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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using flat-surface pH electrodes we continuously measured changes in the brain surface pH during respiratory arrest in anesthetized and paralyzed dogs which were previously ventilated with pure oxygen. Respiratory arrest was induced by halting the respirator. The mean arterial PO2 fell from 502.7 +/- 15.9 (1 SD) to 23.7 +/- 18.5, and the mean arterial PCO2 rose from 36.4 +/- 3.5 to 80.4 +/- 7.1 mm Hg, 10 min after asphyxia. The arterial blood pressure increased gradually over several minutes but fell relatively abruptly and profoundly at the end, due to circulatory failure. Initially, and as long as the arterial blood pressure and, therefore, cerebral blood flow were upheld (phase 1), changes in the brain surface pH were small (delta pH/delta t= -0.026 pH unit/min) in spite of severe hypercapnia. When cerebral perfusion pressure fell due to circulatory failure (phase 2), cerebral ischemia occurred and there was an abrupt fall in brain surface pH (delta pH/delta t= -0.067 pH unit/min). Changes in cisternal CSF [H+] grossly underestimated the magnitude of brain surface acidosis during the period of respiratory arrest; the initial difference between the mean brain surface fluid and cisternal CSF [H+] which was 8.9, rose to 15.1 and 47.4 nmol/L, respectively, 5 and 10 min after asphyxia. Changes in sagittal venous blood acid-base variables were more pronounced than those observed in the arterial blood or cisternal CSF; 5 min after respiratory arrest, arterial and sagittal venous blood and cisternal CSF and brain surface pH were 7.20, 7.09, 7.19 and 7.11, respectively. We conclude that (1) in the course of respiratory arrest cerebral outcome can potentially be determined by circulatory failure as evidenced by simultaneous changes in the arterial blood pressure and brain surface pH; (2) cisternal CSF acid-base changes lag behind those on the brain surface and CSF analyses provide unreliable information about the severity of brain acid-base changes during asphyxia; (3) changes in cerebral venous blood acid-base variables best represent the severity of metabolic aberrations in the brain during respiratory arrest.
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PMID:Changes in the brain surface pH and cisternal cerebrospinal fluid acid-base variables in respiratory arrest. 683 98

We sought to determine whether expression of the inducible, calcium-independent isoform of nitric oxide synthase (iNOS) contributes to the tissue damage produced by focal cerebral ischemia. The middle cerebral artery was occluded in halothane-anesthetized spontaneously hypertensive rats. Twenty-four hours later rats received intraperitoneal injections of the iNOS inhibitor aminoguanidine (100 mg/kg twice per day; n = 10) or of aminoguanidine + L-arginine (300 mg/kg four times per day; n = 7), aminoguanidine + D-arginine (n = 7), arginine alone (n = 6), or vehicle (n = 9). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after induction of ischemia. Administration of aminoguanidine reduced infarct volume by 33 +/- 4% (P < 0.05 from vehicle; analysis of variance and Tukey's test), a reduction that was antagonized by coadministration of L- but not D-arginine. Administration of L-arginine alone did not affect infarct size (P > 0.05 vs. vehicle). In separate rats (n = 10), aminoguanidine attenuated calcium-independent NOS activity in the infarct (P < 0.05 vs. vehicle) without affecting calcium-dependent activity (P > 0.05). Aminoguanidine did not affect resting cerebral blood flow or the cerebrovascular vasodilation elicited by hypercapnia, as determined by laser-Doppler flowmetry (n = 4). We conclude that aminoguanidine selectively inhibits iNOS activity in the area of infarction and reduces the volume of the infarct produced by middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. 753 Sep 27

During most intracranial procedures, the microscope is used to allow the surgeon to work on structures which are deeply located in the brain. Under these circumstances, brain retraction is required for adequate exposure. It was rapidly suspected and later confirmed that brain retraction causes secondary brain damage. This is due not only to direct effect of the retractor on the cortical surface, but also because a pressure is generated under the retractor, on the brain tissue, which compromises local cerebral blood flow and local cerebral perfusion pressure, thus causing cerebral ischaemia. The need for retraction is increased if the lesion is located deeply and/or if the brain is tensed; thus the risk to generate ischaemic conditions is enhanced. These secondary surgical lesions are promoted and worsened by associated systemic conditions such as hypotension, hypoxaemia, hypercapnia. As an attempt to respond to the problem generated by surgical retraction, the "chemical brain retractor" concept is proposed. By compulsively rendering the brain as relaxed and compliant as possible, the chemical brain retractor should allow the surgeon to operate on without the use of a surgical brain retractor and, if such a retractor is still needed, to reduce the pressure under it. These goals are achieved with an osmotic agent like mannitol to improve brain compliance, and intravenous anaesthetic agents, moderate hypocarbia and a normal or elevated blood pressure, to minimize cerebral blood volume. In conjunction with the chemical brain retractor, two other manoeuvres should be used to enhance cerebral compliance: CSF drainage and moderate head up position during the procedure.
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PMID:[Neuro-anesthetic contribution to the prevention of complications caused by mechanical cerebral retraction: concept of a chemical brain retractor]. 767 88

