Responses of the cerebral blood flow to hypo-and hypercapnia after inhibition of prostaglandin biosynthesis by indomethacin

Quantitative investigation of the local cerebral blood flow by the hydrogen clearance method and of the blood flow into the brain by means of an electromagnetic flowmeter showed that inhibition of prostaglandin biosynthesis by indomethacin inhibits the response of the cerebral vessels to hypercapnia, whereas the effects of hypocapnia are not only preserved but are actually enhanced. This difference in the response of the brain vessels to hypo- and hypercapnia during inhibition of prostaglandin biosynthesis suggests that effects of hyper- and hypocapnia are produced by different mechanisms. It is postulated that a decrease in the prostaglandin concentration reduces the sensitivity of the brain vessels to hypercapnia and increases their sensitivity to hypocapnia.Problem Laboratory for Pharmacology of the Cardiovascular System, Department of Pharmacology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 3, pp. 240–243, March, 1979.     

A model of cerebral blood flow control in hypercapnia

A mathematical model of cerebral blood flow control to increases inP _aCO₂ is developed. The controlled system of the model (the brain) is composed of three well-mixed lumped parameter compartments: blood, cerebral extracellular fluid (ECF), and cerebral intracellular fluid (ICF). The conservation of mass equations are written for three chemical species: molecular carbon dioxide, bicarbonate ion, and hydrogen ion in each compartment, yielding nine first-order nonlinear differential equations. For the controller, cerebral blood flow is assumed a function of the chemical species in the compartments; in particular the hypotheses that blood flow is a function of interstitial fluid pH, or a function of interstitial fluid carbon dioxide tension operating through a proportional controller are investigated in detail. The parameters for these controllers were obtained from data in the physiologic literature as well as experiments performed as part of this study. This model is the first attempt to describe the transient behavior of the cerebral circulatory system to acid base disturbances. When the predictions of the model are compared with experimental data it is found that the model predicts a cerebral blood flow change to hypercapnia consistently slower than that found experimentally. This suggests that the cerebral circulatory response to CO₂ inhalation is not exclusively a function of ECF or CO₂ and that therefore other controls and/or mechanisms play a role as well.     

The effect of tolbutamide on cerebral blood flow during hypoxia and hypercapnia in the anaesthetized rat

The increase in blood flow in the cerebral cortex of the anaesthetized rat during hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured using the hydrogen clearance method with acutely implanted platinum electrodes. Hypoxia (PaO₂ 35.3±2.4 Torr) and hypercapnia (PaCO₂ 68.1±5.1 Torr) increased basal CBF from 76.3±9.0 ml/100g/min to 168.1±20.1 ml/100g/min and 162.4±31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia. However, it attenuated the increase of CBF during hypoxia by 66 ±11% (P<0.01). This suggests that opening of tolbutamide-sensitive potassium channels may be involved in the process of hypoxic vasodilation in the rat cerebral cortex.     

Effect of indomethacin on cerebral blood flow and development of oxygen convulsions

Hyperbaric oxygenation modulates cerebral blood flow affecting the development of oxygen convulsions. Before hyperbaric oxygenation-induced convulsions in rats the initial decrease in blood flow gave place to hyperemia, Po₂ increased. In rats receiving cyclooxygenase inhibitor indomethacin no convulsions were observed, blood flow and Po₂ were lower than in controls. Our results indicate that indomethacin prevents hyperemia and alleviates oxygen convulsions under conditions of hyperbaric oxygenation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 31–33, July, 2006     

Local cerebral blood flow velocity in newborn rats in normocapnia and hypercapnia

The local cerebral blood flow (LCBF) in the caudate nucleus was investigated in experiments on unanesthetized newborn rats by determing the rate of hydrogen saturation of the brain tissue and the cerebral blood volume was studied by plethysmography. LCBF in newborn animals was found to be considerably lower than in adults. Inhalation of CO₂ by newborn, unlike by adult rats, did not cause an increase in LCBF and the cerebral blood volume also remained unchanged.Laboratory of Brain Development, Scientific-Research Institute of Pediatrics, Academy of Medical Sciences of the USSR. (Presented by Academician M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 8, pp. 139–141, August, 1977.     

Effects of sensory modality on cerebral blood flow velocity during vigilance

Transcranial Doppler sonography was used to measure cerebral blood flow velocity (hemovelocity, CBFV) from the left and right middle cerebral arteries during the performance of 40-min auditory and visual vigilance tasks. Reductions in stimulus duration were the critical signals for detection in both tasks, which were equated for stimulus salience and discrimination difficulty. Signal detection responses (correct detections and false alarms) and CBFV declined significantly over time in a linear manner for both modalities. In addition, the overall level of CBFV and the temporal decline in this measure were greater in the right than the left cerebral hemisphere. The results are consistent with the view that a right hemispheric system is involved in the functional control of vigilance and that this system operates in a similar manner in the auditory and visual channels.     

Sympathetic effects on cerebral and ocular blood flow in rabbits pretreated with indomethacin

The effects of unilateral stimulation of the cervical sympathetic chain on cerebral and ocular blood flow was investigated in 8 rabbits anesthetized with pentobarbital sodium and pretreated with indomethacin in order to inhibit the formation of prostaglandins. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta. Evans blue was given as a tracer for protein leakage during hypertension. Sympathetic stimulation had no significant effect on the blood flow in the brain under the two conditions studied. In the uvea marked effects of sympathetic stimulation were obtained at normotension as well as at hypertension. There were no indications of breakdown of the blood-brain barrier or the blood-aqueous barrier. Thus, there was no evidence for any prostaglandin-mediated inhibition of sympathetic effects in the brain or the eye.     

