Decrease In Cerebral Vascular Resistance Research Articles

Maternal cerebral blood flow during normal pregnancy: a cross-sectional study

Pregnancy is associated with substantial changes in the maternal circulatory physiology. Our aim was to investigate maternal cerebral blood flow (CBF) during normal pregnancies. We prospectively measured maternal CBF in 210 low-risk pregnant women at different gestational ages, and in 15 nonpregnant women. CBF was assessed by measuring blood flow volume in the internal carotid artery (ICA) by dual-beam angle-independent digital Doppler ultrasound. ICA blood flow volume increased during pregnancy from 318 mL/min ± 40.6 mL/min in the first trimester to 382.1 mL/min ± 50.0 mL/min during the third trimester, corresponding to CBF values of 44.4 and 51.8 mL/min(-1)/100 g(-1), respectively (P < .0001). CBF changes were associated with progressive decrease in cerebral vascular resistance and moderate increase in ICA diameter. Maternal CBF is gradually increasing during normal pregnancy. Vasorelaxing impact of estrogens and other factors on cerebral vessels may explain the changes in CBF during pregnancy.

Cerebral blood flow is increased during controlled ovarian stimulation

Estrogen appears to enhance cerebral blood flow (CBF). An association between CBF and physiologically altered hormonal levels due to menstrual cycle, menopause, or exogenous manipulations such as ovariectomy or hormone replacement therapy has been demonstrated. The purpose of this study was to determine the association between ovarian stimulation and CBF in vivo by measuring blood flow in the internal carotid artery (ICA) after pituitary suppression and during controlled ovarian stimulation in women undergoing in vitro fertilization treatment cycles. ICA volume flows were measured by angle-independent dual-beam ultrasound Doppler in 12 women undergoing controlled ovarian stimulation. Measurements were performed after pituitary/ovarian suppression, in the late follicular phase, and at midluteal phase. Blood flow in the ICA increased by 22.2% and 32% in the late follicular and midluteal phases compared with the respective values obtained during ovarian suppression (P < 0.0005 and P < 0.0001, respectively). There was a significant correlation between increments in estrogen levels and increments in CBF when the late follicular phase was compared with the ovarian suppression period (r = 0.8, P < 0.001). Mean blood flow velocity significantly increased (by 15.7% and 16.9%, respectively) and cerebral vascular resistance significantly decreased (by 17.6% and 26.5%) during the late follicular and midluteal phases compared with respective measures during ovarian suppression. There was a significant correlation between an increase in estrogen levels and a decrease in cerebral vascular resistance when the late follicular phase was compared with the ovarian suppression period (r = -0.6, P < 0.05). These changes imply sex hormone-associated intracranial vasodilation leading to increased CBF during controlled ovarian stimulation.

The heart–brain interaction in the fetus: Cerebrovascular blood flow in the developing human

Fetal blood flow is influenced by multiple factors, including the structure of the heart and the impedance of the distal vascular beds. Many babies with congenital heart disease have restricted intrauterine growth, neurologic abnormalities, and poor neurodevelopmental outcome, independent of surgical intervention. The circulatory alterations that accompany specific anatomic cardiac defects may lead to predictable blood flow disturbances that affect normal brain development. Doppler measurements of vascular resistance in the cerebral circulation and calculations of resistance ratios that quantitate fetal blood flow distribution are altered in growth retarded fetuses and are predictive of growth retardation and poor perinatal outcome in high risk pregnancies. Fetuses with normal hearts but compromised placental perfusion have a compensatory redistribution of blood flow that is believed to enhance cerebral perfusion. This phenomenon, termed “brain sparing”, is due to a decrease in cerebral vascular resistance, which is likely initiated and controlled by an autoregulatory mechanism. Failure of this mechanism to adequately compensate for cerebral hypoxemia in fetuses with congenital heart disease may result in the disproportionate intrauterine growth and neurodevelopmental abnormalities that occur in many of these infants. Investigators have only begun to study whether “brain sparing” occurs in fetuses with congenital heart disease and to determine if alterations in cerebral perfusion impact on fetal neurodevelopment and postnatal neurologic outcome for these high-risk infants.

