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Biomedical subjects

R F Albrecht

Publications and source records attributed to R F Albrecht.

At least 91 records · Page 5Linked to original sources
PubMed1986

Cerebrovascular and cerebral metabolic effects of physostigmine, midazolam, and a benzodiazepine antagonist.

Physostigmine has been reported to reverse the sedation and paradoxical delirium induced by benzodiazepines. Little is known about how these drugs may interact to produce changes in cerebral metabolism and cerebral blood flow (CBF). In the present experiments, the effect of physostigmine on cerebral oxygen consumption (CMRO2) and CBF as well as the ability of physostigmine to reverse the effects of midazolam and 3-carbo-t-butoxy-B-carboline (B-CCT), a benzodiazepine antagonist, was tested in rats. Physostigmine by itself produced dose-dependent increases in blood pressure, CBF, and CMRO2, and it inhibited the decrease in these parameters produced by midazolam. Alone, B-CCT increased CBF and CMRO2, and these changes were potentiated by physostigmine. Thus, physostigmine increases CBF and CMRO2, probably by a direct effect on central cholinergic pathways. The ability of physostigmine to antagonize the metabolic effects of midazolam and to potentiate the stimulation produced by B-CCT suggests an additive effect of the two neurotransmitter systems rather than a direct interaction at the central receptor sites.

Anesthesia, Inhalation↗
PubMed1986

The effects of midazolam on cerebral blood flow and oxygen consumption and its interaction with nitrous oxide.

The effects of the intravenous infusion of midazolam on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured in rats in the presence and absence of nitrous oxide. Midazolam produced 40-45% decreases in CBF with no difference in response between nitrous oxide and nitrogen-ventilated rats. CMRO2 decreased 55% during midazolam infusion in rats ventilated with nitrogen, significantly more (P less than 0.05) than in rats ventilated with nitrous oxide (35%). We conclude that cerebrovascular responses to midazolam infusion were not altered by nitrous oxide and suggest that nitrous oxide may slightly but significantly stimulate brain metabolism during midazolam infusion.

Animals↗
PubMed1986

The effects of nitrous oxide on oxygen consumption by isolated cerebral cortex mitochondria.

The influence of N2O on O2 consumption by mitochondria isolated from the cerebral cortex of goats was examined in incubations preequilibrated with N2O-O2 or N2-O2. Rates of O2 consumption were measured polarographically in a closed system while adenosine triphosphate (ATP) formation was maximal (after addition of excess adenosine diphosphate (ADP), state 3 respiration) and then when it was at zero (after addition of excess oligomycin, state 4 respiration). Compared with 90% N2, 90% N2O produced no change in the rate of state 3 respiration; but an observed 9% decrease in the state 4 rate and an 11% increase in the state 3: state 4 ratio were statistically significant (P less than 0.05). These differences were not seen with N2 and N2O at 70% rather than at 90%, or when succinate rather than pyruvate-malate was used as the respiratory substrate. We conclude the following: Unlike other inhalation anesthetics, N2O at comparable anesthetic concentrations does not inhibit mitochondrial electron transport or ATP formation coupled to it (oxidative phosphorylation). N2O does inhibit one or more other processes, as yet unidentified, which are energetically coupled to electron transport. The increased cerebral O2 consumption that accompanies N2O anesthesia cannot be attributed to a direct effect of N2O on mitochondrial respiration.

Adenosine Triphosphate↗
PubMed1986

Effects of halothane and decreased PO2 on high energy phosphate levels maintained by isolated rat liver mitochondria.

Steady states of oxidative phosphorylation were achieved in mitochondrial suspensions continuously equilibrated with constant gas mixtures, simulating the conditions under which mitochondria contribute to the cellular energy status in vivo. The dependence of the mitochondria-maintained adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio on oxygen and halothane levels was examined at predetermined, clinically relevant concentrations of both gases. Inclusion of 1% halothane in the gas mixture decreased ATP/ADP by about half when mitochondrial respiration was supported by NAD-linked substrate (glutamate); succinate-supported ATP/ADP was not inhibited. With either substrate, and whether or not 1% halothane was present. ATP/ADP was unaffected by decreases in PO2 to values as low as 1.6 mm Hg. Under a range of typical in vivo conditions, therefore, 1% halothane significantly inhibited the mitochondrial contribution to steady state energy balance, whereas decreases in PO2 did not. Combined effects of 1% halothane and reduced PO2 on ATP/ADP were not seen, i.e., halothane did not increase the critical PO2 level (hypoxic threshold) for inhibition of mitochondrial ATP production.

