Fingertip Blood Flow Research Articles

新しいβ１選択性β遮断薬塩酸ｂｅｖａｎｔｏｌｏｌの日本人健常成人における薬物動態と薬理作用

Clinicopharmacological study of bevantolol, a newly developed β1-selective β-blockingagent was carried out in Japanese healthy male volunteers. The pharmacokinetics, pharmacodynamics, and safety were investigated after single and once-daily repeated oraladministration of 100 mg and 200 mg of bevantolol. The following results were obtained.(1) The time to the maximum plasma concentration (tmax) on an empty stomach was about 0.7 hr and the elimination half-life in α-phase (t1/2α) and in β-phase (t1/2β) were about 1. 4 hr and 9 to 10 hr, respectively. The area under the plasma concentration curve (AUC) and the maximum plasma concentration (Cmax), which showed about a threefold interindividual variation, were about two times greater after the 200 mg dose than after the100 mg dose.(2) On a full stomach, tmax was prolonged to 2 hr. No sign of accumulation was noted after seven days of once-daily repeated doses.(3) The reduction in resting blood pressure after dosing of bevantolol was mild, while pulse rate decreased singnificantly. Fall in blood pressure after postural change from supine to standing position was not evident.(4) Exercise-induced tachycardia and increase in rate-pressure product were significantly attenuated by bevantolol. A high correlation existed between the percent reduction [%R] HR in exercise-induced tachycardia and the logarithm of the plasma concentration of bevantolol.(5) Resting fingertip blood flow measured by venous occlusion plethysmography did not decrease after repeated doses of 100 mg of bevantolol.(6) Regarding subjective symptoms, complaints of headache, dull headache, and gastrointestinal disturbance were noted in some subjects. No profound influence was recognized on the clinical laboratory data. After repeated doses of 100 mg of bevantolol, one subject developed transient loss of consciousness accompanied by a fall in blood pressure and pulse rate. Therefore, careful attention should be paid when the drug isused.

Loss of spontaneous variability of fingertip anastomotic blood flow in diabetic autonomic neuropathy.

We have employed a thermal clearance probe to study fingertip blood flow, which comprises predominantly arteriovenous anastomotic flow. In non-diabetic subjects there was a marked variability in resting fingertip blood flow which was of similar magnitude to that in diabetic subjects without autonomic neuropathy. In 20 diabetic subjects with increasing severity of autonomic neuropathy there was a reduction of spontaneous variability in flow (r = 0.59, P less than 0.001), which was not related to differences in basal flow, in skin thickness or in age. There was no relationship between maximal flow and severity of autonomic neuropathy (r = 0.08), although basal flow was decreased in subjects with moderate, but not those with severe, autonomic neuropathy (P less than 0.01 and P less than .04 compared with controls). Our failure to find an increase in basal fingertip flow in autonomic neuropathy could imply that spontaneous variability of anastomic flow is lost before increased arteriovenous shunting becomes apparent, but it could result from the indirect heating employed in the study causing vasodilatation in subjects without neuropathy.

Measurement of fingertip blood flow using thermal clearance reflects anastomotic rather than nutrient blood flow

A thermal clearance probe was used to measure fingertip blood flow. When flow was occluded the baseline value was reproducible (coefficient of variation 2% between subjects), whereas basal and maximum flow were poorly reproducible even within subjects. Synchronous changes in thermal clearance were seen when two probes were used on fingers and toes of different limbs (r = 0.77 - 0.97), in keeping with a central control mechanism. Fingertip blood flow, as measured by thermal clearance, correlated with Po2 of venous blood draining from the dorsum of the hand (r = 0.72 - 0.92). Contralateral hand cooling caused a sharp reduction of fingertip thermal clearance by 44.2 +/- 3.7%. Thermal clearance traces were damped in fingers with heavy keratinization, and improved when keratin was removed. Comparisons with venous occlusion plethysmography (VOP) and photoelectric plethysmography (PPG) showed that thermal clearance correlates with both methods (r = 0.60 - 0.92 for VOP and 0.64 - 0.93 for PPG) but with much integration of the signal and a 10 s lag. It is concluded that the probes used measure predominantly anastomotic flow and not nutrient skin blood flow alone.

