Masahito Kusunoki

Effects of Hematocrit Variations on Cerebral Blood Flow and Oxygen Transport in Ischemic Cerebrovascular Disease

The contribution of hematocrit (Ht) changes on cerebral blood flow (CBF) and brain oxygenation in ischemic cerebrovascular disease is still controversial. In the present study, effects of Ht variations on CBF and oxygen delivery were investigated in patients with ischemic cerebrovascular disease. CBF was measured by the Xe-133 intracarotid injection method in 27 patients, whose diagnoses included completed stroke, reversible ischemic neurological deficit, and transient ischemic attack. Ht values in the patients ranged from 31 to 53%. There was a significant inverse correlation between CBF and Ht in these Ht ranges. Oxygen delivery, i.e., the product of arterial oxygen content and CBF, increased with Ht elevation and reached the maximum level in the Ht range of 40–45% and then declined. The CBF-Ht and oxygen transport-Ht relations observed in our study were similar to those in the glass-tube model studies by other workers rather than to those in intact animal experiments. From these results, it is conceivable that in ischemic cerebrovascular disease, the vasomotor adjustment was impaired in such a manner that the relations among Ht, CBF, and oxygen delivery were different from those in healthy subjects. Further, an “optimal hematocrit” for brain oxygenation was also discussed.

Effect of small deep hemispheric infarction on the ipsilateral cortical blood flow in man.

The effect of small, deep ischemic lesions on the ipsilateral cortical circulation was investigated in 10 patients with persistent mild or moderate neurological deficits due to infarcts in the internal capsule. rCBF studies by the 133Xe intracarotid injection method were performed 14-180 days after the onset of the infarction. The rCBF functional image was made up from the data of 133Xe dynamic images measured by an Anger-type gamma camera and the rCBF values were calculated by the initial slope method. The average value of mean rCBFs (mCBF) in 10 patients was 44.9 +/- 7.1 ml/100g/min (average PaCO2; 39.9 +/- 4.3 mm Hg). In the rCBF functional images, a focal hypoperfusion area was observed in all cases and localized around the central sulcus, especially in the precentral and central areas. Significant decreases of mCBF and the tendency to decrease of the rCBFs in the hypoperfusion focus were noted in the patients with the larger infarcts in comparison with those with the smaller ones. These results suggest that a small, deep ischemic lesion such as a capsular infarct may have remote effects on the ipsilateral cortical circulation, due probably to the damage of a number of fibers passing through the lesion.

Plasma concentrations of thromboxane B2 in patients with hypertension or cerebrovascular disease

Abstract The peripheral venous plasma levels of thromboxane B 2 (TxB 2 ) were determined by radioimmunoassay in 22 control subjects, 12 patients with essential hypertension, 15 patients with cerebrovascular disease (CVD) not taking aspirin and 14 patients with CVD taking aspirin. There was no significant difference in TxB 2 levels among the control subjects, hypertensive patients and CVD patients not taking aspirin. In CVD patients taking aspirin, the plasma TxB 2 levels were significantly lower than those in the other groups. The internal jugular venous concentrations of TxB 2 were measured in 10 CVD patients not taking aspirin. Four of 10 studied patients exhibited significant increases only in the internal jugular venous TxB 2 levels, while peripheral venous and/or femoral arterial TxB 2 levels were not significantly different from peripheral venous TxB 2 levels of control subjects.

Effect of aspirin and ticlopidine on platelet deposition in carotid atherosclerosis: assessment by indium-111 platelet scintigraphy.

The antiplatelet effects of aspirin and ticlopidine were studied by a dual-tracer method, using indium-111 labeled platelets and technetium-99m human serum albumin, in a group of 12 patients with suspected ischemic cerebrovascular disease. The magnitude of platelet accumulation at the carotid bifurcation was expressed as the ratio of radioactivity of indium-111 platelets deposited on the vascular wall to those circulating in the blood-pool (PAI, platelet accumulation index), 48 hr after injection of labeled platelets. PAI values were measured before (baseline studies) and after the antithrombotic therapies (aspirin studies: 325 mg bid for 22.3 +/- 1.3 days, ticlopidine studies: 100 mg tid for 21.8 +/- 2.1 days). At the baseline, the mean PAI value at 24 carotid bifurcations in the patient group was 15.7 +/- 15.3% (mean +/- S.D.) compared to -4.3 +/- 9.1 at 24 carotid bifurcations in 12 normal subjects (p less than 0.01). We defined the upper limit for a normal PAI (%) value to be +13.9, namely the mean PAI plus 2 SD for the carotid bifurcation in normal subjects and used this value for semiquantitative analysis. At the baseline, significant elevation of PAI (more than 13.9%; positive scintigram) was observed at 12 of 24 vessels, while 12 other regions were negative (less than 13.9%). In the lesions with positive scintigraphic results at the baseline, the mean PAI (%) value from the baseline, aspirin and ticlopidine studies was 29.5 +/- 7.0, 11.2 +/- 8.5 (p less than 0.01 versus baseline) and 21.4 +/- 21.3 (not significant from baseline), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet aggregation induced by arachidonic acid and thromboxane generation in patients with hypertension or cerebrovascular disease