Commentary

The effects of lysergide, ephedrine, and nimergoline on the metabolizing ability (demethylation and acetylation of aminopyrine and glucuronoconjugation of oxazepam) of the dog brain isolated in situ were tested. The intracarotid perfusion with lysergide did not induce significant variations in aminopyrine and oxazepam metabolism, while the perfusion with ephedrine or nimergoline significantly increased the disappearance of the tested substances from the extracorporeal circuit, with an increase of some metabolic products. Activation of the tested biotransformation was accomplished by a decrease in cerebral vascular resistance and an increase in oxygen consumption. The action of lysergide, ephedrine, and nimergoline on the depression of the cerebral activity by hypoxia in dogs also was studied. Only ephedrine and nimergoline significantly improved the partial spontaneous reversion of the electroencephalogram depression, accomplished by a recovery of some enzymes (glutamic oxalacetic transaminase, lactate dehydrogenase, and alkaline phosphatase) in the cerebrospinal fluid, which was altered by the condition of hypoxia.

Modificações da hemodinâmica fetal pelo estímulo sonoro: avaliação pela dopplervelocimetria colorida

Objetivos: verificar se ocorrem ou não alterações hemodinâmicas na aréria cerebral média (ACM) aferido pela dopplervelocimetria colorida após realização de um estímulo sonoro. Métodos: trinta fetos de gestantes consideradas clinicamente normais com idade gestacional igual ou superior a 28 semanas foram submetidos a um estímulo sonoro. Examinamos as alterações da velocidade sangüínea na ACM fetal por meio do índice de resistência e da freqüência cardíaca fetal, pelo doppler colorido, antes e depois do estímulo acústico. Resultados: a média da freqüência cardíaca fetal (FCF) antes do estímulo sonoro foi de 142,41 batimentos por minuto (bpm) com desvio padrão de 9,01 e faixa de variação de 122 a 162 bpm. Após o estímulo sonoro, a média da FCF foi de 159,44 bpm com desvio padrão de 15,49, com faixa de variação de 130 a 187 bpm (p<0,01). A média dos valores do índice de resistência (IR) da ACM fetal antes do experimento foi de 75,89% variando entre 64 e 91%. Após o estímulo acústico, a média dos valores do IR foi de 66,93% variando entre 47 e 83% (p < 0,01). Conclusões: observamos que o estímulo sonoro provoca a conhecida elevação imediata e significativa da FCF e a diminuição da resistência vascular cerebral, quando avaliada pelo índice de resistência na artéria cerebral média fetal.

Contribution of hypercapnia and trigeminal stimulation to cerebrovascular dilation during simulated diving.

We investigated the relative contribution of humoral (carbon dioxide) and neural (trigeminal stimulation) inputs in the cerebrovasodilatory response to simulated diving in the rat. The cerebral hemodynamic profile of rats was determined using the brain blood flow tracer N-[14C]isopropyl-p-iodoamphetamine. During a simulated dive response, cerebral vascular resistance (CVR) decreased 63.1%, resulting in a 1.5-fold increase in cerebral blood flow (CBF). To investigate the contribution of hypercapnia to the decrease in CVR during simulated diving, we measured CBF during simulated diving in rats with preexisting hypocapnia. To investigate the contribution of trigeminal input, we measured CBF during periods of trigeminal stimulation alone with continued ventilation. Preexisting hypocapnia abolished the cerebrovasodilatory response to simulated diving. Trigeminal stimulation alone did not produce a significant increase in CBF from control values in any brain region, suggesting that trigeminal input does not contribute to the cerebrovascular response to simulated diving in rats. These results suggest that the cerebrovasodilatory response observed during diving in small mammals is driven primarily by progressive hypercapnia associated with asphyxia.

The cerebral and systemic effects of movement in response to a noxious stimulus in lightly anesthetized dogs. Possible modulation of cerebral function by muscle afferents.

