Biomedical subjects

E Pinard

Publications and source records attributed to E Pinard.

At least 37 records · Page 2Linked to original sources

PubMed1993

Rapid measurement of regional cerebral blood flow in the baboon using 15O-labelled water and dynamic positron emission tomography.

The sensitivity and reproducibility of rapid measurements of regional cerebral flow (rCBF) using a bolus injection of H2 15O and dynamic positron emission tomography (PET) were investigated in anaesthetised baboons. The cerebrovascular reactivity to changes in arterial pCO2 was used as an experimental support. PET data were acquired over 4 min following a single bolus intravenous injection of H2 15O, while arterial blood was withdrawn for continuous activity counting. Images were reconstructed with a dynamic sequence of 45 x 2s + 15 x 10s, including a correction for decay. Regional values of CBF were derived from non-linear least-squares fits of the time activity curves using a four-parameter two-compartment model. The results obtained with a four-parameter fitting method were compared with those obtained with two other rapid estimation methods, first fitting two parameters only, CBF and partition coefficient (p), and secondly autoradiography (with p fixed at 0.95 ml brain ml blood-1). Twelve regions of interest were analysed. The values for the basal CBF obtained from 13 measurements in two baboons were close to published values obtained with other techniques. Reproducibility checks showed a mean variation of 9.7 per cent. The CBF measurements performed in hypercapnic conditions gave results similar to published data in other animal species, showing a 4.5 +/- 0.9 per cent increase in CBF per mm Hg paCO2. The results obtained with the three estimation techniques were closely correlated. The dynamic bolus H2 15O method appeared to be suitable for high blood flow measurements.

Animals↗

PubMed1992

Insulin protects brain tissue against focal ischemia in rats.

The influence of insulin on the infarct volume due to middle cerebral artery (MCA) occlusion was investigated in rats. A small dose of insulin (1 unit/kg) was injected i.p. just after MCA occlusion. The infarct areas were measured by planimetry from brains perfused with 2,3,5-triphenyltetrazolium-chloride (TTC) 48 h after the occlusion. Systemic variables were measured before and at various times after ischemia. The comparison between insulin-treated (n = 14) and control (n = 13) rats provided evidence that insulin significantly reduced the infarct volume due to MCA occlusion. As insulin minimally and transiently decreased blood glucose, the present results suggest that insulin exerts a beneficial effect directly on the central nervous system.

Anesthesia↗

PubMed1992

The acute effects of MK-801 on cerebral blood flow and tissue partial pressures of oxygen and carbon dioxide in conscious and alpha-chloralose anaesthetized rats.

The dynamic effects of the non-competitive N-methyl-D-aspartate receptor antagonist, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine] , on cerebral blood flow and tissue partial pressures of oxygen and carbon dioxide were investigated in the striatal and occipital regions of conscious and anaesthetized rats by mass spectrometry. MK-801 (0.5 and 5 mg/kg, i.p.) induced a large increase in the blood flow of both cerebral regions of conscious rats, without significant changes in local tissue partial pressures of oxygen and carbon dioxide. The increase in cerebral blood flow was maximal within 30 min after injection. Its amplitude was independent of the dose of MK-801, but cerebral blood flow remained elevated for up to 4 h after 5 mg/kg MK-801, while it progressively decreased towards its basal level in rats given 0.5 mg/kg MK-801. The amplitude and time-course of the vascular changes were similar in the two cerebral regions studied. The difference in the changes in tissue partial pressure of oxygen induced by MK-801 and by a 6% CO2 inhalation suggests that the MK-801-induced rise in cerebral blood flow in conscious rats is, at least partly, due to an increase in oxidative metabolism. In contrast, MK-801 induced either no changes or decreases in cerebral blood flow in alpha-chloralose-anaesthetized rats. The present results should be taken into account not only to determine the mechanisms by which N-methyl-D-aspartate receptor antagonists may exert their neuroprotective effects but also to further elucidate the sites of action of MK-801 in the central nervous system.

Anesthesia, General↗

PubMed1992

Differential cerebrovascular and metabolic responses in specific neural systems elicited from the centromedian-parafascicular complex.

