Ischemic brain edema following middle cerebral artery occlusion in baboons: relationship between regional cerebral water content and blood flow at 1 to 2 hours.
The relationship between increase in water content in ischemic brain and levels of regional blood flow has been studied in 11 primates. Flows were recorded using the method of hydrogen (2-minute) clearance, from a total of 128 electrodes in cortex and white matter, and a gradation of ischemia was produced by middle cerebral occlusion transorbitally. The flows were reduced in the area of densest ischemia from control levels of 12.0 +/- 12.0 ml/100g/min to 7.0 +/- 5.4 ml/100g/min, with lesser decreases over the remainder of the ischemic hemisphere. Water content was measured in cortex and white matter, in regions topographically related to those of flow measurements, by densitometric assessment using precalibrated kerosene/bromobenzine columns. The average water content of cortex in regions remote from ischemia was 797.4 +/- 5.8 mg/gm and in white matter 708.5 +/- 8.2 mg/gm. Significant increases in water content (comparing corresponding regions of the two hemispheres) of up to 11.4 +/- 7.5 mg/gm were demonstrated in the most ischemic cortical areas. A gradient of water increase was evident in the ischemic hemisphere, increases water content being greatest in the opercular zone and least in the parasagittal area. Significant differences in white matter water content between the 2 hemispheres were demonstrated only in the most densely ischemic areas in the current experiments where ischemia was limited to 93 +/- 20 mins in the 11 animals without reperfusion. The relationship between ischemic density and water content increase showed that significant increases in water content occurred in regions where terminal flows had been below 20 ml/100g/min, indicating that accumulation of water in ischemic brain begins at flow values comparable to those associated with the failure of synaptic transmission, higher than those associated with failure of the ionic pump of the cell. Possible pathophysiological mechanisms are discussed. (+info
Comparison of retinal transit times and retinal blood flow: a study in monkeys.
PURPOSE: To determine the correlation between transit times of retinal blood flow calculated from fluorescein angiograms and retinal blood flow determined by the microsphere method. METHODS: Two fluorescein angiograms were obtained in each eye of six monkeys, followed by determination of retinal blood flow with labeled microspheres. Angiograms in 10 eyes were analyzed for mean transit time (MTT) and arteriovenous passage time (AVP). MTT was determined in two ways: from dye curves reconstructed by extrapolation of semilogarithmic plots of the recorded curves (MTT(slope)) and by a new technique based on an impulse-response analysis (MTT(ir)). RESULTS: Mean values (+/-SD) for retinal blood flow in 10 eyes were 23.2 +/- 6.9 mg/min. Corresponding values for MTT(ir), MTT(slope), and AVP were 2.22 +/- 0.38, 4.89 +/- 5.89, and 1.08 +/- 0.14 seconds. There was a weak, but not statistically significant, correlation between retinal blood flow and MTT(ir) (r = -0.60, P = 0.06) but no useful correlation between retinal blood flow and either MTT(slope) or AVP. CONCLUSIONS: The relationship between retinal blood flow and transit times determined from fluorescein angiograms is weak. Of the three transit parameters tested, MTT(ir), determined with the recently developed impulse-response technique, had the best correlation with retinal blood flow. Further studies are needed to determine the ability of these transit parameters to detect a change in retinal blood flow and the possibility that transit times may provide useful clinical information unrelated to absolute values of retinal blood flow. (+info
Retinal fluorescein contrast arrival time of young patients with the hepatosplenic form of the Schistosomiasis mansoni.
Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage. (+info
Time course of changes in optic nerve head circulation after acute reduction in intraocular pressure.
