Document Detail


Adenosine enhances cytosolic phosphorylation potential and ventricular contractility in stunned guinea pig heart: receptor-mediated and metabolic protection.
MedLine Citation:
PMID:  17341737     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanisms of adenosine (ADO) protection of reperfused myocardium are not fully understood. We tested the hypothesis that ADO (0.1 mM) alleviates ventricular stunning by ADO A(1)-receptor stimulation combined with purine metabolic enhancements. Langendorff guinea pig hearts were stunned at constant left ventricular end-diastolic pressure by low-flow ischemia. Myocardial phosphate metabolites were measured by (31)P-NMR, with phosphorylation potential {[ATP]/([ADP].[P(i)]), where brackets indicate concentration} estimated from creatine kinase equilibrium. Creatine and IMP, glycolytic intermediates, were measured enzymatically and glycolytic flux and extracellular spaces were measured by radiotracers. All treatment interventions started after a 10-min normoxic stabilization period. At 30 min reperfusion, ventricular contractility (dP/dt, left ventricular pressure) was reduced 17-26%, ventricular power (rate-pressure product) by 37%, and [ATP]/([ADP].[P(i)]) by 53%. The selective A(1) agonist 2-chloro-N(6)-cyclo-pentyladenosine marginally preserved [ATP]/([ADP].[P(i)]) and ventricular contractility but not rate-pressure product. Purine salvage precursor inosine (0.1 mM) substantially raised [ATP]/([ADP].[P(i)]) but weakly affected contractility. The ATP-sensitive potassium channel blocker glibenclamide (50 microM) abolished ADO protection of [ATP]/([ADP].[P(i)]) and contractility. ADO raised myocardial IMP and glucose-6-phosphate, demonstrating increased purine salvage and pentose phosphate pathway flux potential. Coronary hyperemia alone (papaverine) was not cardioprotective. We found that ADO protected energy metabolism and contractility in stunned myocardium more effectively than both the A(1)-receptor agonist 2-chloro-N(6)-cyclo-pentyladenosine and the purine salvage precursor inosine. Because ADO failed to stimulate glycolytic flux, the enhancement of reperfusion, [ATP]/([ADP].[P(i)]), indicates protection of mitochondrial function. Reduced ventricular dysfunction at enhanced [ATP]/([ADP].[P(i)]) argues against opening of mitochondrial ATP-sensitive potassium channel. The results establish a multifactorial mechanism of ADO antistunning, which appears to combine ADO A(1)-receptor signaling with metabolic adenylate and antioxidant enhancements.
Authors:
Karsten Schulze; Conrad Duschek; Robert D Lasley; Rolf Bünger
Related Documents :
15072957 - Acute negative inotropic effects of homocysteine are mediated via the endothelium.
16298137 - Interaction between tumor necrosis factor-alpha and leptin-induced inhibition of cardia...
23993727 - Myocardial fibrosis and qtc are reduced following treatment with spironolactone or amil...
10684527 - Effects of palmitoyl carnitine on perfused heart and papillary muscle.
19549037 - Quantification of left ventricular asynchrony throughout the whole cardiac cycle with a...
1970377 - Assessment of priority for coronary revascularisation procedures. revascularisation pan...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  102     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-07     Completed Date:  2007-04-30     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1202-13     Citation Subset:  IM    
Affiliation:
Abteilung für Kardiologie und Pneumologie, Campus Benjamin Franklin, Charité Berlin, 12200 Berlin, Germany. karsten.schulze@charite.de
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenosine / antagonists & inhibitors,  physiology*
Adenosine Triphosphate / metabolism*
Animals
Coronary Circulation / physiology
Cytosol / metabolism
Energy Metabolism / physiology
Female
Glucose-6-Phosphate / metabolism
Guinea Pigs
Heart Rate / physiology
Inosine Monophosphate / metabolism
Lactic Acid / metabolism
Myocardial Contraction / physiology*
Myocardial Reperfusion
Myocardium / metabolism
Pentose Phosphate Pathway / physiology*
Phosphates / metabolism
Phosphorylation
Potassium Channels / metabolism
Ventricular Function, Left / physiology*
Grant Support
ID/Acronym/Agency:
HL-34579/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Phosphates; 0/Potassium Channels; 131-99-7/Inosine Monophosphate; 50-21-5/Lactic Acid; 56-65-5/Adenosine Triphosphate; 56-73-5/Glucose-6-Phosphate; 58-61-7/Adenosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Binge alcohol exposure in the second trimester attenuates fetal cerebral blood flow response to hypo...
Next Document:  How can practice-based research contribute to the elimination of health disparities?