PubMed Health⌕ Search

Biomedical subjects

R F Albrecht

Publications and source records attributed to R F Albrecht.

At least 73 records · Page 4Linked to original sources
PubMed1989

Comparative ventilatory effects of intravenous versus fourth cerebroventricular infusions of morphine sulfate in the unanesthetized dog.

The ventilatory pharmacodynamics of morphine sulfate (MS) in the awake dog (n = 14) were investigated. Two routes of MS administration were employed: 1) 4 h continuous intravenous (iv) infusion (1 mg.kg-1 loading dose, 10 micrograms.kg-1.min-1 thereafter); and 2) fourth ventricle to cisterna magna perfusion (VCP) at increasing infusate morphine concentrations (0.1-100 micrograms.ml-1). The former was associated with a constant plasma and cisternal CSF (and presumably tissue) free morphine concentration. The latter produced, over 1 h at a constant infusate morphine delivery, a cisternal CSF free morphine concentration that leveled off by 30 min, little or no distribution of drug beyond superficial dorsal and superficial ventral brainstem tissue, and no detectable levels of morphine in plasma. When comparing the two routes of administration, ventilatory depression for a given cisternal free morphine level in the iv infusion studies was of a much greater magnitude than that seen in VCP experiments. Differences in the ventilatory patterns were also noted. Thus, iv delivery produced a decrease in tidal volume (VT) and no change or reduced respiratory frequency (f) with prolonged exposure. VCP delivery was also associated with reduction in VT but produced significant increases in f. An apparent maximal ventilatory depression with 1 h VCP administration was observed at morphine infusate levels of greater than 10 micrograms.ml-1, with higher infusate concentrations and extension of the perfusion period to 3 h producing no significant additional changes. Finally, VCP delivery of the mu-antagonist nalbuphine could only partially reverse the ventilatory depression accompanying iv morphine administration. These findings suggest that the ventilatory depression associated with iv morphine is a result of interactions with brain u-opiate receptors in superficial brainstem tissue and in deep brainstem and/or suprapontine tissue as well.

Animals↗
PubMed1989

The effects of magnesium salts on the duration of epinephrine-induced ventricular tachyarrhythmias in anesthetized rats.

The effects of MgSO4 or MgCl2 infusion on the duration of epinephrine-induced cardiac arrhythmia were evaluated in male rats anesthetized with either halothane or pentobarbital. In addition, the duration of epinephrine-induced arrhythmia in pentobarbital (50 mg/kg) anesthetized rats was compared with the duration of arrhythmia in halothane (1.5%) anesthetized rats. During halothane anesthesia MgSO4 or MgCl2 infused at a dose rate of 8 mg.kg-1.min-1 for 20 min caused a significant reduction in the duration of arrhythmia (100% and 80%, respectively) following a 4-microgram/kg injection of epinephrine and a significant threefold reduction in arrhythmia duration for each salt following an 8- or 16-micrograms/kg injection of epinephrine. Significantly shorter periods of arrhythmia after each dose of epinephrine were seen in rats anesthetized with pentobarbital than were seen in rats anesthetized with halothane. No significant difference was seen between MgSO4 or MgCl2 infusions in any of these studies. Twenty-minute infusions of MgSO4 (8 mg.kg-1.min-1) were compared with propranolol (0.03 mg.kg-1.min-1) and verapamil (0.5 micrograms.kg-1.min-1) infusions on the duration of arrhythmia after epinephrine (8 micrograms/kg) injections in halothane anesthetized rats. MgSO4 and propranolol infusion caused a significant reduction in the duration of arrhythmia (81% and 70%, respectively). Verapamil infusion caused only a 48% reduction in arrhythmia duration. While there was no significant difference between MgSO4 or propranolol, both caused a significantly greater reduction in arrhythmia than verapamil. CaCl2 (0.15 mM.kg-1.min-1) infusion for 5 min caused a significant fivefold increase in the duration of arrhythmia during halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ventilatory effects of fourth cerebroventricular infusions of morphine-6- or morphine-3-glucuronide in the awake dog.

