Hiroto Ohata

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. Conclusion The vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane appears to be mediated, at least in part, via activation of adenosine triphosphate‐sensitive K+ channels.

Intravenous dexmedetomidine inhibits cerebrovascular dilation induced by isoflurane and sevoflurane in dogs.

UNLABELLED Our aim in this study, performed using a closed cranial window preparation, was to investigate the effect of systemic pretreatment with dexmedetomidine on cerebrovascular response to isoflurane or sevoflurane. After instrumentation under pentobarbital anesthesia, 48 dogs were assigned to one of two groups: the isoflurane group or the sevoflurane group (n = 24 each). Twenty-four dogs received saline (n = 6) or one of three different doses of dexmedetomidine (0.5, 1.0, or 2.0 micrograms/kg) (n = 6 each) i.v. Animals were then exposed to three different minimum alveolar anesthetic concentrations (MACs; 0.5, 1.0, and 1.5) of either isoflurane or sevoflurane. Cerebrovascular diameters were measured at each stage. Pretreatment with dexmedetomidine decreased pial vessel diameters. Both isoflurane and sevoflurane significantly dilated both arterioles and venules in a concentration-dependent manner. Isoflurane- and sevoflurane-induced dilation of cerebral arterioles was significantly attenuated in the presence of dexmedetomidine. The dexmedetomidine-induced attenuation of the vascular responses was not dependent on the dose of dexmedetomidine and was not different between isoflurane and sevoflurane. The vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane could be attenuated by the systemic administration of dexmedetomidine, and this interaction between dexmedetomidine and volatile anesthetics showed no evidence of dose-dependency. IMPLICATIONS The systemic administration of dexmedetomidine attenuates the dilation of cerebral vessels induced by isoflurane and sevoflurane in pentobarbital-anesthetized dogs. This interaction was not dependent on the clinical (0.5-2.0 micrograms/kg) dose of dexmedetomidine and was not different between isoflurane and sevoflurane anesthesia.

Direct effects of α1- and α2-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). Conclusion Dexmedetomidine and clonidine constricted spinal vessels in a concentration-dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.

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 vasocon- striction 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 (≥100 &mgr;m) and small (<100 &mgr;m) 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.

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 CO2 reactivity of the cerebral arterioles. Neither topical nor systemic ketamine dilated pial arterioles in either basal-anesthesia group. CO2 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.

Clonidine premedication modifies responses to adrenoceptor agonists and baroreflex sensitivity