Afferentation theory predicts that agents or maneuvers that stimulate muscle stretch receptors (i.e., muscle afferents) will produce cerebral stimulation. From this theory it follows that, regardless of the source (e.g., drug effect, active muscle movement), increases in stretch receptor activity should result in a similar effect on the brain. The present study tested the hypothesis that active muscle movement in lightly anesthetized subjects would result in cerebral stimulation. Studies were conducted in six dogs who were lightly anesthetized with halothane (0.70% end-expired). The following physiologic variables were quantified before and for 6 min after the initiation of a standardized (1-min duration) noxious stimulus to the trachea and the skin overlying the hind limb: cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), cerebral perfusion pressure, cerebral vascular resistance, electroencephalogram activity, electromyogram activity, arterial carbon dioxide partial pressure (PaCO2), central venous pressure, and serum epinephrine and norepinephrine concentrations. Response to stimulation was evaluated initially in unparalyzed dogs and later was evaluated in the same dogs after they were paralyzed with intravenous pancuronium (0.2 mg/kg). In unparalyzed dogs, stimulation produced episodes of coughing plus head and limb movement during the 6-min study period. Accompanying the movement was activation of the electromyogram, an increase in electroencephalogram frequency, and a reduction in electroencephalogram amplitude. There also was a 35% increase in cerebral blood flow, a 25% decrease in cerebral vascular resistance, and a 7% increase in CMRO2 versus the baseline values for each variable. There were no significant increases in either cerebral perfusion pressure, central venous pressure, PaCO2, or serum norepinephrine concentration to account for the cerebral effects; however, serum epinephrine concentrations increased by 61%. In pancuronium-paralyzed dogs, noxious stimulation resulted in a 5% increase in cerebral blood flow, a 7% decrease in cerebral vascular resistance, and an 5% increase in CMRO2 versus baseline levels. Electroencephalogram frequency was increased, but amplitude was unchanged. Central venous pressure, electromyogram activity, and serum norepinephrine concentration were unaffected. The serum epinephrine response was similar to that observed when the dogs were not paralyzed. These data support the hypothesis that active muscle movement in lightly anesthetized subjects has an effect on the brain that is mediated in part by muscle afferent receptors. This cerebral response was manifested as electroencephalogram activation, cerebral vasodilation unrelated to central venous pressure changes, and an increase in cerebral blood flow greater than that required to meet metabolic demands. Paralysis with pancuronium abolished movement induced by stimulation (and, thus, the muscle afferent response) and also attenuated the cerebral blood flow, cerebral vascular resistance, and electroencephalogram responses.

Extracellular potassium activity and cerebral blood flow during moderate hypoglycemia in anesthetized dogs.

Moderate hypoglycemia (MH) may be associated with blunting of cerebral hypocapnic vasoconstriction. Coincident with this change, electroencephalogram (EEG) flattening occurs. Previous reports show that brain extracellular potassium activity ([K+]o) increases in association with the onset of isoelectricity during severe hypoglycemia and that K+ increases cause pial vessel vasodilation. Using a model of MH, we tested the hypothesis that increases in [K+]o (approximately 15 mM) correlate with blunting of cerebral hypocapnic vasoconstriction. Cerebral blood flow (CBF), [K+]o, and EEG were measured during normocapnia [arterial Pco2 (Paco2) = 35 Torr)] and hypocapnia (PaCO2 = 15 Torr) in MH (< 2 mM) and normoglycemic dogs. During MH, increases in [K+]o occurred in association with EEG flattening (from 4.2 +/- 0.5 to 13.8 +/- 3.8 mM). During normoglycemia and MH without [K+]o elevations, hypocapnic vasoconstriction occurred. [K+]o elevations with MH were associated with increased CBF and decreased vascular resistance (146 +/- 5 and 42 +/- 2% of control, respectively) during normocapnia, and blunting of cerebral hypocapnic vasoconstriction (93 +/- 16% normocapnic control) when [K+]o increased during hypocapnia. This study shows that increases in [K+]o during MH are necessary for both normocapnic increases in CBF and blunting of cerebral hypocapnic vasoconstriction. Increases in [K+]o may represent a mechanism for decreases in cerebral vascular resistance during MH.

