Isoflurane and Sevoflurane Induce Vasodilation of Cerebral Vessels via ATP-sensitive K+ Channel Activation

Background: Activation of adenosine triphosphate-sensitive K+ channels causes cerebral vasodilation. To assess their contribution to volatile anesthetic-induced cerebral vasodilation, the effects of glibenclamide, an adenosine triphosphate-sensitive K+ channel blocker, on the cerebral vasodilation induced by isoflurane and sevoflurane were studied.

Methods: Pentobarbital-anesthetized dogs (n = 24) assigned to one of two groups were prepared for measurement of pial vessel diameter using a cranial window preparation. Each dog received three minimum alveolar concentrations (MAC; 0.5, 1, and 1.5 MAC) of either isoflurane or sevoflurane, and the pial arteriolar diameters were measured in the presence or absence of glibenclamide (10-5 M) infused continuously into the window. Mean arterial pressure was maintained with phenylephrine. Furthermore, to assess the direct effect of isoflurane and sevoflurane on cerebral vessels, artificial cerebrospinal fluid was administered topically by being bubbled with isoflurane or sevoflurane. The blocking effect of glibenclamide on the vasoactive effects of these anesthetics also were evaluated.

Results: Isoflurane and sevoflurane both significantly dilated large (>or= to 100 [micro sign]m) and small (< 100 [micro sign]m) pial arterioles in a concentration-dependent manner (6% and 10%, 3% and 8% for 0.5 MAC; 10% and 19%, 7% and 14% for 1 MAC; 17% and 28%, 13% and 25% for 1.5 MAC). Glibenclamide attenuated the arteriolar dilation induced by these anesthetics (not significant in isoflurane). Topical application of isoflurane or sevoflurane dilated large and small arterioles both in a concentration-dependent manner. Such vasodilation was inhibited completely by glibenclamide.     

The effects of topical and intravenous ketamine on cerebral arterioles in dogs receiving pentobarbital or isoflurane anesthesia

To evaluate the effects of ketamine on cerebral arterioles, we used a closed cranial window technique in mechanically ventilated, anesthetized dogs. Fourteen dogs were assigned to one of the following two basal-anesthesia groups: pentobarbital 2 mg. kg(-1). h(-1) or isoflurane 0.5 MAC (n = 7 each). We administered three different concentrations of ketamine (10(-7), 10(-5), and 10(-3) M) under the window and measured arteriolar diameters. For comparison, in another 14 dogs we examined the effect of systemic (IV) ketamine (1 mg/kg and 5 mg/kg) using the same two basal anesthetics. We measured diameters before and after ketamine administration, and we evaluated the effect of ketamine on CO(2) reactivity of the cerebral arterioles. Neither topical nor systemic ketamine dilated pial arterioles in either basal-anesthesia group. CO(2) reactivity of pial arterioles was reduced under systemic ketamine in both basal-anesthesia groups. The results indicate that although ketamine does not dilate pial arteriolar diameters when topically or IV administered, IV ketamine does attenuate hypercapnic vasodilation in dogs under basal pentobarbital or isoflurane anesthesia. These results provide some insight that ketamine is suitable for supplementary neurosurgical anesthesia.     

Direct effects of alpha1- and alpha2-adrenergic agonists on spinal and cerebral pial vessels in dogs.

BACKGROUND: The effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of alpha2- and alpha1-adrenergic agonists on spinal and cerebral pial vessels in vivo. METHODS: Pentobarbital-anesthetized dogs (n = 28) were prepared for measurement of spinal pial-vessel diameter in a spinal-window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 microg/ml; [2.1, 1.9, 2.5, and 2.3] x [10(-6), 10(-5), and 10(-4)] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window. RESULTS: On topical administration, each drug constricted spinal pial arterioles in a concentration-dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 microg/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels). CONCLUSION: Dexmedetomidine and clonidine constricted spinal vessels in a concentration-dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.     

