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R F Albrecht

Publications and source records attributed to R F Albrecht.

At least 37 records · Page 2Linked to original sources
PubMed1994

Role of nitric oxide and endothelium in rat pial vessel dilation response to isoflurane.

Isoflurane induces cerebral hyperemia. We sought to assess whether isoflurane induces cerebral microvessel dilation in vivo, and if so, to determine whether nitric oxide (NO) and endothelium are involved. By using a rat closed cranial window model, pial arterioles and venules of 30-70 microns in diameter were measured using intravital microscopy. The cerebral microvascular dilatory response was recorded as percent change of diameter from baseline. The pial vessels were suffused with sodium nitroprusside (SNP) or S-nitroso-acetyl-penicillamine (SNAP) to verify intact vascular smooth muscle relaxation function, and with adenosine diphosphate (ADP) and/or acetylcholine (ACh) to verify endothelial NO-generating capability. To isolate NO's role in the cerebral microvascular effects of isoflurane (Protocol I), microvessels were studied with and without nitric oxide synthase (NOS) inhibition by topically applied nitro-L-arginine methyl ester (L-NAME). In controls, L-NAME was replaced by its inactive enantiomer, nitro-D-arginine methyl ester (D-NAME). Mercury light plus fluorescein dye (LD) endothelial injury (Protocol II) was used to delineate an endothelium-mediated mechanism. Subsequently, vasodilator applications were repeated to verify the desired effects of the interventions and followed by suffusion of isoflurane 1%, 2%, and 3% (Protocol I) or isoflurane 3% (Protocol II). Suffusions of SNP, ADP, and ACh induced diameter increases of 15%-30%. NOS inhibition with L-NAME greatly attenuated ADP and ACh responses, but did not alter the SNP response, confirming that NO generation was blocked, but not NO action. These responses were unaffected in D-NAME-suffused rats. Isoflurane dilated arterioles 17% and venules 6% in the presence of D-NAME suffusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Nitric oxide synthesis and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat.

The role of nitric oxide (NO) synthesis in the cerebral hyperemic responses to hypercapnia and hypoxia was investigated in anesthetized rats. Regional CBF (rCBF) measurements were obtained in the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) using radiolabeled microspheres. The rCBF responses to either hypercapnia (PaCO2 = 70-80 mm Hg) or hypoxia (PaO2 = 40-45 mm Hg) were compared in rat groups studied in the presence and absence of NO synthase inhibition induced via the intravenous infusion of nitro-L-arginine methyl ester (L-NAME, 3 mg kg-1 min-1). Administration of L-NAME under normocapnic/normoxic conditions produced a 40-60% reduction in baseline rCBF values, indicating the presence of a NO "tone" in the cerebral vasculature. Infusion of L-NAME resulted in a substantial attenuation, in all regions measured, of the rCBF increases that normally accompany hypercapnia. In comparing saline-infused to L-NAME-infused rats, the percentage increases in rCBF (from normocapnic baseline values) were 351% versus 166% (CX), 446% versus 199% (SC), 443% versus 206% (BS), and 483% versus 174% (CE), respectively. The rCBF changes from baseline (delta rCBF in ml 100 g-1 min-1) were 488 versus 57 (CX), 570 versus 60 (SC), 434 versus 72 (BS), and 393 versus 45 (CE), respectively. These differences were all statistically significant (p < 0.05). During hypoxia, when compared to rats not given L-NAME, inhibition of NO synthase activity resulted in significantly greater (p < 0.05) percentage increases in rCBF (from normoxic baseline values) in most regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sympathetic activity enhances glucose-related ischemic injury in the rat.