The effect of electrical stimulation of the centromedian-parafascicular complex on local cerebral blood flow and local cerebral glucose utilization was investigated in anesthetized, paralysed and ventilated rats. Local cerebral blood flow and local cerebral glucose utilization were measured in separate groups of animals using the autoradiographic (14C)iodoantipyrine and (14C)2-deoxyglucose methods, respectively. Because of the well-established centromedian-parafascicular complex neuroanatomical connections, three functional neuronal systems were analysed and compared: the extrapyramidal motor system the limbic system and the reticular formation, also known as the ascending activating system. Cortical regions not included in the limbic system were considered separately. The validity of comparisons between changes in local cerebral blood flow and local cerebral glucose utilization across the brain was verified by assessing the reactivity and stability of the cortical blood flow during long-term centromedian-parafascicular complex stimulation. Centromedian-parafascicular complex stimulation elicited a marked but heterogeneous increase in local cerebral blood flow in 50 of the 52 cerebral structures measured. The most pronounced increases were seen in the lateral habenular nucleus (331 +/- 30% of control), the zona incerta (400 +/- 55%), the mesencephalic reticular formation (415 +/- 122%) and the parietal cortex (211 +/- 35%). In contrast, local cerebral glucose utilization remained statistically unchanged (P greater than 0.05) in 28 of these 50 individual brain regions during centromedian-parafascicular complex stimulation. The most pronounced increases in local cerebral glucose utilization were seen in the zona incerta (123 +/- 28%) and the mesencephalic reticular formation (193 +/- 26%). Local cerebral blood flow and local cerebral glucose utilization were linearly related in unstimulated controls, considering either all brain regions taken as a whole or the three systems separately. The significant increase in the slopes of the regression line between local cerebral blood flow and local cerebral glucose utilization for the reticular formation and the limbic system during centromedian-parafascicular complex stimulation indicates, however, that the coupling mechanisms for these systems, but not for the extrapyramidal motor system, were reset. The local cerebral blood flow to local cerebral glucose utilization ratio was heterogeneous in controls and differentially increased during centromedian-parafascicular complex stimulation, being markedly pronounced in the parietal cortex and in the reticular formation. We conclude that these results, for the first time, provide evidence that, the functionally well-defined neural networks may have different mechanisms whereby changes in vascular and metabolic demands are regulated.

Anesthesia↗

PubMed1992

Effect of MK-801 on focal brain infarction in normotensive and hypertensive rats.

The effects of the noncompetitive N-methyl-D-aspartate antagonist MK-801 on infarct size and systemic variables after middle cerebral artery occlusion in spontaneously hypertensive and Fischer-344 rats were investigated. Two doses (0.5 and 5 mg/kg) administered before the induction of ischemia were studied. MK-801 significantly reduced the neocortical volume of infarction (by about 32% at both doses) in Fischer-344 rats and had no neuroprotective effects in the striatum. In contrast, MK-801 had no significant influence on either cortical or striatal infarcted volume in spontaneously hypertensive rats. The reduction or lack of MK-801-induced neuroprotection in spontaneously hypertensive rats, as compared with Fischer-344 rats, could be attributed to a reduced collateral supply in the marginal area due to difference in the morphology of the pial anastomoses and/or in the effects of ischemia and treatment on arterial pressure. The results may have major clinical implications since a great proportion of human strokes are associated with hypertension.

Animals↗

PubMed1991

Focal cerebral ischemia in chronic hypertension: no protection by (R)-phenylisopropyladenosine.

The effects of the adenosine agonist, (R)-phenylisopropyladenosine on focal cerebral ischemia induced by middle cerebral artery occlusion were investigated in spontaneously hypertensive rats. The drug was given 30 min before occlusion and each hour thereafter for 6 h. The neurological status of the rats was estimated 2, 24 and 48 h after occlusion. Infarct volumes were measured 48 h after occlusion (Cresyl violet-stained sections). (R)-Phenylisopropyladenosine did not significantly reduce infarct size, nor did it modify the neurological score. As there is considerable evidence of the neuroprotective effects of adenosine in normotensive rats, the present results may be due to a more abrupt reduction in cerebral blood flow in the territory surrounding the ischemic core, where neuroprotection could be expected, in the spontaneously hypertensive rat strain. Consequently, neuroprotection may be more difficult when focal cerebral ischemia is associated with hypertension.

Animals↗

PubMed1991

Reduction of infarct volume by magnesium after middle cerebral artery occlusion in rats.

