Table Of ContentMICROCIRCULATION
AS RELATED TO SHOCK
EDITED BY
DAVID SHEPRO
DEPARTMENT OF BIOLOGY
BOSTON UNIVERSITY
BOSTON, MASSACHUSETTS
AND
GEORGE P. FULTON
DEPARTMENT OF BIOLOGY
BOSTON UNIVERSITY
BOSTON, MASSACHUSETTS
SPONSORED BY THE
NATIONAL ACADEMY OF SCIENCES · NATIONAL RESEARCH COUNCIL
and the GRADUATE SCHOOL, BOSTON UNIVERSITY
BOSTON, MASSACHUSETTS
FUNDED BY THE
NATIONAL HEART INSTITUTE, NATIONAL INSTITUTES OF HEALTH
and BOSTON UNIVERSITY
1%8
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LIST OF CONTRIBUTORS
ADFI.RERT AMES 111 KI)WARD H. B~.ocii
Massachusetts General Hospital l~cpart~~ieorfr t Anatotny
Discussant: Ilroin Session Western Reserve University School of
Medicine
E. T. AN(;EI.AKOS
Chairnian of kt’orkshop: Pidro Scanning
Department of Physiology
Procedures
Boston University School of Medicine
Chairman of Workshop: Techniqiies for P-I BRANEMARK
Studying Vascular Sinooth Muscle and Its Ikpartntent of Anatomy
Innervation; Section Editor: Heart; Con- University of Gothenburg, Sweden
ference Local Coniniittee Principal Speaker: Itheological Session;
Workshop: Thernial Condirctiiiity Metli-
EMU. ASCHHEIM
Department of Derniatology 0d.S
Stanford University School of Medicine RAI.PIIB RAUER
Discussant: Skin Session Wrightsville Marine Bio-Medical Labora-
tory, Wilmington, North Carolina
KRuT AUKLAND
IXscussant: Splanchnic Session
Institute for Experimental Medical Re-
search BELTONA . BURROWS
Ulleval Hospital University of Oslo, Nor- Boston University School of Medicine
way Chairman Workshop: Tracer Teclinigires
Principal Speaker: Kidney Session for Flow and Transporl
SILVIOB AEZ JOHNJ . BYRNE
Department of Anesthesiology Department of Surgery
Albert Einstein College of Medicine Boston University School of Medicine
Discussant: Splanchnic Session Section Editor: Splanchnic Session; Con-
ference Local Committee
A. CLIFFORDB ARCER
Department of Physiology STANLEYE. CHARM
Harvard Medical School New England Enzymes’ Center
Discussant : Kidney Session Tufts University School of Medicine
Workshop: Rheological Methods
HERBERJT. BERMAN
Department of Biology DAVIDC . COGAN
Boston University Graduate School Howe Laboratory of Ophthalriiology
Workshop: Techniques for Slurlying I’ns- Harvard University School of Metlicinc
cular Snaooth Muscle and Its Inneriintion Discussant: Eye Session
ROBERTM . BERNE C:~rss R. COKELET
Department of Physiology Departtnent of Chemical Engineering
University of Virginia School of Medicine California Institute of Technology
Discussant: Heart Session Workshop: Rheological Methods
V
vi LIST OF CONTRIBUTORS
ALFRED L. COPLEY GEORGE P. FULTON
Department of Pharmacology Department of Biology
New York Medical College Boston University Graduate School
Workshop: Rheological Methods Conference Chairman
JACK W. CROWELL ROBERT F. FURCHGOTT
Department of Physiology and Biophysics Department of Pharmacology
The University of Mississippi School of Downstate University of New York Col-
Medicine lege of Medicine, Brooklyn
Workshop: Techniques for Studying Vas-
Discussant: Heart Session
cular Smooth Muscle and Its Innervation
COLIN T. DOLLERY L-E GELIN
Postgraduate Medical School, London, Surgical Department I
England University of Gothenburg, Sweden
Principal Speaker: Eye Session Chairman: "Windows and the Microcir-
ROBERT H. EBERT culation"
Harvard Medical School
CARL W. GOTTSCHALK
Keynote Speaker
University of North Carolina Medical
MURRAY EDEN School
Massachusetts Institute of Technology Discussant: Kidney Session
Workshop: Systems Approach to Shock
HAROLD D. GREEN
and Microcirculation
Department of Physiology
JACOB FINE The Bowman Gray School of Medicine
