of the hand and forearm of a comfortable warm subject is maximum, and markedly more distensible during sleep in all subjects. (Received 5 July 1961)

Transcription

1 392 J. Physiol. (1962), 161, pp With 4 text-fgures Printed in Great Britain DISTNSIBILITY OF TH CAPACITY BLOOD VSSLS OF TH HUMAN HAND DURING SLP By W.. WATSON From the Department of Neurology, Churchill Hospital, Oxford (Received 5 July 1961) It has been suggested that the distensibility of the capacity blood vessels of the hand and forearm of a comfortable warm subject is maximum, and that the amount of blood they contain is determined only by the transmural pressure acting across their walls and not by the reactivity of their walls (Glover, Greenfield, Kidd & Whelan, 1958; Kidd & Lyons, 1958). This communication reports measurements of the distensibility of the capacity blood vessels of the hand made in nineteen normal, comfortable, warm subjects before and after they fell asleep. These vessels became markedly more distensible during sleep in all subjects. MTHODS Distensibility of the capacity blood vessels of the hand was measured by comparing the increase in vascular hand volume resulting from intermittent obstruction of the venous return with the associated increase in hand vascular distending pressure. Hand volume changes were measured with a water-filled, stirred plethysmograph of capacity, maintained at a temperature of C throughout each investigation. The hand was contained in a loosely fitting glove of thin rubber. The subject lay supine with the hand in the plethysmograph at the level of the manubrium sterni. The arm was carefully supported so that no movements of the hand occurred when the subject fell asleep. Hand volume changes were derived from pressure changes of the air contained in the turret of the plethysmograph: the plethysmograph was calibrated by introducing known volumes of water with a syringe. The volume-pressure relationship of the air space in the turret of the plethysmograph was linear within the range of hand volume changes found in this investigation. The increase in pressure within the plethysmograph during a period of venous obstruction never exceeded 2 cm H2, and was recorded by means of an air-filled capacitance transducer (Southern Instruments) with a pressure range of -5 cm H2. The volume of the hand within the plethysmograph was determined by subtracting the total volume of water removed from the plethysmograph at the end of an experiment from the known capacity of the plethysmograph. The water within the plethysmograph exerted a hydrostatic pressure within the range 8-11 cm H2 upon the back of the hand. This was measured with a water-filled, thin rubber balloon of 1 ml. capacity containing 5 ml. H2, lying upon the back of the hand within the loosely fitting rubber glove: the pressure was recorded with a capacitance transducer. When the balloon contained 5 ml. water only the differential pressure across its wall was less than -2 cm H2. Ambient temperature was kept constant throughout each investigation within the range C. Hand venous pressure was measured through a nylon catheter of -8 mm internal