Adenosine Diphosphate↗
PubMed1985

A benzodiazepine antagonist inhibits the cerebral metabolic and respiratory depressant effects of fentanyl.

It is reported that benzodiazepines such as diazepam will stimulate the opiate receptor system and that B-carboline drugs, which are benzodiazepine antagonists, may interact with opiate receptors directly. The ability of 3-hydroxymethyl-B-carboline (3-HMC) to antagonize several parameters of fentanyl anesthesia was tested here in rats. Fentanyl (25 and 100 micrograms/kg iv) produced dose dependent depression of cerebral blood flow (CBF), measured by radioactive microspheres, and cerebral oxygen consumption (CMRO2). These effects were significantly inhibited by 10 mg/kg 3-HMC iv. To test for the specificity of this effect, 3-HMC was also given to rats ventilated with inspire concentrations of 2% halothane. Halothane depressed CMRO2 equally in 3-HMC and vehicle treated rats, indicating no significant effect of the benzodiazepine antagonist. Blood pressure was increased in 3-HMC compared to vehicle treated animals during both fentanyl and halothane anesthesia. CBF was increased in 3-HMC vs vehicle treated rats during halothane anesthesia but this could be accounted for by the elevated blood pressure and lack of cerebral autoregulation rather than a direct cerebrovascular effect. 3-HMC decreased the sleep time and respiratory depressant effects of fentanyl but enhanced the analgesic effects of the opiate, as measured by time to respond to a hot plate stimulus. These results indicate that 3-HMC has the ability to specifically antagonize fentanyl anesthesia. These effects may be produced by an action of 3-HMC at the benzodiazepine receptor and/or by an action of the B-carboline at opioid receptors.

Anesthesia↗
PubMed1985

The interaction between benzodiazepine antagonists and barbiturate-induced cerebrovascular and cerebral metabolic depression.

It has been reported that pentobarbital facilities binding to benzodiazepine receptors binding at anesthetic concentrations and that this action may play a role in the anesthetic potency of this barbiturate. The interaction between pentobarbital and benzodiazepine receptors was tested with Ro 15-1788 which is reported to be a pure benzodiazepine antagonist and 3-hydroxymethyl-beta-carboline (3-HMC), an antagonist which has inverse activity alone. Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured in rats after injections of pentobarbital with and without the antagonists. Pentobarbital produced dose-dependent decreases in cerebral blood flow and cerebral oxygen consumption at 15 and 30 mg/kg. The antagonist Ro 15-1788 (10 mg/kg) stimulated cerebral blood flow and cerebral oxygen consumption alone but did not alter the cerebral depression produced by pentobarbital. The cerebral metabolic stimulation produced by Ro 15-1788 was unexpected since the drug is reported to be a pure antagonist without agonistic activity, but the lack of effect on pentobarbital-induced cerebral depression is consistent with other reports. 3-Hydroxymethyl-beta-carboline at 10 mg/kg did not stimulate cerebral blood flow and cerebral oxygen consumption but significantly antagonized the decrease in cerebral oxygen consumption produced by 15 mg/kg pentobarbital. 3-Hydroxymethyl-beta-carboline had no significant effect on decreases in cerebral blood flow and cerebral oxygen consumption produced by phenobarbital, a barbiturate which is reported not to alter binding to benzodiazepine receptors. The ability of 3-HMC to antagonize the effects of pentobarbital would be consistent with an action of both drugs at the benzodiazepine receptor but not by altering binding to an endogenous receptor.

Animals↗
PubMed1985

Plasma and myocardial catecholamine levels in young and aged rats during halothane anesthesia.

Plasma and heart tissue catecholamines were measured in young (4-month) and aged (28-month) Sprague Dawley rats under unanesthetized conditions and following the induction of halothane anesthesia. Arterial blood pressure, blood gases, plasma and heart tissue norepinephrine, epinephrine and dopamine concentrations were measured in separate groups of unanesthetized and halothane anesthetized rats. Young and aged rats were tested under equal anesthetic levels and blood halothane concentrations were measured using gas chromatography. Aged rats required significantly less halothane to maintain anesthesia compared to young animals (7.25 +/- 1.43 vs. 14.91 +/- 0.93 mg/dL, p less than 0.05). Cardiovascular parameters were similar in young vs. aged rats under unanesthetized conditions, but blood pressure decreased significantly more in aged than in young rats during halothane anesthesia (43% vs. 17%, p less than 0.05). Heart tissue catecholamines were not different between young and aged and did not change during halothane anesthesia. Plasma norepinephrine concentrations were consistently elevated in aged vs. young rats under both unanesthetized and anesthetized test conditions, but there was no significant change in these levels from the unanesthetized to the anesthetized state. Results suggest that increased catecholamine levels in aged animals may be necessary to maintain a normal cardiovascular state under unanesthetized conditions and that catecholamines do not increase during the hypotensive state produced by halothane anesthesia in spite of marked hypotension.

