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We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.

Nicorandil is usually considered to be a potent antianginal agent characterized as a potassium channel opener. It has been suggested that it may exert similar action on cerebral vessels. We administered nicorandil to surgical patients under general anesthesia. While the regional cerebral oxygen saturation (rSO2) and blood volume index (BVI) were determined continuously, each patient received the drug at dose of 0.08 mg.kg-1.h-1 initially, and after 15 minutes, the dose was increased by 0.08 mg.kg-1.h-1 at a time. This was repeated until the dose reached 0.40 mg.kg-1.h-1. At every dose level, rSO2 and BVI were determined, and the dose-response relationship was obtained. We found that nicorandil also produces cerebral arterial dilation under clinical conditions.

The purpose of this study was to establish the assessment of gingival blood flow by laser Doppler flowmeter (LDF) using three parameters; Velocity, Volume, and Flow. The gingival blood flow (GBF) at the labial attached gingiva of the maxillary incisor was measured by LDF in 10 healthy subjects, 3 men and 7 women. There were inter- and intra-individual variations in the obtained data. CV (coefficient of variance) values in each parameter of GBF while resting were as follows; Velocity: 10.2 approximately 34.5%, Volume:7.7 approximately 45.6%, and Flow: 15.4 approximately 67.6%. The effects of changing position, cold stimulus, and the vasoconstrictor (0.1w/v% epinephrine) on GBF were assessed. All three parameters significantly decreased (p < 0.01) after the cold stimulus. When the position was changed to the sitting position from the lying one, however, there were significantly decrease in Velocity (p < 0.001) and Flow (p < 0.02). On the other hand, the local application of the vasoconstrictor caused significant decrease in Volume (p < 0.01) and Flow (p < 0.01). Consequently, Flow significantly decreased after all the stimuli in the present study, however, the change of Velocity and Volume were variable depending on the type of stimulus. These results suggested that multiple parameters are needed for precise observation and analysis of blood flow.

Ventricular pressure-volume relationship enables us to understand the relationship among the heart, vasculature, and blood volume, since it provides, on a single plane, the preload, afterload, and cardiac contractility, which are major determinants of stroke volume. In addition, it is also possible to estimate cardio-vascular matching, namely the optimum of cardio-vascular interaction, by an analysis of ventricular pressure-volume relationship. Volatile anesthetics cause circulatory depression due primarily to decreases in cardiac contractility and stressed blood volume. The optimal treatment for it is to restore these decreases produced by volatile anesthetics. Thus, an increase in afterload by vasoactive agents may cause deterioration of cardio-vascular matching. A rationale for optimal perioperative circulatory management can be deduced from understanding a quantitative interaction among the heart, vasculature, and blood volume.

Effects on circulating blood volume (CBV) of the intravenous injection of a nonionic contrast medium, ioversol, with various doses were assessed in order to find a way of injection with less effects on systemic circulation. Ioversol was injected as a bolus to 20 mongrel dogs at doses of A: 3.75 ml/kg (n = 8) or B: 2 ml/kg (n = 6) of a solution containing 320 mg iodine per ml, or C: 2 ml/kg (n = 6) of a 240 mgI/ml solution. Colloid oncotic pressure (COP) of the bloods drawn before and 1, 2, 3, 5 min after the injection of ioversol was measured by a needle type osmometer, and changes in CBV were calculated using the COP values. Upon injection of ioversol CBV increased rapidly and then gradually returned to the preinjection levels. The change in CBV induced by ioversol was significantly less than those reportedly induced by an ionic contrant medium, iothalamate, and a nonionic medium, iopamidol, and comparable to that by another nonionic medium, iohexol. The degree of increase in CBV and the blood concentration of ioversol were related to the amount, but not the volume, of ioversol injected. Thus, ioversol proved to be one of the low osmotic nonionic contrast media with less effects on CBV. Furthermore, it is suggested that the amount, rather than volume, of contrast medium should be taken into consideration when the angiography of the patients with reduced cardiac function, children or aged patients is performed in whom the contrast medium-induced CBV expansion needs to be as less as possible.