Fetal Doppler velocimetry in the internal carotid and umbilical artery during Braxton Hicks' contractions

Using Doppler ultrasound, previous studies revealed a considerable increase in vascular resistance in the uteroplacental circulation during Braxton Hicks' contractions. Consequently, uteroplacental blood flow is reduced and this affects placental oxygen transfer to the fetus, causing a fall in fetal arterial PO 2. In view of the important role of arterial PO 2. In the regulation of cerebral blood flow in the fetus, we hypothesised that Braxton Hicks' contractions cause a decrease in cerebral vascular resistance. A study was undertaken in 16 healthy near term pregnancies, using pulsed-wave Doppler ultrasound to evaluate the influence of Braxton Hicks' contractions on cerebral vascular resistance of the fetus. Flow velocity waveforms (FVWs) were recorded of the fetal internal carotid and umbilical artery and the Pulsatility Index (PI) was calculated. During Braxton Hicks' contractions the PI in the recorded vessels did not change. Fetal heart rate showed also no changes during Braxton Hicks' contractions. These findings indicate that resistance to blood flow downstream of these arteries, is not significantly altered, suggesting that Braxton Hicks' contractions have little or no effect on fetal haemodynamics and on fetal oxygenation in the healthy near term fetus.

Cerebral Hemodynamics During Spinal Cord Stimulation

An increase of cerebral blood flow (CBF) during spinal cord stimulation (SCS) has been shown in man using the 133Xenon inhalation technique. We report the effects of SCS on cerebral hemodynamics studied with transcranial Doppler sonography (TCD). Twenty-six patients with epidural electrodes implanted at the cervical level (11 patients) and at the thoracic level (15 patients) were investigated with recordings of CBF velocity in the middle cerebral arteries before and during SCS. Sixty-three and two-thirds percent of patients with cervical stimulation and 29.4% of patients with thoracic stimulation showed a decrease of cerebral vascular resistance simultaneously with an increase of the velocity of CBF.

The Cerebral Functional, Metabolic, and Hemodynamic Effects of Desflurane in Dogs

The effects of 0.5-2.0 MAC (3.6-15%) desflurane on cerebral function, metabolism, and hemodynamics and on systemic metabolism and hemodynamics were examined in dogs. Desflurane produced a significant dose-related decrease in cerebral vascular resistance from 1.53 +/- 0.21 mmHg.ml-1.min.100 g at 0.5 MAC to 0.50 +/- 0.03 mmHg.ml-1.min.100 g at 2.0 MAC desflurane. This was accompanied by an increase in cerebral blood flow (CBF) from 61 +/- 7 ml.min-1.100 g-1 at 0.5 MAC to 78 +/- 3 ml.min-1.100 g-1 at 1.5 MAC desflurane. At 2.0 MAC desflurane CBF was 52 +/- 2 ml.min-1.100 g-1 but was associated with a decrease in mean arterial pressure (MAP) to 43 +/- 2 mmHg. When MAP was increased to 73 +/- 3 mmHg with phenylephrine, CBF increased to 87 +/- 3 ml.min-1.100 g-1 at this concentration. At 0.5 MAC desflurane, intracranial pressure (ICP) was 15 +/- 5 mmHg, higher than normal, but did not change significantly with increasing concentrations of desflurane. Increasing concentrations of desflurane initially produced on the EEG the common pattern sequence of increasing depth of anesthesia with decreasing frequency and increasing amplitude progressing to burst suppression and then at 2.0 MAC desflurane to regular attenuation with interruption by periodic polyspiking, a pattern similar to that seen with isoflurane. At both 1.5 and 2.0 MAC the EEG pattern initially observed at that concentration changed to one with faster background activity with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of calcium antagonists, felodipine and nicardipine, on cerebral circulation in dogs.