Aging↗
PubMed1985

Regional blood flow and cerebral metabolic changes during alcohol withdrawal and following midazolam therapy.

Regional blood flows and cerebral oxygen consumption (CMRO2) were measured following alcohol withdrawal in alcohol-dependent rats. In addition, the authors tested the ability of midazolam (0.057, 0.575, or 5.75 mg X kg-1) to modify alcohol-induced changes. Rats received a 3-week treatment of daily ad libitum access to a liquid diet containing 6.54% ethanol or a sham treatment with the same caloric intake but with white dextrin substituted for alcohol. Regional blood flow was measured 12 h after alcohol withdrawal with radioactive microspheres. Nitrous oxide (70% in oxygen) was used as the control anesthetic. Rats withdrawn from alcohol treatment had significantly increased heart rate, cortical cerebral blood flow (CBF) (39 +/- 8%, mean +/- SE), and CMRO2 (41 +/- 9%) compared with sham-treated rats (P less than 0.05). Subcortical CBF (49 +/- 8%), myocardial (52 +/- 18%), and hepatic arterial blood flow (298 +/- 47%) also were increased in alcohol-withdrawn rats. Renal blood flow decreased 47 +/- 5%, while skeletal muscle and small intestinal blood flow were not significantly different between the two groups. Midazolam infusion decreased CBF, CMRO2, and hepatic arterial blood flow in alcohol-withdrawn rats to similar levels as sham-treated rats and increased renal blood flow in both groups. Skeletal muscle and intestinal tissues showed no change in blood flow in response to midazolam. The authors conclude that midazolam may be effective in lowering blood pressure and brain metabolism and reversing regional blood flow changes produced by alcohol withdrawal in the rat.

Anesthesia, Inhalation↗
PubMed1985

Midazolam-ethanol interactions and reversal with a benzodiazepine antagonist.

The purpose of these experiments was to analyze the cerebrovascular and cerebral metabolic effects of midazolam, a short-acting water-soluble benzodiazepine, and to investigate its interaction with alcohol in rats. A benzodiazepine antagonist, 3-carbo-t-butoxy-beta-carboline (beta-CCT), was used to test the role of the benzodiazepine receptor in midazolam-alcohol effects. Experiments were carried out under 70% N2O, 30% O2 anesthesia. Rats were tested with intraperitoneal injections of 0.75-5 mg/g ethanol, intravenous infusions of 0.57, 5.75 mg/kg midazolam, and 1.15 mg/kg beta-CCT separately and in combination. Cortical cerebral blood flow (CBF) was measured with radioactive microspheres, and cerebral oxygen consumption (CMRO2) was determined from cortical CBF and arterial-sagittal sinus blood samples 20 min after ethanol treatment and/or after a 15-min drug infusion. Alcohol alone produced dose-related increases in plasma ethanol concentrations but no depression in CMRO2 except at the highest dose (5 mg/g). Midazolam infusions alone decreased cortical CBF and CMRO2 35-40%, while 2.5 mg/g alcohol (which did not depress CMRO2 alone) combined with midazolam produced a 70% depression of cortical CBF and metabolism. An infusion of beta-CCT given alone increased CMRO2 alone and reversed the depression in both cortical CBF and CMRO2 produced by midazolam plus alcohol. These results indicate that the ability of alcohol to potentiate benzodiazepine-induced sedation is not simply an additive effect but may be related to the facilitation by alcohol of benzodiazepine receptor binding. The fact that beta-CCT reversed midazolam-ethanol-induced depression suggests that the effect may be mediated through the benzodiazepine receptor.

Anesthesia, Intravenous↗
PubMed1984

Cerebrovascular and cerebral metabolic effects of flurazepam and a benzodiazepine antagonist, 3-hydroxymethyl-beta-carboline.

