Opening of the Blood-Brain Barrier by Intravenous Contrast Media in Euvolemic and Dehydrated Rabbits

Abstract

It has been suggested that intravenous injections of hypertonic contrast media when used in computed tomography and digital subtraction angiography might raise plasma osmolality sufficiently to open the blood-brain barrier (BBB). The current investigation establishes the threshold of plasma osmolality that causes the the opening of the BBB in euvolemic and dehydrated rabbits. Euvolemic rabbits were allowed food and water ad libitum. Dehydrated rabbits received 4.0 mg/kg of furosemide intramuscularly and were deprived of water for 72 hours. Meglumine/sodium diatrizoate 76 per cent (n=28) or mannitol 20 per cent (n= 12) was administrated intravenously, at a rate of 25 mmol/kg body weight/hour for 2, 3 or 4 hours. Plasma osmolality, blood iodine concentration, blood pressure, heart rate and hematocrit were assessed at regular intervals. Evans blue and 99Tcm-DTPA were used simultaneously as tracers for BBB opening. Rating of BBB opening with 99Tcm-DTPA correlated well with Evans blue staining (r=0.863, p<0.001; n=42). BBB opening was related to plasma osmolality and was similar for both contrast media and mannitol. Widespread BBB opening occurred above 400 mmol/kg while focal BBB opening occurred above 370 mmol/kg. Dehydration per se increased plasma osmolality but did not reduce the threshold for BBB opening.