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R W McPherson

Publications and source records attributed to R W McPherson.

At least 19 recordsLinked to original sources
PubMed1997

Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia and hypoxia in dogs.

We tested the hypothesis that a centrally administered alpha 2-receptor agonist could alter the cerebrovascular response to hypoxia, without evidence of systemic absorption of the drug. Beagle dogs were anesthetized with 1.4% isoflurane and exposed to hypoxic hypoxia (Pao2 approximately 22 mm Hg) before and after ventricular-cisternal perfusion with mock cerebrospinal fluid (CSF group, n = 5) or dexmedetomidine (100 micrograms/mL; total dose 300 micrograms; DEX group, n = 6). Cerebral perfusion pressure, Paco2 and arterial oxygen content were controlled and regional cerebral blood flow (CBF; microspheres) and global cerebral metabolic rate for oxygen consumption (CMRO2) were measured. In another group (n = 5), drug distribution under the experimental conditions was assessed by 3H-clonidine administered by ventricular-cisternal perfusion. In the mock CSF group, flow to the cerebral hemispheres increased during hypoxia under baseline conditions and after CSF infusion: 66 +/- 8 to 170 +/- 15 mL.min-1.100 g-1 (265% +/- 24% of baseline value), 83 +/- 9 to 154 +/- 14 mL.min-1.100 g-1 (201% +/- 54% of post-CSF infusion value). DEX decreased normoxic flow in the cerebral hemispheres from 76 +/- 6 to 44 +/- 4 ml.min-1.100 g-1 with decreases in other regions of similar magnitude. After DEX, the absolute flow in all regions during hypoxia was 52%-55% of that prior to DEX (P < 0.05). However, because DEX also decreased normoxic CBF, the percent increase in flow during hypoxia was similar before and after DEX. CMRO2 was not affected by hypoxia prior to DEX. However, after DEX, hypoxia caused a marked reduction in cerebral oxygen delivery (5.2 +/- 1.0 vs 13.7 +/- 2.3 ml.min-1.100 g-1 for the CSF group) and CMRO2 (2.5 +/- 0.6 vs 3.9 +/- 0.6 ml.min-1.100 g-1). Regional accumulation of intraventricularly administered 3H-clonidine was greatest in periventricular brain structures (e.g., caudate nucleus, dorsal brainstem), and the concentration in the cerebral cortex was approximately 1% of the concentration in the ipsilateral caudate nucleus. We conclude that centrally administered DEX reduces CBF during normoxia and prevents adequate oxygen delivery during hypoxia. The mechanism of DEX-induced CBF reduction is not metabolically mediated, since CMRO2 is maintained at control values during normoxia despite the significant blood flow reduction. We believe that the reduction in CMRO2 during hypoxia in DEX-treated dogs is the result of a reduction of oxygen delivery rather than the underlying mechanism for the observed reduction in CBF during hypoxia.

Adrenergic alpha-Agonists↗
PubMed1997

Pial arteriolar constriction to alpha 2-adrenergic agonist dexmedetomidine in the rat.

Dexmedetomidine (Dex) is an alpha 2-adrenergic agonist that decreases cerebral blood flow (CBF) when administered systemically. It is unclear whether cerebral vasoconstriction is mediated by a local effect on cerebral vessels or by a remote neural mechanism. In the present study, we compared the pial arteriole responses to locally and systemically administered Dex with and without local application of the specific alpha 2-adrenergic antagonist atipamezole. Six groups of male rats (n = 7 each) were anesthetized with isoflurane and prepared for measurements of small (20-39 microns), medium (40-59 microns), and large (60-79 microns) pial arteriole diameter by intravital microscopy or for regional CBF measurement by the radiolabeled-microsphere method. Local application of Dex caused dose-dependent constriction that was significant starting at 10(-8) M for small and medium-sized arterioles and at 10(-7) M for large arterioles. Constriction to 10(-5) M in small [21 +/- 2% (SE)], medium (21 +/- 2%), and large (15 +/- 1%) arterioles was almost completely blocked by local application of 10(-4) M atipamezole. Intravenous administration of Dex at 1 microgram/kg decreased CBF and caused modest arteriolar constriction that began to resolve 8 min after administration. A dose of 10 micrograms/kg constricted arterioles of all sizes with constriction beginning to resolve after approximately 10 min. Local application of atipamezole (10(-4) M) slightly blunted the response to 1 micrograms/kg of intravenous Dex but did not substantially limit constriction after 10 micrograms/kg. These data demonstrate that pial arterioles are capable of substantial constriction to Dex by a local alpha 2-adrenergic mechanism. However, the inability of locally applied atipamezole to substantially inhibit the vasoconstrictor response to systemically administered Dex suggests that Dex might also cause vasoconstriction indirectly through actions at other sites in the central nervous system.