Department of Surgery of Wake Forest University
Harvard Medical School—Beth Israel Hos- Principal Speaker: Brain Session
pital, Boston
DONALD E. GREGG
Discussant: Splanchnic Session: Conference Department of Cardio-Respiratory Diseases
Local Committee Walter Reed Army Institute of Research
Principal Speaker: Heart Session
EDWARD D. FRANK
Department of Surgery
ARTHUR C. GUYTON
Harvard Medical School—Beth Israel Hos- Department of Physiology and Biophysics
pital, Boston The University of Mississippi School of
Principal Speaker: Traumatic and Toxic Medicine
Factors; Section Editor: Kidney; Confer- Chairman of Workshop: Systems Approach
ence Local Committee to Shock and Microcirculation
REGINA FRAYSER ROBERT M. HARDAWAY III
Department of Medicine Headquarters, US ARMY General Hos-
Indiana University School of Medicine pital, Frankfurt
Discussant: Brain Session
Workshop: Rheological Methods
EPHRAIM FRIEDMAN S. G. HERSHEY
Department of Ophthalmology
Department of Anesthesiology
Boston University Medical Center Albert Einstein College of Medicine
Discussant: Eye Session Discussant: Lungs
JULIUS FRIEDMAN JOHN M. HOWARD
Department of Physiology Department of Surgery
Indiana University School of Medicine Hahnemann Medical College and Hospital
Workshop: Tracer Techniques for Flow Chairman: Special Aspects of Low Flow
and Transport States
LIST OF CONTRIBUTORS vii
Z. HRUZA EUGENE M. LANDIS
Department of Pathology Department of Physiology
New York University School of Medicine Harvard Medical School
Workshop: Techniques for Studying Vas- Chairman of Workshop: Micro-Blood
cular Smooth Muscle and Its Innervation Pressure Measurements
CHESTER HYMAN CHARLES K. LEVY
Department of Physiology Boston University Graduate School
University of Southern California School Discussant: Brain Session
of Medicine
Principal Speaker: Skin Session; Work- CHARLES N. LOESER
University of British Columbia
shop: Tracer Techniques for Flow and
Workshop: Video Scanning Procedures
Transport
EDWARD W. MERRILL
MARCOS INTAGLIETTA
Massachusetts Institute of Technology
Department of Bioengineering
Chairman of Workshop: Rheological
University of California, San Diego School
Methods
of Medicine
Workshop: Micro-Blood Pressure Measure-
HERBERT MESCON
ments Department of Dermatology
Boston University School of Medicine
JOHN W. IRWIN
Discussant: Skin Session
Massachusetts Eye and Ear Infirmary,
Massachusetts General Hospital
DAVID MINARD
Section Editor: Lung Session; Workshop:
Department of Occupational Health
Micro-Blood Pressure Measurements;
Graduate School of Public Health
Conference Local Committee
University of Pittsburgh
Discussant: Brain Session
PAUL C. JOHNSON
Department of Physiology
P. A. G. MONRO
The University of Arizona College of Anatomy School
Medicine
University of Cambridge, England
Principal Speaker: Splanchnic Session
Workshop: Micro-Blood Pressure Measure-
ments
RICHARD D. JONES
Department of Surgery
FRANCIS T. MOORE
St. Luke's Hospital, Cleveland
Harvard Medical School
Discussant: Muscle Session
Principal Speaker: Physiological Indices of
Hypoperfusion in Man; Conference Plan-
MELVIN H. KNISELY
Department of Anatomy ning Committee
Medical College of South Carolina
ANTHONY MORECI
Honorary Chairman of the Conference
Department of Biology
VERNON E. KRAHL Boston University Graduate School
Department of Anatomy Workshop: Systems Approach to Shock
University of Maryland School of Medicine and Microcirculation
Discussant: Lung Session
KATASHI MORI
Department of Anatomy
J. PETER KULKA
Department of Pathology Nagoya City University, Japan
Harvard Medical School Workshop: Tracer Techniques for Flow