PurposeTo evaluate the effects of clonidine on responses to adrenoceptor agonists and baroreflex sensitivity, we examined arterial blood pressure (AP) responses to phenylephrine and heart rate (HR) responses to isoproterenol and baroreflex sensitivity (HR response to AP changes due to phenylephrine or nitroglycerin).MethodsWe studied 60 anaesthetized patients who either did or did not receive 5 μg·kg−1 clonidinepo before they were anaesthetized. After induction of general anaesthesia, the patients received 3 gmg·kg−1 phenylephrine, 0.02 μg·kg−1 isoproterenol, or 2–3 μg·kg−1 nitroglycerin, and haemodynamic measurements were taken. Baroreflex sensitivity was expressed as the slope of the linear regression line (msec·mmHg−1; in msec of R-R interval change vs mmHg change in systolic arterial pressure) following the administration of phenylephrine and nitroglycerin.ResultsPatients who received clonidine had greater augmented responses in AP to phenylephrine and in HR to isoproterenol (47.2 ± 15.6% vs 23.7 ± 11.9% for increase in systolic AP and 59.8 ± 22.6% vs 26.2 ± 11.0% for increase in HR,P < 0.05 respectively). There were no differences between the baroreflex sensitivities in the pressor (phenylephrine) test groups (3.77 ± 1.08 vs 4.41 ± 1.66 msec·mmHg−1). In contrast, the slopes of depressor (nitroglycerin) test groups were decreased in patients receiving clonidine (1.98 ± 0.73 vs 3.68 ± 1.72 msec mmHg−1,P < 0.05).ConclusionThe results suggest that premedication with clonidine might enhance critical hypotension during anaesthesia and surgery, but restoration both of AP and HR decrease can be achieved effectively by phenylephrine and isoproterenoliv, respectively.RésuméObjectifAfin d’évaluer les effets de la clonidine sur les réponses des récepteurs adrénergiques agonistes et sur la sensibilité baroréflexe, nous avons enregistré les changements de tension artérielle (TA) liés à la phényléphrine, les modifications de fréquence cardiaque (FC) liées à l’isoprotérénol et la sensibilité baroréflexe (les réactions de la FC aux changements de TA liées à la phényléphrine ou à la nitroglycérine).MéthodeNous avons étudié 60 patients qui avaient reçu ou non 5 μg·kg−1 de clonidinepo avant l’anesthésie. Après l’induction de l’anesthésie générale, les patients ont reçu 3 μg·kg−1 de phényléphrine, 0,02 μg·kg−1 d’isoprotérénol ou 2–3 μg·kg−1 de nitroglycérine, et on a procédé aux mesures hémodynamiques. La sensibilité baroréflexe était exprimée par la pente du tracé de régression linéaire (msec·mmHg−1; en msec de changement dans l’intervalle R-R vs en mmHg de changement dans la tension artérielle systolique) à la suite de l’administration de phényléphrine et de nitroglycérine.RésultatsLes patients qui ont reçu de la clonidine ont présenté des augmentations plus importantes de TA, en réaction à la phényléphrine, et de FC, en réaction à l’isoprotérénol (47,2 ± 15,6 % vs 23,7 ± 11,9 % concernant l’augmentation de la TA systolique et 59,8 ± 22,6 % vs 26,2 ± 11,0% concernant l’augmentation de FC,P < 0,05 respectivement). Il n’y a pas eu de différence de sensibilité baroréflexe entre les groupes testés pour les réactions au médicament stimulant, phényléphrine, (3,77 ± 1,08 vs 4,41 ± 1,66 msec·mmHg−1). En comparaison, les pentes des groupes du test hypotenseur (nitroglycérine) s’abaissaient chez les patients ayant reçu de la clonidine (1,98 ± 0,73 vs 3,68 ± 1,72 msec·mmHg−1,P < 0,05).ConclusionLes résultats laissent voir que la prémédication avec de la clonidine a pu favoriser une hypotension critique pendant l’anesthésie et la chirurgie, mais que le rétablissement de TA et de FC plus basses pouvait être réalisé efficacement avec de la phényléphrine et de l’isoprotérénoliv, respectivement.

Ketamine, Not Propofol, Attenuates Cerebrovascular Response to Carbon Dioxide in Humans With Isoflurane Anesthesia

STUDY OBJECTIVES To investigate the effects of ketamine and propofol on the cerebrovascular response to carbon dioxide (CO(2)) in humans during isoflurane anesthesia. DESIGN Randomized clinical investigation. SETTINGS University hospital of a medical school. PATIENTS 30 ASA physical status I and II adult, elective surgical patients. INTERVENTIONS AND MEASUREMENTS With each patient given air/oxygen/isoflurane anesthesia, the flow velocity in the middle cerebral artery (Vmca) and pulsatility index were measured using the transcranial Doppler method under hypocapnic [arterial CO(2)tension (PaCO(2)) 28-32 mmHg], normocapnic (PaCO(2) 38-42 mmHg), and hypercapnic conditions (PaCO(2) 48-52 mmHg). PaCO(2) was altered by supplementing the inspired gas with CO(2) without changing the respiratory conditions. Patients were then randomly assigned to receive either ketamine 1 mg. kg(-1) or propofol (2 mg. kg(-1)followed by an infusion of 6-10 mg. kg(-1). hr(-1)) (n = 15 for each drug), and the measurements were repeated. MAIN RESULTS Ketamine reduced both absolute and relative cerebrovascular reactivity to CO(2) significantly [2.9 +/- 0.8 (control) vs. 2.6 +/- 1.0 (ketamine) cm. sec(-1). mmHg(-1): p < 0.05; and 3.5 +/- 0.7 (control) vs. 2.8 +/- 0.9 (ketamine) %. mmHg(-1): p < 0.01, respectively]. However, ketamine did not reduce Vmca during hypercapnic conditions (117 +/- 29 cm. sec(-1)) compared with controls (120 +/- 28 cm. sec(-1)). Although propofol decreased Vmca during all conditions, it did not cause any change in either absolute or relative CO(2) reactivity [2.5 +/- 0.8 (control) vs. 2.5 +/- 1.0 (propofol) cm. sec(-1). mmHg(-1), and 3.3 +/- 1.3 (control) vs. 4.1 +/- 1.0 (propofol) %. mmHg(-1), respectively]. CONCLUSIONS In humans given isoflurane anesthesia, a) ketamine reduced cerebrovascular response to CO(2), but cerebral blood flow (CBF) during hypercapnic conditions was comparable with controls, and b) although propofol decreases CBF, it maintains the cerebrovascular response to CO(2).