Adrenergic alpha-Agonists↗
PubMed1995

Effect of nitric oxide synthase inhibition on the cerebral vascular response to hypercapnia in primates.

BACKGROUND AND PURPOSE: The role of nitric oxide in cerebrovascular response to changes in PCO2 is unclear. In the present study, we assessed responses at two levels of hypercapnia in a primate model before and after blockade of nitric oxide synthesis. METHODS: We compared the effects of two levels of hypercapnia, defined as PCO2 of approximately 70 mm Hg (high-CO2 group, n = 5) and PCO2 of approximately 50 mm Hg (moderate-CO2 group, n = 6), on increases in regional cerebral blood flow (microspheres) before and after inhibition of nitric oxide synthase with N omega-nitro-L-arginine methyl ester (L-NAME; 60 mg.kg-1) in isoflurane-anesthetized cynomolgus monkeys (1.0% end-tidal concentration). RESULTS: Before L-NAME administration, hypercapnia increased flow in all regions (eg, forebrain, high-CO2 group 69 +/- 10 to 166 +/- 15 mL.min-1.100 g-1; moderate-CO2 group, 49 +/- 7 to 93 +/- 15 mL.min-1.100 g-1) and decreased cerebral vascular resistance (high-CO2, 1.1 +/- 0.1 to 0.4 +/- 0.1 mm Hg.mL-1.min.100 g; moderate-CO2, 1.4 +/- 0.1 to 0.7 +/- 0.1 mm Hg.mL-1.min.100 g). During normocapnia, L-NAME decreased cerebral blood flow (high-CO2, 37 +/- 9%; moderate-CO2, 40 +/- 6%) and increased cerebral vascular resistance (high-CO2, 93 +/- 33%; moderate-CO2, 88 +/- 20%). After L-NAME, hypercapnia still increased blood flow in all regions (eg, forebrain: high-CO2, 56 +/- 7 to 128 +/- 3 mL.min-1.100 g-1, moderate-CO2, 36 +/- 5 to 57 +/- 8 mL.min-1.100 g-1) and decreased vascular resistance (high-CO2, 1.5 +/- 0.1 to 0.6 +/- 0.1 mm Hg.mL-1.min.100 g; moderate-CO2, 2.0 +/- 0.3 to 1.2 +/- 0.1 mm Hg.mL-1.min.100 g). In both groups L-NAME attenuated hypercapnia hyperemia by approximately 30% in cortex but not in other regions. CONCLUSIONS: Nitric oxide contributes to basal vascular tone but is not a major contributor to the mechanism of hypercapnia-induced cerebral vasodilation, except in cortex, in primates.

Amino Acid Oxidoreductases↗
PubMed1994

Cerebral blood flow in primates is increased by isoflurane over time and is decreased by nitric oxide synthase inhibition.

