Edward H. Bloch

Effect of oxygen on cyclic red blood cell flow in unanesthetized mammalian striated muscle as determined by microscopy

Abstract Using a modified Algire chamber the red cells flowing per unit time were counted in capillaries of striated muscle in unanesthetized mice, from televised microscopic images. Cycles were found in red cell flow patterns with periodicities of 30, 100, and 320 sec, when the animals inspired a gas mixture containing 20% oxygen. The flow patterns and the mean flow rates were temporarily altered when the concentration of oxygen in the inspired gas was reduced below 20%. These altered patterns gradually returned to normal over periods of time that were directly proportional to the degree of hypoxia. However, at 8% oxygen the altered flow patterns persisted for many hours, returning to the normal flow pattern only after read-ministering 20% oxygen. The results suggest that cell flow in capillaries of this mammalian striated muscle is subject to autoregulation, which continues to operate as long as the animal inspires more than 8% oxygen (below 5% the animal dies in approximately 5 min). The results are consistent with the concept of homeokinesis, namely that bioregulation is dynamic and achieved by oscillating processes.

KNOWLESI MALARIA IN MONKEYS II. A FIRST STEP IN THE SEPARATION OF THE MECHANICAL PATHOLOGIC CIRCULATORY FACTORS OF ONE SLUDGE DISEASE FROM POSSIBLE SPECIFIC TOXIC FACTORS OF THAT DISEASE

From the Department of Anatomy, Medical College of South Carolina, Charleston, South Carolina, and the Division of Anatomy and Preventive Medicine, University of Tennessee, Memphis, Tennessee. a The studies on which this paper is based were made possible through support given by the Tennessee Valley Authority through the Division of Preventive Medicine of the University of Tennessee, The work was aided by a grant from the Ella Sachs Plotz Fund and by United States Public Health Service Grants H-4176 and H-7114 and United States Navy Contract NONR:441. b Present address: Department of Anatomy, Medical College of South Carolina, Charleston, South Carolina. c Deceased. d Present address: Department of Anatomy, University of Colorado School of Medicine, Denver, Colorado. e Present address: Department of Anatomy, Western Reserve School of Medicine, Cleveland, Ohio. The fundamental purpose of this paper is to introduce a rigorous experimental method for separating and determining the significance of individual sets of mechanisms of the pathologic physiology of certain disease states. The first step in presenting the material is to state the contrast between the visible circulatory factors in completely healthy-normal rhesus monkeys and in monkeys which are dying of Stage III Knowlesi malaria, a condition in which the blood is very severely agglutinated 1-3 In healthy animals, including man, every formed element of the blood is separate from every other: red cells do not stick together; white cells do not stick together; platelets do not stick together; nor do any individual items of any category stick together with those of any other category. White cells and platelets do not stick to healthy-normal endothelium. Healthy small vessels do not leak microscopically detectable amounts of fluid 4~ Healthy-normal red cells are naked, i.e., uncoated by any opsonizing precipitate. They bump and slide along hepatic phagocytes and are not ingested.’ Capillaries, through which blood must pass to oxygenate and nourish the cells of each and every tissue of the body, are just wide enough to permit one, or, at most, two red cells to pass abreast. The narrowest part of the vascular system, the bottlenecks, are the terminal arterioles just at theAbstract : The fundamental purpose of this paper is to introduce a rigorous experimental method for separating and determining the significance of individual sets of mechanisms of the pathologic physiology of certain disease states. The contrast is noted between the visible circulatory factors in completely healthy-normal rhesus monkeys and in monkeys which are dying of Stage III Knowlesi malaria, a condition in which the blood is very severely agglutinated.

A method for studying the dynamics of transcapillary transfer quantitatively at the microscopic level in situ in living organs.

Presented at the X Microcirculatory Conference, March 20, 1962 in Minneapolis, Minnesota. This work was supported by United States Public Health Service Grant H 5300. * Associate Professor, Department of Anatomy, Western Reserve University, Cleveland, Ohio. * The Osram high pressure mercury arc source was obtained from Epic Manufacturing Company, 150 Nassau St., New York. † The schematic for this power supply may be obtained from S. West, Department of Anatomy, Western Reserve University, Cleveland. If the tangled skein of reactions which are involved in the transfer of large molecules across the walls of small blood vessels are to be un-

The effect of erythrocyte aggregation on the rheology of blood.