BACKGROUND: Studies have shown that increased sympathetic activity or increased blood and brain glucose concentration worsen postischemic brain damage. The authors evaluated the interaction of plasma glucose with epinephrine and norepinephrine during incomplete cerebral ischemia in the rat using ganglionic blockade. METHODS: Rats were anesthetized with 25 micrograms.kg-1.h-1 fentanyl and 70% nitrous oxide in oxygen. Ganglionic blockade was produced in 30 rats using 8 mg/kg hexamethonium intravenously. Three plasma glucose ranges, low < 150 mg/dl, moderate = 150-300 mg/dl, and high > 300 mg/dl, were produced in each group. Ischemia was induced by unilateral carotid ligation and hemorrhagic hypotension to 30 mmHg for 30 min. Plasma norepinephrine and epinephrine were measured by radioimmunoassay. Neurologic outcome was evaluated daily for 3 days after ischemia. RESULTS: Ganglionic blockade decreased blood pressure before the start of ischemia and plasma epinephrine and norepinephrine during ischemia (P < 0.05). Neurologic outcome was significantly worse in rats with high glucose compared with low glucose concentrations with and without ganglionic blockade (P < 0.05). Neurologic outcome and stroke-related mortality were worse in rats with increased plasma epinephrine and norepinephrine compared with rats with ganglionic blockade when plasma glucose was less than 300 mg/dl (P < 0.05). CONCLUSIONS: These results indicate that increased concentration of catecholamines enhance glucose-related injury during incomplete ischemia in rats.

Animals↗
PubMed1993

Effects of remifentanil, a new short-acting opioid, on cerebral blood flow, brain electrical activity, and intracranial pressure in dogs anesthetized with isoflurane and nitrous oxide.

BACKGROUND: A new short-acting opioid, remifentanil, is metabolized by esterase activity in blood and tissue. It is important to know whether remifentanil may decrease the time to recovery of opioid-induced cardiovascular and cerebral effects compared to that of other short-acting agents such as alfentanil. METHODS: Baseline measures were made during 1% end-tidal isoflurane and 50% N2O in oxygen in dogs. Approximately equipotent low- and high-dose remifentanil (0.5 and 1.0 micrograms.kg-1.min-1) or alfentanil (1.6 and 3.2 micrograms.kg-1.min-1) were infused for 30 min each (total infusion time 60 min) followed by a 30-min recovery period. Blood pressure, heart rate, and intracranial pressure were recorded continuously. Electroencephalogram measurements were made using aperiodic analysis, and regional cerebral blood flow using radioactive microspheres. RESULTS: Both remifentanil and alfentanil decreased blood pressure and heart rate 25-30%. Cortex, hippocampus, and caudate blood flow decreased 40-50% during opioid infusion, but flow changes in lower brain regions were modest or absent. The electroencephalogram showed a shift from low-amplitude, high-frequency activity during baseline to high-amplitude, low-frequency activity during opioid infusion. During a 30-min recovery period, heart rate, electroencephalogram, and regional cerebral blood flow recovered to baseline levels in remifentanil--but not in alfentanil--treated dogs. Blood pressure and intracranial pressure decreased during opioid infusion and increased above baseline levels during the recovery period in remifentanil-treated dogs. CONCLUSIONS: These results show that the cardiovascular and cerebral effects of remifentanil and alfentanil are similar but that recovery of these parameters occurs sooner following remifentanil.

Alfentanil↗
PubMed1993

Sympathetic stimulation with physostigmine worsens outcome from incomplete brain ischemia in rats.

