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 postischemic heart are unclear.


METHODS
Prospective, controlled laboratory study.


METHODS
University research laboratory.


METHODS
Isolated, perfused Sprague-Dawley rat hearts.


METHODS
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 microM (n = 8), dobutamine 0.3 microM (n = 8), or phenylephrine 50 microM (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.


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 alpha-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.
Angelos
Mark G
MG
Department of Emergency Medicine, The Ohio State University, Columbus, OH 43210-1270, USA. angelos.1@osu.edu
Murray
Holt N
HN
Waite
Michael D
MD
Gorsline
Robert T
RT
D000227:Adenine Nucleotides / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004837:Epinephrine / Q000494:pharmacology / Q000627:therapeutic use*; D006323:Heart Arrest / Q000188:drug therapy; D006439:Hemodynamics; D066298:In Vitro Techniques; D015425:Myocardial Reperfusion / Q000379:methods*; D017682:Myocardial Stunning / Q000150:complications / Q000188:drug therapy*; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology; D016277:Ventricular Function, Left / Q000187:drug effects
D000227:Adenine Nucleotides; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D004280:Dobutamine; D004837:Epinephrine