Effect of nimodipine on intracellular brain pH, cortical blood flow, and EEG in experimental focal cerebral ischemia

Restricted access

✓ Intracellular brain pH, cortical blood flow, and electroencephalograms (EEG's) were recorded in severely and moderately ischemic regions in 10 control and 10 nimodipine-treated rabbits prior to and following major branch occlusion of the middle cerebral artery (MCA). Preocclusion cortical blood flow was 51 ml/100 gm/min and intracellular brain pH was 7.01 in both the control and the treated animals. After MCA occlusion, the severely ischemic regions in the control group showed initial and 4-hour postocclusion flows of 12.7 and 5.2 ml/100 gm/min with a brain pH of 6.64 and 6.08, respectively. In animals given nimodipine after MCA occlusion, blood flow increased from 10.5 to 18.8 ml/100 gm/min, with an associated elevation in intracellular brain pH from 6.57 to 6.91. Comparable findings were observed in areas of moderate ischemia. Improvements in cortical blood flow, intracellular brain pH, and EEG attenuations produced by nimodipine were all statistically significant. Inspection of the cortex revealed reversal of cortical pallor and small-vessel spasm following treatment with nimodipine. It is hypothesized that nimodipine exerts its effects through reversal of ischemia-induced secondary vasoconstriction, and that this drug may be an important adjunctive treatment for patients with focal cerebral ischemia.

Article Information

Address reprint requests to: Fredric B. Meyer, M.D., Department of Neurologic Surgery, Mayo Clinic, 200 First Street, S.W., Rochester, Minnesota 55905.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Operative exposure showing that the middle cerebral artery (curved arrow) gives off a temporal branch and then bifurcates into two parietal branches (straight black and white arrows). Occlusion of one parietal branch (straight black arrow) will give a zone of severe ischemia (asterisk). There will also be a zone of moderate ischemia (circle) and a region of normal flow (triangle), both supplied by the branch left intact (white arrow). The zone of severe ischemia represents a developing infarct while the moderate ischemia zone corresponds to a zone of ischemic penumbra.

  • View in gallery

    Graph of intracellular brain pH and cortical blood flow (CBF) in 10 severely ischemic sites from control rabbits (solid line) and 10 severely ischemic sites from nimodipine-treated rabbits (broken line). In each rabbit, two measurements of flow and brain pH were performed at a PaCO2 of 40 torr after a normal PaCO2 response curve had been obtained and prior to middle cerebral artery (MCA) occlusion. Preocclusion cortical blood flow was 51.8 ± 4.6 ml/100 gm/min and intracellular brain pH was 7.01 ± 0.04, pooling data from all 20 animals. Initial postocclusion flow was 12.7 ± 2.3 ml/100 gm/min in the control and 10.5 ± 1.3 ml/100 gm/min in the treated animals. Initial brain pH was 6.64 ± 0.06 in the control and 6.57 ± 0.03 in the treated animals. The controls demonstrated a progressive decline in both blood flow and brain pH over 4 hours. With nimodipine, blood flow increased to 24.2 ± 3.3 ml/100 gm/min in the 1st hour (p < 0.001). The improvement in blood flow in the treated versus the control animals was significant at each hourly interval (p < 0.001). Intracellular brain pH improved at each interval, measuring 6.91 ± 0.06 at the 4th hour (p < 0.001). Three additional animals without MCA occlusion (dotted line) underwent measurement of brain pH and blood flow for 4 hours to assess the stability of the preparation.