Hypothermia attenuates the vasodilator effects of dexmedetomidine on pial vessels in rabbits in vivo

Studies have indicated that mild to moderate hypothermia or dexmedetomidine may have neuroprotective properties in animal models. In this study, we investigated the effects of hypothermia on dexmedetomidine-induced responses in cerebral vessels in anesthetized rabbits by using the cranial-window preparation. After instrumentation under pentobarbital anesthesia, 12 rabbits were assigned to 1 of 2 equal groups: normothermic (nasopharyngeal and intrawindow temperature, 38.5 degrees C-39.5 degrees C) or hypothermic (33.0 degrees C-34.0 degrees C). Each rabbit received three different concentrations (10(-7), 10(-5), and 10(-3) M) of dexmedetomidine under the window, and cerebral pial vessel diameters were measured in a sequential manner. In the normothermic group, dexmedetomidine induced a significant concentration-dependent dilation in both large and small arterioles. In the hypothermia group, dexmedetomidine produced a U-shaped dose-response in both large and small cerebral arterioles (concentration-related vasoconstriction at 10(-7) and 10(-5) M, but vasodilation at 10(-3) M). In cerebral venules, a similar pattern of results was obtained, but changes were generally smaller than in arterioles. In conclusion, topically applied dexmedetomidine induces concentration-dependent dilation in cerebral arterioles in normothermic rabbits anesthetized with pentobarbital, but mild to moderate hypothermia attenuates these responses, with smaller dexmedetomidine concentrations causing vasoconstriction. IMPLICATIONS: In normothermic rabbits anesthetized with pentobarbital, topically applied dexmedetomidine induces a concentration-dependent dilation in both large and small cerebral arterioles, but mild to moderate hypothermia attenuates these responses.     

Direct Effects of [Greek small letter alpha]1- and [Greek small letter alpha]2-Adrenergic Agonists on Spinal and Cerebral Pial Vessels in Dogs

Background: The effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of [Greek small letter alpha]2- and [Greek small letter alpha]1-adrenergic agonists on spinal and cerebral pial vessels in vivo.

Methods: Pentobarbital-anesthetized dogs (n = 28) were prepared for measurement of spinal pial-vessel diameter in a spinal-window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 [micro sign]g/ml; [2.1, 1.9, 2.5, and 2.3] x [10-6, 10-5, and 10-4] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window.

Results: On topical administration, each drug constricted spinal pial arterioles in a concentration-dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 [micro sign]g/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels).     

Intrathecal Dexmedetomidine Attenuates Hypercapnic but Not Hypoxic Cerebral Vasodilation in Anesthetized Rabbits

Background: Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia.

Methods: Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 [mu]g/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 [mu]g/kg followed by DXM 2 [mu]g/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 [mu]g/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 [mu]g/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 [mu]g/kg; n = 7).

Results: The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 [mu]g/kg and topical DXM 10-6 m, but not systemic 2 [mu]g/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles.     

The differential effects of stereoisomers of ropivacaine and bupivacaine on cerebral pial arterioles in dogs.

We investigated whether the stereoisomers of ropivacaine and bupivacaine exert differential effects on the cerebral microcirculation. Pentobarbital-anesthetized dogs (n = 16) were prepared for measurement of cerebral pial vessel diameters by using a closed cranial window preparation. We administered three different concentrations (10(-7), 10(-5), and 10(-3) M) of each of three drug solutions [R(+), racemic, and S(-) forms of ropivacaine (n = 8) or bupivacaine (n = 8)] under the window in a randomized manner and measured cerebral pial arteriolar diameters. Various physiologic data were obtained before and after topical application of each test solution. All three forms of ropivacaine constricted cerebral pial arterioles, each in a concentration-dependent manner. The rank order for degree of vasoconstriction was S(-) ropivacaine > racemic ropivacaine > R(+) ropivacaine. In contrast, R(+) and racemic bupivacaine dilated, but S(-) bupivacaine constricted, cerebral pial arterioles, each in a concentration-dependent manner. We could find no difference in vascular reactivity to these drugs between large (> or = microm) and small (<100 microm) arterioles. Topical application of these drugs induced no changes in mean blood pressure or heart rate. The observed differences in the microvascular alterations induced by the stereoisomers of ropivacaine and bupivacaine suggest that the vasoactive effects of these drugs on cerebral arterioles could, at least in part, depend on their chirality. IMPLICATIONS: The differential effects of the stereoisomers of ropivacaine and bupivacaine on cerebral pial vessels could, at least in part, depend on their chirality.     