2 CAPACITY BLOOD VSSLS DURING SLP 393 diameter introduced percutaneously on the dorsal or radial aspect of the radiocarpal joint and directed peripherally, negotiating at least one venous valve, until the end of the catheter lay about 5 cm distal to the site at which the vein had been punctured. Care was taken to ensure that the end of the catheter was not wedged in a venous tributary or within the sinus of a venous valve. The catheter was periodically flushed with -2 ml. of saline containing heparin -1 mg/ml. The pressure was measured with a capacitance transducer with a range -5 mm Hg. An occluding pneumatic cuff, the 'collecting cuff', was placed around the wrist immediately proximal to the plethysmograph and inflated automatically to 4 mm Hg for 1 sec every 2 sec. Records were obtained with a four-channel direct-writing pen unit. The pens were 16 cm long, worked in an arc of 4 cm, and had a peak-to-peak response time of -7 sec. The paper speed used was 5 mm/sec. The characteristics of the capacitance transducers and the recording system was such that the relationship between the imposed pressure and the consequent deflexion of the recording pen was linear over the range of pressures investigated. The venous pressure was determined with an accuracy of + 5 % of the recorded value. The estimated potential error of hand-volume determination was +8 % of the recorded value. Between episodes of inflation of the collecting cuff a base-line value was obtained for hand volume, hand venous pressure and for the hydrostatic pressure imposed upon the back of the hand. When the collecting cuff was inflated the hand volume increased at a rate initially equal to the hand blood flow: this was accompanied by an increase in hand venous pressure. It was demonstrated in other normal subjects that, when a hydrostatic pressure of more than 8 cm H2 is imposed upon the back of the hand supported at the level of the manubrium sterni, the pressure is transmitted directly both to the hand veins and to the extravenous loose connective tissue of the back of the hand. Under these circumstances the hand venous distending pressure, or transmural hand venous pressure is less than 1 cm H2. Tissue pressure was not measured in these subjects because the technique causes discomfort and would prevent the subjects from sleeping. During episodes of inflation of the collecting cuff the increase in hand volume caused an increase in pressure within the plethysmograph. This increase in pressure was transmitted to the extravenous loose connective tissue of the back of the hand. The measured venous pressure therefore exceeded the venous distending pressure during a period of venous obstruction. The venous distending pressure at a given instant during venous obstruction was derived from the measured venous pressure by subtracting the increase in pressure within the plethysmograph measured at the same instant. As the pressure increase within the plethysmograph never exceeded 5 % of the increase in measured venous pressure this correction was small. The increase of venous pressure and of hand volume was measured at intervals of -2 sec throughout each period of venous obstruction and the vascular distending pressure at each interval was derived. The increase in hand volume resulting from each increment of 1 cm H2 of hand venous distending pressure was determined. As the venous return from the hand was obstructed for 1 sec every 2 sec three such series of estimations were obtained each minute. A series of mean values for hand volume at each increment of 1 cm H2 of hand venous distending pressure was obtained from these three values. The vascular volume-pressure relationship of the hand, representing the mean value for 1 min, was obtained by expressing the mean increase in hand volume against the hand venous distending pressure (Fig. 1). The vascular volume-pressure relationship was usually curvilinear. The gradient of the curve which represented vascular distensibility (ml./cm H2) was therefore measured at a constant hand vascular volume in each subject to derive values which were comparable under different circumstances. The hand volume at which distensibility was measured in this investigation was 3 ml. above the base-line hand volume measured at the beginning of the experiment. This constant volume was used both when the subject was

3 394 W.. WATSON awake and when he was asleep, so that no error occurred from change in base-line hand vascular volume when the subject fell asleep. This constant volume is indicated by the horizontal line in Fig. 1. The gradients of the slopes of the volume-pressure curve were estimated by drawing tangents at the constant hand volume. nd-tidal pco2 was derived from the record of an infra-red C2 analyser (Ird-o-meter) sampling continuously at 6-12 ml./min from the external nares or mouth of the subject. The C2 analyser had previously been calibrated with C2-air mixtures: the precise CO2 content of these mixtures was determined with a modification of the Haldane apparatus (Lloyd, 1958). The calibration curve obtained was non-linear and conformed with that supplied by the manufacturers. Procedure. The subject lay on a comfortable couch in a quiet laboratory. No measurement of the distensibility of the capacity vessels was made for about 3 min after the apparatus had been set up, although the collecting cuff was rhythmically inflated and deflated throughout this time. Continuous records were then obtained. The subject was judged to have fallen asleep when he no longer responded to his Christian name called softly, and when his end-tidal PC2 increased. The subject was allowed to continue sleeping until he woke naturally. After the subject had woken up and the distensibility of the capacity blood vessels had become constant, each subject deliberately reduced his respiratory minute volume so that the end-tidal pco2 increased to the level at which it had been maintained during sleep. Vascular distensibility was then measured. Subjects. Twenty-seven male subjects were investigated. Nineteen of these fell asleep. Their ages were within the range years. None had clinical evidence of disease of the respiratory or circulatory systems. RSULTS In Fig. 1 the hand vascular volume increase of one subject is expressed graphically against the increase in venous distending pressure, or transmural hand venous pressure, both when he was awake and when he was asleep. This result is typical of results obtained from all subjects. fa C 6 _ 5- ~ x x 4 x. p3- x. 2- x x ~~~~~X x, I~~~~~~~~~~ Transmural hand venous pressure (cm H2) Fig. 1. Vascular pressure-volume relationship of the hand of one subject when awake, relaxed, warm and comfortable, x when asleep. The horizontal line at 3 ml. indicates the points on the slopes at which tangents were drawn for the estimation of gradients.

