Biomedical subjects

J H Milde

Publications and source records attributed to J H Milde.

At least 55 records · Page 3Linked to original sources

PubMed1987

The detrimental effect of lidocaine on cerebral metabolism measured in dogs anesthetized with isoflurane.

Previous studies in dogs have demonstrated that massive doses of intravenous lidocaine (160 mg X kg-1) can inhibit cerebral oxygen metabolism to a greater degree when administered with pentobarbital than can pentobarbital alone. From these data, it was hypothesized that lidocaine decreases cerebral metabolism by two means: suppression of cortical electrical activity and stabilization of neuronal membranes, and it was suggested that lidocaine might provide protection for the ischemic brain. In an attempt to apply this property clinically, the effect of a lower, clinically tolerated dose of lidocaine (15 mg X kg-1) on cerebral oxygen metabolism and cerebral blood flow was examined in dogs receiving deep isoflurane anesthesia. Once maximal metabolic suppression, as reflected by an isoelectric EEG, was achieved with isoflurane (3% end-expired), the administration of this dose of lidocaine had little effect on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). The CBF was 94 +/- 19 ml X min-1 X 100 g-1 during 3% isoflurane anesthesia, and was 102 +/- 11 ml X min-1 X 100 g-1 with the addition of lidocaine. The CMRO2 was 2.32 +/- 0.23 ml X min-1 X 100 g-1 during isoflurane anesthesia, and was 2.18 +/- 0.09 ml X min-1 X 100 g-1 following the administration of lidocaine. However, this dose of lidocaine did produce a derangement of cerebral metabolites. The cerebral concentration of ATP during 3% isoflurane anesthesia was 2.07 +/- 0.04 mumol X g-1 (cerebral ATP in normal unanesthetized dogs is 2.01 +/- 0.01 mumol X g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1986

Treatment of porcine malignant hyperthermia: lactate gradient from muscle to blood.

Treatment of MH was studied in 21 pigs, using an isolated perfused caudal body preparation (L1 transection). Halothane one per cent triggered MH; data included oxygen consumption, blood/muscle lactate levels, plasma potassium, acid-base balance. Three treatment protocols had two phases each: A-1, discontinue halothane, inject dantrolene 7.5 mg X kg-1; A-2, inject HCO3- (113 +/- 6 mEq). B-1, Discontinue halothane, inject HCO3- (118 +/- 13 mEq); B-2, inject dantrolene 7.5 mg X kg-1; X C-1, Continue halothane, inject dantrolene 7.5 mg X kg-1; C-2, discontinue halothane, inject HCO3- (101 +/- 8 mEq). Dantrolene and HCO3- acted separately and differently: dantrolene reversed the hypermetabolism, both aerobic and anerobic, and HCO3- reversed the extracellular metabolic acidosis. Semitendinosus muscle biopsies demonstrated that both red and white muscle are involved in MH, that muscle lactate (to 35 mumol X g-1) consistently exceeded blood lactate (to 22 mumol X ml-1), and that blood lactate levels were slow to diminish following treatment. One could expect continued release of muscle lactate into blood, despite adequate therapy of MH; this might suggest a recurrence even when such is not the case.

Animals↗

PubMed1986

The effects of nimodipine on cerebral blood flow and metabolism.

Nimodipine, a calcium entry blocker, was administered in increasing doses of 0.1-3.0 micrograms kg-1 min-1 to six dogs after they had recovered consciousness from a surgical preparation that was conducted under general anesthesia and while they were under the influence of total spinal anesthesia. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Nimodipine did not influence either CBF or CMRO2. There was a decrease in the cortical pyruvate level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with six control dogs. It has previously been reported that nimodipine increases the CBF in global ischemia with a potentially beneficial effect on the neurological outcome. With no effect on normal CBF or metabolism, this suggests that nimodipine may be useful in a variety of ischemic situations without fear of either a steal phenomenon or untoward effects on intracranial pressure.

Animals↗

PubMed1986

Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog.

Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min-1 100 g-1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min-1 100 g-1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min-1 100 g-1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.

Adenine Nucleotides↗

PubMed1986

Effect of CO2, calcium, digoxin, and potassium on cardiac and skeletal muscle metabolism in malignant hyperthermia susceptible swine.