  • View in gallery

    Graph of intracellular brain pH and cortical blood flow (CBF) in 10 moderately ischemic sites from control rabbits (solid line) and 10 moderately ischemic sites from nimodipine-treated rabbits (broken line). Preocclusion cortical blood flow was 51.8 ± 4.6 ml/100 gm/min and intracellular brain pH was 7.01 ± 0.04, pooling data from all 20 animals. Initial postocclusion blood flow was 20.0 ± 2.0 ml/100 gm/min in the control and 24.8 ± 1.0 ml/100 gm/min in the treated rabbits. Initial brain pH was 6.92 ± 0.06 in the control and 6.84 ± 0.06 in the treated animals. In the control group, blood flow was maintained for the first 3 hours and then dropped to 14.5 ± 3.6 ml/100 gm/min at the 4th hour. Intracellular brain pH declined in the control group and was 6.74 ± 0.09 (p < 0.01) at the 4th hour. The nimodipine-treated animals had an increase in blood flow to 38.0 ± 3.3 ml/100 gm/min at the 1st hour (p < 0.001). The improvement in blood flow in the treated versus the control group was significant at each hourly interval (p < 0.001). Intracellular brain pH in the treated animals was stable, being 7.07 ± 0.05 at the 4th hour compared to a decline observed in the control group (p < 0.001). Stability of the preparation was assessed in three animals without middle cerebral artery (MCA) occlusion (dotted line).

  • View in gallery

    Electroencephalograms (EEG's) in the control and nimodipine-treated rabbits. Preocclusion EEG of the rabbit has a 6- to 10-Hz rhythm. Upper: Of 10 control animals, eight had postocclusion attenuation, all of which demonstrated progressive deterioration. Center: Of the 10 animals in the treated group, seven had initial postocclusion attenuation, five of which improved. Three animals had normalization to a 6- to 10-Hz rhythm. Lower: Two animals had improvement from a 1- to 2-Hz to a 4- to 6-Hz rhythm.

  • View in gallery

    Experimental changes in the cortical vasculature of a nimodipine-treated rabbit. A: Conducting vessels (arrows) prior to middle cerebral artery occlusion. B: Fifteen minutes after occlusion, secondary vasospasm is present evidenced by cortical pallor and by vasoconstriction of both conducting vessels (large arrows) and penetrating arterioles (small arrows). The draining veins are also constricted. C: Fifteen minutes after nimodipine infusion there is partial reversal of the secondary vasospasm. Cortical pallor is improved, and the conducting vessels (arrows) are dilated. D: Thirty minutes after the nimodipine infusion was begun, the penetrating arterioles (small arrows), the conducting vessels (large arrows), and the draining veins are all dilated.

References

  • 1.

    Allen GSBanghart SB: Cerebral arterial spasm: Part 9. In vitro effects of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries. Neurosurgery 4:37421979Allen GS Banghart SB: Cerebral arterial spasm: Part 9. In vitro effects of nifedipine on serotonin- phenylephrine- and potassium-induced contractions of canine basilar and femoral arteries. Neurosurgery 4:37–42 1979

  • 2.

    Allen GSGross CJHenderson LMet al: Cerebral arterial spasm. Part 4: In vitro effects of temperature, serotonin analogues, large nonphysiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. J Neurosurg 44:5855931976Allen GS Gross CJ Henderson LM et al: Cerebral arterial spasm. Part 4: In vitro effects of temperature serotonin analogues large nonphysiological concentrations of serotonin and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. J Neurosurg 44:585–593 1976

  • 3.

    Anderson REMichenfelder JDSundt TM Jr: Brain intracellular pH, blood flow, and blood-brain barrier differences with barbiturate and halothane anesthesia in the cat. Anesthesiology 52:2012061980Anderson RE Michenfelder JD Sundt TM Jr: Brain intracellular pH blood flow and blood-brain barrier differences with barbiturate and halothane anesthesia in the cat. Anesthesiology 52:201–206 1980

  • 4.

    Anderson REMichenfelder JDSundt TM Jr: Brain pH in focal cerebral ischemia and the protective effects of barbiturate anesthesia. J Cereb Blood Flow Metab 3:4934971983Anderson RE Michenfelder JD Sundt TM Jr: Brain pH in focal cerebral ischemia and the protective effects of barbiturate anesthesia. J Cereb Blood Flow Metab 3:493–497 1983

  • 5.

