Effects of l-NMMA and l-NNA on the Selective ATP-Induced Enhancement of Intratumoral Blood Flow

We studied the effects of NG-monomethyl-l-arginine (l-NMMA) and Nω-nitro-l-arginine (l-NNA) on the selective ATP and adenosine-induced enhancement of intratumoral blood flow in rats measured by the hydrogen clearance method. Both adenosine and ATP produced a selective enhancement of the intratumoral blood flow. Neither l-NMMA nor l-NNA had a significant effect on either the CBF or the intratumoral blood flow. Adenosine-induced enhancement was not inhibited by l-NMMA or l-NNA. On the other hand, the ATP-induced enhancement was totally inhibited by both l-NMMA and l-NNA. The inhibitory action of l-NMMA against ATP was blocked by l-arginine, but not by d-arginine. It is suggested that the ATP-induced increase of intratumoral blood flow is evoked by nitric oxide synthesized from the endothelium of the intratumoral blood vessels.

Changes of blood flow in the adenohypophysis of normal and estrogen pretreated Fisher rats by tamoxifen

Blood flow was measured in the adenohypophysis and in the cerebral cortex of female F344 rats over a period of 90 min using the hydrogen clearance method. Tamoxifen, 1 mg/kg, administered iv reduced the blood flow in the adenohypophysis by 35%, whereas cerebral blood flow and arterial pressure remained unchanged. Seven days sc treatment with tamoxifen (1 mg/kg daily) had no demonstrable effect on blood flow. Anterior pituitary hyperplasia was induced in 15 rats with diethylstilbestrol containing implants. These rats responded to 7 days of sc tamoxifen treatment by 30% increase in adenohypophyseal blood flow. These results suggest that tamoxifen has a different effect on adenohypophysial circulation of the rat depending on whether it is administered in a low- or high-estrogen state.

Cerebral blood flow and the thermal properties of the brain: a preliminary analysis

✓ Safe and effective use of hyperthermia for the treatment of brain tumors requires precise control of the distribution of temperatures (that is, the thermal field) within the tumor and within the adjacent brain. Major influences upon the distribution of temperatures include the passive thermal properties of the brain, such as its specific heat (Cb), and the contribution of cerebral blood flow (CBF). Recently, an electrical-mechanical analog model of heat flow within the brain has been developed from which an expression for CBF has been derived: CBF = Cb/(τρc) where τ is the thermal decay constant, ρ is the density of blood, and c is its specific heat. To test this model a series of experiments was carried out in adult dogs in which stereotaxically implanted microwave antennas operating at 2450 MHz, fluoro-optical thermometry probes, and platinum electrodes were used to simultaneously measure CBF by thermal washout and hydrogen clearance techniques. The correlation coefficient for estimates of CBF derived by the two methods in 52 paired observations was 0.89. Measurements of CBF were more reliable at increased distances from the microwave antenna, since CBF is sensitive to the degree of temperature elevation (ΔT). The ratio of post-heating CBF to pre-heating CBF varies linearly with ΔT and has a correlation coefficient of 0.86. When values of CBF determined by the hydrogen clearance method were employed in the above equation, it was possible to derive Cb as 0.70 ± 0.08 cal/gm-°C. Use of this value for Cb in this equation produces estimates of CBF by thermal clearance that are within 10% of the values for CBF as measured by the hydrogen clearance method. It is concluded that this model of thermal flow within the brain may have heuristic value for treatment planning and that microwave antennas and fluoro-optical probes may represent a new methodology for the clinical estimation of CBF. These methods have recently been employed in patients undergoing combined hyperthermia and chemotherapy.

Hydrogen Clearance Method for Determining Local Cerebral Blood Flow. I. Spatial Resolution

To define the effective spatial resolution of the hydrogen clearance method, serial local CBF (LCBF) measurements were performed at different distances from the cortico–white matter junction of the cat brain. Twenty-five platinum-wire microelectrodes with a sensitive surface of 0.07 mm2 were inserted into the cerebral cortex of three cats through burr holes in the skull and advanced toward the ear-to-ear level in 1- or 0.1-mm steps. Most electrodes passed from high-perfusion regions into low-perfusion areas, indicating that the cortico–white matter junction had been traversed. Whereas within the gray and white matter the LCBF values were fairly constant, a striking decrease of CBF was registered at the cortico–white matter junction. Here the mean LCBF from 12 electrodes showed significant differences in flow between two locations 1 mm apart. On two occasions, a significant difference in CBF was found for locations only 0.1 mm apart. Despite this high spatial resolution, monoexponential clearance curves were detected only in the vicinity of the cortico–white matter junction. It is therefore assumed that factors other than flow might influence H2 clearance.