In congestive heart failure (CHF), a variety of compensatory mechanisms such as activation of sympathetic nervous system, renin-angiotensin system and vasopressin, facilitate water and sodium retention and increase circulating blood volume, which primarily improve systemic perfusion. However, hypervolemia sometimes induces pulmonary edema and afterload elevation, resulting in a further decrease in cardiac output. Diuretics are administered in patients with CHF to cut this vicious cycle by reducing blood volume. Evaluation of hemodynamic states is important in patients with severe CHF, since an excessive reduction in preload could critically decrease cardiac output. Among conventional diuretics, loop diuretics is the most potent and widely used for management of CHF. Inhibition of such compensatory mechanisms such as angiotensin-converting enzyme inhibitors and atrial natriuretic peptide-related agents is shown to exert natriuretic and desirable hemodynamic effects in CHF and is among candidates for future diuretics.

Changes in circulating blood volume during isoflurane or sevoflurane anesthesia under spontaneous breathing were investigated by the dual indicator dilution method in 13 mongrel dogs. The animals were randomly divided into three groups; control (C) group n = 5, isoflurane (I) group n = 5, and sevoflurane (S) group n = 5. Changes in circulating blood volume (ml.kg-1) at 0, 0.5, 1.0 MAC were 87.7 +/- 8.2-->88.7 +/- 5.0-->91.0 +/- 5.9 in the I group and 84.4 +/- 7.0-->91.4 +/- 7.7-->91.4 +/- 10.2 in the S group, respectively. In the S group, circulating blood volume and plasma volume increased significantly, while in the I group the volumes tended merely to increase. Arterial carbon dioxide tension (PaCO2) in the I and S groups increased significantly at 0.5 and 1.0 MAC, but similar changes were also noted (not significantly) in the C group. Mean arterial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure tended to increase at 0.5 and 1.0 MAC in the C and I groups, but tended to decrease in the S group. The results suggest that the increase in vascular compliance with sevoflurane under spontaneous breathing has resulted in the increase in plasma volume and circulating blood volume.

Changes of circulating blood volume during isoflurane or sevoflurane anesthesia were investigated by the dual indicator dilution method in eighteen mongrel dogs. The animals were randomly divided into three groups; control (C) group n = 6, isoflurane (I) group n = 6, and sevoflurane (S) group n = 6. The values of circulating blood volume (ml.kg-1) at 0, 0.5 and 1.0 MAC period were 90.1 +/- 18.7----87.5 +/- 17.2----94.1 +/- 23.6 in the I group and 91.6 +/- 12.5----96.5 +/- 15.0----94.1 +/- 8.5 in the S group, respectively. No significant changes were found in both groups concerning circulating blood volume, red cell volume, and plasma volume, but circulating blood volume and plasma volume tended to increase slightly in both groups at 0.5 and 1.0 MAC period compared with 0 MAC period. Mean arterial pressure decreased 68% of the initial value in the I group at the 1.0 and 78% stages in the S group. Cardiac index tended to increase from 2.6 +/- 0.4 l.min-1.m2 to 3.2 +/- 0.9 in the I group at the stage 1.0 but to decrease from 5.2 +/- 1.4 l.min-1.m2 to 4.1 +/- 0.9 in the S group. It was suggested that the increase of venous pressure resulted in the significant decrease of plasma volume. Increase of intrathoracic pressure during positive pressure ventilation might partially influence the blood volume change. Our data suggest that isoflurane and sevoflurane do not greatly affect the circulating blood volume under control ventilation.

We assessed whether the osmotic expansion of circulating blood volume (CBV) induced by nonionic contrast medium (NCM) is less than that induced by ionic contrast medium (ICM). Iohexol (Io) (NCM: 795 mO sm/kg H2O), 1.28 g iodine/kg, was injected intravenously into 5 mongrel dogs and blood samples were drawn at certain times. One week later, meglumine iothalamate (MI) (ICM: 1470 mOsm/kgH2O), 1.28 g iodine/kg, was injected into the same dogs. Another 5 dogs received MI first and Io one week later. Colloid oncotic pressure (COP) of the blood samples was measured by a needle osmometer, and changes in CBV were calculated from the COP values. The injection of Io or MI resulted in an immediate decrease in COP, and an increase in CBV at 1 min. MI induced significantly more severe and longlasting changes in COP and CBV than Io. Neither MI nor Io modified COP when they were added to the control blood samples. Thus, although NCM considerably expanded CBV, the magnitude of expansion induced by NCM was less than that induced by ICM. This may explain one of the reasons why NCM causes fewer adverse reactions than ICM.