Among the techniques of cerebral protection, the use of controlled arterial hypertension is based on the following arguments: 1) Cerebral ischaemia is the final common pathway of any insult to the brain, particularly through secondary lesions. Causes of secondary cerebral lesions include pressure under the brain retractors, temporary clipping, arterial hypotension, hypoxaemia, anaemia and hypercapnia. 2) In the brain, the critical lower value for cerebral blood flow is around 25 mL.100g-1.min-1, under which two types of ischaemic areas can be defined: the penlucida type where cerebral function is abolished, without permanent cerebral lesion and the penumbra type where cerebral tissue recovers only if flow is rapidly restored. In the latter case the duration of ischaemia is very important. 3) Cerebral blood flow is maintained stable within a large range of variations of mean arterial pressure through the autoregulation mechanisms, which is based on vasomotricity of the cerebral circulation, which implies major variations in cerebral blood volume. However, autoregulation needs several dozens of seconds to be achieved. Therefore, sudden variations in mean arterial pressure are associated with short lasting but major variations in cerebral blood volume. 4) In case of increased intracranial pressure, a decrease in cerebral perfusion pressure causes cerebral vasodilation through the autoregulation mechanism, with an increase in cerebral blood volume which will, in turn, increase intracranial pressure and thus decrease cerebral perfusion pressure, and so on. This is the vasodilatory cascade. The therapeutical increase in mean arterial pressure will correct this phenomenon and decrease intracranial pressure. This is called the vasoconstrictive cascade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Controlled hypertension and cerebral protection]. 767 93

Maintenance of cerebral perfusion pressure is a prerequisite for the prevention of cerebral ischemia. Physiological fluctuations in systemic perfusion pressure are compensated by cerebrovascular autoregulation. Cerebral hypoperfusion could result from (1) systemic hemodynamic failure (eg, distal to severe arterial stenosis), overcharging the vasoregulatory capacity; (2) dysfunction and exhaustion of cerebrovascular autoregulation; or (3) both. Ultrasound offers an excellent temporal resolution, is noninvasive, and is easily applicable for follow-up investigations. Despite its poor spatial resolution, transcranial Doppler sonography has been used for determination of cerebral perfusion reserve studies measuring cerebral blood flow velocity (CBFV) during hypercapnia or application of vasoactive agents (eg, acetazolamide). This approach evaluates vasomotor regulation in patients with hemodynamic compromise distal to severe stenosis or occlusion of the brain supplying arteries. Monitoring CBFV during tilt table examinations directly measures cerebral autoregulation. In patients with systemic orthostatic hypotension, maintainance or failure of cerebrovascular compensation and, even more importantly, cerebrovascular dysautoregulation, despite normal systemic blood pressure regulation, may be demonstrated. Vasoneuronal coupling is reflected by CBFV variations during appropriate neuronal stimulation. Neuronal dysfunction is associated with CBFV abnormalities as exemplified by preconditions of focal cerebral dysfunction in the posterior cerebral artery (PCA) in migraineurs with aura, where massive alteration of vasoneuronal coupling and ischemia is threatening during spreading depression. A highly significant asymmetric gain of vasoneuronal coupling in the interictal state may act as a trigger mechanism in these patients. Testing for vasoneuronal coupling within the middle cerebral artery (MCA) territory is more difficult due to the poor spatial resolution with various neuronal stimuli (eg, motorsensory or cognitive paradigms), only eliciting local neuronal areas underrepresented in the MCA CBFV global changes. However, motor stimulation evoked CBFV may be used to indicate dysintegration of vasoneuronal coupling in the course of acute cerebral ischemia with sensorimotor hemiparesis and, moreover, seems to be of prognostic value regarding the motor deficit.
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PMID:Cerebrovascular regulation and vasoneuronal coupling. 769

