β1 -Selectivity of Dobutamine and its Potential for Cardiovascular Therapy
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The myocardial selectivity of dobutamine is of particular interest in the treatment of heart failure due to acute myocardial infarction. Some cardiologists believe that because inotropic stimulation increases myocardial O2-consumption, infarct size will necessarily expand. This idea has its roots in the experiments of Maroko et al. who showed an extension of infarct size with isoproterenol. However, I think we sometimes forget that infarction is a regional process, and that knowing the oxygen consumption for the whole heart doesn’t reveal what is occurring in the ischemic region. We forget to ask, how can the direct inotropic effect of isoproterenol extend an infarction if the drug does not arrive in that area? If blood flow doesn’t arrive, then neither can the isoproterenol. Or you might think that isoproterenol would sequester into an ischemic area, but catechol-a-methyl transferase which inactivates isoproterenol is ubiquitous and this enzyme works as well in an ischemic area as it does in a well-oxygenated area. So the idea that isoproterenol would accumulate in the ischemic area in excess of the blood supply is untenable. Therefore, ist must be the chronotropic and β2 vascular effects rather than the direct inotropic effect of isoproterenol that are responsible for extending the infarction. Our work with dobutamine substantiates this idea.
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