The effects on whole body or cardiac metabolism of carbon dioxide, calcium, potassium, or digoxin were studied in 16 normal swine and 31 swine susceptible to malignant hyperthermia (MHS). Malignant hyperthermia (MH) was defined as an increase in metabolism that occurred in MHS but not in normal pigs. Whole body response: despite a sustained PaCO2 greater than 130 mmHg, MH did not develop in four intact MHS swine during thiopental-N2O anesthesia and controlled ventilation. Drugs given during total cardiopulmonary bypass: MH did not develop in five MHS pigs with blood ionized calcium to 15 mEq/l, in four MHS pigs with digoxin levels to 60 ng/ml, or in four normal pigs with potassium to 10 mEq/l. In six MHS pigs, oxygen consumption increased from 6.5 to 11.6 ml O2 X min-1 X kg-1 when potassium exceeded 6 mEq/l; lactate did not increase. Cardiac response (during extracorporeal right heart bypass): eight pigs (four normal, four MHS) with blood ionized calcium to 5 mEq/l and eight pigs (four normal, four MHS) with digoxin levels above 7.5 ng/ml had increased myocardial oxygen consumption. Cardiac potassium efflux or lactate production did not occur in normal or MHS pigs. Increased arterial potassium (7.4-8.5 mEq/l) did not alter myocardial oxygen consumption or lactate production in four MHS or four normal pigs. MH responses were initiated only by potassium and only in regard to whole body metabolism. Cardiac metabolism increased as a result of specific drugs (calcium, digoxin), unrelated to MH phenomena. Porcine inbreeding resulting in MH susceptibility of skeletal muscle does not imply abnormality in other tissues.

Animals↗

PubMed1986

Canine cerebral function and blood flow after complete cerebral ischemia: effect of head position.

It has been reported that animals exposed to relatively "bloodless" cerebral ischemia have improved cerebral function post-ischemia. This suggests the possibility that large variations in cerebral blood volume during complete ischemia might affect outcome following reperfusion. The purpose of this study was to determine whether changes in dog head position (and therefore cerebral blood volume) during complete cerebral ischemia produced by occluding the aorta and venae cavae affect post-ischemic cerebral blood flow (CBF), cerebral metabolic oxygen requirements (CMRO2), or neurologic outcome. Two dogs were transfused with 111In-labeled red blood cells. Gamma camera images taken during complete cerebral ischemia showed 45-degree head-up dogs to have 30% of the cranial blood volume of a 10-degree head-down dog. CBF and CMRO2 90 min post-ischemia were not significantly different between the head-up and head-down groups in the 14 dogs studied. There was also no significant difference in neurologic outcome at 48 h post-ischemia between head-up and head-down dogs. The authors conclude that head position during complete cerebral ischemia has a major effect on cranial blood volume, but no effect on post-ischemic CBF, CMRO2, or neurologic outcome.

Animals↗

PubMed1986

Cerebral stimulation following succinylcholine in dogs.

The effects of iv succinylcholine (SCh) on the electroencephalogram (EEG), cerebral blood flow (CBF), cerebral metabolic rate (CMRO2), intracranial pressure (ICP), central venous pressure (CVP), and mean arterial pressure (MAP) were tested in halothane-anesthetized dogs. Six dogs were maintained at 0.87 +/- 0.00% (mean +/- SE) expired halothane (1.0 MAC) and received both SCh 1.0 mg X kg-1 and lactated Ringer's solution placebo 0.05 ml X kg-1. Fasciculations began 24 +/- 4 s after iv SCh. Fasciculations were followed by immediate EEG arousal in five of six dogs and increases in CBF in all six. Average CBF was 151 +/- 14% of control for the 0-15 min measurement period and 127 +/- 7% of control for the 15-30 min period. Both were significantly greater than pre-SCh control values and placebo group values. Peak CBF of 177 +/- 19% of control occurred 3 min after iv SCh and was accompanied by a peak ICP of 435 +/- 131% of control. ICP values were significantly different between SCh and placebo treatments only during the periods of greatest CBF (1 to 5 min after iv SCh). Average PaCO2 values after iv SCh were significantly greater than pre-SCh control values and placebo values during each 15-min measurement interval. Average PaCO2 was 116 +/- 2% of control during the 0-15 min measurement period, 114 +/- 2% of control during the 15-30 min period, and 109 +/- 1% of control during the 30-45 min period. CVP, MAP, and CMRO2 did not significantly change after iv SCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1986

Reversal of the cerebral effects of diazepam in the dog by the benzodiazepine antagonist Ro15-1788.

