Project Details


During the fall in the ratio of O2 supply to O2 demand following myocardial
ischemia, there are still areas of high flow, venous O2 saturation and/or
O2 consumption within the ischemic zone. We have evidence that by reducing
areas of high O2 consumption within the ischemic zone, propranolol can
improve the overall ratio of O2 supply to O2 consumption. Thus, by
affecting the spatial heterogeneity of O2 supply and/or O2 consumption it
is possible to cause beneficial changes in the ischemic zone. In this
grant proposal we would like to study the relationship between O2 supply
and O2 consumption and its variability in normal and ischemic myocardium
with the ultimate intention of improving this relationship. Both
anesthetized open chest dogs and rabbits will be used in five studies. 1.
In this series of experiments we intend to study the relationship between
myocardial "work" and heterogeneity, with the underlying hypothesis that
work controls heterogeneity. In dog, we will study the effect of
increasing work by various means; e.g., pacing, pressure, contractility and
volume, on heterogeneity of venous O2 saturation and coronary flow in
normal and ischemic myocardium. It is possible that by adjusting the type
of work that the heart does, that ischemic damage can be reduced. This
also applies to series 2. It is known that by increasing work in different
ways, one can have very different O2 costs. We intend to measure local
myocardial function through measurements of length and tension and compare
it to local O2 consumption obtained from microsphere and
microspectrophotometric data. Through increases in myocardial work
efficiency it might be possible to reduce ischemic damage. 3. We would
like to prove our observation that beta1 adrenoceptors are involved in the
control of spatial heterogeneity. We will do this through measurements of
beta adrenoceptor number and activity and comparison of these factors to
spatial heterogeneity of flow and venous O2 saturation. The effects of
short and long term up- and downregulation will be explored. 4. We intend
to study various agents that have been proposed to reduce ischemic damage
in our dog ischemia model to study how they alter the relationship between
O2 supply and O2 consumption. 5. We have developed a method to determine
both the total and perfused microvasculature in the heart. This technique
will be used to study the changes in diffusion distance brought on by
ischemia and treatment and whether it can be manipulated in a beneficial
manner. These studies of local O2 supply, O2 consumption, "work", and
diffusion distance allow a complete picture of how ischemia affects a
region and what a treatment does at the local level.
Effective start/end date7/1/816/30/89


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)

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