Alan C. Burton

Distribution of Size and Shape in Populations of Normal Human Red Cells

The diameter, area, and volume of individual human erythrocytes (of 8 subjects, newborn to age 71) were determined by photographing the cells hanging on edge. Measurements from high magnification prints were processed by computer. The distributions of diameter, area, and volume are described statistically, with the unexpectedly linear regression equations for their interrelations. The plot of area vs. volume for the 1016 normal cells from seven subjects (newborn excluded) was remarkably linear with a “straight-line” boundary restricting the distribution. Shape was characterized by a dimensionless” sphericity index” (4.84.volume 2/3/area). Cells of larger volume tended to be thinner than the smaller cells. The red cell can easily be deformed at constant volume, but an increase in membrane area results in hemolysis. A theoretical geometric parameter, the “minimum cylindrical diameter” (MCDiam), in microns, the thinnest cylindrical channel through which each individual cell could pass, predicts the linear boundary of the plot of area vs. volume. The MCDiam value of 3.66 μ ± 0.04 SEM accurately represents the thinnest channel through which 95% of the cells can pass. In two splenectomized patients with hereditary spherocytosis the MCDiam was increased to approximately 4.0 μ, suggesting that the severest restriction is located in the spleen.

Local Postural Vasomotor Reflexes Arising from the Limb Veins

Blood flow of the toes and fingers was studied plethysmographically with the level of the blood vessels below or above the heart, using the contralateral digit as control. The apparent flow is a maximum when the vessels are near the heart level. The decrease of flow when the vessels are raised is explained on the basis of narrowing and closure of vessels when the hydrostatic pressure within them falls. The decrease in flow when the limb is lowered is interpreted as evidence of a vasoconstriction elicited by distension of the local veins. This raises serious doubt about the classic flow method.

Oxygen Consumption of Arterial Smooth Muscle as a Function of Active Tone and Passive Stretch

The mean oxygen consumption of relaxed isolated vascular smooth muscle segments was found to equal 0.61±0.94 SEM μliter/mg wet wt/hr in a medium of buffered Ringer-glucose, and 0.65±0.05 SEM uliter/mg wet wt/hr in a solution of dog plasma. The resting muscle RQ was found to equal 0.99±0.01 SEM in buffered Ringer-glucose solution. When stimulated by addition of epinephrine the muscle segment contracted on the average by 9% of its initial diameter with a corresponding increase of its oxygen consumption by an average of 30% over its relaxed value. It was noticed that with increased initial circumferential stretch of the muscle segment, the amplitude of contraction was much greater when a given amount of catecholamine was added. This increase of sensitivity to catecholamine produced by initial stretch, was accompanied by a parallel increase of oxygen consumption by the contracted muscle. A qualitative correlation between an estimated degree of contraction of arterial muscle and its oxygen consumption was demonstrated. More quantitative correlation will have to depend upon better methods of measuring both the tension developed and the degree of initial stretch.

Theoretical Considerations and Model Experiments on the Validity of Indicator Dilution Methods for Measurements of Variable Flow

• Conventional indirect dilution methods can measure blood flow only when either the flow or the concentration of the indicator in the stream remains constant during the period of measurement. Flow anywhere in the vascular system is rarely constant under physiological conditions because of cardiac pulsations, respiratory variations in flow, and other nonsteady state conditions. When the direct oxygen Fick method is used to measure cardiac output, it is essential that the a-v oxygen difference is constant. However, Wood et al. and Enson and Cournand have shown that there are significant variations in the a-v oxygen difference even at rest. Visscher and Johnson pointed out that the use of time averages of the a-v oxygen difference could lead to errors in calculations of mean flows. Their analysis was extended by Stow and Wood et al. Guyton developed a cardiac output computer which overcame many of the problems which arose from the use of time averages of a-v oxygen differences. However, catheter sampling may damp rapid changes in a-v oxygen differences, e.g., 80% damping of fluctuations in a-v difference due to normal respiration. With the exception of Guytons approach we know of no attempt to measure variable pulsatile flow by indicator dilution techniques. This investigation suggests from theory and experiments in models that under the right conditions a modified method of calculation

Reactive Hyperemia in the Human Finger

Reactive hyperemia in the finger was investigated in 16 experiments on 5 normal subjects, using venous occlusion plethysmography. Since the flow is so variable from moment to moment, the simultaneous “corrected” flow in a control finger, not occluded, was subtracted from the flow in the test finger, so the difference gave the effect of occlusion free from fluctuations of central origin. The absolute amount and the duration of extra blood flow increased with the period of occlusion. The percentage of the calculated “blood flow debt” repaid was variable, with a mean of 51 percent ± 36. S.D. (σM ± 6 per cent). This is greatly in excess of nutritional debt of the skin.