In six dogs initially anesthetized with halothane-N2O-O2 for surgery and maintained during the experiment with high spinal anesthesia and local infiltration, diazepam 3.0 mg X kg-1 converted the EEG from an awake to a sleep pattern. This was accompanied by a significant 21% reduction in cerebral metabolic rate for oxygen (CMRO2) and a 15% reduction in cerebral blood flow (CBF). Substituting nitrous oxide 70% for nitrogen had no additional cerebral effects. The benzodiazepine antagonist Ro15-1788, 2 mg, completely reversed the effects of diazepam on the EEG, CMRO2 and CBF. Cerebral biopsies taken at the end of the study revealed modest but significant decreases in ATP and the energy charge along with increases in AMP, lactate and lactate/pyruvate (L/P) ratio. These changes are unexplained and suggest a possible disturbance in oxidative phosphorylation produced by Ro15-1788 preceded by diazepam.

Anesthesia↗

PubMed1986

Preservation of cerebral metabolites by etomidate during incomplete cerebral ischemia in dogs.

Changes in cerebral high-energy phosphate stores and lactate concentration (as evidence for cerebral protection) were studied in dogs treated with etomidate during incomplete global ischemia, which was of a magnitude insufficient to abolish neuronal synaptic activity (as evidenced by electrical activity on EEG). In six dogs the effects of etomidate (5 mg X kg-1) on the rates of adenosine triphosphate (ATP) and phosphocreatine (PCr) depletion and lactate accumulation during 9 min of oligemic hypotension to 31 mmHg were compared with six untreated dogs. In the dogs treated with etomidate the cerebral energy stores of ATP and PCr and the cerebral energy charge were maintained at higher levels than in the untreated dogs, and the cerebral lactate accumulation was significantly less. This effect of etomidate is similar to that of other anesthetics (thiopental and isoflurane) in this model. The authors conclude that in circumstances of ischemia that are insufficient to abolish neuronal synaptic activity, etomidate may improve tolerance of the brain to ischemia by decreasing cerebral metabolism through its suppression of neuronal synaptic activity.

Adenosine Triphosphate↗

PubMed1985

Nimodipine improves outcome when given after complete cerebral ischemia in primates.

Twenty-seven pigtailed monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia followed by 96 h of intensive care treatment. Fourteen of the monkeys were assigned randomly to the treatment group and received nimodipine 10 micrograms . kg-1 5 min postischemia followed by 1 microgram . kg-1 . min-1 for 10 h. Six monkeys (three treated) failed to meet preestablished protocol criteria and were excluded. The remaining treated and untreated monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome at 96 h postischemia was significantly better in the nimodipine-treated monkeys than in the controls. Eight of the 11 treated animals had an apparent normal level of consciousness; four of these had no detectable neurologic deficits and a fifth had only a slight motor apraxia. Only two of the 10 untreated animals had an apparent normal level of consciousness, and all had major neurologic deficits. Histopathologic examination showed variable ischemic neuronal change and infarction to involve gray matter in distal arterial perfusion zones. Significant white matter changes were not observed. A histopathologic scoring system yielded a significantly better mean score for the treated group than for the untreated group, and there was significant correlation between neurologic function and histopathologic findings. The authors conclude that nimodipine improves the neurologic outcome when given after an episode of complete cerebral ischemia in primates, and they recommend controlled clinical trials in patients resuscitated after cardiac arrest.

Animals↗

PubMed1985

Cerebral and systemic effects of hypotension induced by adenosine or ATP in dogs.

The authors evaluated the systemic and cerebral hemodynamic and metabolic effects of 1 h of hypotension to a mean arterial pressure of either 50 mmHg or 40 mmHg induced by intravenous adenosine or ATP in dogs maintained on 70% nitrous oxide and 0.1% halothane. Following the hypotensive period, brain biopsy specimens were taken for the determination of cerebral metabolites and calculation of the energy charge. Hypotension induced by either adenosine or ATP produced a marked 40-62% decrease in systemic vascular resistance with little change in cardiac index or oxygen consumption but resulted in a mild metabolic acidosis. Because of a profound decrease in cerebral perfusion pressure with hypotension (to 31-33 mmHg at an MAP of 50 mmHg and 22-24 mmHg at an MAP of 40 mmHg) CBF decreased 54-65% and was inadequate to meet the unchanged cerebral oxygen demands, resulting in some anaerobic metabolism with an accumulation of lactate. While the ease with which one can induce and maintain hypotension with these agents may be advantageous in clinical practice, the effects of adenosine and ATP on cerebral hemodynamics and metabolism may offer no advantage over other hypotensive agents.

Acidosis↗

PubMed1985

Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs.