The effects of a calcium antagonist of the dihydropyridine type, felodipine, on the cerebral circulation were studied in comparison with those of nicardipine in pancuronium-bromide immobilized unanesthetized dogs. Felodipine (0.3-10 micrograms/kg, i.v.) and nicardipine (0.3-10 micrograms/kg, i.v.) produced a dose-related decrease in mean blood pressure with almost equal potencies. However, at a dose of 3 micrograms/kg, felodipine produced a more prominent increase in cerebral blood flow (CBF) than nicardipine. Decreases in cerebral vascular resistance were significantly greater in the felodipine group at doses of 0.3 and 3 micrograms/kg, when compared with the nicardipine group. Cerebral oxygen consumption calculated by multiplying the arterio-venous difference of oxygen content by CBF was increased by these two drugs, but the changes were minimal. These data suggest that the increase in CBF produced by felodipine and nicardipine was primarily due to the direct dilatation of the cerebral blood vessels.

Effects of Calcium Antagonists, Feiodipine and Nicardipine, on Cerebral Circulation in Dogs

AbstractThe effects of a calcium antagonist of the dihydropyridine type, feiodipine, on the cerebral circulation were studied in comparison with those of nicardipine in pancuronium-bromide immobilized unanesthetized dogs. Feiodipine (0.3–10 μg/kg, i.v.) and nicardipine (0.3-10 μg/kg, i.v.) produced a dose-related decrease in mean blood pressure with almost equal potencies. However, at a dose of 3 μg/kg, feiodipine produced a more prominent increase in cerebral blood flow (CBF) than nicardipine. Decreases in cerebral vascular resistance were significantly greater in the feiodipine group at doses of 0.3 and 3 μg/kg, when compared with the nicardipine group. Cerebral oxygen consumption calculated by multiplying the arte rio-venous difference of oxygen content by CBF was increased by these two drugs, but the changes were minimal. These data suggest that the increase in CBF produced by feiodipine and nicardipine was primarily due to the direct dilatation of the cerebral blood vessels.

Flumazenil Reversal of Midazolam in Dogs

Large doses of flumazenil, given rapidly (over 5-10 s), are reported to elevate cerebral blood flow (CBF) and intracranial pressure to supranormal values when given to dogs receiving midazolam. This study examined the cerebral effects of giving smaller, graduated doses of flumazenil (0.0025, 0.01, 0.04, and 0.16 mg/kg), slowly (over 60 s), to dogs receiving midazolam and to dogs not receiving midazolam both when cerebrospinal fluid (CSF) pressure was normal and when CSF pressure was elevated (intracranial balloon) to about 30 mm Hg. In dogs with normal CSF pressure that were receiving midazolam, the effects of flumazenil were as follows: (a) low doses of flumazenil caused reversal of the reduction in cerebral metabolic rate for oxygen (CMRO2) and activity of the electroencephalogram produced by midazolam, (b) moderate doses of flumazenil produced a decrease of cerebral vascular resistance, and an increase of CBF and CSF pressure that did not significantly change cerebral perfusion pressure (CPP), and (c) the highest dose of flumazenil increased CBF to supranormal values. All of these flumazenil effects "peaked" at 3-6 min, with values returning to pre-flumazenil levels by 15-30 min. Flumazenil caused no such changes in dogs with elevated CSF pressure that were receiving midazolam or in dogs that were not receiving midazolam. The results are consistent with a specific, doserelated benzodiazepineantagonist action of flumazenil. Lack of flumazenil effect at elevated CSF pressure may reflect reversible changes in cerebral structure, metabolism, or benzodiazepine receptors produced by the intracranial balloon and elevation of CSF pressure. The doses of flumazenil used here to reverse the cerebral effects of midazolam appear unlikely to produce adverse effects because increase of CMRO2 was matched by increase of CBF, the mean increase of CSF pressure was modest (+9 +/- 3 mm Hg, mean +/- SEM), and CPP was unchanged.