The aggregability of platelets to arachidonic acid (AA) was investigated in 26 control subjects, 40 patients with essential hypertension, 20 patients with ischemic cerebrovascular diseases (CVD) not taking aspirin and 11 patients with CVD taking aspirin. The aggregability of platelets was evaluated on the basis of threshold concentrations of AA to induce irreversible platelet aggregation. The enhanced sensitivity of platelets to AA was observed more frequently in hypertensives and/or CVD patients not taking aspirin than in the controls. The relationship between platelet aggregation induced by AA and thromboxane B2 (TXB2) formation from AA or prostaglandin H2 (PGH2) in platelets was also studied in the subjects taking or not taking aspirin. It was proposed that the assessment of platelet aggregability with AA could provide a tool for identifying a subgroup of patients who might substantially benefit from the secondary preventive treatment with aspirin or other anti-platelet drugs. The clinical usefulness of this aggregation test for the management of the patients taking aspirin was also discussed.

Prediction of arterial oxygen partial pressure from intrapulmonary venous admixture

A short program was developed to predict the PaO2 at a given FIO2 by using arterial and mixed venous blood gas data obtained at an FIO2 of 1.0. Our program resolves Adairs equation and the shunt equation inversely, on the assumption that intrapulmonary venous admixture and the arteriovenous oxygen content difference remain constant during the study. The study was conducted on 19 patients with respiratory failure who were intubated and mechanically ventilated. According to linear regression analysis, regression coefficients of 0.91 and 0.97 were obtained between the measured PaO2 values and those estimated by the arterial/alveolar oxygen tension ratio (PaO2/PaO2) and our program, respectively (n = 23). The PaO2 values were predicted more accurately by our program than those calculated by PaO2/PaO2. Because our program is simple enough to be carried out with a pocket computer, it may be helpful in a bedside decision of lowering FIO2, especially in patients who require a high FIO2 level to maintain sufficient arterial oxygenation.

Imaging platelet deposition on Dacron bifurcation grafts in man: Quantification by a dual-tracer method using 111In-labeled platelets and 99mTc-labeled human serum albumin

A dual tracer technique using 111In-labeled platelets and 99mTc-labeled human serum albumin was applied to evaluate the thrombogenicity of Dacron bifurcation arterial grafts. The level of platelet accumulation over the whole of the graft was estimated from the ratio of 111In-platelet radioactivity deposited on the vascular wall to these radioactivity circulating in the blood pool, i.e., the platelet-accumulation index (PAI). Furthermore, the PAI value was calculated for each pixel in digitized images and the PAI distribution image (PAI image) was reconstructed. Eighteen patients with DeBakey knitted Dacron bifurcation grafts and 11 normal volunteers were studied. Of the 18 patients, 11 had no graft occlusion (group I) and the remaining 7 (group II) had occlusion. The mean PAI value (±SD) over the whole of the graft in group I was 32.6%±33.7% as compared to -8.8%±4.5% in the control group (P<0.01). In group I, the PAI value over the entire graft decreased with the age of the fraft (r=-0.763; P<0.01). In contrast, in group II, platelet accumulation did not diminish with time and persisted beyond the time of which platelet accumulation was no longer found in group I. Moreover, analysis of the PAI images revealed enhanced platelet accumulation on the proximal part of the graft to be more frequent in group II than in group I (6/7 vs 0/11; χc2 = 10.55; P<0.005). The method used for platelet imaging in the present study may be useful in the study of platelet reactions on Dacron arterial prostheses.

Role of prostacyclin in the response of cerebral blood flow to CO2

The prostacyclin (PGI2) formation in cerebral vessels, as reflected by the difference in concentration of internal carotid arterial and internal jugular venous radioimmunoassayed 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), was determined under normocapnic and hypercapnic conditions in 5 patients with mild cerebral thrombotic infarction. There was no evidence that endogenous PGI formation in cerebral vessels was stimulated at mild hypercapnia, while an increase of cerebral blood flow (CBF) induced by hypercapnia was observed. These results suggest that endogenous PGI2 may not be a mediator for the response of CBF to CO2.