    Astrup JSymon LBranston NMet al: Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8:51571977Astrup J Symon L Branston NM et al: Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8:51–57 1977

  • 6.

    Berger JRBusto RGinsberg MDet al: Calcium channel blocker: trial in global brain ischemia. Neurology 33 (Suppl 2):1821983 (Abstract)Berger JR Busto R Ginsberg MD et al: Calcium channel blocker: trial in global brain ischemia. Neurology 33 (Suppl 2):182 1983 (Abstract)

  • 7.

    Brandt LLjunggren BAndersson KEet al: Effects of topical application of a calcium antagonist (nifedipine) on feline cortical pial microvasculature under normal conditions and in focal ischemia. J Cereb Blood Flow Metab 3:44501983Brandt L Ljunggren B Andersson KE et al: Effects of topical application of a calcium antagonist (nifedipine) on feline cortical pial microvasculature under normal conditions and in focal ischemia. J Cereb Blood Flow Metab 3:44–50 1983

  • 8.

    Demopoulos HBFlamm ESPietronigro DD: The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand Suppl 492:911191980Demopoulos HB Flamm ES Pietronigro DD: The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand Suppl 492:91–119 1980

  • 9.

    Farber JLChien KRMittnacht S Jr: The pathogenesis of irreversible cell injury in ischemia. Am J Pathol 102:2712811981Farber JL Chien KR Mittnacht S Jr: The pathogenesis of irreversible cell injury in ischemia. Am J Pathol 102:271–281 1981

  • 10.

    Fink OWKoehler WR: pH effects of fluorescence of umbelliferone. Anal Chem 42:9909931970Fink OW Koehler WR: pH effects of fluorescence of umbelliferone. Anal Chem 42:990–993 1970

  • 11.

    Gelmers HJ: Effect of nimodipine (Bay e 9736) on postischaemic cerebrovascular reactivity, as revealed by measuring regional cerebral blood flow (rCBF). Acta Neurochir 63:2832901982Gelmers HJ: Effect of nimodipine (Bay e 9736) on postischaemic cerebrovascular reactivity as revealed by measuring regional cerebral blood flow (rCBF). Acta Neurochir 63:283–290 1982

  • 12.

    Ginsberg MDMela LWrobel-Kuhl Ket al: Mitochondrial metabolism following bilateral cerebral ischemia in the gerbil. Ann Neurol 1:5195271977Ginsberg MD Mela L Wrobel-Kuhl K et al: Mitochondrial metabolism following bilateral cerebral ischemia in the gerbil. Ann Neurol 1:519–527 1977

  • 13.

    Hanson EJ JrAnderson RESundt TM Jr: Comparison of 85krypton and 133xenon cerebral blood flow measurements before, during, and following focal, incomplete ischemia in the squirrel monkey. Circ Res 36:18261975Hanson EJ Jr Anderson RE Sundt TM Jr: Comparison of 85krypton and 133xenon cerebral blood flow measurements before during and following focal incomplete ischemia in the squirrel monkey. Circ Res 36:18–26 1975

  • 14.

    Harper AMCraigen LKazda S: Effect of the calcium antagonist, nimodipine, on cerebral blood flow and metabolism in the primate. J Cereb Blood Flow Metab 1:3493561981Harper AM Craigen L Kazda S: Effect of the calcium antagonist nimodipine on cerebral blood flow and metabolism in the primate. J Cereb Blood Flow Metab 1:349–356 1981

  • 15.

    Harris RJBranston NMSymon Let al: The effects of a calcium antagonist, nimodipine, upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia. Stroke 13:7597661982Harris RJ Branston NM Symon L et al: The effects of a calcium antagonist nimodipine upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia. Stroke 13:759–766 1982

  • 16.

    Harris RJSymon LBranston NMet al: Changes in extracellular calcium activity in cerebral ischaemia. J Cereb Blood Flow Metab 2:2032091981Harris RJ Symon L Branston NM et al: Changes in extracellular calcium activity in cerebral ischaemia. J Cereb Blood Flow Metab 2:203–209 1981

  • 17.

