previously for triamcinolone, another glucocorticoid.

Animals↗
PubMed1984

Effects of a single large dose of methylprednisolone sodium succinate on experimental posttraumatic spinal cord ischemia. Dose-response and time-action analysis.

The ability of a single large intravenous dose of methylprednisolone sodium succinate (MPSS: 15, 30, or 60 mg/kg) to modify the evolution of lumbar spinal cord ischemia in cats undergoing a contusion injury of 500 gm-cm is examined. Repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus were made via the hydrogen clearance technique before and for 4 to 5 hours after injury. The mean preinjury SCBF for all animals was 12.29 +/- 0.77 ml/100 gm/min. Following injury, SCBF began to decrease progressively in vehicle-treated animals to a level of 7.71 ml/100 gm/min, a fall of 37.3%. In contrast, cats that received a 30-mg/kg intravenous dose of MPSS at 30 minutes after injury maintained SCBF within normal limits (p less than 0.05 at 3 and 4 hours after contusion). A 15-mg/kg MPSS dose was less effective at preventing posttraumatic white matter ischemia, and a 60-mg/kg dose was essentially ineffective. It was determined that the 30-mg/kg MPSS dose was optimal for supporting SCBF when the drug was given at 30 minutes after spinal trauma, and a second series of experiments was carried out to examine the ability of this dose, when given at longer latencies, to improve decreased flow. Methylprednisolone given at 1 1/2 hours after injury in four cats produced a slight (12.7%) but transient improvement in SCBF, and when administered at 4 1/2 hours in another three animals was totally ineffective. These results show that MPSS in a 30-mg/kg dose can prevent posttraumatic spinal cord ischemia. However, it would appear that the ability of the steroid to reverse the ischemia once it has developed is limited, and probably lost, within a few hours of onset. This further suggests that the ischemic process is irreversible and underscores the need for early treatment with a large MPSS dose in order to prevent full development of ischemia and to promote neurological recovery.

Animals↗
PubMed1984

Effects of multi-dose methylprednisolone sodium succinate administration on injured cat spinal cord neurofilament degradation and energy metabolism.

Thirty minutes after experimental spinal cord contusion (500 gm-cm) injury, cats were treated with an initial intravenous dose of either vehicle (V) or 30 mg/kg of Solu-Medrol sterile powder (methylprednisolone sodium succinate; MPSS). Two hours later, cats received a second intravenous injection of either V or 15 mg/kg MPSS, giving three treatment groups: V/V; MPSS/V; MPSS/MPSS. At 4 1/2 hours following injury of the cat lumbar spinal cord, the gray and white matter neurofilament protein content was reduced by over 70% within the injured segment of V/V-treated animals. The three major cat spinal cord neurofilament protein subunits of 200,000, 152,000, and 76,000 daltons were reduced in parallel by the injury. Treatment of cats with a single 30-mg/kg dose of MPSS (MPSS/V) provided a clear, although not significant, protection against neurofilament degradation compared with V/V-treated cats when measured at 4 1/2 hours after injury. The lactic acid content of the injured spinal cord segment at 4 1/2 hours after injury was significantly elevated in both V/V- and MPSS/V-treated cats, while the adenosine triphosphate (ATP) content, total adenylates, and energy charge were significantly reduced. The administration of a second intravenous 15-mg/kg dose of MPSS 2 hours after the initial 30-mg/kg dose (MPSS/MPSS) provided complete (p less than 0.01) preservation of neurofilaments within the injured spinal cord segment measured at 4 1/2 hours after injury. The levels of lactate, ATP, total adenylates, and tissue energy charge in MPSS/MPSS-treated cats were not different from those of uninjured spinal cords following laminectomy. The (Na+ + K+)-ATPase activity in the injured spinal segment was enhanced, although highly variable, in MPSS/V-treated animals. On the other hand, spinal cord enzyme activity was significantly and consistently elevated in the MPSS/MPSS-treated group. The results demonstrate that a 30-mg/kg dose of MPSS followed at 2 hours by a 15-mg/kg dose provides significantly better protection against injury-induced ischemia and Ca++-dependent neurofilament degradation than a single 30-mg/kg dose. These findings are in agreement with the spinal cord tissue pharmacokinetics and time-action characteristics of methylprednisolone observed in earlier studies.