4 CAPACITY BLOOD VSSLS DURING SLP 395 ach point shown is a mean value derived from three consecutive episodes of venous obstruction. The change in vascular volume-pressure relationship which occurred with sleep was highly significant (P < 1). Although a slight increase in base-line hand volume occurred, the vascular volume at which the gradient of the volume-pressure curves were measured was constant, and is indicated by the horizontal line at 3 ml. The hand blood flow in this subject increased from 8-4 ml./loo ml. tissue/mi to 11 ml./1 ml. tissue/min when he fell asleep. The vascular distensibility increased from 11 ml./cm H2 when awake, to -23 ml./cm H2 when asleep. >, 1 _.V > Asleep Time (min) Fig. 2. Change of vascular distensibility in a typical subject on falling asleep. The subject was asleep between 32 and 55 min, and between 6 and 95 min. Figure 2 expresses the vascular distensibility of the hand of another subject against time. He fell asleep on two occasions: on each occasion the vascular distensibility increased markedly and remained high while the subject was asleep. This was associated with an increase in hand blood flow from a mean value of 6-7 ml./1 ml. tissue/min to a mean value of 8-9 ml./1 ml. tissue/min. When the subject awoke both the hand blood flow and the vascular distensibility decreased and approached their previous values. In Fig. 3 the vascular distensibility of the hand of each subject when asleep is expressed graphically against the vascular distensibility of the same subject when awake. The capacity blood vessels of the hand of all subjects were more easily distended during sleep. The hand blood flow increased during sleep by a mean value of 15 % in fourteen subjects: in 26 Physiol. 161

5 396 W.. WATSON three subjects the increase in hand blood flow was less than 4 %, and in the two remaining subjects the hand blood flow decreased by less than 5 %. The mean increase in end-tidal pco2 found when the subjects fell asleep was 5 mm Hg (range 2-8 mm Hg). The distensibility of the capacity blood -3 - ;.~~~~~~~ -1.. s~~~ _- UV Vascular distensibility when awake (ml./cm H2) Fig. 3. Mean vascular distensibility during sleep expressed against mean vascular distensibility of the same subject immediately before falling asleep. Results obtained from nineteen subjects. I.3H - et ~~~ U V' -2 _ V =.c U v >4-1'._ U.ȯb1 2 3 Vascular distensibility (ml./cm H2). Subject awake and underventilating Fig. 4. Mean vascular distensibility during sleep expressed against mean vascular distensibility after awaking, while deliberately underventilating. nd-tidal pco, the same asleep and awake.