Intrathecal dexmedetomidine attenuates hypercapnic but not hypoxic cerebral vasodilation in anesthetized rabbits

BACKGROUND: Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia. METHODS: Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 microg/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 microg/kg followed by DXM 2 microg/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 microg/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 microg/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 microg/kg; n = 7). RESULTS: The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 microg/kg and topical DXM 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles. CONCLUSIONS: The presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system.     

Effects of dexmedetomidine on cerebral circulation and systemic hemodynamics after cardiopulmonary resuscitation in dogs

Purpose Our purpose was to examine the effect of dexmedetomidine, when used with phenylephrine during cardiopulmonary resuscitation (CPR), on the cerebral and systemic circulations. Methods In pentobarbital-anesthetized, mechanically ventilated dogs, we evaluated pial vessel diameters, cerebral oxygen extraction, and systemic hemodynamics before and after cardiac arrest (5 min) and resuscitation, in the presence or absence of dexmedetomidine (n = 7 each; dexmedetomidine or control group). Results In both groups: (a) pial arterioles were dilated at 5 and 15 min after CPR, and had returned to baseline diameters at 30 min; (b) sagittal sinus pressure was significantly raised at 5 and 15 min after CPR; and (c) cerebral oxygen extraction was decreased at 5, 15, and 30 min after CPR, and had returned to baseline level at 60 min after CPR. We could find no differences between the two groups in the cerebral circulation after CPR. However, the number of defibrillation electric shocks required to restore spontaneous circulation (5.5 vs 3.6; P < 0.05), the dose of phenylephrine used for CPR (1193 μg vs 409 μg; P < 0.01), and the number of postresuscitation ventricular ectopic beats observed during the first 120 min after successful resuscitation (1606 vs 348; P < 0.05) were all significantly lower in the dexmedetomidine group. Conclusion Although intravenous dexmedetomidine, as used for CPR, does not have a beneficial effect on either cerebral vessels or cerebral oxygen extraction, it may reduce the number of defibrillation shocks needed and the number of postresuscitation ventricular ectopic beats, and help to bring about stable systemic circulation after CPR.     

The effects of alpha-human atrial natriuretic peptide and milrinone on pial vessels during blood-brain barrier disruption in rabbits.

The effects of alpha-human atrial natriuretic peptide (HANP) and milrinone on cerebral pial vessels, especially during blood-brain barrier (BBB) disruption, are not clear. We studied topical HANP (10(-14), 10(-12), and 10(-10) M) or milrinone (10(-7), 10(-5), and 10(-3) M), and IV HANP (0.1, 0.2, and 1.0 microg. kg(-1). min(-1)) or milrinone (0.5, 5.0, and 20.0 microg. kg(-1). min(-1)) with or without hyperosmolar BBB disruption, using a rabbit cranial window preparation. At 10(-12) and 10(-10) M topical HANP produced significant arteriolar (16%, 20%, respectively), but no venular dilation. Topical milrinone (10(-3) M) produced significant arteriolar and venular dilation (21%, 8%, respectively). IV HANP produced no arteriolar or venular changes at any dose except during BBB disruption, when it caused a significant arteriolar (16%, 16%, and 17%, respectively), but no venular dilation. In contrast, IV milrinone caused small but significant arteriolar and venular dilation without BBB disruption (arterioles, 6%, 7% and 8%, respectively; venules, 6% at 20.0 microg. kg(-1). min(-1)). During BBB disruption, these responses to milrinone were similar. Although HANP and milrinone each have a direct vasodilator effect on arterioles, their systemic administration at clinical doses could induce different effects. BBB disruptive conditions could increase the response of pial vessels to systemically administered HANP. Implications: Although alpha-human atrial natriuretic peptide (HANP) and milrinone each have a direct vasodilator effect on cerebral pial arterioles, their systemic administration at clinical doses could have different effects and blood-brain-barrier disruptive conditions could alter the response of pial vessels to HANP, but not to milrinone.     