Cerebral blood flow and interstitial fluid adenosine during hemorrhagic hypotension

This study was designed to assess the role of adenosine in autoregulation of cerebral blood flow (CBF) with the use of the brain dialysis technique to sample cerebral interstitial fluid (ISF) and hydrogen clearance to measure local CBF in ketamine-anesthetized rats. In group 1 (n = 11), animals were hemorrhaged to reduce mean arterial blood pressure (MABP) from control levels (MABP = 101.1 +/- 2.6) to 80, 70, 60, 50, 40, and 30 mmHg. Cerebral autoregulation was evidenced by no significant decrease in CBF until MABP decreased to 60 mmHg. However, dialysate adenosine concentration did not increase until MABP decreased to 50 mmHg. In group 2 (bilateral dialysis; n = 11), in which the left carotid artery was ligated before reductions in MABP, left-side dialysate adenosine concentration increased at a MABP of 70 mmHg. In group 3 (bilateral dialysis; n = 6), one dialysis probe was perfused with artificial cerebrospinal fluid containing 10(-3) M 8(p-sulfophenyl)theophylline (8-SPT), an adenosine receptor antagonist, during reduction of MABP to 50 mmHg. Although there were similar reductions in CBF with or without adenosine receptor blockade, dialysate adenosine concentration was greater on the side of locally infused 8-SPT at a MABP of 50 mmHg. These data suggest that adenosine is not responsible for cerebral autoregulation at blood pressures greater than 50 mmHg but may contribute to the decrease in cerebral vascular resistance observed at arterial pressures below the autoregulatory range.

The effect of acutely raised ICP on cerebral microcirculation (author's transl)

Occurrence of no-reflow phenomenon (NRP) has been repeatedly reported in various experimental models of cerebral ischemia. These models were, however, those of cessation of arterial blood supply to the brain by obliteration of arteries. Since cerebral blood flow (CBF) is lowered by raised intracranial pressure (ICP), occurrence of NRP in such an experimental model is also conceivable. In the present study, the mode of occurrence of NRP was investigated in a raised ICP model in dogs. After immobilization by intravenous infusion of Galamine, artificial ventilation was continued to maintain the normal level of arterial blood gases. Pressure of 200 mmHg was applied to the cisterna magna for 15 min by infusion of warmed saline. CBF was monitored by a double-needle type thermocouple. The cisterna magna pressure, arterial blood pressure, EEG and cerebral impedance according to the method of Mori et al. were continuously recorded on a polygraph. Three hours after cisternal infusion, the brain was perfused with carbon black solution (Pelikan biological ink) via the thoracic aorta of a pressure of 120 mmHg. Prior to sacrifice, 50 ml of 5 % Evans blue was injected intravenously. Specimens for electron microscopy were taken by core-biopsy in a few dogs of each experimental groups. The dogs were divided into three groups. Group I: (5 dogs) Only cisternal infusion was carried out. Group II : (16 dogs) The systemic arterial pressure was lowered to 60-80 mmHg by administration of Arfonad during cisternal infusion. Post-ischemic (PI) arterial pressure was brought up to the normal level by administration of Angiotensin II and Norepenephrine as quickly as possible. Group iII : (5 dogs) Immediately after cisternal infusion combined with arterial hypotension as in group 1 1, cerebral perfusion was carried out. In group I, very rapid and pronounced appearance of reactive hyperemia (RH) was noted, indicating decrease of cerebral vascular resistance (CVR). EEG activity recovered almost completely and the result of cerebral perfusion was also normal. In the group II, however, the appearance of RH was slower and less pronounced than in group I (group II-A, 10 dogs), or entirely absent (group II-B, 6 dogs). Since PI cerebral perfusion pressure was kept in almost the same range in all the groups, this marked reduction of CBF in group II was ascribed to increase of CVR, i.e., presence of NRP. Occurrence of NRP was further confirmed in group f, in which cerebral perfusion carried out immediately after cisternal infusion revealed extensive non-filling of parenchymal capillary networks. As seen in the courses of CBF and cerebral impedance, NRP was transient in group II-A and persistent in group II-B. Recovery of CBF and appearance of RH always preceded the normalization of cerebral impedance and recovery of CBF. Presence of cerebral edema was confirmed in group II-B by macroscopic and electron-microscopic observations.There was also leakage of Evans blue in the cerebral parenchyma. Although this cerebral edema apparently seems due to the result of persistence of NRP, further investigations are required to clarify their causal relationship.

