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Nuklearmedizin 1993; 32(06): 292-298
DOI: 10.1055/s-0038-1632293
Originalarbeit
Schattauer GmbH

Drug Effects on Cerebral Blood Flow in the Baboon Model - Acetazolamide and Nimodipine

D. W. Oliver
1   From the Department of Pharmacology, Potchefstroom University for C. H. E., South Africa
,
I. C. Dormehl
2   The AEC Institute for LIFE Sciences, University of Pretoria, South Africa
,
I. F. Redelinghuys
2   The AEC Institute for LIFE Sciences, University of Pretoria, South Africa
,
N. Hugo
2   The AEC Institute for LIFE Sciences, University of Pretoria, South Africa
,
G. Beverley
3   The H. A. Grové Research Centre, University of Pretoria, South Africa
› Author AffiliationsThe authors thank the University of Pretoria for financial support, Davis and Geek division of S.A. Cyanamide for acetazolamide and financial support, and Bayer-Miles (SA) for nimodipine; also the staff of the HA Grové Research Centre who helped with the handling and care of the animals.
Further Information

Publication History

Received: 05 March 1993

in revised form: 30 July 1993

Publication Date:
03 February 2018 (online)

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Summary

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.

Zusammenfassung

Die Empfindlichkeit eines generell narkotisierten Pavian-Modells bei der Untersuchung mit SPECT mit 99mTc-HMPAO, einer kürzlich von uns entwickelten Methode zur Untersuchung der Hirndurchblutung (CBF), wird hier untersucht unter Verwendung von Pharmaka (Acetazolamid, Karboanhydrase- Inhibitor; Nimodipin, Kalziumkanalblocker), von denen bekannt ist, daß sie den humanen CBF steigern. Eine Steigerung des zerebralen Blutflusses wurde sowohl für Acetazolamid als auch für Nimodipin beobachtet, was mit den Ergebnissen anderer Studien gut übereinstimmt. Regionale Spezifität von statistischer Signifikanz wurde für Acetazolamid und Nimodipin festgestellt. Interessanterweise wurde der zerebrale Blutfluß durch eine Kombination der beiden Medikamente nicht verstärkt, sondern, verglichen mit der Wirkung des individuell gegebenen Medikaments, sogar verringert. Die Ergebnisse wurden mit arteriellem Blutdruck, Herzfrequenz, pCO2 und pO2 korreliert. Beide Mittel verringerten den Blutdruck, während Acetazolamid einen deutlichen Einfluß auf pO2 zeigte. Die Ergebnisse machen deutlich, daß das Pavian-Modell unter Narkose empfindlich genug ist, um die Wirksamkeit eines Pharmakons auf den zerebralen Blutfluß zu bewerten.

Key words

SPECT - acetazolamide - nimodipine - blood flow - baboon model

Schlüsselwörter

SPECT - Acetazolamid - Nimodipin - Hirndurchblutung - Pavian-Modell

This work was performed at the H.A. Grové Research Centre


 