The ventilatory effects of morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) were evaluated in awake dogs (n = 10). A fourth ventricle to cisterna magna perfusion (VCP) system was used for drug administration. This permitted a direct comparison of the dose/ventilatory response characteristics of these morphine metabolites to each other and to morphine and obviated the need to consider the blood-brain barrier delay that would complicate analysis of systemic dose versus ventilatory response relationships among these drugs. The dose/response pattern for morphine was taken from an earlier study in unanesthetized dogs where the identical mode of drug delivery as in the present report was employed. Morphine-3-glucuronide caused, if anything, a ventilatory stimulation (decreased PaCO2 and increased CO2 responsiveness) at the highest infusate concentration studied (50 micrograms/ml) and no significant ventilatory effects at infusate concentrations at or below 10 micrograms/ml. On the other hand, M-6-G produced a profound dose-dependent ventilatory depression. Significant increases in PaCO2 and diminution of CO2 responsiveness were observed even at the lowest infusate concentration evaluated (0.1 microgram/ml). When compared to morphine, M-6-G was found to be about five to ten times more potent as a ventilatory depressant drug. These results imply that M-6-G may play a significant role in the ventilatory depression accompanying systemic morphine administration.

Animals↗
PubMed1989

Cerebral metabolic depression and brain protection produced by midazolam and etomidate in the rat.

Midazolam and etomidate have been shown to depress cerebral metabolism and may protect the brain during ischemia. However, it has been reported that etomidate may produce EEG spiking activity and seizures, which could adversely affect outcome. We compared the effects of midazolam and etomidate on EEG, cerebral blood flow (CBF), and cerebral cortical oxygen consumption (CMRO2) as well as neurologic outcome following incomplete cerebral ischemia in the rat. CBF was measured with radioactive microspheres and cortical CMRO2 was calculated by multiplying cortical CBF by the arterial-sagittal sinus oxygen content. Incomplete ischemia was produced by unilateral carotid artery occlusion combined with hemorrhagic hypotension. In low doses (0.02 mg/kg/min i.v.), both midazolam and etomidate depressed EEG, decreased CMRO2, and improved outcome from ischemia compared to nitrous oxide control rats. At a higher dose (0.2 mg/kg/min i.v.), midazolam further depressed EEG and CMRO2 and again improved outcome compared to N2O controls. In contrast, high dose etomidate (0.2 mg/kg/min) produced spiking EEG activity without further depression of CMRO2 and a worsening of outcome following cerebral ischemia. These results support previous reports that midazolam and etomidate may protect the brain from incomplete cerebral ischemia but suggest that EEG spiking activity associated with high dose etomidate may be associated with a worse outcome.

Journal Article↗
PubMed1989

Phonocardiography as a monitor of cardiac performance during anesthesia.

The usefulness of phonocardiography as a monitor of cardiac performance during anesthesia was investigated in six dogs. Anesthetic depression by halothane, isoflurane and nitrous oxide was demonstrated by the phonocardiogram. Likewise, the stimulating effect of dopamine clearly showed in the recordings. Changes in the amplitude of the first heart sound were found to correlate closely with changes in the maximum rate of rise of left ventricular pressure (r = 0.9551, 0.001). P less than 0.001). Simultaneous changes in cardiac output and arterial pressure also occurred. Cardiac depression from anesthetics and/or disease is a major concern during anesthesia. Perioperative phonocardiography, a simple and noninvasive procedure, merits further investigation as a possible monitor of cardiac performance.

Anesthesia↗
PubMed1988

Neurologic outcome in rats following incomplete cerebral ischemia during halothane, isoflurane, or N2O.

Using rats in which incomplete cerebral ischemia was induced, the authors evaluated the effects of halothane (H) and isoflurane (I) on neurologic outcome compared to nitrous oxide (N2O) controls. Incomplete cerebral ischemia was produced by right carotid artery occlusion combined with hemorrhagic hypotension. Neurologic outcome was evaluated using a graded deficit score from 0 to 5 (0 = normal, 5 = death associated with stroke). Two levels of cerebral ischemia were tested. At moderate ischemia with hypotension of 30 mmHg, an FIO2 of 0.3, and ischemic periods of 30 or 45 min, N2O produced a deficit of 4.7-5.0 and a mortality rate of 90-100%. In contrast, halothane (1 MAC) and isoflurane (1 MAC) resulted in similar deficit scores (H = 1.1-1.8, I = 1.4-1.6) and mortality rates (H = 17-30%, I = 17-20%). Cerebral blood flow (CBF) measured with radioactive microspheres showed a 60-65% decrease in the ischemic hemisphere at this level of hypotension. With severe ischemia with hypotension = 25 mmHg, FIO2 = 0.2, and a 30-min period of ischemia, deficit scores increased to 3.0 and 3.9 with 1 MAC halothane and 1 MAC isoflurane, respectively. Mortality rates also increased to 40% with halothane and 70% with isoflurane. Increasing the concentration of halothane or isoflurane to 2 MAC did not significantly improve outcome. Brain histology demonstrated extensive neuronal damage in striatal, hippocampal, and neocortical regions of N2O control treated rats, and less damage with little difference between H- and I-treated rats at each level of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1988

Neurologic outcome in aged rats after incomplete cerebral ischemia.