Raynaud's phenomenon: blood supply to fingers during indirect cooling, evaluated by laser Doppler flowmetry.

The effect of indirect cooling on finger-tip blood flow patterns were recorded in 31 patients suffering from Raynaud's phenomenon. Fifteen were suffering from generalized scleroderma with acrosclerosis (GS), and 16 from primary Raynaud's phenomenon (PR), and were compared to 13 healthy controls without cold sensitivity. Finger blood flow (FBF) was monitored by a laser Doppler flowmeter. Resting blood flow values were significantly lower in patients compared to controls. After two min of body cooling no difference could be observed in relative flow decrease between patients and controls or between PR and GS, but after 10 min of body cooling, relative flow decrease tended to be more pronounced in GS than in PR. Only in GS was the zero flow situation observed. During the resting condition, skin vessel vasomotion was observed as rhythmical variations in the blood flow of 5-10 cycles per minute. These seemed to be preserved in patients and in chronically sympathectomized patients, and could not be abolished by nerve blockade of the finger. The influence from sympathetic vasomotor fibres on FBF could be observed during cooling as irregular coarse flow fluctuations. This was observed in both patients and controls but not in the chronically sympathectomized patients and disappeared after nerve blockade of the finger. Finger temperature was measured simultaneously during body cooling, but significant changes were observed only in normals and PR.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of thromboxane synthetase inhibition in Raynaud's phenomenon.

To determine whether thromboxane A2 may be of pathogenetic importance in Raynaud's phenomenon, finger hemodynamic and clinical responses to dazoxiben, a thromboxane synthetase inhibitor, were studied in 25 subjects. Thirteen subjects had idiopathic Raynaud's disease and 12 subjects had secondary Raynaud's disease. A double-blind, 2-week crossover study design was used. Dazoxiben dose was 100 mg four times a day. Total fingertip blood flow (FBF) by venous occlusion plethysmography, fingertip capillary flow (FCF) by radioisotope disappearance rate, and finger systolic blood pressure (FSP) were measured in a 28.3 degree and a 20 degree room at the end of each period. Subjects kept diaries of vasospastic attacks. For the 25 subjects and the two subgroups, dazoxiben did not improve total FBF, FCF, or FSP. Subjects with idiopathic Raynaud's disease had a small decrease in the number of vasospastic attacks and an increase in percentage of attack-free days on dazoxiben, but in an overall evaluation by the subjects in both subgroups, dazoxiben did not improve symptoms. It is concluded that thromboxane is not of pathogenetic importance in Raynaud's phenomenon and that thromboxane synthesis inhibition is not of therapeutic benefit.

Nifedipine-induced fingertip vasodilation in patients with Raynaud's phenomenon

The effect of nifedipine on fingertip hemodynamics was studied in 10 patients with Raynaud's phenomenon. Fingertip blood flow (FBF) was determined in a 20°C environment by venous occlusion air plethysmography and fingertip vascular resistance (FVR) was calculated from the mean blood pressure and the FBF. Nifedipine, administered as a 10 mg sublingual dose, increased FBF in 8 of the 10 patients. FVR for the 10 patients decreased 40% from 40.7 ± 10.8 to 24.2 ± 6.1 U ( p < 0.05). Seven of the 10 patients were followed in a crossover placebo-controlled clinical trial. The frequency and severity of Raynaud's phenomenon was less in all seven patients when taking nifedipine as compared to placebo. Nifedipine-induced fingertip vasodilation may contribute to clinical improvement in some patients with Raynaud's phenomenon.

Digital vasodilatation during mental stress in patients with Raynaud's disease.

Fingertip blood flow was measured by venous occlusion plethysmography before and during a stressful mental task consisting of rapid serial arithmetic calculations in a 25 degrees C room. Significant rises in heart rate and blood pressure indicated that stress was actually induced in all individuals. During mental stress in normal subjects, blood flow decreased (46.4 +/- 6.2 to 22.4 +/- 4.9 ml X min-1 per 100 ml tissue; P less than 0.01) and vascular resistance increased (2.1 +/- 0.4 to 7.6 +/- 2.2 units; P less than 0.01). Patients with Raynaud's disease unexpectedly increased blood flow (15.4 +/- 4.2 to 21.6 +/- 5.7; P = 0.05) and decreased vascular resistance (9.7 +/- 2.3 to 7.1 +/- 1.4; P = 0.05). Ten additional normal subjects were studied in a cool room (20 degrees C). Their digits remained vasoconstricted during stress, as blood flow (7.4 +/- 2.9 to 5.1 +/- 1.3) and vascular resistance (31.5 +/- 11.1 to 34.4 +/- 8.2) varied insignificantly (P greater than 0.10). The digital vasodilatation which occurs during mental stress in patients with Raynaud's disease was not altered by pretreatment with oral indomethacin, with intra-arterial propranolol or atropine, or by digital nerve block. These findings suggest the existence of an active digital vasodilatory mechanism in patients with Raynaud's disease.