There is a need in clinical practice for an antagonist which can reverse the sedative action of benzodiazepines. Recently, 3-hydroxymethyl-beta-carboline (3-HMC) has been reported to inhibit the sleep inducing effects of flurazepam. The effects of flurazepam (0.5, 5 and 50 mg/kg) on cerebral blood flow (CBF) and cerebral O2 consumption (CMRO2) were evaluated in rats and the ability of 3-HMC to reverse these changes was determined. Regional CBF was measured with radioactive microspheres and cortical CMRO2 was calculated from sagittal sinus-arterial O2 content differences and cortical CBF. Flurazepam produced dose dependent decreases in CBF and CMRO2 which were significant at 5 and 50 mg/kg. 3-HMC (5 mg/kg) inhibited flurazepam induced changes at the 5 mg/kg dose but had little effect on the CBF and CMRO2 depression produced by 50 mg/kg flurazepam. At a dose of 25 mg/kg, 3-HMC inhibited the effects of both 5 and 50 mg/kg flurazepam. Blood pressure and heart rate were also decreased by flurazepam but these variables were not reversed as effectively by 3-HMC treatment. The results indicate that 3-HMC is an active antagonist of the cerebrovascular and cerebral metabolic depression produced by flurazepam and can stimulate CBF and CMRO2 at high doses when given alone.

Animals↗
PubMed1984

Nitrous oxide markedly increases cerebral cortical metabolic rate and blood flow in the goat.

Studies to date on the influence of N2O on cerebral blood flow (CBF) and metabolism in dogs, rodents, and humans have produced conflicting results. In the present study the authors have employed techniques in the awake, freely breathing nonstressed goat that allowed the authors to 1) serially obtain rapidly frozen cerebral cortical biopsy specimens (for labile metabolite assay) and 2) measure changes in cerebral O2 metabolism (CMRO2) and total and regional CBF (rCBF). Thus, with each animal utilized as its own control, the authors studied N2O effects on the above variables. Two determinations of the effects of 1 h of N2O (70% via a mask) on these variables were performed on each animal. Following introduction of N2O, PaCO2 and arterial blood pressure did not change, but arterial epinephrine levels declined over the 60-min period. Total CBF increased in the first 5 min of N2O exposure, reached a maximum of 165% control at 15 min, and then decreased to 143% control at 60 min. rCBF evaluations showed that much of this CBF increase was confined to cerebral cortical structures (188-246% control at 60 min). Over the same period cortical CMRO2 increased to 170% of control. No appreciable changes in the levels of high-energy phosphates or glycolytic intermediates were found at 60 min of N2O. The authors attribute the described changes solely to the presence of N2O and not to sympathoadrenal influences, altered ventilation, or anything related to the experimental preparation, and they conclude that N2O (at least in goats) is associated with a marked cerebral cortical "activation".

Anesthesia, Inhalation↗
PubMed1984

Evaluation of a system for serial biopsy of cerebral cortical tissue in an awake goat.

No techniques to date have been developed that allow investigators to obtain serial, rapidly frozen brain tissue samples in unanesthetized animals. The design and methods for implantation of cranial windows in goats are described in detail. The cranial window allows one direct and repeated access to the cerebral cortical surface. With each window, a parietal cortical area of 7.9 cm2 (minus the dura) is available for biopsy. Serial tissue samples are obtained using a suction-freezing system. Samples (100-250 mg) are frozen in less than 1 s. Up to six samples can be taken from each site. Goats were studied over a period of 2-5 days. No signs of sampling or immobilization stress were present as evidenced by a relatively constant level of arterial catecholamines and CO2 partial pressure (PCO2). Local cerebral blood flow (CBF) in the tissue under the window was of the same magnitude as that in other cerebral cortical regions and was unaffected by serial sampling. Levels of labile phosphates and of some glycolytic and tricarboxylic acid cycle-associated intermediates were minimally influenced by serial sampling. Greater variability in metabolite levels was seen for biopsies taken 2-5 days apart than for biopsies taken at 1- to 2-min intervals. However, variations within animals were less than variations among animals. This was especially true for acutely biopsied samples. The described methods provide a model for studies of cerebral metabolism in unstressed goats where anesthetic influences are avoided and where each animal can be utilized as its own control.

Animals↗
PubMed1984

Hemodynamic consequences of halothane anesthesia during chronic anemia.

The hemodynamic effects of halothane anesthesia in chronically anemic mongrel dogs were evaluated. Control and anemic animals (13.7 +/- 0.4 g/dl hemoglobin mean +/- SE vs. 3.4 +/- 0.3 g/dl) were exposed to 0.75, 1.5, and 2.25% inspired halothane and changes in cardiac output (CO), heart rate (HR), dp/dt, heart work, heart efficiency, myocardial oxygen consumption (MVO2), mean arterial blood pressure (MABP), central venous pressure (CVP), left ventricular end-diastolic pressure (LVDP), left coronary blood flow (CBF), systemic vascular resistance (SVR), and myocardial lactate metabolism were measured and compared. Anemic dogs showed a significantly lower SVR at each halothane dose when compared with controls. In addition, SVR progressively decreased with increasing halothane in anemic dogs, while SVR remained unchanged in controls. CO, CBF, MVO2, and heart work all were significantly greater in anemic canines compared with controls with each halothane concentration. Heart efficiency, dp/dt, HR, and MABP were not significantly different in anemic and control dogs. Neither control nor anemic dogs demonstrated myocardial hypoxia as evidenced by a lack of myocardial lactate production. The results from this study suggest that anemic animals appear to tolerate large concentrations of halothane.