BACKGROUND: Cerebral blood flow (CBF) decreases over time in dogs and goats during volatile anesthesia. In the current study, we determined CBF during administration of isoflurane for 4 h in cynomolgus monkeys. In addition, we determined if nitric oxide (NO) contributes to cerebrovascular tone during isoflurane anesthesia by determining the CBF (microsphere) response to inhibition of NO synthase with N omega-nitro-L-arginine methyl ester (L-NAME). METHODS: CBF was measured in five monkeys anesthetized with isoflurane (1.0% end-tidal). After 4 h of isoflurane (1.0% = 1 MAC), the effects of intravenous L-NAME (60 mg/kg over 10 min) followed by intravenous L-arginine (600 mg/kg over 10 min) on CBF were measured at constant cerebral perfusion pressure and arterial carbon dioxide tension. RESULTS: CBF was unchanged over time (4 h) in cerebellum but increased by 50 +/- 18% in both forebrain and hindbrain (P < 0.05). CBF decreased by 41-48% (P < 0.05) 20 min after L-NAME in forebrain, cerebellum, and hindbrain, at which time brain NO synthase activity was less than 10% of baseline. Twenty minutes after L-arginine, CBF was increased in cerebellum by 32 +/- 8% and in forebrain by 41 +/- 9% (P < 0.05). The cerebral metabolic rate of oxygen consumption was unaffected by time or by L-NAME or L-arginine. CONCLUSIONS: These data demonstrate that CBF increases over time during isoflurane anesthesia in primates. Tonic production of NO contributes to control of CBF in primates during isoflurane anesthesia. Increased CBF by L-arginine after L-NAME supports the hypothesis that L-NAME decreases CBF via a mechanism requiring NO synthesis.

Amino Acid Oxidoreductases↗
PubMed1994

Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs.

BACKGROUND: The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. METHODS: The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8). RESULTS: In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 +/- 18%, 120 +/- 18%, and 103 +/- 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 +/- 10% and 52 +/- 11% increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine. CONCLUSIONS: We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.

Amino Acid Oxidoreductases↗
PubMed1994

Dexmedetomidine decreases seizure threshold in a rat model of experimental generalized epilepsy.

BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha 2 agonist with marked sedative and analgesic properties thought to be mediated via reduction of central noradrenergic transmission. Because an anticonvulsant effect is associated with increased noradrenergic activity, we investigated the possible proconvulsant effects of DEX in an experimental model of generalized seizures. METHODS: Male rats (n = 82) were administered 0.9% saline as placebo (n = 18) or pretreatment drug(s) before initiation of an infusion of pentylenetetrazol (PTZ) at 5.5 mg.kg-1.min-1. The total dose of PTZ required to elicit electroencephalographic (EEG) and behavioral seizure activity was assessed. Blood samples were obtained 15 min after initiation of infusion (82.5 mg/kg) for determination of serum PTZ concentrations by gas chromatography. Pretreatment drug groups included DEX (20 micrograms/kg [n = 11], 100 micrograms/kg [n = 14], and 500 micrograms/kg [n = 10]); L-medetomidine (500 micrograms/kg [n = 7]); the alpha 2 antagonist atipamezole (500 micrograms/kg [n = 9]); and atipamezole (500 micrograms/kg) before DEX (100 micrograms/kg [n = 7] and 500 micrograms/kg [n = 6]). RESULTS: In control animals, PTZ 25-35 mg/kg induced EEG evidence of epileptiform activity. The mean dose to EEG epileptiform activity and clonic convulsions was 30 +/- 5.8 (SE) and 59 +/- 3.2 mg/kg, respectively. Infusion of DEX at 100 and 500 micrograms/kg resulted in a marked sedative response and reduced the EEG seizure threshold of PTZ to 18 +/- 1.5 and 7 +/- 1.8 mg/kg, respectively (P < 0.05 at both doses). The clonic convulsant threshold also was significantly decreased in both groups, to 37 +/- 3.2 and 28 +/- 2.3 mg/kg (P < 0.01 at each dose). Before clonic convulsion, a significantly greater number of motor seizure manifestations were scored in the DEX-treated animals at all three dose levels compared with the number scored in control animals. The proconvulsant action of DEX was not a result of alteration of PTZ kinetics, because serum concentrations did not differ between control and DEX-treated animals. Animals treated with L-medetomidine demonstrated more paroxysmal motor phenomena before clonic seizures than controls (P < 0.01) although the clonic seizure threshold was not altered. Atipamezole alone did not alter background EEG, nor did it affect the clonic convulsant threshold. Atipamezole did, however, block the proconvulsant behavioral action at both doses of DEX, raising clonic seizure threshold from 37 +/- 3.2 to 59 +/- 5.8 mg/kg (100 micrograms/kg DEX, P < 0.05) and from 28 +/- 2.3 to 59 +/- 6.9 mg/kg (500 micrograms/kg DEX, P < 0.01). CONCLUSIONS: DEX exerted a significant proconvulsant action in the PTZ experimental seizure model. The pharmacodynamic effect was dose-dependent and stereospecific and was blocked by the selective alpha 2-receptor antagonist atipamezole. These data are consistent with previous data demonstrating that inhibition of central noradrenergic transmission facilitates seizure expression. Further evaluation of DEX for possible clinical proconvulsant effects may be warranted.