Laser-Doppler measurement of digital blood flow regulation in normals and in patients with Raynaud´s phenomenon

Finger blood flow was measured continuously by a laser-Doppler flowmeter in normal subjects and in patients suffering from primary or secondary Raynaud´s phenomenon. In normals, skin areas with and without arteriovenous anastomoses could be differentiated. Blood flow in areas with shunt vessels decreased after a deep breath but not during venous stasis or the Valsalva maneuvre, while in other skin areas a decrease in blood flow was observed after all three maneuvres, suggesting a dual innervation of nutritional and shunt vessels. In patients with Raynaud´s phenomenon (scleroderma) fingertip blood flow reacted in the same way as normal skin without shunt vessels. During direct and indirect cooling, finger blood flow in patients with secondary Raynaud´s phenomenon reacted with the same relative reduction as normals but resting blood flow in the patients was significantly decreased and the rewarming period was greatly prolonged. In patients with primary Raynaud´s phenomenon an even more prolonged decrease in blood flow was observed after direct or indirect cooling. Defective function of arteriovenous anastomoses is proposed as an explanation of the deviations from normal. A pathophysiological classification of Raynaud´s phenomenon may be possible on the basis of the function tests described.

Beta-adrenergic vasodilator mechanism in the finger.

The digital vasospastic phenomena, which are induced by beta-adrenergic-blocking agents, suggest a beta-adrenergic finger vasodilator mechanism. We measured fingertip total blood flow with venous occlusion plethysmography and studied nutritional blood flow with Na131I clearance. During fingertip vasoconstriction caused by branchial artery infusion of norepinephrine or angiotensin, intra-arterial isoproterenol caused a sustained increase in fingertip total blood flow. Furthermore, propranolol significantly potentiated the vasoconstriction caused by intra-arterial norepinephrine and attenuated the vasodilator action of isoproterenol. No change in branchial artery blood pressure occurred to explain the changes in fingertip blood flow. Isoproterenol did not change nutritional flow, implying beta-adrenergic vasodilation solely of the fingertip arteriovenous shunts. When fingertip vasoconstriction was induced by reflex sympathetic nerve action during environmental cooling and mental stress, or by norepinephrine release from sympathetic nerves caused by intra-arterial tyramine infusion, isoproterenol and propranolol had no effect on fingertip total blood flow. This effect is probably specific for the beta-receptor agonist, since intra-arterial histamine caused a large increase in finger blood flow during environmental cooling. We conclude that there is a beta-adrenergic vasodilator mechanism in human digital arteriovenous shunts that may be humorally activated, but which has no apparent functional role in modulating sympathetic vasoconstriction. Our results suggest a spatial dissociation of the effector sites for vasoactive humoral agents and sympathetic vasoconstrictor nerves.

Changes of nasal airway resistance caused by breath holding. I. Results in normal subjects (author's transl)

Various effects upon respiratory and circuratory systems induced by breath holding have been investigated by many physiologists for a long time. For instance, it increases the systoric and diastoric blood pressure, and decreases the rate of finger tip blood flow and finger tip volume.These circuratory effects have been considered by the excitation of the sympathetic nerve. The nasal mucous membrane is rich in vessels and these vessels are innervated by sympathetic and parasympathetic nerves. In this paper, it was investigated whether breath holding could have any effect on the vessels in the nasal mucosa. For this purpose, the changes of nasal airway resistance (NAR) were examined. In fifteen normal adults, NAR was determined before and after breath holding. For the determination of NAR, the combined method was used, and the variant ratio of NAR (NAR after breath holding/NAR before breath holding) was calculated. The mean value of fifteen normal adults was 0.57 and the standard deviation was 0.18 In order to investigate the sympathetic effect on this reflex, changes of NAR by breath holding were estimated in four patients with sudden deafness who were treated by stellate ganglion block.In these patients, changes of NAR were not observed. In conclusion, this reflex is highly suspected to be transmitted by the sympathetic nerve.