Dexmedetomidine, an alpha 2-adrenergic agonist, decreases cerebral blood flow in the isoflurane-anesthetized dog

The purpose of this study was to examine the effects of dexmedetomidine, an alpha 2-adrenergic agonist, on cerebral blood flow and metabolic rate in dogs anesthetized with 0.64% isoflurane. After intubation and institution of mechanical ventilation, arterial, venous, pulmonary artery, and sagittal sinus catheters were inserted. Measurements of cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRo2), mean arterial pressure, cardiac output, and blood gas tensions were made at various levels of isoflurane anesthesia (0.64%, 1.9%, and 2.8%), after the administration of 10 micrograms/kg of dexmedetomidine (a dose that has been shown to reduce anesthetic requirements in dogs by greater than 90%) and finally after 0.3 micrograms/kg of the alpha 2-adrenergic antagonist idazoxan. Despite an increase in arterial pressure, dexmedetomidine caused a marked reduction (greater than 45%, P less than 0.05) in CBF when compared with all preceding concentrations of isoflurane. The administration of dexmedetomidine had no effect on the CMRo2. The electroencephalogram showed a loss of high-frequency activity in a pattern similar to that seen with 1.90% isoflurane. Administration of dexmedetomidine was associated with a 57% decrease in cardiac output (to 0.89 L/min). Administration of idazoxan (an alpha 2-adrenergic antagonist) resulted in an increase in cardiac output and a reversal of the electroencephalogram effects. This experiment indicates that 10 micrograms/kg of dexmedetomidine in isoflurane-anesthetized dogs is associated with a profound decrease in CBF and cardiac output in the face of an unaltered CMRo2. Despite the large reduction in the CBF/CMRo2 ratio, there was no evidence of global cerebral ischemia.     

Cerebral autoregulation during sevoflurane or isoflurane anesthesia: evaluation with transient hyperemic response]

We investigated dynamic cerebral autoregulation during N2O-O2/fentanyl anesthesia (baseline) plus 1.0 and 2.0 minimum alveolar anesthetic concentrations (MAC) of sevoflurane or isoflurane anesthesia in 14 patients undergoing non-neurosurgical operation. Cerebral blood flow velocity in the right middle cerebral artery (Vmca) was measured continuously using transcranial Doppler ultrasonography. At normocapnia, dynamic cerebral autoregulation was tested by transient hyperemic response (a response of Vmca after a brief compression of the ipsilateral common carotid artery). For quantitative comparisons, ratio of systolic Vmca before, to immediately after compression (THRR) was calculated. Values of THRR were 1.14 +/- 0.03 (mean +/- SD), 1.15 +/- 0.04, and 1.12 +/- 0.03 during baseline, 1.0, and 2.0 MAC sevoflurane anesthesia, respectively. THRR was not significantly different among the 3 conditions. In contrast, THRR values were 1.17 +/- 0.03, 1.07 +/- 0.02, and 1.01 +/- 0.01 during baseline, 1.0, and 2.0 MAC isoflurane anesthesia, respectively. THRR was significantly attenuated in a dose dependent manner during isoflurane anesthesia. These results indicate that dynamic cerebral autoregulation is preserved during 2.0 MAC sevoflurane anesthesia, but not during 1.0 MAC isoflurane anesthesia.     