Constrction of the Neonatal Aorta by Raised Oxygen Tension

A preparation consisting of the great arteries around the heart from neonatal guinea pigs was perfused at constant flow by physiological saline solutions in a bath in which various gases (95% N2 + 5% CO2, air + 5% CO2 and 95% O2 + 5% CO2) were bubbled. The pressure drop across the aorta, including the preductal area, was recorded and the changes in resistance in response to these gas tensions were calculated. The well-known closure of the ductus with increased Po2 occurred, but in addition there was a reversible increase, up to 400%, in the resistance of the aortic segment. This was maximal 1 to 2 days after birth, diminishing with age until after 6 days it was very slight. In very young animals (1 to 2 days), responses to air and oxygen were roughly proportional to the Po2. Inspection of injection casts of the vessels showed that the constriction was local in the preductal area, closely resembling that of aortic coarctation. Segments of aorta that did not include the preductal area, and from animals of comparable age, showed very slight constriction to raised Po2. The neonatal vessels of pigs, rabbits and cats showed similar O2 sensitivity of different degrees, and with different peculiarities as to time lag and repeatability. Neither the ductus nor the neonatal aorta of dogs appears to constrict to increased Po2, and closure of the ductus in this species must be by a different mechanism. These observations may be interpreted as evidence for the Skodaic theory that infantile aortic coarctation may occur in association and coincident with the closure of the ductus at birth. The administration of high O2 gases at birth might, in cases of abnormal development, lead to permanent coarctation.

Cancer and altitude. Does intracellular pH regulate cell division

Abstract Tissue culture growth rate is very sensitive to changes in pH of the external medium (H. Eagle), suggesting that the concentration in cells of + H or − OH might be the key factor controlling synthesis and eventual mitosis in normal and cancerous tissue. Since physiological acclimatization to higher altitudes produces changes in alkali-reserve in man and animals remaining at altitude, a possible correlation with statistics on cancer has been investigated. Available data on registrations of cancer (International Committee Against Cancer) and of cancer deaths (World Health Organization) have been analyzed for possible correlation of age-specific rates with a population-weighted mean altitude for each region surveyed. There is no “altitude-effect” below 60 or 65 years, but a statistically significant negative correlation ( r > 0·5. P 8, in 7 ) was found for older ages in 15 of 16 sets of independent data. The drug acetazolamide has been used to produce “artificial acclimatization”, producing similar acid-base changes, and is reported (Evans) to have produced relief of intractable pain in terminal cancer patients. Some diseased states, such as achlorhydria and emphysema, in which there are chronic disturbances of acid-base relations, exhibit unexpected cancer rates. Some other possible explanations of the apparent “altitude-effect”, particularly that it is related to inefficiency of collection of data at high altitudes, seem implausible.

Active Constriction of Small Pulmonary Arteries in Rabbit

This communication deals with the demonstration of active pulmonary vasomotion by injecting plastic material (vinyl acetate) which forms casts of the small pulmonary arteries simultaneously on a control side and on the test side submitted to action of vasoconstrictor drugs. Comparisons were made by direct microscopic observations and by weighing the casts after the lung tissue had been digested. Other indices such as relative weight of the two lungs, relative denseness of vascularity and estimates of pulmonary resistance supplied supplementary evidence of pulmonary vasomotion.

The Design of a Simple Microflowmeter for Biological Perfusion Experiments

Various types of flowmeters are discussed with reference to their use at very small flows. The differential pressure type, using rubber membranes, appears most suitable. The steps are outlined in the design of an instrument sensitive to flows as low as 0.01 ml/min. yet with a response time less than 10 sec. In this instrument a completely differential linkage between two membranes is accomplished by the use of an incompressible fluid. The theory of the response is developed. This gives a prediction of the speed of response from the sensitivity and the diameter of the membrane used.

Method of Using a Compensated Gradient to Improve Time Response of an Animal Calorimeter

Rapid response of a gradient calorimeter can be achieved by reducing changes of heat stored in the wall and by using an air flow circuit to facilitate heat transfer. A servomechanism controls the power to a heater on the inner surface of the wall to maintain constant the temperature gradient and heat flow through the wall. The 98% response to a step change from an electrical heat source requires 2.5 min with servo‐control compared to 12 min without the feedback circuit. The reason for this decreased time of response is discussed.