The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection.

Animals↗

PubMed1991

[Link between cerebral blood flow and brain metabolism: validity and limits].

A century ago, Roy and Sherrington suggested that there was a direct relationship between cerebral metabolism and brain blood flow. While this concept is now generally accepted, it is still the subject of considerable debate. There is undoubtedly a link between local metabolism and local blood flow, but the mechanisms involved remain unknown. Several factors, such as H+, K+, CO2, lactate, and recently adenosine, have been suggested as chemical modulators adapting the blood flow in the tissue to local metabolic demand. The demonstration of a functional innervation of the pial and intracerebral blood vessels has led to the hypothesis of autonomic and central nervous regulation of cerebral blood flow (CBF). Most neurotransmitters and neuromodulators, appear to be implicated in this regulatory mechanism. The endothelial cells also play a part in vasomotor effects, as they can produce relaxing (EDRF) and constricting (EDCF) factors in response to a variety of stimuli. Thus it is now no longer possible to consider metabolism as the only factor regulating cerebral blood flow; nervous, endothelial, myogenic and humoral factors must also be included.

Blood Flow Velocity↗

PubMed1990

Effect of chronic cervical sympathectomy on local cerebral blood flow during limbic seizures in rat.

The vascular changes in the hippocampus and neocortex during kainic acid-induced seizures were investigated in control rats and in rats with chronic, bilateral, cervical sympathectomy. Seizures were induced in unanesthetized, spontaneously breathing rats. The increase in blood flow in the hippocampus of the sympathectomized rats was significantly reduced during the motor seizures, while the reduction in the neocortex was only significant when the increased blood flow was maximal.

Animals↗

PubMed1990

Kynurenate does not reduce infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats.

The effects of the excitatory amino acid receptor antagonist, kynurenate, were investigated in spontaneously hypertensive rats after middle cerebral artery occlusion. Kynurenate did not significantly modify either the infarct volume, measured 48 h after occlusion, or the neurological score. The absence of a neuroprotective effect of kynurenate in this study, which contrasts with results in normotensive rats, is suggested to be due to impaired collateral circulation in spontaneously hypertensive rats.

Animals↗

PubMed1990

Theophylline reduces cerebral hyperaemia and enhances brain damage induced by seizures.

Hippocampal and neocortical blood flows and tissue pO2 were investigated by mass spectrometry in unanaesthetized spontaneously breathing rats during kainic acid-induced seizures to determine whether adenosine is involved in the coupling of cerebral blood flow to metabolism during enhanced metabolic demand. The possible involvement of adenosine in the neuronal damage induced by seizures was also analyzed. The intrinsic effects of theophylline and the duration of the adenosine receptor blockade by this xanthine were first tested in 8 rats. Two groups of rats were then compared: one (n = 6) received kainic acid, and the other (n = 10) theophylline 15 min prior to kainic acid administration. An additional group of 10 rats was taken for classical histology 48 h after kainic acid treatment. Theophylline significantly reduced the hyperaemia observed during seizures, prevented any tissue hyperoxia and enhanced brain damage. This strongly suggests that adenosine is partly responsible for the increase in cerebral blood flow during kainic acid-induced seizures and has neuroprotective properties.

Adenosine↗

PubMed1989

Role of adenosine in cerebral hypoxic hyperemia in the unanesthetized rabbit.

The present study was undertaken to determine the importance of adenosine in the cerebrovascular response to hypoxia. The mass spectrometry method was used to investigate local blood flow, tissue pO2 and pCO2 in 3 cerebral structures: caudate nucleus (n = 8), thalamus (n = 5) and hippocampus (n = 5) in unanesthetized, spontaneously breathing rabbits. After having tested the reproducibility of the hypoxic response each animal was exposed twice to moderate hypoxia. I.v. theophylline (10 mg/kg) was administered between the first and second exposures to hypoxia. The principal finding is that in each cerebral region, the vasodilatation induced by hypoxia was significantly decreased by pretreatment with theophylline despite the low theophylline dose used. It is concluded that adenosine is partly responsible for the cerebral vasodilatation observed during hypoxia. Several other mechanisms possibly involved in this cerebrovascular response are discussed.

Adenosine↗

PubMed1988

Dynamic cerebral and systemic circulatory effects of adenosine, theophylline and dipyridamole.