Adrenergic alpha-Agonists↗
PubMed1994

Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow.

We tested the hypothesis that NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/- 4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE) ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10 micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x 100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L-NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O2 transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1994

Inhibition of nitric oxide synthase does not affect alpha 2-adrenergic-mediated cerebral vasoconstriction.

We assessed whether blocking nitric oxide (NO) synthase alters the cerebral blood flow (CBF) response to alpha 2-adrenergic stimulation during isoflurane anesthesia in dogs. In control animals (n = 6), CBF (microspheres), cerebral oxygen consumption (CMRO2), and electroencephalograph (EEG) were measured after 1 h of isoflurane (1.4% end-tidal) and before and 5, 10, and 20 min after injection of an alpha 2-adrenergic receptor agonist (dexmedetomidine 10 micrograms/kg, intravenous bolus). Dogs in a second group (n = 6) were treated similar to control animals except that an irreversible blocker of NO synthase, N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg) was administered 1 h before induction of anesthesia. In control dogs, dexmedetomidine decreased CBF by 37% (P < 0.05). Blood flow remained decreased for the 20 min observation period in all brain regions except cerebellum and caudate. In the L-NAME group, control CBF was 45% less than baseline flow in the control group (P < 0.05) and dexmedetomidine further decreased CBF from 41 +/- 7 mL x 100 g-1 x min-1 to 24 +/- 2 mL.100 g-1 x min-1 (P < 0.05). There was no difference between groups in the percent of reduction of blood flow in any region after dexmedetomidine administration. Control CMRO2 was similar in the two groups and was unchanged by dexmedetomidine. These data demonstrate that L-NAME reduces CBF and that block of NO synthase does not affect alpha 2-adrenergic-mediated decreases in CBF during isoflurane anesthesia.

Amino Acid Oxidoreductases↗
PubMed1994

A cholinergic agonist induces cerebral hyperemia in isoflurane- but not pentobarbital-anesthetized dogs.

We tested whether the cerebral blood flow (CBF) response to the cholinergic agonist oxotremorine (OXO) is affected by the choice of anesthetics in dogs. We studied two anesthetics, pentobarbital and isoflurane, which produce similar levels of cerebral metabolic depression but have opposing effects on CBF. We also tested the contribution of nitric oxide (NO, or a NO-containing compound) in mediating the CBF response to OXO by determining whether NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) would attenuate OXO-induced hyperemia in both anesthetic groups. CBF (microspheres) was measured before and after OXO administration (50 micrograms.kg-1.min-1 intravenously [i.v.] for 10 min). Animals were divided randomly to receive OXO alone (n = 10) or L-NAME (40 mg/kg i.v.) followed by OXO (n = 10). Within each group, half of the animals received pentobarbital anesthesia (30 mg/kg i.v.) and half received isoflurane (1.4% end-tidal). In pentobarbital-anesthetized animals OXO produced no change in blood flow to cerebrum, caudate, diencephalon, neurohypophysis, or cerebellum in the absence (e.g., cerebrum 37 +/- 2 vs 42 +/- 5 mL/min/100 g) or presence of L-NAME (e.g., cerebrum, 29 +/- 4 vs 30 +/- 3 mL.min-1 x 100 g-1). In isoflurane-anesthetized animals, however, blood flow to forebrain regions increased after OXO (e.g., cerebrum 108 +/- 10 vs 232 +/- 15 mL.min-1 x 100 g-1; P < 0.05) without alteration in oxygen consumption in cerebrum (CMRO2) or blood flow to hindbrain regions. In isoflurane-anesthetized animals, L-NAME decreased baseline blood flow to cerebrum, caudate, diencephalon, cerebellum, and neurohypophysis (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1994

