Document Detail

The effect of reduced myocardial cyclic AMP content on the response to milrinone in the isolated guinea pig heart.
MedLine Citation:
PMID:  9229294     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cardiac beta receptor down-regulation is associated with a reduction of tissue cyclic adenosine monophosphate (AMP) content. Milrinone exerts its effects by inhibiting the metabolism of existing cyclic AMP. The purpose of this study was to evaluate the effect of reduced myocardial cyclic AMP content on the pharmacologic action of milrinone. METHODS: A reduction of myocardial cyclic AMP content was produced by creating catecholamine depletion in the hearts of adult guinea pigs with intraperitoneal reserpine. Control animals received the reserpine vehicle. Isolated heart perfusion was maintained with modified Krebs buffer, and hearts were paced at 270 beats/min. A latex balloon and transducer-tipped catheter were inserted into the left ventricle. Isovolemic work was maintained at a constant balloon volume. Hearts from control and reserpine treated animals were perfused for 20 minutes with buffer containing either no milrinone, 1.7 x 10(-6), or 1.0 x 10(-4) mol/L milrinone (n = 12 for each dose). Maximal positive and negative dP/dt were assessed. The hearts were then frozen and cyclic AMP was measured. RESULTS: Cyclic AMP content was significantly lower in the reserpine-treated hearts at each milrinone concentration (0.33 +/- 0.01 vs 0.46 +/- 0.01; 0.33 +/- 0.01 vs 0.53 +/- 0.01; 0.30 +/- 0.01 vs 0.61 +/- 0.02 pmol/mg wet weight, p < 0.05). Milrinone significantly increased positive and negative dP/dtmax (p < 0.05), but no difference was observed between control and reserpine-treated hearts. CONCLUSIONS: Endogenous catecholamine depletion reduces myocardial cyclic AMP content but does not attenuate the response to milrinone in the isolated heart.
C H Kehler; J R Hebl; C L Soule; W J Gallagher; A J Houlton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  16     ISSN:  1053-2498     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-09-18     Completed Date:  1997-09-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  636-42     Citation Subset:  IM    
Department of Anesthesiology, University of Minnesota, Minneapolis 55455, USA.
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MeSH Terms
Cardiotonic Agents / pharmacology*
Cyclic AMP / metabolism*
Dose-Response Relationship, Drug
Guinea Pigs
Myocardium / metabolism*
Phosphodiesterase Inhibitors / pharmacology*
Pyridones / pharmacology*
Reserpine / pharmacology
Sympatholytics / pharmacology
Reg. No./Substance:
0/Cardiotonic Agents; 0/Phosphodiesterase Inhibitors; 0/Pyridones; 0/Sympatholytics; 50-55-5/Reserpine; 60-92-4/Cyclic AMP; 78415-72-2/Milrinone

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