Discussant: Skin Session and Transport
viii LIST OF CONTRIBUTORS
MARK NICKERSON SAM F. SEELEY
Department of Pharmacology antl Thera- Professional Associate
peutics National Academy of Sciences, National
University of Manitoba Faculty of Medi- Research Council
cine, Canada
EWALD E. SELKURT
Workshop: Techniques for Studying Vas-
Department of Physiology
cular Smooth Muscle and Its Innervation
Indiana University School of Medicine
PAUL A. NICOLE Chairman of Workshop: Thermal Con-
Department of Physiology ductivity Methods
Indiana University School of Medicine
JOHN T. SHEPHERD
Workshop: Micro-Blood Pressure Measure- Mayo Clinic
ments Rochester, Minnesota
WILLIAM PERL Workshop: Thermal Conductivity Meth-
New York University Research Service ods
Goldwater Memorial Hospital, New York
DAVID SHEPRO
Workshop: Thermal Conductivity Methods
Boston University Graduate School
ALAN PETERS Chairman: Local Committee; Conference
Department of Anatomy Planning Committee
Boston University School of Medicine
HARRY S. SOROFF
Section Editor: Brain Department of Surgery
LYSLE H. PETERSON Tufts University School of Medicine
Bockus Research Institute Section Editor: Skin; Conference Local
University of Pennsylvania Committee
Workshop: Systems Approach to Shock
WENDELL N. STAINSBY
and Microcirculation Department of Physiology
CARLO PIOVELLA University of Florida College of Medicine
Institute of Pathology Principal Speaker: Muscle Session
University of Pavia, Italy
NORMAN C. STAUB
Chairman: Walls and the Microcirculation Cardiovascular Research Institute
BRUCE POMERANZ University of California, San Francisco,
Department of Biology School of Medicine
Massachusetts Institute of Technology Discussant: Lungs Session
Discussant: Kidney Session
WILLIAM C. ULLRICK
SEARLE B. REES Department of Physiology
Elliott P. Joslin Research Laboratory, Boston University School of Medicine
Boston Section Editor: Muscle
Discussant: Eye Session
U. S. VON EULER
EUGENE M. RENKIN Physiological Institute
Department of Pharmacology Karolinska Institute, Sweden
Duke University Medical Center Guest Panelist: Special Aspects of Low
Principal Speaker: Neurogenic Factors; Flow States
Discussant: Muscle Session; Conference
ROE WELLS
Planning Committee
Department of Surgery
HERBERT J. ROBB Harvard Medical School
Department of Surgery Moderator: Organs and Systems Involved
Wayne State University School of Medicine in Shock; Section Editor: Eye; Conference
Discussant: Muscle Session Local Committee
LIST OF CONTRIBUTORS
GEOFFREY B. WEST DAVID YUDILEVICH
The British Industrial Biological Research Faculty of Science
Association, England University of Chile
Principal Speaker: Humoral Factors Workshop: Tracer Techniques for Flow
and Transport
JOHN B. WEST
Postgraduate Medical School, London
BENJAMIN W. ZWEIFACH
Principal Speaker: Lungs Session
Department of Bioengineering
CURT A. WIEDERHIELM University of California, San Diego, School
Department of Physiology and Biophysics
of Medicine
University of Washington School of Medi-
Principal Speaker: Conclusions from Con-
cine
ference; Discussant: Splanchnic Session;
Workshop: Video Scanning Procedures;
Conference Planning Committee
Conference Planning Committee
EARL WOOD
Mayo Clinic
Rochester, Minnesota
Workshop: Video Scanning Procedures
ACKNOWLEDGMENT OF ASSISTANCE
ABBOTT LABORATORIES S. Ε. MESSENGILL COMPANY
Chicago, Illinois Bristol, Tennessee
CI Β A PHARMACEUTICAL COMPANY MERCK SHARP AND DOHME
Summit, New Jersey Worcester, MassachusetIs
HARVARD APPARATUS SMITH KLINE AND FRENCH LABORATORIES
Dover, Massachusetts Ρ h i la de Ip h ia, Pe η nsy ha η ia
HOFFMANN-LA ROCHE INC. U.S. VITAMIN AND PHARMACEUTICAL CORP.