Adenine Nucleotides↗
PubMed1983

Glucocorticoid modification of spinal dopamine receptor activation by apomorphine.

The effects of an intensive short-term glucocorticoid (e.g. triamcinolone) regimen in cats have been studied on the actions of the dopamine (DA) receptor agonist apomorphine (APO) on spinal lumbar primary afferent excitability (dorsal root reflex or DRR) and monosynaptic reflex (MSR) transmission. Glucocorticoid dosing significantly decreased the APO-induced depression of the spinal DRR, but not the similar action of APO on the MSR. This complex effect of triamcinolone on spinal dopaminergic activation by APO may represent a differential action of glucocorticoid on two types of spinal DA receptors with one type, but not the other, undergoing partial desensitization.

Afferent Pathways↗
PubMed1983

Beneficial action of glucocorticoid treatment on neuromuscular transmission during early motor nerve degeneration.

The effects of a short-term, high-dose glucocorticoid pretreatment regimen (triamcinolone diacetate, 8 mg/kg i.m. daily for 7 days) were examined on neuromuscular transmission deficits observed in the in vivo cat soleus nerve-muscle preparation at 48 hr after soleus nerve transection. The pretreated preparations had 20% more functional motor nerve terminals than the untreated. This was evidenced by a significantly (P less than 0.01) lesser difference in the indirectly evoked isometric contractile tensions between the denervated muscle and the contralateral intact preparation as a result of prior glucocorticoid treatment. The glucocorticoid pretreatment also significantly improved the capacity of the trophically deprived soleus motor nerve terminals to maintain transmission during high-frequency activation (100 to 400 Hz for 10 s). Moreover, triamcinolone treatment before nerve transection completely prevented the development of an increased sensitivity to d-tubocurarine neuromuscular block in untreated, 48-h nerve-transected preparations. These results demonstrate an ability of an intensive high-dose glucocorticoid treatment to sustain single and repetitive neuromuscular transmission during early anterograde nerve degeneration.

Animals↗
PubMed1983

Actions of guanidine hydrochloride on cat spinal monosynaptic reflex transmission.

The effects of a single intravenous dose of guanidine hydrochloride were examined on the function of the lumbar dorsal-ventral root and triceps surae nerve-ventral root monosynaptic reflex (MSR) in unanesthetized acute spinal (C-1 sectioned) cats. Guanidine, in a dose of 25 mg/kg, consistently depressed the amplitude of the monosynaptic reflex response while a dose of 200 mg/kg always exerted a facilitatory action. Intermediate doses of 50 or 100 mg/kg produced variable actions on the amplitude of the monosynaptic reflex from one preparation to another. The differential effects of guanidine on the evoked monosynaptic reflex are postulated to represent the ability of the drug to enhance both excitatory and inhibitory transmission, the latter predominating at smaller doses and the former becoming apparent with an increasing dose of guanidine. The facilitatory and the depressant effects of guanidine on the function of spinal reflexes were slow to develop, suggesting an intracellular site of action. These results may have significance for an understanding of the possible efficacy of guanidine in motor neuron disease in man.

Animals↗
PubMed1983

Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester.

The uptake and elimination of methylprednisolone by the injured cat lumbar spinal cord were examined following a single 30-mg/kg intravenous bolus injection of the sodium succinate ester. The findings were considerably different from those previously reported for normal lumbar cord. When the glucocorticoid was administered 30 minutes after a 400 gm-cm contusion injury, peak tissue concentrations in both injured and uninjured segments of traumatized spinal cord were not achieved until 30 minutes following drug administration. The elimination of methylprednisolone from injured spinal cord tissue was biphasic in nature, with a rapid elimination phase occurring between 1 and 2 hours after drug administration. This rapid elimination phase was followed by a slower phase which paralleled the constant elimination rate from uninjured tissue of traumatized cord (approximate half-time = 6 hours). Significantly more methylprednisolone accumulated in the injured segment of traumatized spinal cord than in an uninjured segment adjacent to the injury site. This was only true, however, if the drug was administered at times up to 1 hour after injury. If injected after 1 hour, uptake by the injured segment decreased significantly with time after trauma and was no different from that observed for the uninjured segment in the same animal, which showed no significant variation with time after trauma. The probable basis for these differences and the possible clinical implications of these pharmacokinetic characteristics are discussed.