Dilation by isoflurane of preconstricted, very small arterioles from human right atrium is mediated in part by K(+)-ATP channel opening

The adenosine triphosphate (ATP)-sensitive potassium channels (K(+)-ATP channels) are activated by decreases in intracellular ATP and help to match blood flow to tissue needs. Such metabolism-flow coupling occurs predominantly in the smallest arterioles measuring 50 microm or less in diameter. Previous studies demonstrated that isoflurane may activate the K(+)-ATP channels in larger arteries. We examined whether isoflurane also activates the channels in the smallest arterioles of approximately 50 microm. Microvessels of approximately 50 microm were dissected from right atrial appendages from patients undergoing coronary artery bypass surgery and were monitored in vitro for diameter changes by videomicroscopy. With or without preconstriction with the thromboxane analog U46619 1 microM, vessels were exposed to isoflurane 0%-3% either in the presence or absence of the K(+)-ATP channel blocker glibenclamide 1 microM. Without preconstriction, isoflurane neither dilated nor constricted the vessels significantly. After preconstriction, isoflurane had a concentration-dependent dilation of the small arterioles (39 +/- 13% [mean +/- SD] dilation at 3% isoflurane) (P < 0.001), and this effect was significantly attenuated by glibenclamide (18 +/- 5% dilation at 3% isoflurane) (P < 0.01). In comparison, nitroprusside 10(-4) M produced 79 +/- 6% dilation, and adenosine diphosphate 10(-4) M produced 29 +/- 7% dilation. We conclude that isoflurane-mediated dilation of the smallest resistance arterioles may be in part based on activation of the K(+)-ATP channels when the arterioles are relatively constricted. IMPLICATIONS: Vasodilation of very small coronary arterioles by isoflurane depends on preexisting tone and may in part be mediated by the K(+)-ATP channels.     

The comparative effects of prostaglandin E1 and nicardipine on cerebral microcirculation in rabbits

We compared the effects of the systemic hypotensive drugs prostaglandin E1 (PGE1) and nicardipine on the cerebral microcirculation and on the cerebrovascular reactivities to hypercapnia and hypoxia. In isoflurane-anesthetized rabbits (n = 48), we measured cerebral pial vessel diameters using a cranial-window preparation: (a) during IV PGE1- or nicardipine-induced mild or moderate hypotension (to 80% or 60% of initial mean arterial blood pressure), (b) after topical administration of these drugs, and (c) during hypercapnia or hypoxia induced during such mild or moderate hypotension. Pial arteriolar diameters were (a) unchanged when hypotension (mild or moderate) was induced by PGE1 but increased when it was induced by nicardipine and (b) increased dose-dependently by topical administration of nicardipine but not PGE1. Only small changes in cerebral venular diameter were observed in these experiments. The pial arteriolar dilator response to hypercapnia was potentiated during hypotension (mild or moderate) when it was induced by PGE1 but decreased when it was induced by nicardipine, whereas the response to hypoxia was maintained during PGE1-induced hypotension but decreased during nicardipine-induced hypotension. In conclusion, as a systemic hypotensive drug, PGE1 does not dilate cerebral arterioles and maintains cerebrovascular reactivities to hypercapnia and hypoxia, whereas nicardipine dilates such vessels and reduces these cerebrovascular reactivities. IMPLICATIONS: When given systemically to produce mild or moderate hypotension, prostaglandin E1 does not induce cerebral vasodilation and maintains cerebrovascular reactivity to hypercapnia and hypoxia, whereas nicardipine dilates cerebral vessels and reduces both reactivities.     

Potency and time course of mivacurium block during sevoflurane, isoflurane and intravenous anesthesia