BACKGROUND: It has been suggested that anesthetics may protect the brain during incomplete cerebral ischemia by inhibition of sympathetic activity. This study evaluated whether physostigmine may increase plasma epinephrine and norepinephrine during carotid occlusion with hypotension and worsen ischemic outcome in rats and if this effect could be reversed by dexmedetomidine, an alpha 2-adrenergic agonist. METHODS: Anesthesia was maintained with fentanyl (25 micrograms.kg-1.h-1) combined with 70% N2O ventilation in oxygen. Ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mmHg for 30 min. Plasma epinephrine and norepinephrine were measured during ischemia. Neurologic outcome was evaluated for 3 days after ischemia. There were three groups: control (n = 10), physostigmine (1 mg/kg intraperitoneal 3 min before the start of ischemia, n = 10), and physostigmine plus dexmedetomidine (100 micrograms/kg intraperitoneally 15 min before the start of ischemia, n = 10). Brain tissue glutamate concentrations were measured by microdialysis in separate studies. RESULTS: Compared to control rats, physostigmine increased plasma epinephrine and norepinephrine 10-fold and worsened neurologic outcome. The increases in epinephrine and norepinephrine were blocked by dexmedetomidine before treatment, and neurologic outcome was improved. Outcome was not correlated with blood glucose during ischemia (r = 0.11). Ischemia increased brain tissue glutamate from < 100 microM to 400 microM during ischemia. This increase was not altered by physostigmine treatment. CONCLUSIONS: These results suggest that physostigmine worsens ischemic outcome by a mechanism that is associated with increases in plasma epinephrine and norepinephrine.

Animals↗
PubMed1993

The effects of midazolam and sufentanil sedation on middle cerebral artery blood flow velocity in awake patients.

Midazolam and sufentanil are commonly used for sedation. Cerebrovascular effects of low-dose midazolam have not been studied previously, and cerebrovascular effects of sufentanil remain controversial. Forty ASA I and II patients were studied preoperatively. These patients were given midazolam (20 or 40 micrograms/kg) or sufentanil (0.1 or 0.2 micrograms/kg) i.v. Transcranial Doppler recordings of middle cerebral artery mean blood flow velocity (Vm) were recorded before administration of the study drug and for the 5-min investigation period. Mean arterial pressure, heart rate, and end-tidal CO2 remained constant during the investigation and did not vary between treatment groups. Vm decreased 17 to 21% with both midazolam doses (p < 0.05), returning to baseline within 5 min. Vm did not change with either sufentanil dose. These results suggest that midazolam decreases cerebral blood flow (CBF) by increasing cerebral vascular resistance (CVR). The low sedative doses of sufentanil used in this study did not affect Vm over 5 min in unanesthetized patients.

Adult↗
PubMed1993

Halothane vasodilation and nitric oxide in rat pial vessels.

We investigated whether halothane (HAL), administered via cerebral cortical suffusion at concentrations of 1, 2, and 3%, could induce cerebral microvascular dilatation in vivo and whether the vasodilatory response was dependent on nitric oxide (NO) synthesis. The studies were performed using N2O/fentanyl-anesthetized, paralyzed, and mechanically ventilated rats. A closed cranial window and an intravital microscopy technique were employed. This system permitted the controlled delivery of various vasoactive agents in an artificial cerebrospinal fluid (aCSF) solution and the measurement of diameters of pial arterioles and venules. Each experiment included evaluations of (a) the direct smooth muscle relaxing action of NO, using sodium nitroprusside (SNP), and (b) the capacity for generation and release of endogenous NO, using adenosine diphosphate (ADP). Following confirmation of an intact NO-relaxing and generating capacity, HAL (in aCSF) was suffused at increasing concentrations. Nitric oxide synthase (NOS) inhibition was established with topical nitro-L-arginine (L-NA) or its methyl ester (L-NAME) and the above sequence repeated. The results for rats treated with L-NA (n = 5) or L-NAME (n = 5) were analyzed separately and as a combined group. No significant differences in vascular responses were observed when comparing the two groups. Initially, both SNP and ADP produced significant diameter increases (all groupings) in arterioles (14-28% change) and venules (14-25% change). For all groups, suffusions of 1 to 3% HAL produced arteriolar dilation, ranging from a 10 to 25% increase over baseline diameter. A statistically significant dose dependency was only observed with the combined data.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

The effects of propofol on cerebral and spinal cord blood flow in rats.