Animals↗
PubMed1983

Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone.

The lactate content and the lactate/pyruvate ratio of the acutely traumatized cat spinal cord have been studied and were found to rise rapidly following a 400 gm-cm injury. Lactate levels rose nearly twofold within 5 minutes after injury, peaked at 2 hours after injury, and remained significantly elevated for at least 8 hours compared to an adjacent uninjured segment of traumatized cord. Pyruvate levels, on the other hand, fell acutely in the injured section of cord during the 1st hour after injury then rose slowly over an 8-hour period. The changes in tissue lactate and pyruvate metabolism in the spinal cord following injury are consistent with a marked injury-induced reduction in blood flow. The elevation in lactate and the fall in pyruvate levels observed at 1 hour after injury were completely prevented by the intravenous administration of a single 30-mg/kg dose of methylprednisolone sodium succinate at 30 minutes after injury. Lower or higher doses of methylprednisolone were far less effective. The effects of the 30-mg/kg dose of methylprednisolone on tissue lactate content were associated with high tissue levels of the glucocorticoid and were short-lived, paralleling the accumulation and elimination pattern of steroid from the injured tissue. The results suggest that, in addition to other reported beneficial actions of large intravenous doses (30 mg/kg) of methylprednisolone on the injured cord, the glucocorticoid may also improve blood flow to the injured segment as has been suggested by others. The use of high glucocorticoid doses, early therapy initiation, and rigorous maintenance dosing is discussed.

Animals↗
PubMed1983

Acute cardiovascular response to a single large intravenous dose of methylprednisolone and its effects on the responses to norepinephrine and isoproterenol.

The cardiovascular actions of single 10-micrograms/kg iv doses of norepinephrine (NE) and isoproteronol (ISO), before and after the administration of a single 30-mg/kg iv dose of the glucocorticoid methylprednisolone (MP) (sodium succinate ester), were compared in adult cats. Methylprednisolone increased both systolic and diastolic pressures as well as the pulse pressure by approximately 50%. These steroid effects persisted unabated for the duration of the experiment (40 min). Heart rate was unaffected by MP. MP treatment significantly reduced the increase in systolic and diastolic pressures caused by NE. This MP effect was unrelated to the higher baselines for these two parameters caused by the steroid. The systolic blood pressure and positive chronotropic effects of ISO were also significantly blunted by MP. These observations suggest that a single large dose of MP may cause a depression of cardiovascular alpha- and beta-1-receptor sensitivity. The results are discussed in relation to the actions of massive dose glucocorticoid administration in certain shock states and central nervous system trauma and stroke.

Animals↗
PubMed1983

Acute manganese toxicity and the absorption and biliary excretion of manganese in cattle.

The concentration of manganese in the duodenum of three steers was increased by infusing manganese chloride intraduodenally at approximately 100, 515 and 840 mumol per minute for 30 hours and the rate at which manganese was excreted in bile was measured. In one steer an infusion of manganese chloride at 529 mumol per minute was toxic and in two steers infusions at approximately 840 mumol per minute were also toxic, causing inappetence, a reduced bile flow and abdominal discomfort. The maximum rates at which manganese was excreted in bile during the first three hours of the infusions at 515 and 840 mumol per minute were between 2.1 and 3.6 per cent of the rate of infusion. During the last three hours of all nontoxic infusions the rate of excretion of manganese in bile was 0.82 +/- 0.08 per cent of its rate of infusion. Systemic plasma manganese concentrations did not increase during these infusions. In a fourth steer the longer term capacity of the liver to excrete manganese in bile when the manganese chloride was given intravenously was measured, the concentration of manganese in the portal vein being increased by infusions of manganese chloride solution into a mesenteric vein. The rate of infusion was increased at hourly intervals. The liver's capacity to remove all manganese during first pass was only exceeded at an infusion rate of 84 mumol per minute. Infusions could be made into the mesenteric vein at 24 and 35.8 mumol per minute for 53 and 26 hours respectively before signs of toxicity were observed. Following signs of toxicity the excretion of copper in bile was decreased for two days.