6 CAPACITY BLOOD VSSLS DURING SLP 397 vessels of the hand of each subject was measured when he had increased his end-tidal pco2 to the same level (±2 mm Hg) as during sleep by deliberate underventilation. The results obtained are shown in Fig. 4. The vascular distensibility of the hand of each subject during sleep is expressed graphically against the vascular distensibility measured in the same subject when awake, but with a constant end-tidal pco2 equal to that found during sleep. The difference in vascular distensibility accompanying sleep, but not a consequence of elevation of arterial pco, was highly significant in sixteen subjects (P < 1) and significant in the remaining three (P <.5). DISCUSSION The technique used in this investigation for measuring the distensibility of the capacity blood vessels of the hand is similar to that employed by Sharpey-Schafer (1961) for determining the distensibility of the capacity blood vessels of the forearm. It is related to the plethysmographic methods of measuring 'venous' distensibility in vivo (Clark, 1933; Kidd & Lyons, 1958; Glover et al. 1958; ckstein & Horsley, 196), but allows changes in vascular distensibility to be followed with greater rapidity. It is known, however, that the value obtained for vascular distensibility varies with the rate of vascular distension: if the volume of the capacity vessels increases rapidly, the pressure required to attain any particular volume is greater than if the volume-pressure relationships were examined during states of equilibrium (Alexander, 1948, 1954; Alexander, dwards & Ankeney, 1953). Ideally the dynamic vascular distensibility investigated by this technique should be measured at a constant rate of distension under different circumstances, that is, with a constant hand blood flow. This is not, however, possible. This potential source of error cannot be the cause of the change in vascular distensibility observed in this investigation, for when the subjects fell asleep the capacity blood vessels became more distensible although the rate of distension, or hand blood flow, increased in the majority of subjects. It is possible that the true increase in vascular distensibility is greater than the measured increase. The marked increase in distensibility of the capacity blood vessels of the hand which occurred in sleep was associated with an increase of end-tidal PCO2 in all subjects. This increase of end-tidal PCO2 is of the same order as that observed by Reed & Kellogg (1958). It is not the cause of the increase in vascular distensibility, because a similar increase of end-tidal pco in the same subject when awake did not produce a comparable rise in vascular distensibility. All subjects were warm and comfortably relaxed before they fell asleep, and the vascular distensibility of all increased when sleep occurred. It is 26.2

7 398 W.. WATSON concluded that the distensibility of the capacity blood vessels of the hand is not maximum in warm comfortable subjects when they are awake, and that the volume of blood that they contain is determined in part by the reactivity of the vascular walls. These findings are contrary to the hypothesis of Glover et al. (1958) and of Kidd & Lyons (1958). SUM4ARY 1. The distensibility of the low-pressure capacity blood vessels of the hand was measured in nineteen normal subjects both when they were asleep and when they were awake. 2. The low-pressure capacity blood vessels became more easily distensible in all subjects during sleep. This was not a consequence of altered rat of vascular distension or of change in arterial PC2' 3. It is concluded that the volume of blood contained in the lowpressure capacity blood vessels of a warm comfortable subject at rest is determined in part by the reactivity of their walls. This finding is contrary to previous hypothesis. I am greatly indebted to Drs W. Ritchie Russell and J. M. K. Spalding for the opportunity to study patients under their care and for research facilities. The investigations were supported by a grant from the National Fund for research into poliomyelitis and other crippling diseases. RFRNCS ALXANDR, R. S. (1948). In vivo observations on the distensibility of the femoral venous system. Proc. Soc. exp. Biol., N.Y., 67, ALXANDR, R. S. (1954). The influence of constrictor drugs on the distensibility of the splanchnic venous system, analysed on the basis of an aortic model. Circuk4ion Res. 2, ALXANDR, R. S., DWARDS, W. S. & ANNY, J. L. (1953) The distensibility characteristics of the portal vascular bed. Circulation Res. 1, CLAR, J. H. (1933). The elasticity of veins. Amer. J. Physiol. 15, CKSTIN, J. W. & HORSLY, A. W. (196). ffects of hypoxia on peripheral venous tone in man. J. Lab. dlin. med. 56, GLOvR, W.., GRNFILD, A. D. M., KxDn, B. S. L. & WHLAN, R. F. (1958). The reactions of the capacity blood vessels of the human hand and forearm to vaso-active substances infused intra-arterially. J. Phy8iol. 14, KIDD, B. S. L. & LYONS, S. M. (1958). The distensibility of the blood vessels of the human calf determined by graded venous congestion. J. Phy8iol. 14, LLOYD, B. B. (1958). A development of Haldane's gas-analysis apparatus. J. Phy8-iol. 143, 5-6P. RD, D. J. & KLLOGG, R. H. (1958). Changes in respiratory response to CO2 during natural sleep at sea level and at altitude. J. appl. Phy8iol. 13, SHARPY-SCHAFR,. P. (1961). Venous tone. Brit. med. J. (ii),