Cerebral oxygen transport and metabolism during graded isovolemic hemodilution in experimental global ischemia

To verify the optimal hematocrit (Hct) level in the treatment of cerebral ischemia, cerebral oxygen transport (CTO₂) and cerebral oxygen metabolism (CMRO₂) in graded isovolemic hemodilution were evaluated during cerebral ischemia. Isovolemic hemodilution with low molecular weight dextran to stepwise lower Hct from 43% to 36%, 31%, and 26% was carried out in 13 splenectomized dogs, 6 h after global cerebral ischemia. Global ischemia of the animals was produced by multiple intra- and extracranial ligations of cerebral arteries. Cerebral blood flow (CBF) was measured with radioisotope labeled microspheres. CTO₂, CMRO₂, and oxygen extraction fraction (OEF) were calculated from CBF, arterial oxygen content (CaO₂), and venous oxygen content (CvO₂). In dogs with global cerebral ischemia, CBF increased with graded isovolemic hemodilution (r=−0.73, P<0.05). CTO₂ reached its highest value at a Hct level of 31.3%. CTO₂ at Hct of 36.1% and 31.3% was statistically different from the value measured at a Hct of 43.3%, and there was a decrease when Hct was lowered to 25.9%. CMRO₂ was the highest when Hct was at 31.3% and differed significantly from the value measured at a Hct of 43.3%. There was a 10% increase of OEF when Hct was at 25.9%; however this change was not statistically significant compared with the OEF at Hct of 36.1% and 31.3%, respectively. These findings indicate that CTO₂ and CMRO₂ were the highest when Hct was reduced to 31% in hemodilution. Hct at 31% is the optimum for cerebral metabolism in ischemic status. Uncoupling of CTO₂, CMRO₂ with CaO₂ was also observed in this study. This phenomenon suggests that hemodilution to augment cerebral circulation may be at least partially attributed to the beneficial effects of hemorheologic improvement in the microcirculation of the ischemic brain.     

Autoregulatory capacity and the effect of isovolemic hemodilution on local cerebral blood flow

The effect of isovolemic hemodilution with dextran 40 on local cerebral blood flow was measured in eight cats by means of the hydrogen clearance technique. Under normotension the decrease of hematocrit from 35% to 25% causes a sudden increase of up to 30% in local cerebral blood flow. After lowering the mean arterial blood pressure from 140 to 80 mm Hg, hemodilution did not alter cerebral blood flow significantly. From this observation it is concluded that the increase of cerebral blood flow following hemodilution is caused by compensatory vasodilatation and not by reduction of blood viscosity. This could imply that hemodilution cannot improve blood flow in areas of impaired autoregulation.     

Mechanism of cerebral blood flow augmentation by hemodilution in rabbits.

BACKGROUND AND PURPOSE: Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. METHODS: Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. RESULTS: In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. CONCLUSIONS: Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia.     

Cerebral blood flow after carotid occlusion and extracranial-intracranial bypass.

Eleven patients with occlusion of one internal carotid artery showed marked reduction of regional cerebral blood flow (rCBF) through the hemisphere on the affected side with high rCBF on the opposite side. Six of the patients had no surgery, during follow-up of 2 to 5 years. rCBF increased on both sides leaving a persisting asymmetry of rCBF. Five patients had extracranial-intracranial bypass; rCBF increased on the affected side but not on the opposite side. Asymmetry of rCBF between the hemispheres remained but was much less than in the non-operated group.     

Cerebral blood flow and common carotid flow in neurologically asymptomatic carotid endarterectomy patients

To define subgroups in 50 neurologically asymptomatic patients with carotid stenosis (mean diam. of stenosis 81.1 ± 12.5%) regional cerebral blood flow (rCBF) and common carotid artery flow were measured by means of the intravenous Xenon-133 technique and a Doppler flowmeter; respectively. The rCBF studies were performed both at rest and after administration of acetazolamide (Diamox). In this asymptomatic cohort of 50 patients we found subgroups with significant hemispheric baseline asymmetry (BA) (five patients; BA = 7.2 ± 1.8%) and/or pathological Diamox asymmetry enhancement (DAE) (five patients; DAE = 8.8 ± 1.3%). Carotid endarterectomy in these cases resulted in a significant reduction of hemispheric differences of rCBF (postoperative BA = 0.4 ± 3.4, postoperative DAE = 1.7 ± 3.8). Measurements of common carotid flow revealed significantly higher flow rates in the postoperative period and compensation of intercarotid flow asymmetry. In pathophysiologically defined preclinical subgroups of cerebrovascular disease with hemispheric rCBF differences and/or impairment of the cerebral vascular reserve capacity surgical procedures might be useful.     