Alpha 2-adrenergic agonist effects on normocapnic and hypercapnic cerebral blood flow in the dog are anesthetic dependent.

alpha 2-Adrenergic receptors are found on large and small cerebral vessels, but their role in control of cerebral blood flow (CBF) and cerebral vascular reactivity is unclear. We assessed the effects of dexmedetomidine (DEX), a highly selective alpha 2-adrenergic agonist, on the cerebrovascular response to hypercapnia in dogs anesthetized with either pentobarbital (PENTO) or isoflurane (ISO), drugs which produce different levels of CBF at a similar level of cerebral oxygen consumption (CMRO2). Dogs were anesthetized with either PENTO, 30 mg/kg, n = 6, or ISO 1.4% end-tidal, n = 7. CBF (radiolabeled microspheres) was determined during normocapnia and hypercapnia at baseline (pre-DEX), after DEX (10 micrograms/kg, intravenous bolus, plus an additional 5 micrograms/kg during hypercapnia), and after administration of a selective alpha 2-adrenergic receptor antagonist (atipamezole, 500 micrograms/kg, intravenous bolus). In the PENTO group, CBF increased from 31 +/- 3 to 137 +/- 24 mL.min-1.100 g-1 in response to hypercapnia (PCO2 approximately 90 mmHg) at pre-DEX and there was no change in normocapnic CBF or hypercapnic blood flow after DEX or atipamezole. In the ISO group, at pre-DEX, CBF increased from 86 +/- 8 to 166 +/- 19 mL.min-1.100 g-1 in response to hypercapnia (PCO2 approximately 90 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-2 Receptor Agonists↗
PubMed1993

N omega-nitro-L-arginine methyl ester prevents cerebral hyperemia by inhaled anesthetics in dogs.

The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 +/- 4 to 56 +/- 6 mL.min-1 x 100 g-1 and 43 +/- 6 to 78 +/- 12 mL.min-1 x 100 g-1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 +/- 0.2; isoflurane, 2.0 +/- 0.2 mL.min-1 x 100 g-1). On the contrary, nitrous oxide increased CBF similarly (40 +/- 6 to 57 +/- 8 mL.min-1 x 100 g-1), but increased cerebral oxygen consumption (2.2 +/- 0.3 to 3.0 +/- 0.3 mL.min-1 x 100 g-1). L-NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Spinal cord stimulation evoked potentials during thoracoabdominal aortic aneurysm surgery.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Monitoring of spinal cord stimulation evoked potentials during thoracoabdominal aneurysm surgery.

Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic injury to the spinal cord. Standard monitoring of somatosensory evoked potentials, which relies upon peripheral nerve stimulation, becomes nonspecific and insensitive during this surgery when aortic cross-clamping produces lower extremity ischemia causing a peripheral conduction block. Techniques for the insertion of percutaneous epidural electrodes, developed originally for pain management, have been adapted to this setting to permit direct stimulation of the spinal cord for intraoperative monitoring of evoked potentials. The clinical outcome in patients monitored by this technique has been consistent with evoked potential findings.

Aorta, Abdominal↗
PubMed1991

Changes in cerebral CO2 responsivity over time during isoflurane anesthesia in the dog.