The effect of age on outcome after induced cerebral ischemia was tested in rats. Cerebral ischemia was produced by unilateral carotid ligation and hemorrhagic hypotension to 30 mm Hg (moderate ischemia) or 25 mm Hg (severe ischemia) in young (6 month) and old (26-28 month) rats anesthetized with 1 MAC halothane. Young rats had significantly better neurologic outcomes than old rats after similar ischemic challenges. This advantage disappears, however, when the inspired oxygen tension is altered to produce similar PaO2 in both age groups during ischemia. Measures of regional CBF with radioactive microspheres showed a 70% decrease in cortical blood flow in the ischemic cerebral hemisphere in both young and old rats. Plasma glucose concentrations increased from 150 to 250 mg/100 mL during ischemia in both age groups. Histologically, the brains showed similar signs of focal ischemic damage in striatum, hippocampus, and cortex in young and old rats. These results indicate that when blood pressure and respiratory factors are controlled experimentally during ischemia, young and aged rats have similar neurologic outcomes after cerebral ischemia.

Aging↗
PubMed1987

The cerebrovascular effects of curare and histamine in the rat.

The effects of histamine and curare on cerebral blood flow (CBF) were measured in rats with an intact blood-brain barrier (BBB) and in rats in which the BBB was disrupted by hypertonic urea. Using radioactive microspheres cortical and subcortical CBF were measured in paralyzed ventilated rats anesthetized with 70% N2O, 30% oxygen. Blood gas tensions were controlled by mechanical ventilation. In rats with an intact BBB, neither histamine infusion (10 micrograms X kg-1 X min-1) nor curare (1 and 5 mg/kg) increased CBF. Twenty minutes after the BBB was disrupted by 2 M urea, histamine (10 micrograms X kg-1 X min-1) produced an increase in cortical (180-210 ml X 100 g-1 X min-1) and subcortical CBF (103 to 124 ml X 10 g-1 X min-1). Twenty minutes after BBB disruption, curare also produced a significant increase in cortical CBF (1 mg/kg: 176-201 ml X 100 g-1 X min-1, 5 mg/kg: 190-209 ml X 100 g-1 X min-1). The increases in CBF produced by curare were completely blocked by pretreatment with 30 mg/kg cimetidine, a histamine H2 receptor antagonist, 3 min before curare. The results indicate that curare may produce cerebrovasodilation and increases in CBF by release of histamine and stimulation of central nervous system H2 receptors. These effects occur only when the BBB is disrupted and circulating histamine has access to brain perivascular tissue.

Animals↗
PubMed1987

Halogenated anesthetics increase oxygen consumption in isolated hepatocytes from phenobarbital-treated rats.

Using suspensions of hepatocytes isolated from phenobarbital-treated and untreated rats (+PB cells and -PB cells, respectively), the authors examined the effects of halothane, enflurane, and isoflurane on O2 consumption (VO2) and on extracellular PO2 and energy status at steady states of O2 and energy metabolism. In +PB cells, all three agents produced increases in VO2 which were largest at 1 MAC and progressively smaller at 2 and 3 MAC. At all three doses, VO2 increases were largest with enflurane (48% at 1 MAC), intermediate with halothane (24%), and smallest with isoflurane (11%). These anesthetic-induced VO2 increases were abolished by prior addition of a cytochrome P450 inhibitor (metyrapone) to the incubations. In -PB cells, all three agents produced slight and comparable decreases in VO2 at 1 MAC, with further decreases at 2 and 3 MAC. In +PB cell suspensions at steady states of O2 and energy metabolism, 1 MAC enflurane or halothane, but not isoflurane, produced significant declines in steady state PO2 (from initial values of 24 mmHg to values less than 10 mmHg) and reductions in adenosine triphosphate/adenosine diphosphate ratio (ATP/ADP). These changes were absent in -PB cells exposed to the same conditions or in +PB cells not exposed to anesthetic. The authors conclude that clinical doses of enflurane and, to a lesser extent, halothane produce statistically significant increases in O2 consumption, reflecting enhanced cytochrome P450 activity, in liver cells isolated from phenobarbital-treated rats. Such increases in O2 demand represent a mechanism by which anesthetic metabolism could contribute to intrahepatic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1987

Cerebral vascular and metabolic effects of fentanyl and midazolam in young and aged rats.

Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured, and electroencephalogram (EEG) was recorded in young (6-month-old) and aged (28-month-old) rats during ventilation with 70% N2O/30% O2 and following fentanyl or midazolam administration. Cerebral blood flow (CBF) was measured with radioactive microspheres, and cerebral oxygen consumption (CMRO2) was calculated from the arterial-sagittal sinus oxygen content difference and CBF measurements. Fentanyl at the highest dose used (200 micrograms/kg and 400 micrograms.kg-1.h-1) depressed the EEG and decreased CBF 49% and CMRO2 39% in young rats, whereas in old rats, this fentanyl dose decreased CBF 37% and CMRO2 34%, both significantly less than in young rats (P less than 0.05). Midazolam at the highest dose used (5.75 mg/kg) also depressed EEG in both age groups, and decreased CBF 51% and CMRO2 38% in young rats. This depression was significantly less than the 62% decrease in CBF and 59% decrease in CMRO2 produced by midazolam in old rats (P less than 0.05). These results indicate that aging attenuates the cerebrovascular and cerebral metabolic depression produced by fentanyl, but potentiates the same effects produced by midazolam. The enhanced cerebral metabolic depression produced by midazolam in the aged is similar to that seen with phenobarbital, and suggests a similar action of these drugs at the central GABA-benzodiazepine-barbiturate receptor complex.

Aging↗
PubMed1987

Effect of superfused insulin on cerebral cortical glucose utilization in awake goats.

The effect on cortical cerebral glucose utilization (CMRglu) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) solution employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMRglu were assessed using a modification of a sequential 2-[3H]- then 2-[14C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff (Brain Res. 153: 375-381, 1978). Initial experiments employing 125I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMRglu, generally established that present methods were adequate to induce and detect CMRglu changes. However, it was also shown experimentally and using a mathematical model that 2-[3H]DG test/control tissue ratios could be influenced by subsequent changes in CMRglu and the dephosphorylation rate. Thus 3H ratios could not be used to establish preexperimental test/control CMRglu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMRglu changes from 2-[14C]DG/2-[3H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMRglu. A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated.

Animals↗
PubMed1987

Time course of radiolabeled 2-deoxy-D-glucose 6-phosphate turnover in cerebral cortex of goats.

The in vivo dephosphorylation rate of 2-deoxy-D-glucose 6-phosphate (DGP) in the cerebral cortex of goats injected intravenously with radiolabeled 2-deoxy-D-glucose (DG) was investigated. Serial rapidly frozen samples of parietal cortical gray tissue were obtained at regular intervals over time periods from 45 min to 3 h in awake goats or in paralyzed and artificially ventilated goats maintained under 70% N2O or pentobarbital sodium anesthesia. The samples were analyzed for glucose content and separate DG and DGP activities. The rate parameters for phosphorylation (k3*) and dephosphorylation (k4*) were estimated in each animal. The glucose phosphorylation rate (PR) was calculated over the intervals 3-5 (or 6), 3-10, 3-20, 3-30, and 3-45 min, assuming k4* = 0. As the evaluation period was extended beyond 10 min, the calculated PR became increasingly less when compared with that calculated over the 3- to 5- (or 6) min interval (PRi). Furthermore, as metabolic activity decreased, the magnitude of the error increased such that at 45 min pentobarbital-anesthetized goats underestimated the PRi by 46.5% compared with only 23.1% in N2O-anesthetized goats. This was also reflected in the greater than twofold higher k4*/k3* ratio in the pentobarbital vs. N2O-anesthetized group. It is concluded that when using the DG method in the goat, DGP dephosphorylation cannot be ignored when employing greater than 10-min evaluation periods.

Animals↗
PubMed1986

Effect of sympathetic blockade on central prostaglandin E2-induced hyperthermia.

The mechanisms by which intracerebroventricular (i.v.t.) prostaglandin E2 (PGE2) produce hyperthermia in the rat were investigated. I.v.t. PGE2 produced dose-related increases in blood pressure, heart rate and rectal temperature which were significant with a dose of 0.5 ng. Oxygen consumption also increased and remained above baseline over an hour with 50 and 500 ng PGE2 doses. Ganglionic blockade with hexamethonium (20 mg/kg) attenuated the blood pressure and heart rate response to PGE2 but metabolic rate and rectal temperature increases were unchanged. Propranolol (2 mg/kg i.v.) decreased the heart rate response to PGE2 but had no significant effect on blood pressure, metabolic rate and rectal temperature responses. These results suggest a similar sensitivity of central receptors for mediating cardiovascular and metabolic rate/temperature increases but suggest that the mechanisms mediating these effects are separate.