Animals↗
PubMed1982

Determination of methylprednisolone in central nervous tissue and plasma using normal-phase high-performance liquid chromatography.

A sensitive and specific high-performance liquid chromatographic technique is described for the quantitative measurement of the synthetic glucocorticoid methylprednisolone in central nervous tissue (spinal cord) and plasma. Following intravenous administration, methylprednisolone is extracted from spinal cord tissue with diethyl ether-methylene chloride (60:40, v/v). The extract is washed sequentially with alkali, acid and water, concentrated, then chromatographed on an NH2 column using a mobile phase of methylene chloride-isopropanol (85:15, v/v). Steroid elution is monitored with an ultraviolet detector set at 254 nm. Such a system has a detection limit of 2.8 ng methylprednisolone. Extraction of methylprednisolone from spinal cord tissue is linear with tissue concentration and the recovery is around 70%. Endogenous hydrocortisone or other metabolites in the tissue do not interfere with the methylprednisolone peak. A description of the quantitation of methylprednisolone in cat lumbar spinal cord and plasma samples after single intravenous doses of methylprednisolone sodium succinate is given.

Animals↗
PubMed1982

Glucocorticoid effects on the electrical properties of spinal motor neurons.

The effects of an intensive 7 day glucocorticoid (e.g. methylprednisolone) regimen have been studied on the electrical properties of cat lumbar spinal motor neurons via intracellular recording. The results reported in this paper have shown that glucocorticoid dosing produces numerous effects on motor neuron excitability and impulse generation and conduction. These include a resting hyperpolarization, a slowed conduction of an antidromic action potential through the initial axon segment and an increased threshold, a slowed rate of depolarization and a prolonged refractoriness of the soma-dendritic portion of the neuron. On the other hand, the excitability of the initial axon segment, where the nerve impulse is physiologically triggered, is increased as demonstrated by a decrease in the rheobasic current and an increased slope of the current-frequency relationship for repetitive discharge. An additional effect of the steroid is to augment the action potential after-depolarization. These results suggest a complex glucocorticoid action on specific ionic mechanisms which is discussed along with possible neurological and psychiatric implications.

Animals↗
PubMed1982

Acute effects of intravenous glucocorticoid on cat spinal motor neuron electrical properties.

The acute effects of a single large intravenous dose of methylprednisolone were examined on the resting membrane potentials and the antidromic action potentials characteristics in cat lumbar spinal motor neurons via intracellular recording. A 30 mg/kg glucocorticoid dose was found to cause a 3.5 mV hyperpolarization of the resting membrane potential. An examination of the effects of the single dose on the conduction and generation of an antidromic action potential revealed an increased conduction velocity along the myelinated motor axon, a decreased conduction rate through the unmyelinated initial axon segment, an increased threshold for antidromic soma-dendritic activation, a decreased action potential zero overshoot and a faster repolarization. All of these effects were greatest after the 30 mg/kg methylprednisolone dose except for the increase in the antidromic soma-dendritic threshold which was even greater after 60 mg/kg. The 30 mg/kg dose also caused a stimulus-bound repetitive discharge in a third of the motor neurons which appeared to arise in the myelinated motor axon or initial axon segment. The neurophysiological implications of these acute glucocorticoid actions are discussed.

Animals↗
PubMed1982

Glucocorticoid mechanisms in acute spinal cord injury: a review and therapeutic rationale.

This review seeks to provide pharmacological evidence that intensive glucocorticoid dosing can enhance sensorimotor recovery after blunt spinal cord trauma. It is suggested that high doses of glucocorticoids can beneficially affect the injured cord through the influence of at least three mechanisms. These are: (1) a facilitation of neuronal excitability and impulse conduction; (2) an improved blood flow; and, perhaps most importantly, (3) the preservation of cord ultrastructure through a reduction of injury-induced, free radical--catalyzed lipid peroxidation. In the case of methylprednisolone, the minimal intravenous dosage required to initially achieve each of these effects is in the range of 15 to 30 mg per kilogram of body weight, which is beyond that used currently for neurosurgical purposes. In addition, based upon the hypothesized mechanism of action and the tissue pharmacokinetics, the earliest possible initiation of therapy is imperative and rigorous maintenance dosing for an as yet undetermined length of time is needed.

Acute Disease↗