Anemia↗
PubMed1983

Use of heart cell cultures as a tool for the evaluation of halothane arrhythmia.

The effects of various combinations of epinephrine-halothane and epinephrine-enflurane were tested on beating myocardial muscle cells cultured from 2- to 3-day-old rats. A series of culture plates containing myocytes were exposed to 0.5, 1.0, 1.5, and 2% halothane. At each halothane concentration, 9 ng of epinephrine was added, and the rate of contraction and rhythm of myocytes were observed. With increasing halothane concentrations, a significant and progressive increase in the percentage of plates demonstrating arrhythmia was observed. In a separate series of experiments, doses of epinephrine were added following exposure to 1.5% halothane. As the dose of epinephrine was increased progressively more plates displayed arrhythmia. In addition, culture plates were exposed to enflurane (3 and 6%), and epinephrine was added to each plate. No arrhythmia was observed in any of the 3% enflurane exposed plates. However at 6%, 100% of the plates displayed arrhythmia. In another series of experiments the efficaciousness of quinidine, procaine amide, lidocaine, propranolol, and verapamil in converting cell culture arrhythmia to normal rhythm following epinephrine and halothane was tested. Quinidine converted 96% of all arrhythmic plates to normal rhythm, procaine amide 80%, lidocaine 50%, and propranolol 10%. Verapamil failed to convert any arrhythmic plates to normal rhythm. It was concluded from this study that halothane directly "sensitizes" heart cells in tissue culture, and that the "sensitization" process is a linear, dose-dependent phenomenon.

Action Potentials↗
PubMed1983

Regional cerebral blood flow measurement in rats with radioactive microspheres.

The effect of the method of heart catheterization on the measurement of cerebral blood flow (CBF) with radioactive microspheres was evaluated during various experimental procedures in male Sprague-Dawley rats. Catheters were inserted into the left ventricle via the right carotid or right subclavian artery or directly into the left atrium for microsphere injections. CBF was measured in cerebral cortical and subcortical tissues under control anesthetized (70% N2O, 30% O2), hypoxic or hypercapnic test conditions. Under control conditions, CBF was similar in the right vs the left cerebral hemisphere in subclavian artery and atrial catheterized rats but was greater in the left vs the right cortex in carotid catheterized animals (p less than .05). During hypoxia and hypercapnia CBF increased equally in both cerebral hemispheres in atrial catheterized rats. The increase in CBF was significantly attenuated in the cerebral hemisphere ipsilateral to carotid catheterization during hypoxia and hypercapnia, although the percentage increase in flow was similar in both hemispheres. The results indicate the limitations of measuring regional CBF changes under experimental test conditions in rats with a ligated carotid artery and suggest that atrial catheterization is the method of choice when comparable changes in CBF are desired in both cerebral hemispheres.

Animals↗
PubMed1983

A comparison of the cardiovascular and orofacial blood flow changes resulting from hypotension induced by sodium nitroprusside and adenosine triphosphate in the rat.

These experiments compared the cardiovascular effects and the alterations in orofacial blood flow resulting from hypotension induced with sodium nitroprusside and adenosine triphosphate infusions in 30 male rats. The authors found that sodium nitroprusside did not significantly change heart rate or cardiac output, while adenosine triphosphate caused a significant decrease in heart rate associated with a small increase in cardiac output. Both hypotensive agents produced similar profound decreases in total peripheral resistance. Blood flows to orofacial structures were qualitatively similar with both agents. Both adenosine triphosphate and sodium nitroprusside caused decreased flows to the maxilla and mandible. Sodium nitroprusside increased flows to masseter and suprahyoid muscles. Adenosine triphosphate caused increased flows to suprahyoid muscles but masseter muscle flows were not significantly changed. Tongue flows responded similarly to both agents, initially decreasing, then returning to normotensive levels. Finally, sodium nitroprusside-induced hypotension was associated with the development of tachyphylaxis in some animals, whereas no similar problem was observed with use of adenosine triphosphate. The demonstration of reduced blood flows to orofacial bony structures and the absence of resistance or tachyphylaxis during adenosine triphosphate-induced hypotension support its usefulness as a hypotensive agent during orthognathic and other surgery.

Adenosine Triphosphate↗