PURPOSE: To study the time course of changes in circulation in the optic nerve head (ONH) after acute reduction in intraocular pressure (IOP) and to evaluate the effects of a calcium antagonist, a nitric oxide synthetase (NOS) inhibitor, indomethacin, and sympathetic nerve amputation on the changes in ONH circulation after reduction of IOP. METHODS: In anesthetized albino rabbits, acute reduction of IOP (acute increase in ocular perfusion pressure [OPP]) was manometrically achieved and normalized blur (NB), a quantitative index of tissue blood velocity obtained with the laser speckle method, was serially monitored for 30 seconds and 60 minutes. The effects of systemic administration of 1 microg/kg per hour nilvadipine (a calcium antagonist), 300 microg/kg Nomega-nitro-l-arginine (l-NAME, a nonselective NOS inhibitor), and 5 mg/kg indomethacin or sympathetic nerve amputation on the changes in NB after reduction of IOP were studied. RESULTS: During changes in IOP from 10 to 40 mm Hg and then back to 10 mm Hg, NB exhibited no significant change. During changes in IOP from 10 to 60 mm Hg and then back to 10 mm Hg, NB initially decreased with an increase in IOP to 60 mm Hg and then increased to baseline level when IOP was returned to 10 mm Hg. In the nilvadipine-treated rabbits, during changes in IOP from 10 to 40 mm Hg and back to 10 mm Hg and during the changes from 10 to 60 mm Hg and back to 10 mm Hg, NB decreased with increase in IOP to 40 or 60 mm Hg and then increased to slightly above the baseline when IOP returned to 10 mm Hg. l-NAME, indomethacin, and sympathetic nerve amputation each had little effect on the time course of change in NB. CONCLUSIONS: ONH circulation was stably maintained after reduction of IOP from 40 to 10 mm Hg but not after that from 60 to 10 mm Hg. The changes in NB after reduction of IOP occurred quickly and were partially impaired with a calcium antagonist, but not with the NOS inhibitor, indomethacin, or sympathetic nerve amputation. These findings suggest the importance of vascular smooth muscle in maintaining stable ONH circulation against reduction of IOP in a fashion nearly independent of NO, endogenous prostaglandins, and the sympathetic nervous system. (+info
Analysis of blood flow in the entire coronary arterial tree.
A hemodynamic analysis of coronary blood flow must be based on the measured branching pattern and vascular geometry of the coronary vasculature. We recently developed a computer reconstruction of the entire coronary arterial tree of the porcine heart based on previously measured morphometric data. In the present study, we carried out an analysis of blood flow distribution through a network of millions of vessels that includes the entire coronary arterial tree down to the first capillary branch. The pressure and flow are computed throughout the coronary arterial tree based on conservation of mass and momentum and appropriate pressure boundary conditions. We found a power law relationship between the diameter and flow of each vessel branch. The exponent is approximately 2.2, which deviates from Murray's prediction of 3.0. Furthermore, we found the total arterial equivalent resistance to be 0.93, 0.77, and 1.28 mmHg.ml(-1).s(-1).g(-1) for the right coronary artery, left anterior descending coronary artery, and left circumflex artery, respectively. The significance of the present study is that it yields a predictive model that incorporates some of the factors controlling coronary blood flow. The model of normal hearts will serve as a physiological reference state. Pathological states can then be studied in relation to changes in model parameters that alter coronary perfusion. (+info
Lack of effect of pravastatin on cerebral blood flow or parenchymal volume loss in elderly at risk for vascular disease.
