Recollections of Professor Henry Barcroft, F.R.S.

Professor Henry Barcroft, MD, FRS, Emeritus Professor of Physiology in St. Thomas' Hospital Medical School in London died on 11 January 1998, aged 93. He was born in Cambridge on 18 October 1904 where his father, Joseph Barcroft, a famous physiologist, worked with Foster and Langley and subsequently was appointed to the Chair of Physiology. Henry Barcroft followed in his father's footsteps. During his career as Professor of Physiology firstly at The Queen's University of Belfast and subsequently at St. Thomas's Hospital London, he made significant studies on the nervous and humoral control of human blood vessels. His success as a research scientist stemmed partly from his ability to simplify complex phenomena in a way that permitted them to be broken into component parts and tested and partly from his technical ingenuity that permitted simple, inexpensive measurements of difficult physiological variables. Perhaps the most important factor, however, was his ability to bring out and stimulate aptitudes and enthusiasms in others. Completely unselfish himself, he gave individuals every opportunity to develop their talents, and so make themselves known to a wide circle of interested medical scientists. In many ways, his life was a guidebook for young scientists on how to make the most of their opportunities.

The effect of acute changes in blood flow on local lymph flow in the limbs of anesthetized sheep.

A study was made of the effects of acute changes in local blood flow on lymph flow in the feet of anesthetized sheep. Lymph outflow pressure and flow and venous pressure were measured in cannulated vessels draining the foot region. Local volume changes were also measured. Acute reductions in blood flow were produced by sudden occlusion of the circulation to the limbs with a pneumatic cuff for periods of up to 1.5 hours. During the first 10 min of occlusion, there was little change reaching about 25% of its control value after 40 min of arrest. On release of the circulation, lymph flow rose almost immediately to levels above the control value, resulting in a hyperlymphia whose size and duration was related to the duration of the circulatory arrest and the limb volume changes that followed. The results indicated that lymph flow can continue, albeit at reduced rates for long periods after circulatory arrest and that during reactive hyperaemia, there is a brisk hyperlymphia whose size and time course is similar to that of the limb volume changes.

Lymph flow in sheep limbs during local exposure to subatmospheric pressure.

1. Lymph flow and pressure were measured via cannulae inserted into afferent lymphatics draining the feet of anaesthetized sheep. 2. When the cannula outlet was at limb level, local exposure of the limb to graded decreases in ambient pressure caused graded increases in lymph flow with pressure values down to -50 mmHg. 3. When the cannula outlet was lowered below limb level to offset the negative pressure gradient imposed on the lymphatic vessels by suction, lymph flow rose progressively with decreasing ambient pressure values down to -70 mmHg. 4. When negative pressure gradients were imposed on the lymphatic vessels by raising the lymphatic cannula outlet in progressive steps above limb level, the vessels were able to expel lymph against gradients of up to 50 mmHg but lymph flow was greatly reduced against a gradient of 70 mmHg. 5. The results suggest that subatmospheric pressure may affect local lymph flow in two ways. By increasing blood capillary transmural pressure it may increase lymph flow by increasing tissue fluid formation. By imposing a negative pressure gradient along the lymphatics it may decrease lymph flow, especially at the most negative pressures, and the lymph flow response to subatmospheric pressure may be the algebraic sum of both effects.

Comparison of fluid transport systems in lymphatics and veins.

In the anesthetized sheep, pressure pulses generated in the feet are transmitted downstream in the veins but not in the lymphatics at normal intralymphatic pressure. When the sheep is tilted on a tilt table, gravitational changes occur in venous pressure but not in the pressure in adjacent lymphatics. These results suggest that in limb lymphatics, unlike limb veins, the column of fluid is incomplete. This makes extrinsic pumping less effective for propelling fluid in lymphatics than in veins. At normal intralymphatic pressures, intrinsic pumping seems to be mainly responsible for lymph propulsion. The incompleteness of the fluid column in lymphatics might also protect these vessels against the hydrostatic problems experienced by veins during gravitational stress.

Resistance in the sheep's lymphatic system.

Saline was infused in a downstream direction into the afferent lymphatics in the metacarpal region of anesthetized sheep. The changes in inflow pressure were measured over 10 min periods with flow rates ranging from 10-2000 microliters/min. Flow rates in the physiological range generated mean pressures of about 30 mmHg and flows of 1 ml/min generated mean pressures of about 60 mmHg. Resistance was relatively high at flow rates in the range of 10-15 microliters/min but sharply decreased above that and was relatively constant at flows greater than 500 microliters/min. Adding isoprenaline (1 microgram/min) to the infusate reduced spontaneous contractile behavior in the infused system and lowered the resistance at the lower flow rates. It is concluded that the peripheral lymphatic system in the sheep offers substantial resistance to lymph flow and that substantial intralymphatic pressure is needed to return lymph from the periphery especially at higher flow rates.

Peripheral lymphatic responses to outflow pressure in anaesthetized sheep.