PURPOSE: To determine the potency and time course of action of mivacurium neuromuscular block under routine clinical conditions during sevoflurane, isoflurane and intravenous anesthesia. METHOD: Patients were anesthetized with nitrous oxide 66% in oxygen and 1.5 MAC sevoflurane or isoflurane or a propofol infusion, neuromuscular block being monitored using mechanomyography. Potency was determined using administration of single doses of mivacurium of 40-100 micrograms.kg-1 and construction of dose-response curves (n = 72). The onset and duration of action were determined following a bolus dose of 0.2 mg.kg-1 of mivacurium (n = 30). RESULTS: The ED50 and ED95 (with 95% confidence limits) were estimated to be 42 (35-51) and 86 (74-98) micrograms.kg-1, 52 (45-60) and 89 (72-110) micrograms.kg-1, and 53 (45-62) and 95 (81-112) micrograms.kg-1 during sevoflurane, isoflurane and propofol anesthesia respectively (P < 0.05 between sevoflurane and propofol). Following administration of the 0.2 mg.kg-1 dose, neither the times (mean +/- SD) to maximum block (1.6 +/- 0.31, 1.7 +/- 0.21 and 1.6 +/- 0.45 min, respectively) nor the times to 25 and 90% recovery of T1 (20 +/- 4.5 and 33 +/- 8.8 min, 21 +/- 3.8 and 33 +/- 6.5 min, and 18 +/- 4.1 and 28 +/- 5.8 min respectively) were different among groups. The times to recovery of TOF ratio to 0.8 were 40 +/- 10.0, 36 +/- 8.5 and 29 +/- 5.5 min in the sevoflurane, isoflurane and propofol groups respectively (P = 0.017 between the sevoflurane and propofol groups). CONCLUSIONS: Under usual conditions of clinical anesthesia the potency of mivacurium was slightly enhanced during sevoflurane compared with intravenous anesthesia but the duration of action was only minimally prolonged during sevoflurane and isoflurane anesthesia.     

In Vivo Effects of Dexmedetomidine on Laser-Doppler Flow and Pial Arteriolar Diameter

Background: The alpha2 -adrenergic agonist dexmedetomidine alters global cerebral blood flow (CBF). However, few studies have investigated the action of dexmedetomidine on the cerebral microcirculation. This investigation examined the effects of dexmedetomidine on (1) regional CBF in the rat cerebral cortex using laser-Doppler flowmetry and (2) on pial arteriolar diameter.

Methods: Halothane-anesthetized rats were fitted with instruments to measure CBF as determined by laser-Doppler flow (CBFldf) or to measure pial arteriolar diameter by preparing a cranial hollow deepened until a translucent plate of skull remained, thereby maintaining the integrity of the cranial vault. In both groups, 20 micro gram/kg dexmedetomidine was infused intravenously. Thirty minutes later, the mean arterial pressure was restored to control values with an infusion of phenylephrine (0.5 to 5 micro gram/kg/min).

Results: Administration of dexmedetomidine was associated with decreases in end-tidal and arterial carbon dioxide. The CBFldf and pial arteriolar diameter were measured during normocapnia (controlled carbon dioxide) and during dexmedetomidine-induced hypocapnia. Intravenous administration of dexmedetomidine significantly decreased systemic arterial pressure concurrent with a decrease in CBFldf (22% in normocapnic animals, 36% in hypocapnic animals). Restoration of mean arterial pressure increased CBFldf in normocapnic but not in hypocapnic animals. Similarly, dexmedetomidine significantly reduced pial vessel diameter in both normocapnic (9%) and hypocapnic animals (17%). However, vessel diameters remained decreased in the normocapnic and hypocapnic animals after the mean arterial pressure was restored.     

Direct Effects of Ropivacaine and Bupivacaine on Spinal Pial Vessels in Canine: Assessment with Closed Spinal Window Technique

Background: Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique.

Methods: Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10 sup -8 -10 sup -3 M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol.

Results: Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR.     

Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries

Purpose

Hypocapnia causes cerebral arterial constriction, whereas volatile anaesthetics cause dilatation. The purpose of this study was to compare the direct effects of halothane, isoflurane and sevoflurane on hypocapniainduced constnction of isolated cerebral arteriesin vitro.

Methods

Basilar and middle cerebral arteries of mongrel dogs (n= 11) were cut into nngs and mounted for isometnc tension recording in organ baths containing Krebs’ bicarbonate solution, aerated with CO₂ 5% and O₂ 95% at 37°C. After constnction with 20 mM KCl, hypocapnia was induced by replacing the aerating gas with CO₂ 2.5% and O₂ 97.5% in the presence or absence of anaesthetics.