  • References

  • 1 Baethmann A, Schürer L, Uterberg A, Wahl W, Staub F, Kempski O. Mediatorsubstanzen des Hirnödems bei der zerebralen Ischämie. Arzneim Forsch/Drug Res 1991; 41: 310-5.
    Google Scholar
  • 2 Bonte FJ, Devous MD, Reisch JS. The effect of acetazolamide on regional cerebral blood flow in normal human subjects as measured by single photon emission computed tomography. Invest Radiol 1988; 23: 564-8.
    CrossrefPubMedGoogle Scholar
  • 3 Burt RW, Reddy RV, Mock BM, Wellman HN, Schanwecker DS, Witt R. Acctazolamide enhancement of H1PDM brain blood flow distribution imaging. J Nucl Med 1986; 27: 1627-31.
    PubMedGoogle Scholar
  • 4 Dormehl I, Rcdelinghuys F, Hugo N, Oliver DW, Pilloy W. The baboon model under anaesthesia for in vivo cerebral blood flow studies using single photon emission tomographic (SPECT) techniques. J Med Primatol 1992; 21: 270-4.
    PubMedGoogle Scholar
  • 5 Goodman, Gilman’s. The Pharmacological Basis of Therapeutics. 8th ed. Gilman AG, Rail TW, Nies AS, Taylor P. (eds) New York: Pergamon Press; 1990: 716-7.
    Google Scholar
  • 6 Harper AM, Craigen L, Kazda S. Effect of calcium antagonist, nimodipine, on cerebral blood flow and metabolism in the primate. J CBF and Metab 1981; 01: 349-56.
    Google Scholar
  • 7 Hauge A, Nicholaysen G, Thoresen M. Acute effects of acetazolamide on cerebral blood flow in man. Acta Physiol Scand 1983; 117: 233-9.
    CrossrefPubMedGoogle Scholar
  • 8 Herman CLU, McKee AE, Chilling PW, Dickson LG, Hörwitz DL, Coran AG, Crycr PE, Capriva CJ, Forscher BK, Lillchei RC, Stubbs S. Baboon as a sub-human primate shock model in shock, high and low flow states. Amsterdam Exepta Medica 1972; 42-8.
    Google Scholar
  • 9 Höllerhage H-G, Gaab MR, Zumkeller M, Walter GF. The influence of nimodipine on cerebral blood flow autoregulation and blood brain barrier. J Neurosurg 1988; 69: 919-22.
    CrossrefPubMedGoogle Scholar
  • 10 Jakobsen R. Mikkelsen EO. Determination of nimodipine by gas chromatography using electron-capture detection; external factors influencing nimodipine concentrations during intravenous administration. J Chromatogr 1986; 374: 383-7.
    PubMedGoogle Scholar
  • 11 Krieglstein J, Peruche B. Pharmakologische Grundlagen der Therapie der zerebralen Ischämie. Arzneim-Forsch/Drug Res 1991; 41: 303-9.
    Google Scholar
  • 12 Langley MS, Sorkin EM. Nimodipine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in cerebrovascular disease. Drugs 1989; 37: 669-99.
    PubMedGoogle Scholar
  • 13 Laux BE, Raichle ME. The effect of acetazolamide on cerebral blood flow and oxygen utilization in the rhesus monkey. J Clin Invest 1978; 62: 585-92.
    CrossrefPubMedGoogle Scholar
  • 14 McGalden TA, Nath RG. Cerebrovascular autoregulation is resistant to calcium channel blockade with nimodipine. Experientia 1989; 45: 305-6.
    CrossrefPubMedGoogle Scholar
  • 15 McCalden TA, Nath RG, Thiele K. The effects of a calcium antagonist (nimodipine) on basal cerebral blood flow and reactivity to various agonists. Stroke 1984; 15 (03) 527-30.
    CrossrefPubMedGoogle Scholar
  • 16 Mithoefer J, Mayer P, Stocks J. Effect of carbonic anhydrase inhibition of the cerebral circulation of the anesthetized dog. Fed Proc 1957; 16: 88-9.
    Google Scholar
  • 17 Niashikibe M, Kamei K, Nagura J, Suzuki K. Effect of the newly synthesized calcium antagonist isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-l,4-dihydropyridine-3,5-dicarboxylateon cerebral venous outflow in dogs. Arzneim-Forsch/Drug Res 1989; 39: 678-81.
    Google Scholar
  • 18 Nowotnik DP, Canning LR, Cumming SA, Harrison RC, Higley B, Nechvatal G, Pikkett RD, Piper IM, Bayne VJ, Forster AM, Weisner PS, Neirincks RD, Volkert WA, Troutner DE, Holmes RA. Development of a 99mTC-labelled radiopharmaceutical for cerebral blood flow imaging. Nucl Med Comm 1985; 06: 499-506.
    CrossrefPubMedGoogle Scholar
  • 19 Pozzilli C, Dipiero V, Pantano P, Lenzi GL. Influence of nimodipine on cerebral blood flow in human cerebral ischaemia. J Neurol 1989; 236: 199-202.
    CrossrefPubMedGoogle Scholar
  • 20 Vorstrup S, Henricksen L, Paulson OB. Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen. J Clin Invest 1984; 74: 1634-9.
    CrossrefPubMedGoogle Scholar
  • 21 Walovitch RC, Williams SJ, Safrance ND. Radiolabeled agents for SPECT imaging of brain perfusion. Nucl Med Biol 1990; 17 (01) 77-93.
    Google Scholar