| Gary Merrill
Professor
Rutgers University
Cell Biology and Neuroscience
Nelson Lab. Room B222
Piscataway. NJ 08854
(732) 445-2320
FAX - 5870
merrill@biology.rutgers.edu
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Ischemic heart disease. hypoxia and reoxygenation. metabolic control of coronary
circulation
The major objective of our research is to determine the
roles of physiologically important regulators in the control of coronary
circulation and ventricular rhythmicity. Our main focus has been on the
role of the adenine nucleoside. adenosine. We have also examined regulators
such as estrogen. We routinely use hypoxia and ischemia and reperfusion
to challenge the heart before and after interventions designed to augment
or attenuate the actions of adenosine. estrogen. etc. We have shown that
adenosine deaminase (ADA). the enzyme that inactivates adensine by removing
an amino group from the purine ring. is a good research tool for investigating
the regulatory roles of adenosine. For example. we hypothesized that myocardial
release of adenosine contributes significantly to the coronary vasodilation
caused by regional hypoxia in the anesthetized. instrumented dog. To test
this hypothesis. we pretreated dogs with commercially-available ADA before
causing regional myocardial hypoxia. Coronary circulatory responses to hypoxia
were significantly attenuated in the presence of administered ADA. In more
recent years we hypothesized a role for adenosine in the ventricular arrhythmias
caused by systemic hypoxia. Using administered ADA. we saw a significant
reduction in the incidence of ventricular arrhythmias caused by hypoxia.
Blocking the actions of endogenous ADA with erythro-9-(2-hydroxy. 3-nonyl)
adenine (EHNA) significantly increased the incidence of hypoxia-induced
ventricular arrhythmias. Most recently. we have found that the acute pretreatment
of dogs (both male and female) with estrogen markedly and significantly
attenuates the ventricular arrhythmias caused by regional myocardial ischemia
and reperfusion. We plan to continue these lines of research in the future.
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