Cerebral blood flow and common carotid flow in neurologically asymptomatic carotid endarterectomy patients

To define subgroups in 50 neurologically asymptomatic patients with carotid stenosis (mean diam. of stenosis 81.1 +/- 12.5%) regional cerebral blood flow (rCBF) and common carotid artery flow were measured by means of the intravenous Xenon-133 technique and a Doppler flowmeter, respectively. The rCBF studies were performed both at rest and after administration of acetazolamide (Diamox). In this asymptomatic cohort of 50 patients we found subgroups with significant hemispheric baseline asymmetry (BA) (five patients; BA = 7.2 +/- 1.8%) and/or pathological Diamox asymmetry enhancement (DAE) (five patients; DAE = 8.8 +/- 1.3%). Carotid endarterectomy in these cases resulted in a significant reduction of hemispheric differences of rCBF (postoperative BA = 0.4 +/- 3.4, postoperative DAE = 1.7 +/- 3.8). Measurements of common carotid flow revealed significantly higher flow rates in the postoperative period and compensation of intercarotid flow asymmetry. In pathophysiologically defined preclinical subgroups of cerebrovascular disease with hemispheric rCBF differences and/or impairment of the cerebral vascular reserve capacity surgical procedures might be useful.     

Asymptomatic carotid stenoses. Course and discussion of their treatment

Asymptomatic carotid stenoses are common. They are associated with the risk factors for arteriosclerosis and are a specific risk factor for coronary artery disease, with an annual morbidity/mortality (MM) rate of 8-10%. Detection of a carotid stenosis should therefore be followed by a complete risk factor analysis and modification, if appropriate; a thorough cardiological diagnostic investigation is particularly important. Individual risk indicators for stroke (annual MM 1-2%) are a rapid progression of the degree of stenosis, certain morphological patterns and the presence of extra- and intracranial multi-vessel disease. Trials available so far on the treatment of asymptomatic carotid stenosis have not revealed any significant parameters that would justify individual decisions on whether or not surgery is appropriate. There is therefore a danger that many patients will be exposed to a severe risk of stroke, which cannot be justified unless the centres where such interventions are performed have proven MM complication rates of <3%, the life expectancy of the patients treated is not restricted as the result of other illnesses and the patients explicitly request surgery after a thorough explanation of the risks. Conservative treatment strategies provide the best protection for the majority of patients.     

Internal carotid arterial blood flow velocity in infants.

The differences in the velocity and pulsatility indexes in the internal carotid artery were evaluated in 62 normal controls, 42 infants with cerebral palsy, and 22 infants with mental retardation, all within the first year of life. In the normal controls, the average maximal blood flow velocity (A/L), and the maximal end-diastolic flow velocity increased during the first year of life. Pulsatility index decreased significantly between the ages of newborn to 2 mos and 3-5 mos, and remained constant thereafter. Compared with normal controls, the average maximal blood flow velocity and the maximal end-diastolic flow velocity values were significantly reduced in infants with cerebral palsy during the first 6 months of life, while no differences in these values were observed in infants with mental retardation. There were no differences in the pulsatility index values in the 3 subject groups throughout the first year of life. Flow velocity in the internal carotid artery could reflect the status of the cerebral circulation in infants within the first year of life.     

Cerebral blood flow in infants: comparison of carotid blood flow and cerebral blood velocity

Carotid blood was measured with a ultrasonic volume flow meter in 38 infants. The carotid blood flow was 1.50 +/- 0.55 ml/sec. At the same time peak systolic flow velocity, mean blood velocity, end diastolic velocity, pulsatility index (PI) and resistance index (RI) in the middle and anterior cerebral arteries were measured by duplex Doppler scanning. There was a correlation between the carotid blood flow and the mean blood velocity in middle and anterior cerebral arteries. However, PI and RI were not well correlated with carotid blood flow.     

Symptomatic and asymptomatic high-grade carotid stenoses in Doppler color-flow imaging.

We examined 63 patients with 31 symptomatic and 44 asymptomatic carotid stenoses with Doppler color-flow imaging (DCFI); conventional Doppler duplex had shown a hemodynamic obstruction (greater than or equal to 80% stenosis) in all patients. Analysis of plaque surface morphology demonstrated more ulcerated plaques in symptomatic (43%) than asymptomatic (23%) stenoses. Although the frequency of homogeneous and heterogeneous plaques was not different, calcific lesions were more frequent in asymptomatic (46% versus 29%), and echolucent plaques, probably indicating mural thrombi, were more frequent in symptomatic (29% versus 11%) stenosis. Color-coded hemodynamic patterns, such as jet flow, poststenotic turbulence, or reversed flow, were not different in symptomatic and asymptomatic stenoses. Comparison of DCFI with 30 angiograms showed agreement in plaque surface analysis in 70%. DCFI measurements of area reduction in cross sections correlated with angiography in 85%, while DCFI tended to underestimate the degree of stenosis from diameter reduction in longitudinal cuts. The advanced DCFI technique identified distinct morphologic features but no hemodynamic patterns, separating symptomatic from asymptomatic high-grade carotid stenoses.