Results

Exposure of cerebroartenal rings to the hypocapnic gas produced sustained vasoconstnction (418 ± 19 mg), reaching a plateau within 10 to 15 min. Halothane (0.5, 1, 2 MAC) attenuated the hypocapnia-induced constnction (P< 0.05). In contrast, isoflurane and sevoflurane attenuated this constriction only at 2 MAC (P< 0.05). Attenuation by halothane was greater than that by isoflurane or sevoflurane at each concentration(P< 0.05). N^G-nitro-L-arginine (3 × 10^?5 M) did not alter the contractile response to hypocapnia. When a similar degree of constnction was induced by addition of 10 mM KCl, halothane (1 and 2 MAC) preferentially attenuated the constriction induced by hypocapnia to a greater extent than that induced by 10 mM KCl (P< 0.01)

Conclusion

Hypocapnia-induced vasoconstnction of isolated dog cerebral arteries precontracted with KCl is more susceptible to halothane than isoflurane or sevoflurane. This may account for the greater increase in cerebral blood flow dunng halothane than isoflurane or sevoflurane anaesthesia.     

Sevoflurane speeds recovery of baroreflex control of heart rate after minor surgical procedures compared with isoflurane.

Volatile anesthetics attenuate arterial baroreflex functions, whereas noxious stimuli may modify baroreflex-induced circulatory responses during anesthesia. We designed the present study to compare baroreflex control of heart rate during sevoflurane and isoflurane anesthesia in young healthy surgical patients. Baroreflex sensitivity was assessed in 24 patients randomized to receive either sevoflurane (n = 12) or isoflurane (n = 12) for general anesthesia. After an 8- to 10-h fast and no premedication, measurements of RR intervals obtained from electrocardiography and systolic blood pressure (SBP) measured through a radial artery catheter were made at conscious baseline (Awake), during end-tidal sevoflurane 2% or isoflurane 1.2% plus 67% nitrous oxide before incision (Anesth), during surgery at end-tidal sevoflurane 2% or isoflurane 1.2% plus 67% nitrous oxide (Surg), and 20 min after tracheal extubation (Recov). Baroreflex responses were triggered by bolus i.v. injections of phenylephrine (100-150 micrograms) and nitroprusside (100-150 micrograms) to increase and decrease SBP by 15-30 mm Hg, respectively. The linear portions of the baroreflex curves relating RR intervals and SBP were determined to obtain baroreflex sensitivities. Baroreflex sensitivities to both pressor and depressor tests were significantly depressed during Anesth and Surg periods compared with Awake values in both anesthetic techniques. The pressor test sensitivity during the Recov period returned to the Awake value after sevoflurane (12.9 +/- 3.7 vs 11.0 +/- 8.7 ms/mm Hg [mean +/- SD]) but was still depressed after isoflurane anesthesia (13.9 +/- 8.0 vs 4.8 +/- 3.2 ms/mm Hg; P < 0.05). The depressor test sensitivities during the Recov period remained depressed after both anesthetic techniques. We conclude that both sevoflurane and isoflurane depress arterial baroreflex function during anesthesia and surgery, but the pressor test sensitivity was restored more quickly after sevoflurane than after isoflurane anesthesia. Implications: Arterial baroreflex function is an important neural control system for maintaining cardiovascular stability. We found that baroreflex control of heart rate due to hypertensive perturbation returned to the preanesthetic level more quickly after sevoflurane than after isoflurane anesthesia.     

异氟醚、七氟醚吸入麻醉对鼠骨骼肌微循环白细胞活动的影响

目的 探讨异氟醚、七氟醚吸入麻醉对鼠骨骼肌微循环白细胞活动的影响。方法 选择SD雄性大鼠20只,随机分为两组,制备提睾肌微循环模型。吸入异氟醚、七氟醚麻醉后,分别记录吸入异氟醚、七氟醚1．5MAC3h内微循环、小动脉A1的直径和血流速度,微循环毛细血管后微静脉的白细胞滚动和粘附数量。结果 吸入异氟醚、七氟醚1．5MAC3h内HR,MAP,CVP和A1的直径和血流速度无明显改变（P＞0．05）。微循环毛细血管后微静脉的白细胞流动和粘附数量显著增加（P＜0．01）。结论 长时间吸入异氟醚、七氟醚后,可引起大鼠骨骼肌微循环毛细血管后微静脉的白细胞滚动和粘附数量显著增加。