    Haws CWGourley JKHeistad DD: Effects of nimodipine on cerebral blood flow. J Pharmacol Exp Ther 225:24281983Haws CW Gourley JK Heistad DD: Effects of nimodipine on cerebral blood flow. J Pharmacol Exp Ther 225:24–28 1983

  • 18.

    Hayashi SToda N: Inhibition by Cd2+, verapamil and papaverine of Ca2+-induced contractions in isolated cerebral and peripheral arteries of the dog. Br J Pharmacol 60:35431977Hayashi S Toda N: Inhibition by Cd2+ verapamil and papaverine of Ca2+-induced contractions in isolated cerebral and peripheral arteries of the dog. Br J Pharmacol 60:35–43 1977

  • 19.

    HeffezPassonneau JV: Effect on nimodipine on cerebral metabolism during ischemia and recirculation in the Mongolian gerbil. J Cereb Blood Flow Metab 5:5235281985Heffez Passonneau JV: Effect on nimodipine on cerebral metabolism during ischemia and recirculation in the Mongolian gerbil. J Cereb Blood Flow Metab 5:523–528 1985

  • 20.

    Hoffmeister FBenz UHeise Aet al: Behavioral effects of nimodipine in animals. Arzneimittelforsch 32:3473601982Hoffmeister F Benz U Heise A et al: Behavioral effects of nimodipine in animals. Arzneimittelforsch 32:347–360 1982

  • 21.

    Hoffmeister FKazda SKrause HP: Influence of nimodipine (BAY e 9736) on the postischaemic changes of brain function. Acta Neurol Scand 60 (Suppl 72):3583591979Hoffmeister F Kazda S Krause HP: Influence of nimodipine (BAY e 9736) on the postischaemic changes of brain function. Acta Neurol Scand 60 (Suppl 72):358–359 1979

  • 22.

    Högestätt EDAndersson KEEdvinsson L: Effects of nimodipine on potassium-induced contraction and noradrenaline release in cerebral and extracranial arteries from rabbit. Acta Physiol Scand 114:2832961982Högestätt ED Andersson KE Edvinsson L: Effects of nimodipine on potassium-induced contraction and noradrenaline release in cerebral and extracranial arteries from rabbit. Acta Physiol Scand 114:283–296 1982

  • 23.

    Hossmann KAPaschen WCsiba L: Relationship between calcium accumulation and recovery of cat brain after prolonged cerebral ischemia. J Cereb Blood Flow Metab 3:3463531983Hossmann KA Paschen W Csiba L: Relationship between calcium accumulation and recovery of cat brain after prolonged cerebral ischemia. J Cereb Blood Flow Metab 3:346–353 1983

  • 24.

    Jeppsson PGOlin T: Cerebral angiography in the rabbit. An investigation of vascular anatomy and variation in circulatory patterns with conditions of injection. Lund Univ Arrskr 56(14):1561960Jeppsson PG Olin T: Cerebral angiography in the rabbit. An investigation of vascular anatomy and variation in circulatory patterns with conditions of injection. Lund Univ Arrskr 56(14):1–56 1960

  • 25.

    Kazda SHoffmeister FGarthoff Bet al: Prevention of the postischaemic impaired reperfusion of the brain by nimodipine (BAY e 9736). Acta Neurol Scand 60 (Suppl 72):3023031979Kazda S Hoffmeister F Garthoff B et al: Prevention of the postischaemic impaired reperfusion of the brain by nimodipine (BAY e 9736). Acta Neurol Scand 60 (Suppl 72):302–303 1979

  • 26.

    Kazda STowart R: Nimodipine: a new calcium antagonistic drug with a preferential cerebrovascular action. Acta Neurochir 63:2592651982Kazda S Towart R: Nimodipine: a new calcium antagonistic drug with a preferential cerebrovascular action. Acta Neurochir 63:259–265 1982

  • 27.