Ideally the rheology of blood should be analyzed in the intact subject, since only in the living is it possible to obtain the factors which characterize the flow property of blood. For example, direct microscopic observation of the blood in man has shown that the rheology is influenced by the size, configuration and number of cellular elements per unit volume as well as by the configuration of the vessels. Furthermore considerable variation can occur in the state of aggregation of the cellular elements which can be detected only in the living circulation. The most frequent abnormality is the occurrence of erythrocyte aggregation. Such aggregates vary as to number per unit volume, size, configuration and physical consistency, and are further modified by the shearing forces acting on them. Their stability is continually influenced by the variation of the shearing forces (or the blood pressure) acting on them. Thus their size is usually inversely proportional to the shearing force. This means that the largest aggregates occur in stationary blood and the smallest are seen in arterioles. The shapes of the vessels as well as the pressures within them also influence the rheology of the blood. It has been established that arterioles and venules are cones whose decreasing cone diameters are in the direction of the capillaries, which are cylinders. Thus the greatest resistance to flow, in any one vessel, occurs in terminal arterioles. In these vessels the cells are driven toward a con-

In vivo microscopy of hamster renal allografts

Abstract Nine hundred hamster renal allografts were examined to evaluate them as a dynamic model of the mammalian nephron. Grafts invariably vascularized so that glomeruli and tubules became viable. Glomeruli were readily visualized so that all morphological components usually visible with the light microscope could be identified. Glomerular blood flow responded to variations in anesthesia, epinephrine, and hemorrhagic shock by involvement of preglomerular vessels. Graded permeability of glomerular capillaries was demonstrated by using dye tracers which revealed that these vessel walls were not permeable to protein. Passive anaphylaxis produced by rabbit-anti-hamster kidney serum had a profound effect on glomerular blood flow by abruptly stopping flow without involving pre- or postglomerular vessels. Specific identification of tubules was limited to the origin of proximal tubules and the terminal segments of distal tubules with collecting tubules. In addition to the above structures both the renal pelvis and ureter could be viably maintained. It was concluded that the grafts are excellent for examining the structure and dynamic responses of glomeruli but may be of lesser value for studying the tubular system.

The Effect of Cellular Aggregation On Pressure-Flow Relationships in the Microvascular System

aggregation on the gross and microvascular systems.2 With the modification of the capacitance nanometer by Rappaport3 it became possible to me this equipment for recording the dynamic pressures in small blood vessels. Irwin4 and I3loch,5 using such equipment, have shown that it was possible to obtain dynamic pressure pulses of the microvascular system with cannulas as small as 30 jn and were able to obtain continuous recordings for hours. For the past seven years they have tested the equipment and have described its advantages and limitations. 6

DIABETES MELLITUS AND THE LIVING MICROVASCULAR SYSTEM

Can anything be learned about the mechanism that damages blood vessels in diabetes mellitus by studying the dynamic morphology of the superficial microvascular system in man? The current opinion in regard to the answer to this question will be derived through a review of: (1) the preferential site for the study of the microvascular system, (2) the structures that can be visualized in this tissue, (3) the recording of the dynamic morphology, (4) the statistical validity of data derived from superficial microvascular systems, and (5) an analysis of the studies to date.

Sludged Blood, Human Disease and Chemotherapy

The fluidity of the blood can be reduced during the course of some human diseases and this change in the fluidity has been described under the generic name of “Sludged Blood” (e.g. Knisely and Bloch, 1942; Knisely et.al., 1947; Bloch, 1956). The potential consequences of such pathology for structures and functions have been demonstrated in experimental animals. It was found that sludged blood could produce thrombosis and infarction resulting in tissue degeneration or necrosis as well as producing symptoms (e.g. muscle pain)(e.g. Knisely et.al., 1945; Bloch, 1953; Gelin, 1956; Fajers and Gelin, 1959; Stalker, 1967; Bicher and Beemer, 1967). Such pathology could be prevented or ameliorated by de-sludging the blood (e.g. Knisely et.al., 1945; Gelin, 1956; Zederfelt, 1965; Bicher, 1972). The need for specific chemotherapy for de-sludging is essentially restricted to those diseases where no specific effective therapy against the etiological agent exists because when effective therapy is instituted it destroys the etiological agent and the blood is de-sludged.

Edmund P. Fowler, Jr. 1905-1964: A Tribute

P. Fowler, Jr., M.D., Professor of Otolaryngology of Columbia University whose demise occurred at the age of 58 years on January 13, 1964. He had given generously of his time and efforts to make these Conferences successful by serving as chairman on the executive and program committees and by presenting significant contributions. The tradition of service was deeply ingrained in him, as exemplified not only through his heritage-he was a sixth generation physician-but also by his multifaceted interests that embraced the care of patients, teaching and research. He was born on February 16, 1905, in New York City. His secondary education was received at the Storm King School where he graduated in 1922. He went to college at Dartmouth, where he received a Bachelor of Arts degree, in 1926. He then returned to New York City to attend the College of Physicians and Surgeons of Columbia University, where he received in 1930 his Doctor off