Essential hyperhidrosis: Correlation of digital blood flow and capillary ultrastructure after unilateral sympathectomy

A patient with essential hyperhidrosis was studied in whom complete relief was effected on the left side by unilateral sympathectomy, whereas the nonsympathectomized right side remained hyperhidrotic. Rheoplethysmographic recordings of digital blood flow were obtained, and capillaries in digital biopsy specimens from right and left fingertips were examined electron microscopically. The volumes and rates of inflow were greater in the nonsympathectomized right fingertip than in the sympathectomized left fingertip in a comfortable environment; and the volumes and rates of blood flow in the right fingertip changed appreciably with ambient temperature changes, whereas the blood flow to the left fingertip changed little. The lumens of the capillaries in the nonsympathectomized right fingertip appeared dilated as compared with those of the left fingertip which were constricted. These data indicate that (1) the cells of the capillary endothelium may change significantly in size and shape to alter capillary luminal diameter, and (2) capillaries may participate in the generalized disorder of the sympathetic nervous system associated with essential hyperhidrosis.

Studies on the diagnosis and pathogenesis of Raynaud's phenomenon of occupational origin.

<b>Okada, A., Yamashita, T., Nagano, C., Ikeda, T., Yachi, A., and Shibata, S. (1971).</b><i>Brit. J. industr. Med.,</i><b>28,</b> 353-357. <b>Studies on the diagnosis and pathogenesis of Raynaud9s phenomenon of occupational origin.</b> Experiments were designed to investigate tests for the diagnosis of Raynaud9s phenomenon of occupational origin between attacks and to investigate the pathogenesis, particularly with reference to factors in the patient. The fingertip blood flow was low not only in subjects with Raynaud9s phenomenon (positive group) but also in other users of vibrating tools who did not have Raynaud9s phenomenon (negative group). This criterion combined with urinary vanillyl mandelic acid and haptoglobin was examined by analysis of discriminant function. The probability of false discrimination was 3%. Histamine iontophoresis performed after noradrenalin iontophoresis with subsequent comparison of pulse wave amplitudes is useful for identification of the positive group. Haptoglobin was significantly increased and the subjects in whom IgM was increased formed a high proportion of the positive group.

Reserpine and Raynaud's phenomenon.

By dividing total fingertip blood flow into its two component parts, arteriovenous-shunt flow and the nutritionally important capillary flow, Coffman and Cohen (see page 259) have made some interesting observations in patients with Raynaud's phenomenon. Some of the seemingly contradictory reports of total hand or finger blood flow in patients with Raynaud's phenomenon might have been less confusing if previous investigators had measured capillary as well as total flows. The relative contributions of capillary flow and arteriovenous-shunt flow to total flow vary so greatly under different circumstances that it would be hazardous if not impossible to estimate capillary flow from . . .

Total and capillary fingertip blood flow in Raynaud's phenomenon.

Abstract Total (plethysmography) and capillary (radioisotope disappearance rate) fingertip flows were measured in 24 patients with Raynaud's phenomenon and compared to 10 normal subjects in a warm room and during reflex sympathetic nerve stimulation by body cooling. Arteriovenous shunt flow was estimated by subtraction of capillary from total flow. Patients with Raynaud's phenomenon had a significantly smaller capillary flow in both warm (6.4 vs. 10 ml per 100 g per minute) and cool (4.0 vs. 7.0 ml) rooms than normal subjects. With body cooling, total and arteriovenous shunt flow, but not capillary flow, decreased significantly in normal controls, whereas all three decreased in Raynaud's phenomenon. During oral reserpine treatment, 11 patients with Raynaud's phenomenon showed a significantly larger capillary flow during warming (8.7 vs. 5.7 ml) and cooling (6.2 vs. 2.8 ml). Patients with Raynaud's phenomenon have a smaller finger nutritional (capillary) flow than normal subjects, and this flow decreases s...