BACKGROUND AND PURPOSE: Ageing is associated with a decline in cerebral blood flow. Animal studies have shown that cholesterol-lowering therapy with statins might preserve cerebral blood flow (CBF). We examined the effect of 40 mg pravastatin on the decline in CBF and brain volume in a subset of elderly subjects participating in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. METHODS: Randomization was not stratified according to whether or not subjects participated in the MRI substudy. In 391 men (n=226) and women (n=165) aged 70 to 82 years (mean+/-SD, 75+/-3.2), we measured total CBF (in mL/min) at baseline and after a mean+/-SD follow-up of 33+/-1.4 months with a gradient-echo phase-contrast MRI technique. Total CBF was defined as the summed flows in both internal carotid and vertebral arteries. Parenchymal volume (whole brain) was segmented with the use of in-house-developed semiautomatic software. RESULTS: Total CBF significantly declined in the placebo-allocated group, from 521+/-83 to 504+/-92 mL/min (P=0.0036) and in the pravastatin-allocated group from 520+/-94 to 506+/-92 mL/min (P=0.018). This decline was not significantly different between treatment groups (P=0.56). There was also a significant reduction in brain volume over time (P<0.001), which was not different between the treatment groups (P=0.47). When expressed per unit of parenchymal volume, the decline in CBF over time was no longer statistically significant. CONCLUSIONS: Elderly people at risk for cerebral vascular disease had a significant decline in CBF with increasing age that was explained by a concomitant reduction in brain volume. Treatment with 40 mg pravastatin daily had no beneficial effect on total CBF. (+info
Non-invasive measurement of circulation time using pulse oximetry during breath holding in chronic hypoxia.
Pulse oximetry during breath-holding (BH) in normal residents at high altitude (3510 m) shows a typical graph pattern. Following a deep inspiration to total lung capacity (TLC) and subsequent breath-holding, a fall in oxyhemoglobin saturation (SaO(2) is observed after 16 s. The down-pointed peak in SaO(2) corresponds to the blood circulation time from the alveoli to the finger where the pulse oximeter probe is placed. This simple maneuver corroborates the measurement of circulation time by other methods. This phenomenon is even observed when the subject breathes 88% oxygen (PIO(2) = 403 mmHg for a barometric pressure of 495 mmHg). BH time is, as expected, prolonged under these circumstances. Thus the time delay of blood circulation from pulmonary alveoli to a finger is measured non-invasively. In the present study we used this method to compare the circulation time in 20 healthy male high altitude residents (Group N with a mean hematocrit of 50%) and 17 chronic mountain sickness patients (Group CMS with a mean hematocrit of 69%). In the two study groups, the mean circulation time amounted to 15.94 +/-2.57 s (SD) and to 15.66 +/-2.74 s, respectively. The minimal difference was not significant. We conclude that the CMS patients adapted their oxygen transport rate to the rise in hematocrit and blood viscosity. (+info
Cerebral blood flow thresholds for mRNA synthesis after focal ischemia and the effect of MK-801.
BACKGROUND AND PURPOSE: MK-801 is a noncompetitive antagonist of N-methyl-d-aspartate subtype glutamate receptors with protective efficacy in experimental stroke. This study examined the impact of MK-801 on cerebral blood flow (CBF) and its relationship to gene expression changes during focal ischemia. METHODS: Spontaneously hypertensive rats were subjected to surgical occlusion of the middle cerebral artery and ipsilateral common carotid artery after 30 minutes pretreatment with 5 mg/kg MK-801 or saline vehicle. After 2.5 hours of ischemia, regional CBF was evaluated by [14C]iodoantipyrine autoradiography and compared with distributions of gene expression changes evaluated by in situ hybridization detection of mRNAs encoding several immediate-early genes and the stress protein, hsp72. RESULTS: MK-801 increased CBF in contralateral cortex from 93+/-15 to 187+/-37 mL/100 g per minute and produced a significant 25% reduction in the volume of ischemic cortex ipsilateral to occlusion. The extent of cortex failing to express inducible mRNAs correspondingly decreased, but the CBF threshold for mRNA synthesis remained unchanged (25 to 30 mL/100 g per minute). Widespread immediate-early gene expression in the neocortex became restricted to periinfarct regions after MK-801 treatment, and hybridization patterns in the striatum and hippocampus reflected the altered topography of cortical activation after drug treatment. CONCLUSIONS: MK-801 alters ischemia-induced gene expression by 2 distinct mechanisms. Generalized increases in CBF reduce the volume of cortex falling below ischemic injury thresholds, protecting tissue and facilitating transcription of inducible genes proximal to the ischemic focus. In addition, MK-801 attenuates the signals that induce expression of immediate-early genes in cortical and subcortical regions remote from the middle cerebral artery territory. (+info