Changes in calcitonin gene‐related peptide, atrial natriuretic peptide and brain natriuretic peptide in patients undergoing coronary artery bypass grafting

Summary The initiation of cardiopulmonary bypass creates significant derangements in cardiovascular volume status and both endocrine and autonomic nervous system function. To examine whether such derangements might differ in patients with different pre‐operative physical status scores, we measured the plasma concentrations of calcitonin gene‐related peptide, atrial natriuretic peptide and brain natriuretic peptide, catecholamines and antidiuretic hormone, as well as haemodynamic variables, during and after cardiopulmonary bypass in 27 consecutive patients undergoing coronary artery bypass grafting. The pre‐operative levels of atrial natriuretic peptide and brain natriuretic peptide differed significantly between ASA II patients and III and IV patients [mean (SD) brain natriuretic peptide levels = 14 (8.2) vs. 129 (51) pg.ml−1]. Plasma calcitonin gene‐related peptide increased significantly in both groups after the initiation of cardiopulmonary bypass, and remained increased throughout cardiopulmonary bypass. The changes in plasma epinephrine, norepinephrine and antidiuretic hormone were similar to those reported previously. The changes in plasma calcitonin gene‐related peptide, atrial natriuretic peptide and brain natriuretic peptide did not correlate with any changes in haemodynamic variables before or after cardiopulmonary bypass. Measurement of plasma brain natriuretic peptide might usefully be included in the pre‐operative evaluation of patients with cardiac disease.

Pulmonary Arterial and Right Ventricular Responses to Prophylactic Albumin Administration Before Aortic Unclamping During Abdominal Aortic Aneurysmectomy

During abdominal aortic aneurysmectomy (AAAectomy) and before aortic unclamping (XU), we studied the effects of albumin administration on pulmonary arterial and right ventricular responses in 39 anesthetized patients using a modified thermodilution technique.Group 1 patients (n = 18) were given no extra IV fluids. Group 2 patients (n = 21) were given additional albumin administration (5% albumin at 10 mL/kg) before XU. After XU, mean arterial blood pressure (MAP) decreased significantly in each group, and MAP and stroke volume index (SVI) were not significantly higher in Group 2 than in Group 1. At 5 min after XU, the patients in Group 2 had a higher mean pulmonary arterial pressure and pulmonary vascular resistance index and a lower right ventricular ejection fraction than those in Group 1 (P < 0.05), but their SVIs were well maintained. These results indicate that albumin administration before XU may not always prevent post-XU hypotension. It caused a significant increase in right ventricular afterload and a significant dilation of the right ventricular cavity; however, right ventricular function was almost equally maintained in both groups. However, because SVI did not increase in some patients (Group 2) with the increase in right ventricular end-diastolic volume index after XU, albumin administration should be performed carefully before XU during AAAectomy. Implications: We studied the effects of albumin administration before aortic unclamping on pulmonary arterial and right ventricular responses during abdominal aortic aneurysmectomy using a modified thermodilution technique. Albumin administration before aortic unclamping may not always prevent hypotension, and it may cause a higher pulmonary arterial pressure than in patients without albumin administration. (Anesth Analg 1998;87:1020-6)

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

PurposeOur purpose was to examine the effect of dexmedetomidine, when used with phenylephrine during cardiopulmonary resuscitation (CPR), on the cerebral and systemic circulations.MethodsIn 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).ResultsIn 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.ConclusionAlthough 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.