    Kukovetz WRPöch GHolzmann S: Cyclic nucleotides and relaxation of vascular smooth muscle in Van Houtte PMLeusen I (eds): Vasodilatation. New York: Raven Press1981 pp 339353Kukovetz WR Pöch G Holzmann S: Cyclic nucleotides and relaxation of vascular smooth muscle in Van Houtte PM Leusen I (eds): Vasodilatation. New York: Raven Press 1981 pp 339–353

  • 28.

    Kuwashima JNakamura KFujitani Bet al: Relationship between cerebral energy failure and free fatty acid accumulation following prolonged brain ischemia. Jpn J Pharmacol 28:2772871978Kuwashima J Nakamura K Fujitani B et al: Relationship between cerebral energy failure and free fatty acid accumulation following prolonged brain ischemia. Jpn J Pharmacol 28:277–287 1978

  • 29.

    Lassen NA: The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 2:111311151966Lassen NA: The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 2:1113–1115 1966

  • 30.

    McCalden TABevan JA: Sources of activator calcium in rabbit basilar artery. Am J Physiol 241:H129H1331981McCalden TA Bevan JA: Sources of activator calcium in rabbit basilar artery. Am J Physiol 241:H129–H133 1981

  • 31.

    Meyer FBAnderson RESundt TM Jret al: Intracellular brain pH indicator tissue perfusion, electroencephalography and histology in severe and moderate focal cortical ischemia in the rabbit. J Cereb Blood Flow Metab (In press 1986)Meyer FB Anderson RE Sundt TM Jr et al: Intracellular brain pH indicator tissue perfusion electroencephalography and histology in severe and moderate focal cortical ischemia in the rabbit. J Cereb Blood Flow Metab (In press 1986)

  • 32.

    Mohamed AAMcCulloch JMendelow ADet al: Effect of the calcium antagonist nimodipine on local cerebral blood flow: relationship to arterial blood pressure. J Cereb Blood Flow Metab 4:2062111984Mohamed AA McCulloch J Mendelow AD et al: Effect of the calcium antagonist nimodipine on local cerebral blood flow: relationship to arterial blood pressure. J Cereb Blood Flow Metab 4:206–211 1984

  • 33.

    Nowicki JPMacKenzie ETYoung AR: Brain ischaemia, calcium and calcium antagonists. Pathol Biol (Paris) 30:2822881982Nowicki JP MacKenzie ET Young AR: Brain ischaemia calcium and calcium antagonists. Pathol Biol (Paris) 30:282–288 1982

  • 34.

    Peroutka SJAllen GS: Calcium channel antagonist binding sites labeled by 3H-nimodipine in human brain. J Neurosurg 59:9339371983Peroutka SJ Allen GS: Calcium channel antagonist binding sites labeled by 3H-nimodipine in human brain. J Neurosurg 59:933–937 1983

  • 35.

    Rehncrona SMela LSiesjö BK: Recovery of brain mitochondrial function in the rat after complete and incomplete cerebral ischemia. Stroke 10:4374461979Rehncrona S Mela L Siesjö BK: Recovery of brain mitochondrial function in the rat after complete and incomplete cerebral ischemia. Stroke 10:437–446 1979

  • 36.

    Rehncrona SRosén ISiesjö BK: Excessive cellular acidosis: an important mechanism of neuronal damage in the brain? Acta Physiol Scand 110:4354371980Rehncrona S Rosén I Siesjö BK: Excessive cellular acidosis: an important mechanism of neuronal damage in the brain? Acta Physiol Scand 110:435–437 1980

  • 37.

    Roy MWDempsey RJMeyer KLet al: Effects of verapamil and diltiazem on acute stroke in cats. J Neurosurg 63:9299361985Roy MW Dempsey RJ Meyer KL et al: Effects of verapamil and diltiazem on acute stroke in cats. J Neurosurg 63:929–936 1985

  • 38.