1. Lymph flow and pressure fluctuations were measured by cannulating popliteal efferent and distal hind-limb afferent lymphatic vessels in anaesthetized sheep. The cannula outflow height was raised above the vessels to increase lymphatic outflow pressure. 2. Lymph flow decreased non-linearly as the outflow was raised. The rate of decrease increased with increasing outflow height. 3. Lymphatic contraction frequency rose and stroke volume fell with increasing outflow height. 4. The calculated power necessary to move lymph along the cannula initially increased with outflow height but it reached a peak and was reduced again by raising the outflow further. Calculated lymphatic stroke work followed a very similar pattern. 5. Lymph flow was maintained up to a greater outflow height in afferent than in efferent vessels. Curves relating frequency, power and stroke work to outflow height were shifted to the right in the afferent lymphatics. 6. These results are consistent with an intrinsic lymphatic pump which can be stimulated by increasing pressure. At high pressures, however, the pump fails.

Measurement of capillary pressure in humans using a venous occlusion method.

The venous occlusion technique was used to measure capillary pressure in the forearm and foot of man over a wide range of venous pressures. In six recumbent subjects venous pressure (Pv) in the forearm (mean +/- SE) was 9.3 +/- 1.4 mmHg and the venous occlusion estimate of capillary pressure (Pc) was 17.0 +/- 1.6 mmHg, whereas in another six subjects Pv in the foot was 17.1 +/- 1.2 mmHg and Pc was 23.4 +/- 2.5 mmHg. Venous pressure in the limbs was increased either by changes in posture or by venous congestion with a sphygmomanometer cuff. On standing Pv in the foot increased to 95.2 +/- 1.5 mmHg and Pc rose to 112.8 +/- 3.1 mmHg. The relationship established between venous pressure and capillary pressure in the forearm is Pc = 1.16 Pv + 8.1, whereas in the foot the relationship is Pc = 1.2 Pv + 1.6. The magnitude and duration of the changes in capillary pressure were also recorded during reactive hyperemia. The venous occlusion method of measuring capillary pressure is simple and easily applied to studies in humans.

The effect of local temperature on the response of an extremity to indirect heating in man.

Venous occlusion plethysmography was used to measure blood flow through the extremities of five normal subjects before and during exposure to a standard heat load with one extremity maintained at a cold (15 degrees C) and the other at a neutral (35 degrees C) temperature. In the foot, local cold (15 degrees C) delayed the onset and reduced by about 92% the vasodilatation during release of sympathetic vasoconstrictor tone caused by body heating. Similar results were obtained in the hand exposed to cold (15 degrees C) but the suppression of the reflex vasodilatation in response to body heating was about 66%. This difference between the hand and foot did not appear to be related to the greater length of the foot since the distal half of the foot reacted like the total foot: local cooling suppressed the reflex vasodilatation by 88%. The results suggest that sympathetic release tests should not be carried out in a laboratory with an environmental temperature as low as 15 degrees C, especially when the circulation to the foot is under investigation.

Bradykinin-induced contractions of bovine mesenteric lymphatics.

The mode of action of bradykinin (BK) on bovine mesenteric lymphatics was investigated by recording isometric tensions and action potentials in the isolated longitudinal segments. Addition of BK in concentrations from 10(-10) to 4 X 10(-6) M caused dose-related tonic contractions. BK in a low concentration accelerated the rhythm of action potential discharges in the spontaneously beating preparations and elicited frequent discharges of action potentials and a rapid rise in smooth muscle tone associated with phasic contractions. BK in high concentrations (more than 10(-7) M) caused a further rise of tension in the preparations which had already been depolarized in a high-K solution. The contraction induced by 4 X 10(-9) M-BK in the standard solution was abolished in a Ca-free environment or in the presence of a Ca-antagonist, 10(-4) M-D-600, though more than 50% of the contraction caused by 10(-6) M-BK still remained in both circumstances. In a Ca-free solution containing 1 mM-EGTA (Ca-free standard solution), 10(-6) M-BK caused a slight contraction even after high-K-induced contractions were completely blocked. The contractile response to 10(-6) M-BK in the Ca-free standard solution was augmented after activation of beta-receptors. It is concluded that the BK-induced contractions may be closely related to an increased Ca influx through the membrane and release of membrane-bound and intracellular Ca. The increased uptake of Ca into the BK-sensitive intracellular store may contribute to the relaxing effect of beta-agonist.

The effect of intravenous adrenaline and noradrenaline infusion of peripheral lymph flow in the sheep.

Pressure fluctuations and lymph flow were measured in popliteal, prefemoral and mesenteric efferent lymphatic vessels in conscious sheep. Intravenous adrenaline infusion increased frequency of lymphatic contraction and lymph flow in all three vessels. In the case of the prefemoral vessels flow remained high after the infusion had stopped. Intravenous noradrenaline infusion also increased frequency of contraction and lymph flow in all three vessels but prefemoral flow was depressed after the infusion had stopped. Lymphatic frequency of contraction and lymph flow increased when the animals were started. Anaesthetizing the animals with pentobarbitone did not abolish lymphatic contractions, nor did it prevent the response to adrenaline and noradrenaline infusion. The most obvious interpretation of these results is that adrenaline and noradrenaline act by increasing frequency and force of pumping of lymphatic vessels.