The effects of low and high doses of propofol on global cerebral blood flow (CBF) and spinal cord blood flow (SCBF) as a function of mean arterial blood pressure were investigated. CBF and SCBF during propofol infusion were compared to the levels in rats anesthetized with nitrous oxide (N2O) and fentanyl. Rats in the fentanyl/N2O group (control, n = 13) received 70% N2O in O2 plus fentanyl (bolus: 10 micrograms/kg; infusion: 25 micrograms.kg-1 x h-1). Rats in the low-dose propofol group (n = 10) received 30% O2 in air and propofol infusion (0.5 mg.kg-1 x min-1). Rats in the high-dose propofol group (n = 8) received 30% O2 in air and propofol infusion (2.0 mg.kg-1 x min-1). Blood flow autoregulation was tested by manipulating the mean arterial blood pressure with phenylephrine infusion or trimethaphan infusion and blood withdrawal by measuring CBF and SCBF using radioactive microspheres. Arterial blood gases, pHa, and skull temperature were controlled. Cerebral and spinal cord vasculature showed autoregulation in all treatment groups with a pressure range of 50-140 mm Hg. Within this pressure range, when compared to fentanyl/N2O, propofol decreased cortical CBF 60% (P < 0.001), subcortical CBF 40% (P < 0.001), midbrain blood flow 30% (P < 0.001), and SCBF 20% (P < 0.05). These results indicate that propofol maintains CBF and SCBF autoregulation.

Animals↗
PubMed1993

Interaction of catecholamines and nitrous oxide ventilation during incomplete brain ischemia in rats.

The interaction of plasma catecholamines and nitrous oxide (N2O) ventilation was examined during brain ischemia in rats. Group 1 (n = 19) was anesthetized with 50 micrograms.kg-1 x h-1 of fentanyl and ventilated with 70% nitrogen in oxygen. Group 2 (n = 19) was anesthetized with intravenous fentanyl (25 micrograms.kg-1 x h-1) and 70% N2O ventilation in oxygen. Group 3 (n = 10) received 25 micrograms.kg-1 x h-1 of fentanyl and 70% N2O ventilation and 100 micrograms/kg of dexmedetomidine, an alpha 2-adrenergic receptor agonist that decreases sympathetic activity. Incomplete brain ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 min. Plasma catecholamines were measured during ischemia. Cerebral blood flow (CBF) was evaluated by using laser Doppler. Neurologic outcome was evaluated for 3 days after ischemia. Plasma epinephrine and norepinephrine and were decreased 20% and neurologic outcome was significantly worse in Group 2 ventilated with N2O compared with fentanyl-anesthetized controls (P < 0.05). Dexmedetomidine-treated rats had lower plasma catecholamines (20% of control) and larger decreases in CBF during ischemia compared with controls. Dexmedetomidine (Group 3) improved outcome from ischemia in comparison to both Groups 1 and 2 (P < 0.05). These results suggest that catecholamines play a major role in worsening ischemic outcome. N2O ventilation may increase neuronal injury by enhancing the sympathetic response to ischemia.

Adrenergic alpha-Agonists↗
PubMed1993

Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs.

The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1993

Brain alpha 2-adrenergic receptor binding during incomplete cerebral ischemia in the rat.

alpha 2-Adrenergic agonists decrease sympathetic activity and improve outcome from brain ischemia. We evaluated whether changes in alpha 2-adrenergic receptor binding activity may be important in the sympathetic depressant and cerebral protective effects of halothane (1.1% inspired) or isoflurane (1.4% inspired) compared to fentanyl/nitrous oxide (N2O) anesthesia. Brain alpha 2-adrenergic receptor binding was measured using [3H]-clonidine in each of four treatment conditions: 1, unanesthetized; 2, anesthetized (fentanyl/N2O, halothane, or isoflurane): 3, anesthetized with ischemia; 4, after 4 h recovery from ischemia. Ischemia was produced by right carotid artery ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 min. Both halothane and isoflurane decreased alpha 2-adrenergic receptor density 20% compared to unanesthetized values (P < 0.01). This decrease was attenuated in ischemic tissue. There were no consistent changes in receptor affinity. These results suggest that inhaled anesthetics decrease the number of alpha 2-adrenergic receptors. This decrease appears to be unrelated to plasma catecholamine concentrations but may be influenced by the degree of ischemia.