    Sagawa KGuyton AC: Pressure-flow relationships in isolated canine cerebral circulation. Am J Physiol 200:7117141961Sagawa K Guyton AC: Pressure-flow relationships in isolated canine cerebral circulation. Am J Physiol 200:711–714 1961

  • 39.

    Sandahl BAndersson KEAronsen KFet al: Effect of the calcium antagonist nifedipine on uterine blood flow in non-treated and oestradiol-treated rats. Gynecol Obstet Invest 9:2382431978Sandahl B Andersson KE Aronsen KF et al: Effect of the calcium antagonist nifedipine on uterine blood flow in non-treated and oestradiol-treated rats. Gynecol Obstet Invest 9:238–243 1978

  • 40.

    Schanne FAXKane ABYoung EEet al: Calcium dependence of toxic cell death: a final common pathway. Science 206:7007021979Schanne FAX Kane AB Young EE et al: Calcium dependence of toxic cell death: a final common pathway. Science 206:700–702 1979

  • 41.

    Siesjö BK: Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1:1551851981Siesjö BK: Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1:155–185 1981

  • 42.

    Siesjö BK: Cerebral circulation and metabolism. J Neurosurg 60:8839081984Siesjö BK: Cerebral circulation and metabolism. J Neurosurg 60:883–908 1984

  • 43.

    Smith MLKågström ERosén Iet al: Effect of the calcium antagonist nimodipine on the delayed hypoperfusion following incomplete ischemia in the rat. J Cereb Blood Flow Metab 3:5435461983Smith ML Kågström E Rosén I et al: Effect of the calcium antagonist nimodipine on the delayed hypoperfusion following incomplete ischemia in the rat. J Cereb Blood Flow Metab 3:543–546 1983

  • 44.

    Steen PANewberg LAMilde JHet al: Cerebral blood flow and neurological outcome when nimodipine is given after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 4:82871984Steen PA Newberg LA Milde JH et al: Cerebral blood flow and neurological outcome when nimodipine is given after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 4:82–87 1984

  • 45.

    Steen PANewberg LAMilde JHet al: Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 3:38431983Steen PA Newberg LA Milde JH et al: Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 3:38–43 1983

  • 46.

    Sundt TM JrAnderson RE: Intracellular brain pH and the pathway of a fat soluble pH indicator across the blood-brain barrier. Brain Res 186:3553641980Sundt TM Jr Anderson RE: Intracellular brain pH and the pathway of a fat soluble pH indicator across the blood-brain barrier. Brain Res 186:355–364 1980

  • 47.

    Sundt TM JrAnderson RE: Umbelliferone as an intracellular pH-sensitive fluorescent indicator and blood-brain barrier probe: instrumentation, calibration, and analysis. J Neurophysiol 44:60751980Sundt TM Jr Anderson RE: Umbelliferone as an intracellular pH-sensitive fluorescent indicator and blood-brain barrier probe: instrumentation calibration and analysis. J Neurophysiol 44:60–75 1980

  • 48.

    Sundt TM JrAnderson REVan Dyke RA: Brain pH measurements using a diffusible, lipid soluble pH sensitive fluorescent indicator. J Neurochem 31:6276351978Sundt TM Jr Anderson RE Van Dyke RA: Brain pH measurements using a diffusible lipid soluble pH sensitive fluorescent indicator. J Neurochem 31:627–635 1978

  • 49.

    Sundt TM JrDavis DH: Reactions of cerebrovascular smooth muscle to blood and ischemia: primary versus secondary vasospasm in Wilkins RH (ed): Cerebral Arterial Spasm. Baltimore: Williams & Wilkins1980 pp 244250Sundt TM Jr Davis DH: Reactions of cerebrovascular smooth muscle to blood and ischemia: primary versus secondary vasospasm in Wilkins RH (ed): Cerebral Arterial Spasm. Baltimore: Williams & Wilkins 1980 pp 244–250

  • 50.