Animals↗
PubMed1986

Energy deficits in hepatocytes isolated from phenobarbital-treated or fasted rats and briefly exposed to halothane and hypoxia in vitro.

Experimental factors implicated in the pathogenesis of halothane hepatotoxicity in the phenobarbital-hypoxia rat model were examined for direct effects on the energy status of isolated rat liver cells in vitro. Intact hepatocytes were isolated after collagenase perfusion of livers of adult male Fischer 344 rats previously treated with phenobarbital (0.1% in drinking water for 5-7 days) and/or deprived of food for 48 h. Cells were incubated in Krebs-Henseleit buffer + substrates for 10 min at steady states of energy metabolism, with extracellular PO2 constant at 32, 16, or 4 mmHg +/- 1% halothane. Fasting produced the largest energy deficits in incubated hepatocytes, regardless of phenobarbital treatment status, PO2 value, or presence/absence of halothane. The combination of hypoxic PO2 (4 mmHg) and 1% halothane shifted lactate metabolism toward lactate production, whereas hypoxia or halothane alone did not. Prior phenobarbital treatment plus hypoxia decreased adenosine triphosphate/adenosine diphosphate (ATP/ADP) and increased lactate production compared with drug treatment or hypoxia alone. We conclude that pathogenic factors that interact to produce halothane hepatotoxicity act directly and jointly on isolated liver cells to produce energy deficits within 10 min. Differences in the relative importance of pathogenic factors in vitro and in vivo suggest that short-term, direct effects on hepatocellular energy status are not solely responsible for halothane hepatotoxicity.

Adenosine Diphosphate↗
PubMed1986

Effects of phenobarbital on cerebral blood flow and metabolism in young and aged rats.

The cerebrovascular and cerebral metabolic changes produced by intraperitoneal injection of phenobarbital (50, 150, and 250 mg/kg) were studied in young adult (6-month) and senescent (28-month) Wistar rats. Cerebral blood flow (CBF) was measured using radioactive microspheres and cerebral oxygen consumption (CMRO2) was obtained by multiplying cortex CBF by the arterial-sagittal sinus oxygen content difference. Control values for blood pressure, blood gas tensions, CBF, and CMRO2 were similar in the young and aged animals during 70% N2O/30% O2. Intraperitoneal phenobarbital produced dose-dependent decreases in CBF with no significant difference between young and aged rats at each phenobarbital dose. At the highest phenobarbital dose (250 mg/kg) CBF was reduced by 49% in the young rats and 52% in the aged rats (P greater than 0.10). CMRO2 was also depressed in a dose-dependent fashion in both young and aged animals with each phenobarbital dose. However, the decrease produced by the highest phenobarbital dose was significantly greater in the aged rats (55%) than the young rats (43%, P less than 0.05), even though the EEG was isoelectric in both groups. The difference in CMRO2 between young versus aged rats at a time when the EEG is isoelectric suggests that high-dose phenobarbital may depress nonelectrical cerebral metabolic processes more in aged rats.

Aging↗
PubMed1986

Verapamil reduces glucose and fatty acid metabolism of beating and nonbeating rat heart cells.

The effects of various dosages of verapamil on glucose or fatty acid utilization by beating or nonbeating rat heart myocytes in tissue culture were determined. Myocytes were incubated with verapamil and either D-6-14C glucose or 1-14C palmitic acid as substrate. After incubation the subsequently generated 14CO2 was captured with hyamine hydroxide and the equivalent oxygen values were calculated. Low doses of verapamil (50 ng/ml) treatment produced a 52% reduction in myocyte glucose utilization and a 16% reduction in fatty acid utilization that appeared to be independent of its effect on myocyte contractile rate since these effects were evident in both beating and nonbeating myocytes. In addition, verapamil treatment caused differences in the myocyte handling of substrate. Verapamil (50 ng/ml) lowered cellular accumulation of glucose by 21% compared to controls. Contrary to glucose, myocyte concentrations of palmitic acid were significantly increased by 117% relative to controls in verapamil treated cultures. These results suggest that verapamil may have a direct effect on basal heart cell metabolism in a way that is unrelated to myocyte contractile activity. In addition, verapamil may interfere with glucose membrane transport.

Animals↗