Arthur C. Guyton

Role of the Baroreceptor Reflex in Daily Control of Arterial Blood Pressure and Other Variables in Dogs

Normal and sinoaortic baroreceptor–denervated dogs were monitored continuously (24 hours a day) to quantify the role of the baroreceptors in determining the average level and the variability of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance. The frequency of occurrence over 24-hour periods was obtained for each variable using a fiber optic curve-scanning system to read the variables from continuously recorded charts and a digital computer system to plot curves. The results indicate that the degree of hypertension previously reported for this preparation has been highly exaggerated, presumably due to the methods of study. The average 24-hour mean arterial blood pressure was 101.6 mm Hg in normal dogs and only 112.7 mm Hg in baroreceptor-denervated dogs. The normal dogs exhibited narrowly distributed 24-hour frequency distribution curves for blood pressure; in contrast the denervated dogs exhibited curves with twice the 24-hour standard deviation. Similar analysis indicated that the baroreceptors exerted less influence on the daily stabilization of heart rate than they did on arterial blood pressure and that they had very little if any influence on the daily stabilization of cardiac output and total peripheral resistance. Hemodynamic variables during postural changes were studied along with diurnal rhythms. We concluded that the primary function of the baroreceptor reflex is not to set the chronic level of arterial blood pressure but, instead, to minimize variations in systemic arterial blood pressure, whether these variations are caused by postural changes of the animal, excitement, diurnal rhythm, or even spontaneous fluctuations of unknown origin.

Effect of Elevated Left Atrial Pressure and Decreased Plasma Protein Concentration on the Development of Pulmonary Edema

In 97 dogs left atrial pressure was elevated to various levels up to 50 mm. Hg by partial constriction of the aorta. The effect of these pressures for from 30 min. to 3 hours on the accumulation of lung edema was then studied. Edema was estimated by determining the ratio of the weight of the wet lung to the weight of the same lung after drying. In animals with normal plasma protein concentrations fluid began to transude into the lungs when the left atrial pressure rose above an average of 24 mm. Hg. In another series of animals the plasma protein concentrations were reduced by plasmapheresis at the beginning of each experiment until the plasma protein concentration averaged 47 per cent of the control value. In these animals fluid began to transude into the lungs when the left atrial pressure rose above a critical value of 11 mm Hg. Furthermore, the rate at which fluid accumulated in the lungs, in all series of experiments, was directly proportional to the rise in left atrial pressure above the critical pressure at which fluid began to collect in the lungs.

A Concept of Negative Interstitial Pressure Based on Pressures in Implanted Perforated Capsules

Over 200 perforated plastic capsules were implanted in different tissues of the dog, and the wounds were allowed to heal. After one month, pressures measured by inserting a needle through the skin and then through a perforation of the capsule into its cavity were always negative in normal tissues, averaging−6.4 mm Hg. The pressure was always positive in edematous tissues. Evidence is presented to indicate that the pressure measured in the capsule is equal to, or nearly equal to, the interstitial fluid pressure in the tissue spaces surrounding the capsule. On the other hand, pressure measurements made by a needle technic failed except in rare instances to give negative values in normal tissues but in edematous tissues gave almost exactly the same values as those recorded by the capsules. Also, pressures measured by the capsules changed in accordance with Starlings law of the capillaries when (a) venous pressure was raised, (b) when arterial pressure was lowered, (c) when the tissues were dehydrated by intravenous infusion of dextran, or (d) when the tissues were hydrated by intravenous infusion of saline. Pressures measured by a needle technique failed to change in accordance with this law in these same experiments. Therefore, it is concluded that needle pressure determinations in non-edematous tissue do not measure the interstitial fluid pressure.

Interaction of Vasopressin and the Baroreceptor Reflex System in the Regulation of Arterial Blood Pressure in the Dog

The hemodynamic effects of 1-hour intravenous infusions of vasopressin were evaluated in trained, unanesthetized dogs in the normal state and following sinoaortic baroreceptor denervation. Pressor sensitivity to vasopressin was greatly enhanced following baroreceptor denervation; threshold sensitivity was increased 11-fold and sensitivity at higher dose levels was increased 60–100-fold. Infusion of physiological levels of vasopressin caused an average increase in arterial blood pressure of 33 mm Hg in conscious, baroreceptor-denervated dogs compared with an increase of 5 mm Hg in normal dogs. In contrast, similar intravenous infusions of norepinephrine at physiological levels resulted in a 3-fold increase in pressor sensitivity with no change in threshold dose. Hy-pophysectomy of baroreceptor-denervated dogs did not significantly alter their pressor sensitivity to vasopressin in the conscious state. The arterial blood pressure response to intravenous vasopressin infusions was greatly depressed when a high background level of circulating vasopressin was present. Decapitated, spinal, anesthetized dogs maintained with a small continuous infusion of norepinephrine exhibited the greatest sensitivity to vasopressin; the threshold dose for a pressor response was similar to that in conscious baroreceptor-denervated dogs, but pressor sensitivity at physiological dose levels was increased nearly 8, 000-fold. The elevations in arterial blood pressure resulting from vasopressin infusions of less than 1.0 munits/kg min−1 were large enough to implicate the direct pressor effect of vasopressin in the normal control of arterial blood pressure.