Influence of adenosine and lowered cerebral blood flow on the cerebrovascular efefct of theophylline

The responses of brain vessels to theophylline infused intra-arterially was evaluated. The experiments were performed on isolated canine brains perfused by donor dogs. Thus secondary effects due to theophyline were eliminated. Arterial pO 2, pCO 2, pH and brain temperature were kept constant. Cerebral vascular resistance (CVR) was calculated from total venous outflow and cerebral perfusion pressure. A 2 mg doses of theophylline per brain was given at normal cerebral perfusion pressure (about 81 mm Hg), at lowered perfusion pressure (about 37 mm Hg), and during and adenosine infusion lasting 10 min (10 −7 mol/min). At normal pressure theophylline showed a significant 15% decrease of CVR, but at lowered perfusion pressure a significant 19% increase occured. During infusion of adenosine, which decreased CVR by 23%, theophylline again increased CVR by 20% thus demonstrating an edonosine-theophylline antagonism. From our results, it is suggested that adenosine could be involved in the vasodilatation of cerebral vessels in the hypoxic brain.

Action of Lysergide, Ephedrine, and Nimergoline on Brain Metabolizing Activity

The effects of lysergide, ephedrine, and nimergoline on the metabolizing ability (demethylation and acetylation of aminopyrine and glucuronoconjugation of oxazepam) of the dog brain isolated in situ were tested. The intracarotid perfusion with lysergide did not induce significant variations in aminopyrine and oxazepam metabolism, while the perfusion with ephedrine or nimergoline significantly increased the disappearance of the tested substances from the extracorporeal circuit, with an increase of some metabolic products. Activation of the tested biotransformation was accomplished by a decrease in cerebral vascular resistance and an increase in oxygen consumption. The action of lysergide, ephedrine, and nimergoline on the depression of the cerebral activity by hypoxia in dogs also was studied. Only ephedrine and nimergoline significantly improved the partial spontaneous reversion of the electroencephalogram depression, accomplished by a recovery of some enzymes (glutamic oxalacetic transaminase, lactate dehydrogenase, and alkaline phosphatase) in the cerebrospinal fluid, which was altered by the condition of hypoxia.

The effects of a new drug (Hexobendine) on cerebral hemodynamics and oxygen consumption

A new drug, hexobendine, when injected intravenously, produced an increase in cerebral blood flow (CBF) of approximately 15% accompanied by a decrease in cerebral vascular resistance (CVR) which persisted for 35 min. The effective intravenous dosage was 1.5 mg/kg, and following intraduodenal injection, 4 mg/kg were comparatively effective. The mean arterial blood pressure (MABP) was decreased. There was a small but significant increase in the cerebral metabolic rate for oxygen (CMRO 2) for the first 5 min following injection of the drug. It is believed that the drug may have a direct effect on cerebral metabolism just as reports from other laboratories suggest that the drug increases myocardial metabolism. The CBF was also increased following the intraduodenal administration of hexobendine; this began 20 min after the drug was given and persisted for 70 min in some animals. Hexobendine appears to be a potent and long-lasting cerebral vasodilator drug when administered either intravenously or orally.

Effects of ergot alkaloids (Hydergine) on cerebral hemodynamics and oxygen consumption in monkeys

The cerebral venous outflow of monkeys (baboons) was monitored by means of electromagnetic flow probes before, during, and after the intravenous injection of Hydergine. Cerebral blood flow (CBF), cerebral vascular resistance (CVR), arteriovenous oxygen differences, cerebral oxygen consumption (CMRO 2), arterial blood pressure (MABP), end-tidal CO 2, and the EEG were also monitored. Hydergine in doses of 0.06 mg/kg body weight produced statistically-significant but short-lasting increases in CBF and CMRO 2 accompanied by decreases in CVR and MABP. There were no changes in the EEG.