The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia

The cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO,) in the rat during normocapnia and hypercapnia were investigated by means of the intraarterial ¹³³Xenon injection technique; measurements were performed during normocapnia and hypercapnia and the effect of propranolol upon CBF and CMRO₂ was studied. The CBF technique applied to rat yield reliable results even in high flow situations. A steady state period of only 10–15 s is all that is necessary to obtain the initial slope of the ¹³³Xenon clearance curve from which CBF is calculated and measurements may be repeated within minutes. Hypercapnia caused an increase in CMRO₂ of 35% which confirms the findings of other investigators. The beta-adrenergic receptor blocker propranolol (2 rag per kg i.v.) prevented this increase and could eliminate an increase in CMRO₂ already induced; this indicates that CO₂ affects adrenergic mechanisms. Although propranolol eliminated the CMRO₂ response to hypercapnia, it only reduced the CBF response; this dissociation of CBF and CMRO₂ response occurred probably because the beta-receptor blockage only eliminated a CBF increase mediated through an increased CMRO₂ (cellular response) whereas a direct CO₂ effect upon the arterioles (vascular response) persisted.     

The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia.

The cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) in the rat during normocapnia and hypercapnia were investigated by means of the intraarterial 133Xenon injection technique; measurements were performed during normocapnia and hypercapnia and the effect of propranolol upon CBF and CMRO2 was studied. The CBF technique applied to rat yield reliable results even in high flow situations. A steady state period of only 10--15 s is all that is necessary to obtain the initial slope of the 133Xenon clearance curve from which CBF is calculated and measurements may be repeated within minutes. Hypercapnia caused an increase in CMRO2 of 35% which confirms the findings of other investigators. The beta-adrenergic receptor blocker propranolol (2 mg per kg i.v.) prevented this increase and could eliminate an increase in CMRO2 already induced; this indicates that CO2 affects adrenergic mechanisms. Although propranolol eliminated the CMRO2 response to hypercapnia, it only reduced the CBF response; this dissociation of CBF and CMRO2 response occurred probably because the beta-receptor blockage only eliminated a CBF increase mediated through an increased CMRO2 (cellular response) whereas a direct CO2 effect upon the arterioles (vascular response) persisted.     

Effects of indomethacin on regional blood flow in conscious rabbits--a microsphere study.

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 +/- 0.17 g . min-1 . g-1 from a level of 1.64 +/- 0.24 g . min-1g-1. In jejunum the corresponding figures were 0.44 +/- 0.12 and 1.26 +/- 0.17 and in the brain 0.29 +/- 0.10 and 1.24 +/- 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 +/- 0.02 g . min-1 . g-1 from a level of 0.13 +/- 0.02 g . min-1 . g-1. In the retina there was a reduction in blood flow by 2.75 +/- 1.03 mg . min-1 from a starting level of 15.1 +/- 2.3 mg . min-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina--tissues which are likely to be rather active under such conditions.     

Phrenic blood flow in hypoxia and hypercapnia

Laboratory of Pathophysiology of Respiration and Bioengineering Laboratory, Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow. (Presented by Academician of the Russian Academy of Medical Sciences A. G. Chuchalin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 12, pp. 580–583, December, 1992.     

Effect of cerebrocrast on local cerebral blood flow and EGG in cats after brain hemorrhage

Laboratory of Pharmacology of the Cerebral Circulation, Research Institute, of Pharmacology, Tomsk Scienctific Center, Academy of Medicial Sciences of Russia. Institute of Organic Synthesis, Academy of Sciences of Latvia, Riga. (Presented by Academician of the Russian Academy of Medical Sciences E. D. Gol'dberg.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 7, pp 49–52, July, 1992.     

Effects of sympathetic stimulation on cerebral and ocular blood flow Modification by hypertension,hypercapnia, acetazolamide,PGI2 and papaverine

The effect of unilateral, electrical stimulatio of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI₂ was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI₂. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12 % blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI₂-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.     

The effect of hypercapnia on myocardial blood flow and metabolism

1. In closed-chest dogs anaesthetized with trichlorethylene, the inhalation of carbon dioxide sufficient to increase the arterial P(CO2) from 40 to about 100 mm Hg, increased myocardial blood flow (measured using a (133)Xe clearance technique) and right atrial pressure. There were no consistent changes in mean arterial blood pressure, heart rate or cardiac output.2. The effect of hypercapnia on myocardial blood flow was not influenced by the previous administration of atropine and propranolol or of bretylium. It can be concluded, therefore, that the elevated arterial P(CO2) has a direct vasodilator effect on the myocardial microcirculation.3. During hypercapnia the coronary sinus P(O2) was increased and the coronary arteriovenous oxygen content difference, and calculated myocardial oxygen consumption, reduced. It is suggested that this latter effect may be the result of myocardial depression produced by the decrease in arterial blood pH.4. There was no evidence of myocardial glucose uptake either before or during hypercapnia. The myocardial extraction of lactate and pyruvate at rest varied between 0 and 55%. During acute hypercapnia the extraction of lactate usually fell.5. When the arterial P(CO2) was maintained at 100 mm Hg for a period of 1 hr the effects on myocardial blood flow and on oxygen consumption were not sustained.6. Stepwise increments and decrements in arterial P(CO2) of 10-20 mm Hg produced corresponding increases and decreases in myocardial blood flow and demonstrated that changes in arterial P(CO2) of 20-30 mm Hg can markedly affect blood flow in the myocardium.