We assessed cerebrovascular responsivity to changes in arterial carbon dioxide tension (PaCO2) during 3 h of 1 MAC isoflurane anesthesia to determine whether it parallels previously reported time-dependent decrease in normocapnic cerebral blood flow (CBF). Twelve dogs were studied under pentobarbital anesthesia (30 mg kg iv bolus) and twelve dogs under isoflurane anesthesia (1.4% end-tidal). In six animals of each anesthetic group, hypocapnia was compared to normocapnia; in the remaining six animals, hypercapnia was compared to normocapnia. At 1, 2, and 3 h after anesthesia induction, and again 10 min after blood gas alteration (hypocapnia or hypercapnia) normocapnic CBF was determined by the radiolabelled microsphere method. In animals receiving pentobarbital, total CBF during normocapnia, hypocapnia, and hypercapnia at 1 h was 40 +/- 4, 24 +/- 3, and 113 +/- 13 ml min 100g, respectively, and there was no significant change (p >0.05) at each respective level of CO2 over the 3 h of the study. Cerebral metabolic rate for oxygen (CMRO2) was unchanged with time or CO2 alteration. CO2 responsivity (change in CBF/change in PaCO2) during hypercapnia was 0.8 +/- 0.2 ml min 100g mm Hg and during hypercapnia was 3.4 +/- 0.6 ml min 100g mm Hg at 1 h and both were unchanged from those value at 3 h. In animals receiving isoflurane and subjected to hypocapnia, total CBF during normocapnia at 1 h was 97 +/- 10 ml min 100 g and declined to 56 +/- 9 ml min 100 g at 3 hr (p <0.05). Over the same time period (1-3 h), hypocapnic CBF decreased from 44 + 5 to 27 +/- 3 ml min 100g (p <0.05). In animals receiving isoflurane and subjected to hypercapnia, normocapnic CBF decreased from 68 +/- 10 to 46 +/- 6 ml min 100 g at 3 h (p <0.05) and hypercapnic flow over the same time declined from 184 +/- 24 ml min 100 g to 135 +/- 18 ml min 100g (p <0.05). CMRO2 was not changed by either time or CO2 alteration. Between 1 and 3 h, CO2 responsivity during hypecapnia decreased from 4.1 +/- 0.9 to 1.8 +/- 0.4 ml min 100 g mm Hg (p <0.05). CO2 responsivity during hypocapnia decreased from over the same period decreased from 9.0 +/- 1.0 to 5.1 +/- 0.9 ml min 100 g mm Hg (p <0.05). Similar time-dependent trends were observed in most brain regions. We conclude that normocapnic CBF and cerebral CO2 responsivity decrease over time during isoflurane anesthesia and that these changes are not caused by changes in brain metabolism.

Journal Article↗
PubMed1990

Changes in cerebral blood flow over time during isoflurane anesthesia in dogs.

The present study assessed the impact of time (6 h) on cerebral blood flow (CBF) during isoflurane anesthesia with and without vasopressor administration. All animals were prepared for measurement of CBF by the radiolabeled microsphere method under 1.4% end-tidal (1.0 MAC) isoflurane anesthesia. Surgery required 45 min and was followed by a 15 min stabilization period. In group 1 (n = 6), isoflurane 1.4% was administered for 6 h. CBF after 1 h of isoflurane was 92 +/- 9 ml/min/100 g (mean +/- SEM) and declined to 61 +/- 5 ml/min/100 g at 2 h and further declined to 37 +/- 5 ml/min/100 g at 6 hr. In group 2 (n = 6), isoflurane 1.4% was administered during the first hour. Thereafter, isoflurane 1.4% was continued, angiotensin II (0.3 mug/kg/min) was administered intravenously, and blood was withdrawn to maintain CPP constant for an additional 5 h, with hourly CBF determination. In this group, control CBF was 95 +/- 16 ml/min/100 g and flow was maintained at the control level through 4 h and then declined to 50 +/- 5 ml/min/100 g at 5 and 6 h. In group 3 (n = 6), 1.4% isoflurane was administered and phenylephrine (2.0 mug/kg/min) infusion was combined with hemorrhage to maintain control CPP in an identical sequence to group 2. In group 3, control CBF was 88 +/- 14 ml/min/100 g. As in group 1, CBF decreased significantly at 2 h (p < 0.05) to 68 +/- 13 ml/min/100 g and further declined to 49 +/- 7 ml/min/100 g at 6 h. In all three groups, CMRO2 remained at control levels and there were no changes in arterial carbon dioxide or CPP for the duration of the study. These data demonstrate that the hyperemia caused by isoflurane resolves over time during stable 1 MAC isoflurane anesthesia. The unanticipated interaction of angiotensin II and isoflurane producing a sustained cerebral hyperemia suggests that previous studies that used angiotensin II to support MABP during isoflurane may have reported the effects of angiotensin II in addition to or rather than the effects of isoflurane.

Journal Article↗
PubMed1989

Cerebrovascular responsiveness to carbon dioxide in dogs with 1.4% and 2.8% isoflurane.