The effects of a continuous infusion of etomidate on cerebral function, metabolism, and hemodynamics and on the systemic circulation were examined in six dogs. The infusion rate of etomidate was progressively increased at 20-min intervals from 0.02 to 0.4 mg X kg-1 X min-1 for 2 h. Cerebral oxygen consumption (CMRO2) decreased until there was cessation of neuronal function as reflected by the onset of an isoelectric EEG. This occurred during an infusion of 0.3 mg X kg-1 X min-1 etomidate when the animals had received a total of 10.7 mg X kg-1 over 91 min. At this time the CMRO2 was 2.6 ml X min-1 X 100 g-1, 48% of control. Thereafter, despite continued administration of etomidate to a total dose of 21.4 mg X kg-1, CMRO2 did not decrease further. Cerebral blood flow (CBF) decreased in association with a marked increase in cerebrovascular resistance but was independent of changes in CMRO2. CBF decreased precipitously from 145 +/- 23 to 72 +/- 6 ml X min-1 X 100 g-1 during the lowest infusion rate of 0.02 mg X kg-1 X min-1 etomidate and stabilized at 34-36 ml X min-1 X 100 g-1 during an infusion rate of 0.1 mg X kg-1 X min-1. CBF remained at this level despite the continued administration of etomidate and a further decrease in CMRO2. Etomidate produced physiologically minor but statistically significant changes in the systemic hemodynamic variables. Assays of cerebral metabolites taken at the end of the infusion revealed a normal energy state and a very mild but significant increase in cerebral lactate to 1.49 mumol X g-1. We conclude that etomidate is a potent, direct cerebral vasoconstrictor that appears to be independent of its effect on CMRO2 and that the cerebral metabolic effects of etomidate are secondary to its effect on neuronal function, with little if any direct or toxic effects on metabolic pathways.

Anesthesia, Intravenous↗

PubMed1985

The cerebral effects of pancuronium and atracurium in halothane-anesthetized dogs.

Pancuronium decreases the minimal alveolar anesthetic concentration (MAC) of halothane in humans, while atracurium has a metabolite, laudanosine, which is a known cerebral stimulant. To determine if these muscle relaxants significantly alter cerebral function, their effects on cerebral metabolic rate (CMRo2), cerebral blood flow (CBF), intracranial pressure (ICP), EEG, and the cerebral energy state were studied in halothane-anesthetized dogs. Group A dogs (n = 6) were maintained at 0.86% end-expired (1.0 MAC) halothane. Thereafter, a sequence of 1) pancuronium 0.1 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; and 3) pancuronium 0.2 mg . kg-1 produced no changes in CMRo2, CBF, ICP, or EEG. Group B dogs (n = 6) also were maintained at 0.86% end-expired halothane and received the following in sequence: 1) atracurium 0.5 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; 3) atracurium 1.0 mg . kg-1; and 4) atracurium 2.5 mg . kg-1. There were no changes in CMRo2, CBF, or ICP; EEG evidence of cerebral arousal occurred in only one dog with the final dose of atracurium. Group C dogs (n = 6) received tetracaine spinal anesthesia and the minimal halothane concentration (mean +/- SE = 0.69 +/- 0.03% end-expired) that would maintain an "anesthetic" EEG pattern. Each Group C dog received the following in sequence: 1) atracurium 1.0 mg . kg-1, and 2) atracurium 2.5 mg . kg-1. EEG evidence of cerebral arousal occurred in all six Group C dogs. Arousal was not accompanied by significant increases in CBF, CMRo2, or ICP.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1985

Electrical stimulation triggers porcine malignant hyperthermia.

Metabolic, haemodynamic and neuroendocrine responses to electrical neuromuscular stimulation were measured in five normal and five malignant hyperthermia-susceptible pigs. Normal animals recovered after stimulation but susceptible pigs showed malignant hyperthermia-like responses. Catecholamine levels were higher in malignant hyperthermia-sensitive than in normal pigs at all sampling times.

Animals↗

PubMed1984

Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog.

Ten minutes of complete cerebral ischemia was produced in 26 dogs by temporary ligation of the aorta and the venae cavae. Twenty dogs received nimodipine, a calcium entry blocker, 10 micrograms kg-1 i.v. 2 min after the ischemic period, followed by 1 microgram kg-1 min-1 for 2-3 h. Six dogs received only the solvent used for nimodipine. Fourteen dogs received nimodipine for 3 h and were subsequently evaluated neurologically up to 48 h postischemia. In the 12 other dogs, CBF and metabolism were followed for 2 h postischemia while either nimodipine or the solvent only was infused. The results were compared to previously published results for untreated dogs and dogs given nimodipine before the ischemic event. Nimodipine had the same effect on postischemic CBF whether started before or after the ischemic event, nearly doubling the flow when compared with untreated controls, whereas the solvent alone caused only a slight increase in CBF over control. By contrast, nimodipine initiated in the preischemic period significantly improved the neurologic outcome, but when initiated in the postischemic period the results were equivocal, such that the outcome was not significantly different from either the untreated group or the group in which nimodipine was initiated preischemia. Metabolic measurements did not give any indication of a specific effect of nimodipine, nor could the metabolic results be used as an indicator of neurologic outcome. The results are consistent with a beneficial effect of nimodipine following complete cerebral ischemia; however, evaluation of neurologic functional effects will require a more sensitive model.