    Sundt TM JrMichenfelder JD: Focal transient cerebral ischemia in the squirrel monkey. Effect on brain adenosine triphosphate and lactate levels with electrocorticographic and pathologic correlation. Circ Res 30:7037121972Sundt TM Jr Michenfelder JD: Focal transient cerebral ischemia in the squirrel monkey. Effect on brain adenosine triphosphate and lactate levels with electrocorticographic and pathologic correlation. Circ Res 30:703–712 1972

  • 51.

    Sundt TM JrSharbrough FWAnderson REet al: Cerebral blood flow measurements and electroencephalograms during carotid endarterectomy. J Neurosurg 41:3103201974Sundt TM Jr Sharbrough FW Anderson RE et al: Cerebral blood flow measurements and electroencephalograms during carotid endarterectomy. J Neurosurg 41:310–320 1974

  • 52.

    Sundt TM JrWaltz AG: Experimental cerebral infarction: retro-orbital extradural approach for occluding the middle cerebral artery. Proc Staff Meet Mayo Clin 41:1591681966Sundt TM Jr Waltz AG: Experimental cerebral infarction: retro-orbital extradural approach for occluding the middle cerebral artery. Proc Staff Meet Mayo Clin 41:159–168 1966

  • 53.

    Tanaka KGotoh FMuramatsu Fet al: Effects of nimodipine (Bay e 9736) on cerebral circulation in cats. Arzneimittelforsch 30:149414971980Tanaka K Gotoh F Muramatsu F et al: Effects of nimodipine (Bay e 9736) on cerebral circulation in cats. Arzneimittelforsch 30:1494–1497 1980

  • 54.

    Teasdale GTamura AGraham Det al: Vasoconstriction in focal cerebral ischemia in Cervós-Navarro JFritschka E (eds): Cerebral Microcirculation and Metabolism. New York: Raven Press1981 pp 7781Teasdale G Tamura A Graham D et al: Vasoconstriction in focal cerebral ischemia in Cervós-Navarro J Fritschka E (eds): Cerebral Microcirculation and Metabolism. New York: Raven Press 1981 pp 77–81

  • 55.

    Towart R: The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium-antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine. Circ Res 48:6506571981Towart R: The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium-antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine. Circ Res 48:650–657 1981

  • 56.

    Van Breemen CSiegel BKalinoski Let al: The Ca++ cycle of arterial smooth muscle in Wilkins RH (ed): Cerebral Arterial Spasm. Baltimore: Williams & Wilkins1980 pp 6167Van Breemen C Siegel B Kalinoski L et al: The Ca++ cycle of arterial smooth muscle in Wilkins RH (ed): Cerebral Arterial Spasm. Baltimore: Williams & Wilkins 1980 pp 61–67

  • 57.

    Waltz AGSundt TM Jr: The microvasculature and microcirculation of the cerebral cortex after arterial occlusion. Brain 90:6816961967Waltz AG Sundt TM Jr: The microvasculature and microcirculation of the cerebral cortex after arterial occlusion. Brain 90:681–696 1967

  • 58.

    Wolfe LS: Eicosanoids: prostaglandins, thromboxanes, leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids. J Neurochem 38:1141982Wolfe LS: Eicosanoids: prostaglandins thromboxanes leukotrienes and other derivatives of carbon-20 unsaturated fatty acids. J Neurochem 38:1–14 1982

  • 59.

    Yanagihara TMcCall JT: Ionic shift in cerebral ischemia. Life Sci 30:192119251982Yanagihara T McCall JT: Ionic shift in cerebral ischemia. Life Sci 30:1921–1925 1982

  • 60.

    Yoshida SInoh SAsano Tet al: Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. Lipid peroxidation as a possible cause of postischemic injury. J Neurosurg 53:3233311980Yoshida S Inoh S Asano T et al: Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. Lipid peroxidation as a possible cause of postischemic injury. J Neurosurg 53:323–331 1980

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 76 76 6
Full Text Views 231 231 0
PDF Downloads 122 122 0
EPUB Downloads 0 0 0

PubMed

Google Scholar