Cerebral blood flow changes with enalapril.

Patients with carotid artery occlusive disease (CAOD) may be at increased risk of iatrogenic cerebral hypoperfusion. Using the 133xenon-inhalation technique, we evaluated the effects of enalapril on regional cerebral blood flow (CBF) in 14 patients with chronic hypertension, 7 with CAOD and 7 without CAOD (no CAOD). Regional CBF and blood pressure were measured before and 60 minutes after a single dose of enalapril. Changes in mean arterial pressure after enalapril were not significantly different between the two groups: CAOD -4.67 +/- 8.7 mm Hg, no CAOD -6.18 +/- 8.2 mm Hg. Changes in mean CBF after enalapril were also not statistically different: CAOD -1.0 +/- 3.9, no CAOD 1.0 +/- 2.8. In the CAOD group only, however, changes in CBF were significantly related to increasing age (r = -0.9253, p less than 0.01), such that in patients 65 years or older CBF tended to decrease, whereas in younger patients it increased. Elderly patients with CAOD may be at increased risk of iatrogenic cerebral hypoperfusion, and it may be appropriate to evaluate prospectively the effects of antihypertensive medications on CBF.     

Altered hepatic blood flow and drug disposition.

For some drugs, delivery to the liver by the hepatic circulation is an important determinant of removal by this organ. Classical pharmacokinetic analyses cannot predict the changes produced by altering any of the biological determinants of drug elimination by the liver; hepatic blood flow, metabolic enzyme activity, drug binding and route of administration. However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid. Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice logical changes affecting the circulation. For drug clearance to be affected significantly by these changes in flow, the drug must be avidly removed by the liver as reflected in a high hepatic extraction ratio and intrinsic hepatic clearance. This latter term is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation. The clearance of drugs with low intrinsic clearance will not be affected significantly by changes in liver blood flow.     

The effect of nisoldipine on apparent liver blood flow and effective renal plasma flow.

The effects of the acute and continued administration of the calcium antagonist nisoldipine on hepatic and renal blood flow and on renal function were studied in nine normotensive volunteers. There were no significant changes in supine blood pressure or heart rate but acute administration significantly increased both apparent liver blood flow and effective renal plasma flow. With continued administration these increases were attenuated and were not significantly different from placebo after 4 days treatment. Acute nisoldipine administration was also associated with significant increases in glomerular filtration rate and urinary sodium excretion.     

Carboxyhemoglobin and brain blood flow in humans.

It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain-blood flow (BBF) develops. The BBF response in humans has been shown to be quite variable. Two experiments were conducted in which humans were exposed to sufficient carbon monoxide (CO) to produce COHb levels up to 18.4%. BBF was measured by the method of impedance plethysmography. The first was a pilot study in which BBF in 14 men was studied after transient exposure to various concentrations of CO in air. BBF increased as a function of COHb but not to the same extent (or at all) in some subjects. In a confirmatory experiment with 12 men, BBF was measured once per h during a 4-h experiment. All 12 subjects received CO. The variation of the BBF response among subjects was large and statistically significant whereas the variation over time was not significant. Thus it appears that the magnitude of the BBF response is unique for a given subject and differs across subjects. These results may help predict CO-induced behavioral decrements in future studies if subjects whose BBF response to COHb is small or absent are also more susceptible to impairment by acute CO exposure.     

Cocaine decreases uteroplacental blood flow in the rat.

Although cocaine administration reduces blood flow to the fetus in the pregnant ewe, the effects of cocaine on uterine and placental blood flow in the pregnant rat have not been adequately documented. The current study tested the hypothesis that cocaine decreased uterine and placental blood flow in awake and freely moving pregnant rats 17 min following gastric intubation. Blood flow was determined using [14C]iodoantipyrine in pregnant Sprague-Dawley rats 1 day prior to parturition. On the day of the experiment, rats were intubated with either 60 mg/kg cocaine or the vehicle and 17 min later infused i.v. with 75 microCi [14C]iodoantipyrine. Ten arterial blood samples were taken over 1 min through a femoral arterial catheter placed on the previous day. At 1 min the animal was decapitated and the entire uterus rapidly removed and frozen. After processing for autoradiography, the amounts of radioactivity in the tissues were determined by computerized image analysis. The results show that cocaine reduced blood flow in the uterus by 27% and decreased blood flow in the placenta by 30%. While cocaine reduced the total amount of iodoantipyrine reaching the fetus, the distribution of tracer within the fetus did not appear to be altered by cocaine. Maternal blood pressure and heart rate decreased by 5% and 13% respectively (paired t-test), while maternal and fetal blood gases were not altered. These data indicate that acute cocaine administration reduces uteroplacental blood flow in the rat. The duration of this effect and whether these decreases are sufficient to produce neurobehavioral changes in the offspring remain to be determined.