Nut ley, New Jersey New York, New York
E. LFITZ
New York, New York
X
PREFACE
In retrospect and based upon our impressions derived from the delibera-
tions of the participants at the Conference on the Microcirculation as
Related to Shock held at Boston University on March 29 through
April 1, 1967, we as conveners and editors of the proceedings are inclined
to agree with Dr. Francis Moore who has pointed out that the term
"shock" as used in the cardiovascular literature is actually a misnomer
and might better be replaced by the phrase "low flow state" or "state
of hypoperfusion." In this respect the observations of the classic micro-
circulationists are most convincing, namely, that shock is characterized
eventually by slow and stagnant blood flow in small vessels, associated
with aggregations of erythrocytes and hemoconcentration brought about
by local changes in permeability of the microvasculature. Circulatory
events in shock were delineated in the pioneering studies of Melvin
Knisely (Honorary Chairman of this Conference) and Benjamin W.
Zweifach, in collaboration first with Robert Chambers and later with
Ephraim Shorr. Because of tradition (historical usage and ingrown
habit), it is unlikely that the generic term "shock" will be replaced,
but refinement of the connotation of the word is always possible as we
reflect upon the program of the Conference as a whole.
Reduced blood flow in the microcirculation was perhaps the unifying
thread that seemed to ramify through all of the reports and discussions.
The mere fact that we could rally so many leaders in shock research, in
basic cardiovascular physiology, and in cognate interdisciplinary fields
under the banner of "microcirculation as related to shock" is by itself sug-
gestive of a general recognition of the primary involvement of the blood
flow in the small blood vessels. Perhaps the most important aspect of the
Conference has been the implication of microcirculatory hypoperfusion
as the focal point of shock.
If we accept the concept of microcirculatory hypoperfusion as the focal
point, it may be useful to relate the substance of the meeting to a series
of questions such as follows:
1. What are the causative factors that produce the state of low blood
flow as found in shock?
xi
Xll PREFACE
2. Can microcirculatory hypoperfusion be prevented in man and once
produced, can it be reversed by treatment?
3. Can microcirculatory hypoperfusion be identified as such, and how
can it be measured in the patient?
We do not presume to know the answers to these and similar questions,
but some of the presentations and discussions at the Conference may
provide leads or suggestions.
One additional question is in order, namely, what avenues are promis-
ing for further research? We respectfully suggest that greater emphasis be
given to the measurement of blood viscosity, shear stress, and rheological
factors as indices of the degree of hypotension. Reliable methods are
wanting for the measurement and continuous monitoring of extracellular
fluid volume to serve as a basis for estimating the loss of fluids from the
microvasculature during shock. Computer systems analyses to evaluate all
of the parameters now under study would be a desirable development.
There is also an urgent need for improved blood substitutes, particu-
larly during national emergencies. Finally, there is the quintessential need
for a pharmaceutical substance that will prevent or reverse the tendency
of the microvasculature to become more permeable during shocklike
emergencies, thus precluding the loss of intravascular fluid.
We wish to take this opportunity to thank all of the participants, the
organizers and planners, the sponsoring and funding agencies, and the
private concerns whose seriousness of purpose and generosities, respec-
tively, contributed immeasurably to the management and success of the
Conference.
GEORGE P. FULTON
DAVID SHEPRO
Boston, Massachusetts
March, 1968