Eighteen anesthetized cats were randomly divided into 3 groups. One group was treated with 10 ml/kg of 6% hydroxyethyl starch (HES). Another group was treated with 15 ml/kg, and there was a control group. There were six cats in each group. Cerebral pial arterial reactivities were measured by means of intravital microscopic observation through a cranial window. Middle cerebral artery (MCA) was clipped for 70 minutes using a transorbital approach. Five hours later, Evans blue dye was injected intravenously and then the animals were killed. Administration of HES or Ringer's solution (control) was started 15 minutes before clipping of MCA. Systemic arterial pressure was elevated by using dopamine at the same time as the MCA occlusion was carried out. Pial arteries dilated soon after the clipping of MCA in all three groups, but showed different patterns in each group after recirculation of MCA. In the control group, they returned to 20% of their dilated state first, but, after about 4 hours, they redilated by 45% at the end of experiment periods. In the group treated with 10 ml/kg of 6% HES, they remained in an almost resting state after MCA recirculation, but in the group with 15 ml/kg, they constricted by 10% at the end of the experiment periods. Regarding the Evans blue dye extravasation, cerebral edema and infarction, they were largest in the control group. But animals treated with 15 ml/kg of 6% HES showed significantly larger Evans blue dye extravasation and cerebral edema than that of animals with 10 ml/kg. However cerebral infarctions were almost the same sizes in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Local cerebral blood flow (LCBF), local cerebral glucose utilization (LCGU) and capillary permeability were studied in rats with tumor-induced brain edema. Moreover, effects of methylprednisolone on these physiological parameters were studied to analyse a possible role of steroid on treatment of peritumoral brain edema. A cubic millimeter pellet of Walker 256 tumor was transplanted to the left sensorimotor cortex of the rat brain. Animals were randomly divided into two groups. One group was treated with methylprednisolone (15 mg/kg/day) for 5 days starting at 5 days after tumor inoculation, and the other group received no treatment. These rats were used for autoradiographic study at 10 days after tumor inoculation. Local CBF, LCGU and capillary permeability were measured with 14C-iodoantipyrine, 14C-deoxyglucose and 14C-alphaaminoisobutyric acid, respectively. In the untreated group, LCBF and LCGU were widely depressed in the cortex and deep structures of the hemisphere ipsilateral to the tumor. Of the methylprednisolone treated animals LCBF and LCGU were significantly better than that of untreated animals. Capillary permeability of the untreated animals were highly increased in the viable part of the tumor. Some increase was also noted in the peripheral edge of the tumor and adjacent brain. In the methylprednisolone treated groups, capillary permeability was significantly lower than that in untreated group. The data suggest that methylprednisolone decreases capillary permeability in the viable part of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of treatment with bacterial preparations on blood flow in normal and malignant tissues was investigated, clinically and experimentally. The time course of the local effect of the preparations was recorded by Laser Doppler Velocimetry (LDV) via a probe on the surface of normal and malignant tissues directly over the injection site. Experimentally, no definite enhancement of blood flow with OK-432, a streptococcal preparation, was observed in nude mice. Clinically, intradermal administration of OK-432 or tuberculin (PPD) resulted in an approximate 11-or 4-fold increase in blood flow, respectively. The injection of OK-432 into malignant tissues, such as dermal cancer and breast cancer with direct extension to the skin, resulted in an approximate 3.5-fold increase. The results suggested that bacterial preparations can act as an adjuvant to enhance drug delivery to tumor tissue in cancer chemotherapy, and that the enhancement of blood supply is induced by immune response.