Anesthesia, Inhalation↗
PubMed1993

The effect of halothane and isoflurane on neurologic outcome following incomplete cerebral ischemia in the rat.

The relation between sympathetic activity and neurologic outcome was evaluated during fentanyl/nitrous oxide (N2O) (25 micrograms.kg-1.min-1 plus 70% N2O in oxygen), halothane (1.1% inspired), and isoflurane (1.4% anesthesia in a rat model of incomplete cerebral ischemia. Ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 min. Plasma catecholamines were measured during ischemia. Neurologic outcome was measured for 3 days following incomplete ischemia. Both halothane and isoflurane decreased plasma catecholamines 50-80% and improved ischemic outcome compared to fentanyl/N2O anesthesia (P < 0.05). These results indicate a relation between the ability of inhaled anesthetics to decrease sympathetic activity and to improve outcome from incomplete cerebral ischemia.

Anesthesia, Inhalation↗
PubMed1992

The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats.

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Ketamine decreases plasma catecholamines and improves outcome from incomplete cerebral ischemia in rats.

Central neuroexcitatory receptors (N-methyl-D-aspartate [NMDA], non-NMDA) may affect outcome from cerebral ischemia by altering sympathetic nervous system activity. We tested whether ketamine, an NMDA antagonist, and NBQX, a non-NMDA antagonist, improve outcome from incomplete cerebral ischemia in the rat and whether a change in outcome is related to changes in plasma catecholamines. There were five treatment groups: group 1 (control, n = 10) received a fentanyl infusion at a rate of 25 microgram.kg-1.h-1 and ventilation with 70% N2O in O2. Group 2 (n = 10) received the same anesthetic treatment and were given an intraperitoneal injection of 30 mg/kg NBQX 15 min prior to ischemia. Group 3 (n = 10) received a ketamine infusion of 1.0 mg.kg-1.min-1 and ventilation with room air. Group 4 (n = 10) received a ketamine infusion of 1.5 mg.kg-1.min-1. Group 5 received a ketamine infusion of 1 mg.kg-1.min-1 plus a 6 ml/kg intraperitoneal injection of 40% glucose solution 15 min before the start of ischemia. Ischemia was produced by right common carotid ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Blood gases, pH, and skull temperature were controlled during ischemia. Plasma glucose increased during ischemia in all groups but was lower in ketamine-anesthetized rats (groups 3 and 4). Glucose-loaded ketamine-anesthetized rats (group 5) had plasma glucose concentrations similar to the control group. Plasma epinephrine and norepinephrine concentrations were significantly less in ketamine-anesthetized rats (groups 3, 4, and 5) during ischemia compared to controls (P less than 0.05). Neurologic outcome was significantly better (P less than 0.05) in all ketamine-treated rats (groups 3, 4, and 5) compared to the control group, regardless of plasma glucose concentration during ischemia. NBQX did not improve neurologic outcome. These results suggest that ketamine improves neurologic outcome from incomplete cerebral ischemia by a mechanism related to a decrease in plasma catecholamine activity.

Animals↗
PubMed1992

Cerebral and spinal cord blood flow in awake and fentanyl-N2O anesthetized rats: evidence for preservation of blood flow autoregulation during anesthesia.

Blood flow responses to alterations in mean arterial blood pressure (MABP) were measured in the cerebral cortex, subcortex, midbrain, and spinal cord of awake rats. Data were compared with those of rats anesthetized with an i.v. fentanyl infusion and inspired nitrous oxide (N2O). Regional cerebral blood flow was measured using radioactive microspheres in the following blood pressure ranges: (a) <40 mm Hg; (b) 40-60; (c) 60-80; (d) 80-100; (e) 100-120; (f) 120-140; (g) 140-160; and (h) >160. Blood pressure was increased with phenylephrine or decreased with trimethaphan combined with blood withdrawal. Cerebral blood flow was not measured when MABP was less than 60 mm Hg in awake rats. Autoregulation was seen in all brain areas between 60 and 140 mm Hg in both treatment groups. Although regional cerebral blood flow was not different between the two treatment groups, PaCO2 was 2-4 mm Hg lower in awake rats. This suggests that PaCO2-corrected cerebral blood flow may be 10-20% lower with fentanyl-N2O anesthesia.

