DRUG STUDIES ON ISOLATED ANIMAL AND 
HUMAN CARDIAC AND VASCULAR TISSUES: 
ADVANTAGES AND LIMITATIONS 
Joseph V. Levy* 
The use of isolated cardiac and vascular tissues for 
characterizing the actions of drugs has long been held 
as a necessary and rational prelude to studies on the 
intact organism. However, there is an increasing aware- 
ness that important qualitative and quantitative differ- 
ences exist between various animal species with regard 
to the efficacy and toxicity of various agents. Tradition- 
ally, a variety of animal cardiac and vascular tissues 
have been used in an attempt to predict the cardiovas- 
cular actions of agents in man. However, with the ad- 
vent of open-heart surgery, another dimension has 
been added to the pharmacologist's methodology: The 
availability and use of fresh biopsied cardiac and vascu- 
lar human tissue for in vitro drug studies. Our own re- 
search over the past 12 years has shown the feasibility 
of routinely obtaining viable cardiac and vascular tis- 
sues for drug and physiological studies in the labora- 
tory. For example, our recent research has dealt with a 
characterization of the actions of beta-adrenergic block- 
ing drugs, prostaglandin Ez, glucagon, ouabain, papav- 
erine, aminophylline and other agents on isolated 
human atrial tissue. Comparisons have been made with 
the effects on rabbit atrial tissue preparations. Impor- 
tant qualitative and quantitative differences in human 
and animal tissue responses were noted with several of 
these drugs and substances. Isolated human saphenous 
veins also have been used as a model of human vascu- 
lar tissue. Comparisons with animal vascular tissue 
have been made. Again, important qualitative and 
quantitative differences have been noted between 
human and animal vascular tissue responses to drugs. 
While the use of human tissues has added an important 
new tool to the pharmacologist's armamentarium of 
tests, caution must be exercised in interpreting results 
with such tissues because of known or unknown disease 
processes or uncontrollable conditions which can mod- 
ify and influence in vitro drug responses. In one way 
this is a major limitation. On the other hand, the use of 
diseased tissues for drug studies might have more rele- 
vance in terms of predicting drug effects on intact man 
afflicted with this disease. A discussion of methods cur- 
rently being used for in vitro studies also is presented. 
♦ Laboratory of Pharmacology and Experimental Therapeutics, 
Pacific Medical Center, San Francisco, California. 
INTRODUCTION 
The purpose of this paper is to present a sur- 
vey and discussion of the use of certain isolated 
animal and human tissues for characterizing 
the action of bioactive substances on the heart 
and blood vessels. 
Of course, the use of isolated organs and tis- 
sues from various animals long has been held as 
a vital test system for characterizing the car- 
diac and vascular effects of a v^ide spectrum of 
natural and synthetic substances. In vitro 
models have become standarized and widely ac- 
cepted as an important part of the pharmacolo- 
gist's armamentarium in his search for nev^^ 
drugs, or characterizing the mechanism of ac- 
tion of agents already in therapeutic use. Yet, 
the major disadvantages and limitations of 
these convenient in vitro animal models too 
often have been ignored. Moreover, their useful- 
ness and limits as models for predicting in vivo 
action in animals and man have not been fully 
appreciated. 
In our ov^n laboratory, v^e felt that v^hile the 
classical in vitro animal tissue models v^^ere 
more often right than v^^rong in terms of assess- 
ing actions in vivo, the major exceptions caused 
us to develop in vitro systems for the routine 
and systematic study of isolated human tissues. 
Hopefully, the use of these isolated human tis- 
sues might add another dimension to our ability 
to predict cardiovascular drug efficacy or toxic- 
ity in man. 
GENERAL PRINCIPLES 
Before detailing specific examples of the ad- 
vantages or limitations of animal and human in 
vitro tissue models, I think it is important to 
outline some basic principles which are often 
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