Cerebral blood flow was measured in 10 patients with subarachnoid hemorrhage using the 133Xe inhalation methods. Regional cerebral blood flow (r-CBF) values were calculated with initial slope index, their values were compared with the blood flow response to the administration of low dose dopamine (DA). CBF values of just after and continuous administration of DA were compared with control values. The measurement of r-CBF was performed immediately after the infusion of 5 micrograms/kg/min DA for 30 min. The focal ischemic lesions decreased, bi-hemispheric mean CBF value (7 cases without A-Com patients) increased by 10.3% significantly (paired T test), affected hemispheric mean CBF value increased by 8.7% significantly and non-affected hemispheric mean CBF value increased by 16.6% significantly. The PaCO2 value didn't change but the mean systemic blood pressure increased by 5.1% significantly. The CBF values of continuous administration of DA for 10 days to 2 weeks were measured. The CBF values increased during the administration of DA. The mean CBF values increased without the steal phenomenon and the mean arterial blood pressure increased slightly after the administration of DA. These phenomena were observed more significantly in non affected side than affected side. We suggest that the administration of DA increase the CBF values in patients with subarachnoid hemorrhage due to the stimulation of DA receptor.

Review was made on the effect of adenosine triphosphate, 1.0-3.0 mg/kg intravenously, on the cerebral circulation and the presence of the dilating action on the cerebral blood-vessels in cats. 1. The group of the normal intra-cranial pressure showed, as reported previously, the transient hypotension and its complicated decrease of cerebral blood-circulation at the initial period for 30-100 check, then demonstrating the increase of cerebral blood-flow for 200-1000 check. Its increased volume and duration were dose-dependent. 2. The group of the loaded intracranial pressure of 20-30 mmHg (slightly elevated group) showed the increase of cerebral blood-flow, like the group of the normal intracranial pressure. However, the effect of ATP showed the decrease or disappearance in accordance with the elevation of the loaded pressure. 3. Cerebral vasodilating effect of ATP was promptly observed after the administration, and its degree was 30-50% in photographical observation. 4. Increasing effect on cerebral blood-flow and cerebral vasodilating action of ATP were similar in the pattern to that of vasodilators such as papaverine hydrochloride.

The effect of intravenous administration of diltiazem on cerebral circulation and brain function were studied in animals. Diltiazem, at a dose of 150 micrograms/kg BW, was administered intravenously over a period of 5 minutes beginning 30 minutes after ligation of the right brachiocephalic artery in 9 cats in order to investigate its effects in the acute stage of cerebral ischemia. In 5 animals, mean arterial blood pressure was recorded and blood flow in the basilar artery was measured transdurally by use of an ultrasonic Doppler flow-meter. Mean arterial blood pressure began to elevate immediately after ligation of the right brachiocephalic artery, but the degree of elevation was minimal. It began to fall during diltiazem injection and returned to the preadministration value 30 minutes after injection. Basilar artery flow decreased slightly during injection of diltiazem, but began to increase after completion of injection. The increase relative to the preadministration value was 62 +/- 31% 10 minutes after injection, 88 +/- 38% 20 minutes after, and 24 +/- 53% 30 minutes after. The short latency somatosensory evoked potentials (short latency SEP) recorded in the other 2 animals showed no noticeable change either in amplitude or latency during the same procedures. In 1 of 2 animals in which brainstem auditory evoked potentials (BAEP) were monitored, the latency of peak IV increased after ligation of the right brachiocephalic artery, and decreased 20 minutes after injection of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

The usefulness of hydrocortisone for the treatment of cerebral vasospasm was investigated using dogs by measuring changes in cerebral arterial diameter in angiograms as well as in other parameters such as blood pressure, intracranial pressure and CBF. The intrathecal (50-300 mg) or intravenous (100 mg/kg) injection of hydrocortisone resulted in a marked dilatation of cerebral arteries both in control animals and vasospastic animals after subarachnoid hemorrhage. The intrathecal injection caused a temporary rise in blood pressure immediately following the injection. Cerebrospinal fluid pressure was increased progressively. On the other hand, the intravenous injection resulted in a fall in blood pressure and a transient rise in cerebrospinal fluid pressure. CBF showed a tendency to increase both with intrathecal and intravenous injection. With intravenous injection a high CSF level of cortisol was found 1 and 2 hours after the injection and it was correlated to the degree of cerebral arterial dilatation, indicating that a significant amount of hydrocortisone could penetrate into the CSF and dilate the intracranial vessels by its direct pharmacological action.