Cerebral blood flow (CBF) responsiveness to alterations in arterial CO2 tensions (PaCO2) during 1.4% and 2.8% isoflurane anesthesia was assessed. Dogs were initially anesthetized with thiopental (12 mg/kg, iv bolus), their tracheae intubated, after which anesthesia was maintained with 1.4% isoflurane. In eight animals three levels of PaCO2 (25, 40, and 60 mmHg) were studied during 1.4% and 2.8% isoflurane. Mean arterial blood pressure, sagittal sinus pressure, and cerebrospinal fluid pressure were measured and CBF was determined using radiolabeled microspheres. Cerebral perfusion pressure (CPP) was maintained constant at approximately 80 mmHg by inflation of a balloon in the midthoracic aorta. CBF during normocapnia was 70 +/- 14 and 118 +/- 18 ml.min-1.100 g-1 with 1.4% and 2.8% isoflurane, respectively. As PaCO2 was decreased and increased, CBF decreased and increased to 42 +/- 7% and 185 +/- 16% of control, respectively, during 1.4% isoflurane. During 2.8% isoflurane, hypocapnia decreased CBF to 39 +/- 6% of control, but CBF did not increase with hypercapnia. In a second group of animals (n = 8), the effects of changes in CPP during hypercapnia with 1.4% and 2.8% isoflurane were assessed. Increasing CPP approximately 25 mmHg with both 1.4% and 2.8% isoflurane increased CBF but did not change CVR from control. With 1.4% isoflurane, the cerebral vasculature constricts with hypocapnia and dilates with hypercapnia, whereas with 2.8% isoflurane, vasoconstriction to hypocapnia is retained but vasodilation to hypercapnia is absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1989

Effect of time and dose on scalp-recorded somatosensory evoked potential wave augmentation by etomidate.

Bolus etomidate transiently increases the amplitude of scalprecorded somatosensory evoked potentials (SSEPs). The reproducibility of this augmentation and its dose-response relationship are unknown. In unpremedicated patients, we studied the effect on the SSEP of repetitive administration of single doses of etomidate (0.1 mg/kg i.v. bolus) in six patients and increasing doses of etomidate in six additional patients. Anesthesia was induced with fentanyl (15-20 microg/kg i.v.) plus thiopental (1-2 mg/kg i.v.) and maintannined with 0.4-0.8% isoflurane in oxygen, and the surgical incision was infiltrated with bupivicaine (0.5% without epinephrine). Etomidate administration was delayed for 30 min following anesthesia induction. In group 1, 0.1 mg/kg etomidate was administered intravenously as a bolus three times at 30-min intervals. In group 2, 0.05, 0.1, or 0.2 mg/kg was administered at 30-min intervals in random order in each patient. SSEPs were measured immediately before and once each minute for 5 min after etomidate administration following nondominant median nerve stimulation. In group 1, administration of 0.1 mg/kg etomidate (three trials) increased latency of an early negative wave (N20; latency approximately 20 ms) and a positive wave following N20 (P23; latency approximately 23 ms) by 1.0-1.4 and 1.3-2.6 ms, respectively (p < 0.05). P15N20 amplitude was increased by approximately 50% (range 36-76%; p < 0.05) and N20P23 amplitude was increased to 174% of control (range 173-178%; p < 0.05) and the amplitude increase was similar during the three etomidate administrations for both P15N20 and N20P23. Latency remained elevated by approximately 1.5 ms and amplitude remained elevated (P15N20 = 138%; N20P23 = 150%) 5 min following injection. Mean arterial blood pressure was unchanged by 0.1 mg/kg etomidate. In group 2, 0.05 mg/kg etomidate altered neither amplitude nor latency. However, 0.1 and 0.2 mg/kg increased N20P23 amplitude to 161 +/- 33 and 230 +/- 10% of control (p < 0.05), respectively. N20 and P23 latency were increased by 0.1 mg/kg etomidate by approximately 1.0 ms, while 0.2 mg/kg increased N20 latency by 1.0 ms and P23 latency by 1.5 ms. Bolus administration of etomidate (0.1 mg/kg) reproducibly increased SSEP amplitude and a larger dose (0.2 mg/kg) further increased amplitude augmentation. Thus, intermittent injection of etomidate can be used to augment small SSEP waves with reproducible increases in wave amplitude.

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