The effects of intravenous adenosine, dipyridamole and theophylline on local cerebral blood flow were studied in conscious rabbits. Long-term quantitative blood flow measurements were performed in 5 cerebral structures together with tissue pO2 and pCO2 measurements by a mass spectrometry technique. In an additional study, the time course of the cerebrovascular changes was determined by thermal clearance. It was found that: firstly, adenosine failed to modify local blood flow except in the caudate nucleus; secondly, dipyridamole increased cerebral blood flow in all 5 structures under study, and lastly, theophylline decreased cerebral blood flow in the same 5 structures. The increase in caudate blood flow induced by adenosine was instantaneous and lasted only for the duration of the infusion, whereas the cerebrovascular changes induced by dipyridamole and theophylline were gradual and persisted after their administration. Theophylline blocked the systemic and cerebrovascular changes caused by adenosine alone and by dipyridamole alone. In anesthetized rabbits, the intracarotid infusion of adenosine showed that the caudate reaction only occurred in the ipsilateral hemisphere. Taken together, our findings suggest that the transport system for adenosine in cerebral vessels is not only species-dependent but also structure-dependent. Furthermore, perivascular adenosine helps to maintain resting cerebrovascular tone and finally, cerebral adenosine may be involved in the control of cerebral blood flow via specific adenosine receptors.

Adenosine↗

PubMed1988

Effect of stimulation of the sphenopalatine ganglion on cortical blood flow in the rat.

The effects of electrical stimulation of the sphenopalatine ganglion on cortical blood flow and gas partial pressures (PO2 and PCO2) were studied in the anesthetized rat. Tissue PO2, PCO2, and local CBF were measured simultaneously in both parietal cortices by means of mass spectrometry. Stimulation of the sphenopalatine ganglion increased CBF and tissue PO2 by approximately 50 and 20%, respectively, in the ipsilateral parietal cortex. Smaller but significant increases in CBF and tissue PO2 were simultaneously seen in the contralateral parietal cortex. These variations were also accompanied by small decreases in PCO2 in both parietal cortices and a 5% increase in mean arterial pressure, whereas cortical electrical activity did not change. We conclude that the cholinergic (and vasoactive intestinal polypeptidergic) innervation of the cerebral blood vessels, arising from the sphenopalatine ganglion has significant vasomotor potential and that this system may be of functional importance.

Acetylcholine↗

PubMed1987

Systemically administered adenosine increases caudate blood flow in rabbits.

Adenosine has been proposed to be a chemical link between cerebral metabolism and blood flow. In the present study, we investigated whether the intravenous or intracarotid administration of adenosine could influence regional cerebral blood flow in anesthetized rabbits. The study was performed with the [14C]ethanol tissue sampling technique which enables quantitative, instantaneous, multiregional blood flow measurements. With either mode of adenosine administration, no change in cerebral blood flow was observed, except in the caudate nucleus in which a significant vasodilation took place. These data indicate that, in rabbits exogenous adenosine increases blood flow in highly specific brain areas, by mechanisms that are discussed.

Adenosine↗

PubMed1987

Continuous determination of the cerebrovascular changes induced by bicuculline and kainic acid in unanaesthetized spontaneously breathing rats.

