Stanley E. Bradley

Some Effects of Nitroglycerin upon the Splanchnic, Pulmonary, and Systemic Circulations

Splanchnic, pulmonary, and systemic hemodynamics were studied in 18 patients afterthe sublingual administration of nitroglycerin. The drug, contrary to expectations, produced an over-all vasoconstrictive effect on the splanchnic circulation rather than vasodilatation. There was no evidence of venous pooling in this bed, and indeed the data may indicate a splanchnic supportive role in augmenting venous return to the heart with disengorgement of its own volume. In contrast, there was vasodilatation and pooling of blood in the pulmonary vascular bed. The systemic circulation probably sustains several effects by nitroglycerin, including arterial vasodilatation. A direct change in large artery distensibility probably explains the modest fall in systolic blood pressure seen. Further decline in arterial pressure may depend on venous pooling of a small or large degree. Probably the fall in systemic and specific organ flows is also linked to decreased venous return and the vascular readjustments provoked thereby. Pulsus alternans was produced by nitroglycerin, a previously unreported effect of the drug, but the mechanism by which it arose could not be defined.

The Effect of Digoxin in the Splanchnic Circulation in Ventricular Failure

Splanchnic hemodynamics were examined in 22 patients with heart disease, 16 of whom had evidence of ventricular insufficiency at the time of study. The response of the splanchnic vasculature to the exhibition of intravenous digoxin was also studied in nine of these subjects.Ventricular insufficiency was associated with splanchnic vasoconstriction proportional to a generalized increase in peripheral vascularresistance. Splanchnic blood volume was disproportionately increased with respect to total blood volume in patients having visceral congestion with right ventricular failure and combined ventricular failure. A significant relationship between central venous pressure and splanchnic blood volume was demonstrated in these cases. The greater elevation of the former than of the latter suggested the presence of splanchnic venoconstriction.The vascular readjustment to digoxin resulted in a relative intensification of the already existing vasoconstriction of the splanchnic bed as compared to the diffuse systemic vasodilatation which occurred at the same time as the consequence of the inotropic action of the drug: estimated splanchnic blood flow and splanchnic blood volume diminished at a time when systemic flow rose and peripheral vascular resistance decreased. The ultimate distribution of the volume of blood translocated out of the splanchnic bed during this process remains to be determined.

Hepatic Hemodynamics During Viral Hepatitis in Man

Hepatic blood flow (EHBF) was measured by the clearance-and-extraction method using indocyanine green (ICG) in 15 patients hospitalized with acute viral hepatitis. In 10, the single injection technique (corrected for hepatic extraction and mean splanchnic circulation time, colloidal denatured human serum albumin-labeled with radioiodine, CA131I) was employed simultaneously to estimate flow (CABF).Despite considerable clinical diversity (plasma bilirubin ranging, for example, from 2.4 to 32.0 mg%), EHBF fell within normal limits (930 to 2,130 ml per min) in all but two patients (A.V., 890 ml per min and C.G., 2,430 ml per min), and was in good agreement with CABF. Although hepatic extraction of sulfobromophthalein was so greatly reduced (less than 10%) that it could not be employed for estimating EHBF, both ICG and CA131I extractions were well maintained (21 to 73%, normal 63%, and 50 to 76%, normal 95%, respectively). Extraction of ICG returned to normal levels as jaundice cleared whereas CA131I extraction remained depressed indicating improvement in hepatocellular function without redistribution of blood flow within the liver during recovery.Since the liver was obviously enlarged in all patients and since measurements of circulating splanchnic blood volume by the regional dilution method fell below the normal mean in eight of 10 patients, it was inferred that hepatomegaly was a result of augmented cell mass rather than vascular engorgement and that hepatic blood flow decreased relativeto tissue volume. Splanchnic oxygen arteriovenous difference and oxygen uptake also fell within normal limits in five patients suggesting that the increment in liver mass might be ascribed chiefly to cellular hydration.Normal values for wedged hepatic venous pressure (10 patients) indicated that postsinusoidal resistance remained unaltered and that cellular swelling did not affect postsinusoidal resistance or perfusion. The observation reported by other workers that portal venous pressure may increase during the course of acute viral hepatitis must, therefore, be attributed to an increase in pre-sinusoidal portal venular resistance. It was concluded that inflammatory infiltration and increased capillary permeability within the portal tracts may contribute to the disease process by interfering both with portal venous inflow and biliary outflow.

