Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1984-8-22
|
| pubmed:abstractText |
The direct myocardial protection afforded by three structurally distinct calcium antagonists (0.1 micron nifedipine, 0.1 micron verapamil and 0.4 micron diltiazem), and a calmodulin antagonist (20 micron W-7) was assessed in isolated working rat hearts subjected to 30 min global ischaemia followed by 30 min reperfusion. At these concentrations, no drug-induced cardiac depression nor coronary vasodilatation was observed prior to ischaemia. All four agents improved recovery of cardiac function (assessed as total cardiac output) on reperfusion (by 49%, 29%, 64% and 72% respectively, compared to controls), attenuated the release of lactate dehydrogenase (by 52%, 55%, 65% and 66% respectively) and inhibited intracellular 45Ca accumulation (by 42%, 35%, 49% and 45% respectively). Despite the increased tissue calcium and enzyme leakage in reperfused hearts, the [3H]inulin-impermeable space was not decreased, suggesting specific changes in membrane permeability rather than partial sarcolemmal rupture. Drug treatment did not alter the rate nor extent of high-energy phosphate depletion during ischaemia, thus eliminating ATP preservation and negative inotropy as mechanisms for the protective effects observed in this system. Improved restoration of coronary flow was obtained in treated hearts but we believe this was more likely to be a consequence of myocardial protection rather than direct coronary vasodilatation. Thus, the beneficial effects observed probably resulted from direct preservation of cellular viability. When given only during the reperfusion phase, nifedipine and W-7 were almost as effective as when given before ischaemia, whereas verapamil and diltiazem were inactive. This highlights differences between the various structural subclasses of calcium antagonists. Furthermore, the efficacy of the calmodulin antagonist, W-7, in this system suggests a possible key role for calmodulin-activated enzymes in the progression of reperfusion damage.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Monophosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Diltiazem,
http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Nifedipine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphocreatine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil,
http://linkedlifedata.com/resource/pubmed/chemical/W 7
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0022-2828
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
16
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
427-38
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:6737483-Adenosine Diphosphate,
pubmed-meshheading:6737483-Adenosine Monophosphate,
pubmed-meshheading:6737483-Adenosine Triphosphate,
pubmed-meshheading:6737483-Animals,
pubmed-meshheading:6737483-Calcium,
pubmed-meshheading:6737483-Calcium Channel Blockers,
pubmed-meshheading:6737483-Calmodulin,
pubmed-meshheading:6737483-Cardiac Output,
pubmed-meshheading:6737483-Coronary Circulation,
pubmed-meshheading:6737483-Coronary Disease,
pubmed-meshheading:6737483-Diltiazem,
pubmed-meshheading:6737483-L-Lactate Dehydrogenase,
pubmed-meshheading:6737483-Male,
pubmed-meshheading:6737483-Myocardium,
pubmed-meshheading:6737483-Nifedipine,
pubmed-meshheading:6737483-Perfusion,
pubmed-meshheading:6737483-Phosphocreatine,
pubmed-meshheading:6737483-Rats,
pubmed-meshheading:6737483-Rats, Inbred Strains,
pubmed-meshheading:6737483-Sulfonamides,
pubmed-meshheading:6737483-Verapamil
|
| pubmed:year |
1984
|
| pubmed:articleTitle |
Prevention of reperfusion damage in working rat hearts by calcium antagonists and calmodulin antagonists.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|