The causes of the adverse responses to contrast media (CM) are not well understood but may involve CM-induced alterations of the central nervous system (CNS). The blood brain barrier (BBB) strictly controls access of substance to the CNS. The rate of cerebrospinal fluid (CSF) production is a key factor in eliminating substances from the CNS. These two factors thus maintain and control the chemical environment of the CNS. If either factor is disrupted, toxic manifestations could occur. Both factors can be altered by CM. Contrast media are up to several hundred times more toxic in the CNS than systemically, and are able to disrupt the BBB. Experiments in dogs from this laboratory show that moderate doses of both ionic and non-ionic intravenous CM substantially decrease CSF production. Therefore, CM might be expected to alter the environment of the CNS and result in toxicity. The mechanisms of CM effects on the production of CSF will be studied in the proposed work. Conscious and anesthetized laboratory animal models and in vitro preparations will be employed to determine: the mechanisms of CM-induced ecreased CSF production; the extent of CNS toxicity resulting from this action of CM; changes in the concentration, retention and kinetics of substances in the CNS caused by CM; enhancement by certain risk factors of CM-induced toxicity by additionally decreasing CSF production or by predisposing the BBB to damaging effects of CM; and if it is possible to protect from these effects of CM pharmacologically.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040119-03
Application #
3179662
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1985-09-30
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1989-07-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Harnish, P P; Mukherji, M (1989) Penetration of vascular contrast media into brain tissue and cerebrospinal fluid. An experimental study in rats. Invest Radiol 24:463-6
Harnish, P P; Northington, F K; Samuel, K A (1988) Diatrizoate levels in cerebrospinal fluid following intravenous administration. Role of fluid production rate. Invest Radiol 23:377-80
Harnish, P P; Samuel, K (1988) Reduced cerebrospinal fluid production in the rat and rabbit by diatrizoate. Ventriculocisternal perfusion. Invest Radiol 23:534-6
Harnish, P P; Samuel, K (1988) Pharmacologic manipulation of the flushing action of cerebrospinal fluid. Effect on CSF diatrizoate levels. Invest Radiol 23:914-7
Harnish, P P; Hagberg, D J (1988) Contrast media-induced blood-brain barrier damage. Potentiation by hypertension. Invest Radiol 23:463-5
Harnish, P P; Northington, F K; Samuel, K A (1988) Iohexol inhibits adenylate cyclase. Invest Radiol 23:139-42
Harnish, P P; Zuniga, J; Northington, F K et al. (1988) Effect of contrast media on beta-endorphin secretion. An in vitro study. Acta Radiol 29:741-3
Harnish, P P; Mukherji, M; Northington, F K et al. (1987) Opiate involvement in contrast media-induced blood pressure changes. Invest Radiol 22:905-7
Harnish, P; Mukherji, M; Kido, D K (1987) Physiologic effects of contrast media in the rabbit. Invest Radiol 22:901-4