Die Messung der Leberdurchblutung von Mensch und Tier

ZusammenfassungDie Leber- bzw. Eingeweidedurchblutung kann mit brauchbarer Genauigkeit mit einer indirekten Methode an Menschen und an Versuchstieren ohne erforderliche chirurgische Maßnahmen oder Narkose gemessen werden. Die Methode gründet sich auf die Voraussetzung 1. daß Bromsulfalein oder Bengalrot unter bestimmten Bedingungen fast vollständig durch die Leber aus dem Blut extrahiert wird; 2. daß die Bromsulfaleinkonzentration im Arterienblut derjenigen des in die Leber einströmenden Blutes gleich ist und 3. daß das durch venöse Katheterisierung einer einzelnen Lebervene erhaltene Blut hinsichtlich seiner BSP-Konzentration dem gemischten Lebervenenblut gleich ist. Die Leberdurchblutung läßt sich sodann berechnen, indem man die Größe der hepatischen BSP-Ausscheidung (die der Infusionsgeschwindigkeit gleichgesetzt werden kann, wenn die arterielle BSP-Konzentration konstant ist) durch die arterio-hepatisch-venöse BSP-Konzentrationsdifferenz dividiert. Es wurde ferner die technische Durchführung der Methode beschrieben und die Grundlagen im einzelnen erörtert. Man kann den begründeten Schluß ziehen, daß die Methode Werte der Leberdurchblutung liefert, die nur wenig von der tatsächlich vorhandenen Durchströmung abweichen und dies auch bei großen Stromstärkeschwankungen und unter den verschiedensten physiologischen Bedingungen.

Dimensional Interrelationships of the Proximal and Distal Tubules of the Nephrons in the Dog

Summary Measurements of the dimensions of proximal and distal tubules were made on nephrons obtained by microdissection from the kidneys of three female dogs. In any nephron, the length, average cross section, and volume (as for a cylinder) of the proximal tubule from its attachment to the glomerulus to the thin portion of Henles loop were always larger than the same values for the distal tubule measured from the point of attachment to the glomerular vascular pole to entry into the collecting tubule. Proximal-distal volume ratios averaged 5.34 ± 1.32 (SD), 5.88 ± 1.46, and 7.59 ± 1.51 for each of the three dogs. The proximal convolutions accounted for 74.8 ± 9.1%, 71.0 ± 7.6%, and 77.0 ± 6.0% of the total proximal volume in the same animals. The convolutions bulked equally large in the distal tubule, making up 75.3 ± 10.9%, 70.0 ± 10.3%, and 69.1 ± 9.3% of the total, respectively. Proximal convolutions exceeded distal convolutions in volume, with ratios of 5.46 ± 1.97, 5.66 ± 1.67, and 8.95 ± 2.25 times, respectively. The volumes of proximal and distal tubules in the same nephron were significantly correlated in keeping with an intersegmental functional balance between residual filtered load leaving the proximal tubule and the capacity of the distal tubule to deal with it. The relative size of proximal and distal convolutions suggests that proximal reabsorbate determines the microenvironment of the distal convolutions.

Difficulties in the appraisal of disturbances in fluid and electrolyte metabolism in clinical medicine.

Four important oversimplilications have played unique roles in the development of the modern view of the normal and abnormal physiology of the water and electrolytes in the body. According to the first of these, a product of the work and thought of many investigators beginning with Matthias Schleiden and Theodor Schwann in the early years of the Nineteenth Century, the body may be considered as, quintessentially, a set of Chinese boxes: the cell within the extracellular compartment. The second is associated in particular with the name of Claude Bernard, who pointed out the function of the extracellular fluid as the immediate environment of the cells, the milieu intkrieur, which serves as a cushion to modify and to reduce the ill effects of rapid changes in the physical environment. The realization that the plasma is extracellular fluid (ECF) has resulted in the further simplifying assumption that, with due regard to factors of molecular dimensions, capillary permeability, and time lag, the plasma concentrations of diffusible solutes may be taken as their concentrations in the ECF. Finally, Walter B. Cannon may be credited with putting forward the concept (and its label) of “homeostasis.” On these four principles, compartmentalization, the extracellular fluid buffer, vascularextravascular equilibrium, and homeostasis, has been founded an elaborate theoretical structure that is justified to some extent by the facts of anatomy and physiology and, more significantly, by the fruitfulness of the research it has stimulated and tied together. Nevertheless, as more and more data accumulate it is becoming apparent that a more reliable theoretical basis is required for an adequate understanding of disturbances in electrolyte and water metabolism.

Anglo-American views of health and the family.

Excerpt By all accounts the family is in a perilous state. Changes in patterns of behavior, moral constraints, freedom, responsibilities, communications, and consequences of technology coupled with...

Persistence of the Natriuretic Response to Isotonic Saline Load During Hemorrhagic Hypotension in the Dog

Summary Water, sodium, and potassium outputs increased well above control values in normal hydrated fasting dogs during the intravenous administration of isotonic saline solution. With the reduction in arterial pressure to a constant level close to 50 mm Hg by controlled hemorrhage in these animals, all three outputs decreased in association with diminished glomerular filtration rate (inulin clearance), hematocrit, and plasma protein concentration but never to levels as low as those observed during the control phase. Since the blood loss was more than replaced by the isotonic saline infused, it may be presumed that extracellular extravascular fluid volume increased while blood volume fell. The persistence of natriuresis indicates continued tubular rejection of sodium, possibly as a result of a change in interstitial volume or vascular perfusion of the kidney.