Postischemic inotropic support of the dysfunctional heart

Objective: To determine relative adenine nucleotide regeneration and improvement in left ventricular (LV) function using three commonly used adrenergic agents- epinephrine, dobutamine, and phenylephrine- during reperfusion after a period of global ischemia. After initial resuscitation from cardiac arrest, adrenergic agents are frequently required to support postischemic LV dysfunction. However, the relative effectiveness and associated bioenergetic changes associated with these agents in the post-ischemic heart are unclear. Design: Prospective, controlled laboratory study. Setting: University research laboratory. Subjects: Isolated, perfused Sprague-Dawley rat hearts. Interventions: After 20 mins of global ischemia, isolated rat hearts were reperfused for 30 mins with Krebs-Henseleit solution alone (control, n = 8), or with the addition of equipotent doses of epinephrine 1 muM (n = 8), dobutamine 0.3 muM (n = 8), or phenylephrine 50 muM (n = 8). In a second experiment, an alpha-1 antagonist, prazosin was given with phenylephrine to block the presumed alpha-1 agonist effect of phenylephrine. Measurements and Main Results: A constant volume balloon was placed in the left ventricle to measure LV pressure and derived parameters of LV function. Adenine nucleotide concentrations were derived at various time points using high-performance liquid chromatography. During reperfusion, the phenylephrine group had significant improvement in LV function and cardiac efficiency in contrast to epinephrine and dobutamine. Total adenine nucleotides tended to be highest in the phenylephrine group with significant increases in adenosine diphosphate and adenosine monophosphate and no significant loss of adenosine triphosphate. The phenylephrine-induced increase in heart rate and developed pressure could be blocked with an a-1 antagonist, prazosin. Conclusions. In the isolated reperfused heart, phenylephrine, mediated by alpha-1 agonism, significantly improves postischemic LV dysfunction without worsening the overall myocardial metabolic state.