Animals↗

PubMed1984

Systemic and cerebral effects of isoflurane-induced hypotension in dogs.

The systemic and cerebral effects of hypotension induced with isoflurane were examined in 12 dogs. Hypotension to a mean arterial pressure of either 50 mmHg or 40 mmHg for 1 h was produced by 2.5 +/- 0.1-2.9 +/- 0.3% end-expired isoflurane anesthesia. Before and during the period of hypotension the following were measured or derived: arterial and pulmonary artery pressures; arterial, mixed venous, and sagittal sinus blood gases; cardiac output and cerebral blood flow; whole body and cerebral oxygen consumption; systemic and cerebral vascular resistance; intracranial pressure, serum lactate, and pyruvate concentrations; and blood glucose. At the end of the period of hypotension, brain biopsy specimens were taken for the determination of ATP, ADP, AMP, phosphocreatine, lactate, and pyruvate concentrations. Isoflurane-induced hypotension produced a significant decrease in systemic vascular resistance (27-43%) associated with a significant decrease in cardiac output (39-42%) and a smaller decrease in whole-body oxygen consumption (14-21%). Isoflurane also produced a significant decrease in cerebral oxygen consumption (40-44%) accompanied by a decrease in cerebral blood flow (60-62%). Following both the 40 and 50 mmHg periods of hypotension, the cerebral energy state was normal, indicating the preservation of normal aerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1983

Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog.

Ten minutes of complete ischemia was produced in 11 dogs by temporary ligation of the aorta. Immediately before the ischemic episode, the dogs received nimodipine, a new calcium entry blocker, 10 micrograms kg-1, i.v., followed by an infusion of 1 microgram kg-1 min-1 for 2 h. Post-ischemic cerebral blood flow and metabolism were measured for 120 min in six dogs. Neurologic recovery was evaluated 48 h post-ischemia in five dogs. The results were compared to previously determined controls. Nimodipine nearly doubled cerebral blood flow in the delayed post-ischemic hypoperfusion period, compared to untreated dogs (approximately 45% versus 25% of pre-ischemic control values), but had no significant effect on metabolism. Nimodipine also improved neurologic recovery. Four of five treated dogs were normal and one was moderately damaged, whereas six of seven controls were either severely damaged or dead. This suggests that the delayed hypoperfusion state occurring after complete cerebral ischemia probably does contribute to the ultimate neurologic damage, and that nimodipine offers a potential protective effect.

Animals↗

PubMed1983

Canine whole body and organ system tolerance during 24 hours deep pentobarbital anesthesia.

The impact of tolerance on the metabolism of the whole body, skeletal muscle, brain, kidneys, splanchnic region, and heart during prolonged pentobarbital anesthesia was evaluated in 80 dogs. Oxygen consumption (VO2) for each organ system and whole body was calculated from measured blood flow rate and the difference in blood oxygen content between arterial and venous blood during four periods of continuous and unvarying deep pentobarbital anesthesia: 0-3 h, 3-6 h, 12-15 h, and 21-24 h. VO2 increased with time in whole body (12%), gastrocnemius muscle (83%), calculated entire skeletal muscle (15%), brain (27%), kidneys (20%), and splanchnic area (10%); it decreased in the heart (20%). In all studies, the electroencephalogram indicated a constant deep burst-suppression level of 2-6 bursts/min and blood pentobarbital levels ranged from 4.5-6 mg/dl. About one-fifth of the increase in gastrocnemius VO2 could be accounted for by the effect of a continuous infusion of succinylcholine, and about two-thirds of the rise in renal VO2 by increased renal function. The decrease in heart VO2 was associated with increased cardiac output and decreased systemic vascular resistance. The sustained increase in metabolism was significant and otherwise unexplained in whole body, skeletal muscle, and the brain; it occurred after 3 h had continued through 24 h of pentobarbital anesthesia. This was presumably due to tolerance, and was manifested as increased metabolism during steady deep anesthesia with unchanged blood levels of pentobarbital rather than as a greater requirement for pentobarbital.

Anesthesia↗