Pressor responsiveness to angiotensin II (A II) or norepinephrine (NE) in anesthetized nonpregnant and pregnant dogs, and the changes in renal blood flow (RBF) and uterine blood flow (UBF) elicited by the pressure rise in pregnant dogs were studied. Intervention of prostaglandins (PGs) in these hemodynamic responses was also examined, comparing the responses before and after the administration of indomethacin (IDM). The pressor responsiveness to the pressor substances was diminished in near term pregnant dogs in common with normal human pregnancy, and the refractoriness disappeared after the administration of IDM. RBF decreased following the infusion of A II or NE, and IDM enhanced the responses. A characteristic increase in UBF was observed following the infusion of A II exhibiting the maximum response at a dose of 0.05 microgram/kg, while it decreased following the infusion of NE, and these responses remained almost unchanged after IDM administration, although there was a 24.2% decrease in the base line value of UBF. It seems appropriate to conclude that PGs play a pivotal role in the development of the relative vascular refractoriness to infused pressor substances characterizing normal pregnancy, and also in preservation of RBF and UBF during pregnancy. Moreover, PGs attenuate the response of the renal vascular bed as well as systemic vascular bed to the pressor substances. However, the refractoriness of uterine vascular bed to A II remained almost unchanged regardless of PGs synthesis, suggesting the existence of another competitive factor involved in the effect of A II.

Hemodynamic responses to propranolol and isoproterenol were examined in elderly patients with heart failure. The results obtained are as follows: 1. Patients with mild heart failure showed greater reduction than control group in heart rate and cardiac output after intravenous propranolol. These enhanced hemodynamic responses to propranolol would be the evidence of increased adrenergic activity even in mild heart failure. 2. Intravenous propranolol in the small dosage of 0.03 mg/kg showed only a negligible hemodynamic deterioration even in patients with heart failure. 3. Hemodynamic responses to beta-adrenergic stimulator, isoproterenol, were depressed in severe heart failure.

Using positron emission tomography with 15O-labelled CO2 O2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO2) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol.

Since the first description by Aukland and co-authors in 1964, the hydrogen washout has been shown to be an accurate method in determining regional tissue blood flow. The presence of hydrogen molecules within the tissue is detected with a platinum electrode where a small amount of current is generated by oxidation of molecular hydrogen to hydrogen ions. Therefore, construction of the suitable electrode for the tissue to be measured is essential. The author applied the hydrogen washout technique to the blood flow measurement of bone, muscle, skin, digit and peripheral nerve, and found that the technique was valuable in basic and clinical studies in orthopedics. As a typical experimental study using the hydrogen washout technique, the study on the effect of adrenaline on bone blood flow was presented and the experimental method was explained in detail. Although the hydrogen washout technique has been developed to measure the blood flow, the technique has been found useful in detecting the pathways of microcirculation between different tissues. As an example, the study on nutritional pathways of the intervertebral disk was described. Since the hydrogen gas is harmless, it is possible to apply the technique to the clinical studies including the blood flow measurement of replanted digits, diagnosis of the compartment syndrome and the blood flow measurement of skin flaps. Furthermore, several problems in the hydrogen washout technique were discussed.

Various types of gastric tubes for esophageal substitute were constructed and their advantages and disadvantages were compared. The most important point in esophageal reconstruction is to obtain a gastric tube with sufficient blood supply and with adequate length for the reconstruction. The author constructed 4 types of gastric tube in dogs, that is, whole stomach (A) and gastric tubes with 6 cm (B), 3 cm (C) and 1.5 cm (D) in width respectively, dissecting the lesser curvature side of the stomach to the various extents. The tissue blood flow was measured at the point 3 cm oral from the uppermost pulsation of right gastroepiploic artery using a hydrogen clearance method. The flow rates were found to be 32.8, 30.9, 50.9 and 27.9 ml/min/100 g in gastric tubes A, B, C and D, respectively. It was also found that the blood flow rates in the right gastroepiploic artery were nearly the same in tubes A, B and C, but it decreased remarkably in tube D. Histologic study revealed that the microvasculature of the gastric tube A, B and C was well preserved although that of the tube D was damaged to some extent, resulting in decreased circulation in site. These results clearly indicated that the gastric tube C with 3 cm width is the best choice among the various types of gastric tubes compared, giving adequate blood supply and sufficient length to meet any route in esophageal reconstruction.