Journal Article↗
PubMed1992

The effects of propofol on cerebral blood flow in correlation to cerebral blood flow velocity in dogs.

This study correlates the effects of propofol on cerebral blood flow (CBF) and middle cerebral artery blood flow velocity in dogs. CBF was measured using radioactive microspheres. Cerebral oxygen consumption (CMRO2) was measured with each CBF determination. Blood flow velocity was measured through a transtemporal window using a pulsed 8 MHz transcranial Doppler ultrasound system (TCD). Electroencephalogram (EEG) was continuously recorded over both cerebral hemispheres. Cardiac output (CO) was measured using an electromagnetic flow probe placed on the pulmonary artery. Baseline measures were made in all dogs (n = 11) with 0.7% isoflurane end tidal and 50% N2O in O2. There were two treatment groups. In group 1 (n = 6), propofol (0.8 mg/kg/min) was infused and a second measurement made at induction of EEG burst suppression (12 +/- 2 min). CBF and CMRO2 decreased by 70% and mean blood flow velocity decreased by 60%. Blood pressure, heart rate, and CO did not change. Propofol infusion was discontinued and all parameters were measured following recovery of EEG to baseline activity (48 +/- 9 min). CBF and blood flow velocity increased 35 and 25%, respectively, and CMRO2 increased by 32% during this period. A second propofol infusion (0.8 mg/kg/min) was started and all cerebral and systemic hemodynamic parameters were again determined at induction of EEG burst suppression (12 +/- 2 min). CBF decreased 35% and blood flow velocity decreased 25% to levels seen during the first propofol infusion. Over the entire study, changes in CBF correlated with changes in blood flow velocity (r = 0.86, p < 0.05). In group 2 (n = 5), four control measures were made at the same time intervals as in group 1. Baseline CBF and blood flow velocity were lower in group 2 compared to group 1 but these measures did not change over time. Our results show that propofol produces marked decreases in CBF in dogs and that these changes are closely correlated with CBF velocity.

Journal Article↗
PubMed1992

Diminished muscarinic receptor-mediated cerebral blood flow response in streptozotocin-treated rats.

Endothelium-dependent vascular relaxation in the brain may be impaired in the streptozotocin-treated chronically hyperglycemic diabetic (D) rat. To study this, we measured regional cerebral blood flow (rCBF) changes induced by intracarotid (ic) or intravenous (iv) infusions of the blood-brain permeant muscarinic receptor (MR) agonist oxotremorine (Oxo). In nondiabetic (ND) rats, both ic and iv Oxo resulted in significant (P less than 0.05) rCBF increases from values obtained during saline infusions in the regions analyzed. The maximum rCBF values measured during Oxo (expressed as percent iv or ic saline value) were 358-403% in the cortex (CX), 236-260% in the subcortex (SC), 162-186% in the brain stem (BS), and 143-158% in the cerebellum (CE). The iv or ic Oxo response in D vs. ND rats was reduced by 60-70% in the CX and SC, lost in the BS, and unchanged in the CE. The CBF response was associated with no change in cortical CMRO2 and was completely blocked during ic atropine-Oxo co-infusion or iv co-infusion of Oxo with the nitric oxide (NO) synthesis inhibitor L-nitroarginine methyl ester, demonstrating, respectively, no role for metabolic activation, the exclusive role of MR values, and the critical role for the release of the putative endothelium-dependent relaxation factor NO in mediating this effect. These findings indicate a significant, but regionally variable, impairment of the mechanism for endothelium-dependent vascular relaxation in the diabetic brain.

Animals↗