Cerebral blood flow was sequentially determined (every 2-3 min) with helium clearance in two "vulnerable" structures: the hippocampus and the frontoparietal cortex during bicuculline (n = 11) and kainic acid (n = 9)-induced seizures in unanaesthetized, spontaneously breathing rats. Tissue partial pressures of oxygen and carbon dioxide were continuously and simultaneously evaluated in the same brain areas. All these variables were measured by mass spectrometry with a single gas sampling cannula previously implanted in each structure. The systemic variables, arterial blood pressure, arterial partial pressures of oxygen and carbon dioxide, pH, and bicarbonate concentration were also determined. Arterial and venous catheters were chronically implanted several days prior to the definitive experiments. Bicuculline induced short (about 15 min), recurrent, generalized seizures, with an abrupt rise in arterial blood pressure, an arterial metabolic acidosis and comparable blood flow increases (4-fold) in the hippocampus and the neocortex. A marked increase in tissue partial pressure of oxygen was always preceded by an increase in tissue partial pressure of carbon dioxide. After the seizures, in the 5 rats that survived, cerebral blood flow was significantly lowered; tissue partial pressure of oxygen and partial pressure of carbon dioxide also decreased, but to a lesser extent. Histological examination revealed two types of lesions: predominantly selective chromatolysis but also ischaemic cell change. Kainic acid first induced a decrease in arterial pressure and then hypertension during status epilepticus, with a return of arterial pressure towards basal levels during the recovery period (4 h after the injection). Respiratory alkalosis occurred throughout the experiment. Cerebral blood flow increased progressively to become maximal during status epilepticus. This vasodilatation was greater in the hippocampus (x 8) than in the neocortex (x 4). During recovery, cerebral blood flow tended to decrease but remained significantly elevated. In both structures, tissue partial pressure of oxygen was first lowered while tissue partial pressure of carbon dioxide was elevated; with the occurrence of the wet dog shakes, tissue partial pressure of O2 increased and tissue partial pressure of CO2 decreased. The changes in tissue gases were maximal during status epilepticus and tended to return to their basal levels thereafter, but no decrease in tissue partial pressure of O2 was observed, even 4 h after kainic acid administration. Histological analysis demonstrated ischaemic cell changes, particularly in the limbic system.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1986

Transmural gradient of tissue gas tensions in the canine left ventricular myocardium during coronary clamping and reactive hyperemia.

Mass spectrometry was used for the continuous, simultaneous and quantitative measurement of oxygen (PO2) and carbon dioxide (PCO2) partial pressures in the subendocardial and subepicardial layers of the left ventricle in 11 anaesthetized ventilated dogs. Under control conditions, PO2 was significantly lower in the subendocardium (13.5 +/- 4.5 mm Hg) than in the subepicardium (20.7 +/- 2.3 mm Hg), whereas PCO2 did not differ significantly (43 +/- 8.8 and 51 +/- 9.2 mm Hg respectively). These variables were not correlated with blood pressure or coronary blood flow. Subendocardial and subepicardial PO2 decreased less than 5 s after coronary occlusion. These changes were more rapid and severe in the subendocardium. After occlusion for 90 s: subendocardial PO2 was 4.1 +/- 6.3 mm Hg while subepicardial PO2 was 6.7 +/- 15.0 mm Hg (P less than 0.05). PCO2 reached peak values of 56 +/- 25 mm Hg subendocardial and 82 +/- 22 mm Hg subepicardial at 2.67 +/- 0.71 min and 3.43 +/- 0.93 min after coronary clamping. A reactive hyperemia occurred after coronary unclamping with different time courses and amplitudes for systolic and diastolic stroke flows while PO2 recovered with different kinetics. Subendocardial PO2 increased with a lower initial slope, probably in relation with the delay in the diastolic hyperemia. The observed delayed subendocardial hyperoxia, unrelated to the hyperemia, may indicate a delay in the recovery of normal work and metabolism in the inner layers of the myocardium.

Animals↗

PubMed1986

Two neural mechanisms in rat fastigial nucleus regulating systemic and cerebral circulation.

We have studied in anesthetized (alpha-chloralose) and paralyzed (d tubocurarine) rats the effects of electrical stimulation of the fastigial nucleus (FN) on local cerebral blood flow (lCBF) and its relationship to intracerebral PO2, and PCO2 and to the systemic arterial pressure (Pa). Mass spectrometry was used to measure quantitatively lCBF (repetitively) and cerebral PO2 and PCO2 (continuously). A systematic exploration of the FN for an increase in Pa and/or lCBF revealed that the most active sites for the rise in Pa were localized within the rostral FN, while those that elicited an increase in lCBF were found throughout the rostrocaudal extent of the FN. The increase in lCBF elicited from the caudal FN was not associated with changes in Pa. The increase in lCBF was concomitant with an increase in intracerebral PO2 and a slight decrease in PCO2. Although the increases in Pa and lCBF were dependent on stimulus frequency, their frequency-response curves were different. We conclude that 1) in contrast to the neurons or fibers of passage of the rostral FN, which mediate an increase in Pa, the neurons or fibers of passage that elicit changes in lCBF are localized along the rostrocaudal axis of the FN; 2) changes in the local gas partial pressures are not responsible for the vasodilation observed; and 3) the cerebral vasodilation and systemic vasoconstriction evoked by FN stimulation are probably mediated by two different neural mechanisms.

Animals↗