Interstitial Fluid Pressure: II. Pressure-Volume Curves of Interstitial Space

Pressure-volume curves of the interstitial fluid spaces were estimated using four different methods. Interstitial fluid pressure was measured from implanted perforated capsules while interstitial fluid volume was varied (a) by perfusing the isolated hind limb of the dog with several types of fluid and at different perfusion pressures, (b) by elevating the venous pressure so that fluid would transude into the interstitial compartment, (c) by infusing large quantities of Tyrodes solution into the whole animal, and (d) by intravenous infusion of concentrated dextran solution. In all these studies, the compliance of the interstitial fluid system was found to be very low when the interstitial fluid pressure was negative but very high when the pressure rose slightly above atmospheric pressure. A physical model of the interstitial spaces was also constructed. Pressure-volume curves recorded from this model demonstrated a pattern of compliance changes similar to that shown by the interstitial pressure-volume curves recorded from dogs. These experiments give further support to the concept that the interstitial fluid pressure is normally negative but becomes positive as edema fluid accumulates.

Hypertension Caused by Salt Loading in the Dog

Experimental hypertension was produced in dogs by salt loading after renal mass had been surgically reduced to an estimated one-third normal. Salt loading was accomplished in one group of five dogs by administering isotonic saline in lieu of drinking water and in another group of six dogs by continuously infusing isotonic saline. Arterial pressure, cardiac output, heart rate, stroke volume, and total peripheral resistance were determined at frequent intervals during a 1-week control period and a 2-week salt-loading period in both groups. In addition, right atrial pressure, blood urea nitrogen, serum sodium, and serum potassium were determined in the group that was continuously infused. Both groups demonstrated an increase in mean arterial pressure to hypertensive levels, transiently increased cardiac output and stroke volume, initially depressed then subsequently increased total peripheral resistance, and initially depressed and variable heart rate. It is concluded that salt loading in a partially nephrectomized dog causes elevated arterial pressure that is initially induced by increased cardiac output but that is eventually sustained by increased peripheral resistance. Possible mechanisms are discussed.

Effect of Hematocrit on Venous Return

In 18 dogs, the major factors besides blood hematocrit that are known to affect venous return were exactly controlled, while the hematocrit itself was varied from 9.5 up to 65. In general, the changes in venous return in these experiments were approximately the reciprocal of the changes in blood viscosity, as estimated from standard blood viscosity curves. An interesting sidelight of these studies was the fact that the minute volume of red blood cells transported by the arterial blood to the tissues, as calculated by multiplying the hematocrit times the venous return, reached a maximum at a hematocrit of 40. The minute volume of red blood cells fell drastically in anemia because of decreased hematocrit and in polycythemia because of greatly reduced venous return.

The surprising kidney-fluid mechanism for pressure control--its infinite gain!

In this short paper, I have tried to explain the elation that we felt when we first realized that the kidney-fluid mechanism for controlling the arterial pressure has an infinite feedback gain property. Because of this, all the other pressure control mechanisms, none of which has ever been shown to have a similar infinite gain property, must themselves alter the kidney-fluid mechanism if they are to succeed in causing long-term changes in the arterial pressure. We have not been able to refute this principle despite many experiments over the last 2 decades. For this reason, our first understanding of the infinite gain property of the kidney-fluid mechanism was like a light at the end of the tunnel. I hope that I can explain to the reader the excitement of those few seconds when we first recognized the principle in 1966.

Permeability of the Alveolar Membrane to Solutes

The lower lobe of the left lung of 54 dogs was isolated and perfused with a dextran-Tyrodes solution. The alveoli were filled with Tyrodes solution, and permeability coefficients were measured for diffusion of several substances across the alveolar membrane. The permeability coefficients of the pulmonary membrane for K42, urea, Na24, glucose, D2O, and dinitrophenal(DNP) were 56.5 ± 3.5, 22.9±9.2, 7.5±2.1, 3.1±0.7, 400, and 400×10−7 cm/sec, respectively. The effect of varying the flow rate on the permeability coefficient of Na24 was investigated, and the data failed to show any significant correlation between the flow limits of 3.8 to 12. 8 cm/min/g lung tissue. The effect of two different procedures for filling the alveoli with fluid on the permeability coefficients was also investigated and no difference could be discerned in the results. The data support the thesis that the alveolar membrane has permeability characteristics similar to those of the usual cell membrane. The interstitial fluid volume of the lung (extravascular sodium space) was measured and yielded a value in normal lungs of 0.250 ± 0.129 cc/g lung tissiue. In three edematous lungs, this space averaged three times the normal value.

The Limits of Right Ventricular Compensation Following Acute Increase in Pulmonary Circulatory Resistance

The ability of the right ventricle to compensate as the pulmonary artery is constricted appears to be determined by four major factors: (1) there occurs the well-known increased force of contraction as the right heart becomes distended; (2) the adequacy of the coronary circulation determines to a great extent the Degrees of pulmonary arterial constriction which can occur before failure occurs; (3) the circulatory reflexes apparently aid the compensation to a moderate extent; and (4) the greater the blood volume, the greater is the limit of compensation before right ventricular failure occurs.