Hypoglycemia increases the vulnerability of the perinatal brain to asphyxia, but it is not known if hypoglycemia-induced changes in cerebral hemodynamics and vascular reactivity underlie this vulnerability. This study tested the hypothesis that hypoglycemia exacerbates postischemic hypoperfusion, and impairs postischemic CO2 reactivity. The authors also examined the hypothesis that postischemic hypoperfusion is associated with a reduction in the interstitial concentration of the vasodilator metabolite adenosine. Global cerebral ischemia of 10 minutes duration was induced in newborn pigs anesthetized with isoflurane by occlusion of subclavian and brachiocephalic arteries; cortical cerebral blood flow (CBF) and interstitial adenosine concentration were evaluated simultaneously using the combined hydrogen clearance/microdialysis technique. Hypoglycemia (blood glucose < 25 mg/dl) was induced by regular insulin (25 IU/kg) administered intravenously 2 hours prior to induction of ischemia. In the eight normoglycemic animals, baseline CBF was 38 +/- 4 ml/min/100 gm and baseline adenosine concentration was 1.2 +/- 0.1 microM; in the eight hypoglycemic animals, these values were 39% (p < 0.05) and 62% (p < 0.05) greater, respectively, under baseline conditions. At 1 hour of postischemic reperfusion in normoglycemic animals, CBF was reduced 39% relative to the preischemic baseline (p < 0.01), concomitant with a 27% reduction (p < 0.05) in adenosine concentration, suggesting that this lowered concentration may underlie delayed hypoperfusion. These postischemic reductions in CBF and interstitial adenosine concentration were significantly greater in hypoglycemic animals, with CBF and adenosine concentration reduced 70% (p < 0.001) and 71% (p < 0.01), respectively, relative to baseline. In nine animals preischemic reactivity to hypercapnia was unaffected by hypoglycemia. Postischemic hypercapnic reactivity was retained in the eight normoglycemic animals, but was attenuated 73% (p < 0.05) in hypoglycemic animals. Thus, in the newborn pig, hypoglycemia exacerbates postischemic cortical hypoperfusion and impairs postischemic cerebrovascular reactivity to hypercapnia.
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PMID:Effect of hypoglycemia on postischemic cortical blood flow, hypercapnic reactivity, and interstitial adenosine concentration. 796 18

We tested the hypothesis that administering polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the time of reperfusion would alter recovery of cerebral blood flow (CBF; microspheres) response to alteration in arterial PCO2 in pentobarbital-anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after ischemia (10 min aortic cross clamp). To determine the effect of preischemic versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a randomized, blinded fashion before ischemia and just before reperfusion. Cerebral oxygen consumption and somatosensory evoked potentials were measured during reperfusion as an assessment of brain function. During reperfusion, no group demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not different from preischemic values with either preischemic or postischemic PEG-SOD treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not attributable to improved postischemic cerebral oxygen consumption. Somatosensory evoked potential amplitude was decreased similarly during reperfusion (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyethylene glycol-conjugated superoxide dismutase improves recovery of postischemic hypercapnic cerebral blood flow in piglets. 825 89

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.
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PMID:Superoxide scavengers do not prevent ischemia-induced alteration of cerebral vasodilation in piglets. 838 55

We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.
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PMID:Transforming growth factor-beta attenuates ischemia-induced alterations in cerebrovascular responses. 844 54

It now appears that at least some members of all classes of vertebrates exhibit ventilatory responses to changes in CO2/pH per se, including fishes. With the transition from aquatic to aerial respiration, there is an increase in the sensitivity of animals to this complex of stimuli, an increase in the variety of putative receptors possibly involved in eliciting ventilatory responses and an increase in the relative importance of this complex of stimuli in the genesis of resting ventilation. The variety of CO2-sensitive chemoreceptors present in air-breathing lower vertebrates adds considerable complexity to experimental studies of ventilatory responses to CO2/pH. Because of the locations, discharge characteristics and reflex effects of the different receptor groups, most air-breathing lower vertebrates show different responses to increases in CO2/[H+] due to cerebral ischemia, anoxia, metabolic acidosis and environmental hypercarbia. In some cases the differences are only quantitative, while in other cases the responses are qualitatively very different. These differences appear to reflect differences in the relative strength of the reflexes elicited by the various receptor groups and the net sum of their modulating influences when CO2/pH are altered via different routes. Although the situation is simpler in the higher vertebrates, in all cases the input from all of the CO2/[H+]-sensitive receptors appears to act as a biasing input which summates with other afferent information to modulate respiratory motor output, even in those species that breathe intermittently.
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PMID:The role of CO2/pH chemoreceptors in ventilatory control. 872 42


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