Document Detail

ATP gated potassium channels in acute myocardial hibernation and reperfusion.
MedLine Citation:
PMID:  7923294     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: ATP gated potassium (KATP) channels and adenosine are of crucial importance in coronary blood flow regulation and activation of KATP channels and adenosine receptor stimulation protect against infarction and development of stunning. The aim of this study was to test the hypothesis that opening of KATP channels and adenosine receptor stimulation are involved in perfusion-contraction matching, in acute hibernation, and in recovery after reperfusion. METHODS: 30 isolated piglet hearts (2-10 d old) and 20 isolated rabbit hearts were studied. The isolated piglet hearts were perfused with modified Krebs Henseleit (KH) solution enriched by washed human red blood cells; the isolated rabbit hearts were perfused with modified KH buffer. The effects of the KATP channel opener aprikalim (1 microM), the KATP channel antagonist glibenclamide (30 microM), and the adenosine receptor antagonist 8-(p-sulphophenyl)theophylline (SPT, 300 microM) on 2 h of low flow (10%) ischaemia and 1 h reperfusion were compared with saline in the piglet hearts. The effects of aprikalim (1 microM), glibenclamide (30 microM), and saline during 90 min of low flow (10%) ischaemia followed by 1 h reperfusion were also examined in the isolated rabbit hearts. RESULTS: At constant coronary flow aprikalim reduced perfusion pressure from 53(SEM 5) to 25(1) mm Hg (p < 0.001) in piglet hearts and from 55(5) to 39(5) mm Hg (p < 0.05) in rabbit hearts. Glibenclamide increased perfusion pressure from 47(5) to 61(6) mm Hg (p < 0.01) in piglet hearts and from 45(4) to 81(5) mm Hg (p < 0.001) in rabbit hearts. SPT increased perfusion pressure from 55(6) to 67(6) mm Hg (p < 0.05) in piglet hearts. Left ventricular systolic pressure remained unchanged in both models. During stepwise reductions in coronary flow a parallel stepwise reduction in left ventricular systolic pressure was observed in all groups. At 2 h of low flow ischaemia systolic pressure was 39(4)%, 37(5)%, 41(4)%, and 37(3)% of control for hearts treated with saline aprikalim, glibenclamide, and SPT, respectively. During the low flow period systolic pressure and MVO2 stabilised. An almost identical pattern occurred in rabbit hearts. After 30 min of recovery of piglet hearts left ventricular systolic pressure increased to 78(5)% (saline), 74(5)% (aprikalim), 84(5)% (glibenclamide), and 77(4)% (SPT) of control. The recovery as percentage of control in rabbit hearts was 63(11) (saline), 69(8) (aprikalim) and 56(13) (glibenclamide). CONCLUSION: Coronary vascular tone is highly responsive to KATP channel modulation and adenosine receptor blockade. KATP channels do not modulate either perfusion-contraction matching or acute hibernation and functional recovery during reperfusion in the red blood cell perfused piglet heart or the crystalloid perfused rabbit hearts. Moreover, adenosine receptor antagonism does not affect these phenomena in piglet hearts.
J Offstad; K A Kirkebøen; A Ilebekk; S E Downing
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  28     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-10-24     Completed Date:  1994-10-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  872-80     Citation Subset:  IM    
Institute for Experimental Medical Research, Ullevål Hospital, Oslo, Norway.
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MeSH Terms
Adenosine Triphosphate / metabolism*
Glyburide / pharmacology
Ion Channel Gating / drug effects,  physiology*
Myocardial Infarction / prevention & control*
Myocardial Reperfusion / methods
Myocardial Stunning / metabolism*
Myocardium / metabolism*
Picolines / pharmacology
Potassium Channels / drug effects,  physiology*
Pyrans / pharmacology
Theophylline / analogs & derivatives,  pharmacology
Vasodilator Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Picolines; 0/Potassium Channels; 0/Pyrans; 0/Vasodilator Agents; 10238-21-8/Glyburide; 56-65-5/Adenosine Triphosphate; 58-55-9/Theophylline; 80206-91-3/8-(4-sulfophenyl)theophylline; 89544-10-5/aprikalim

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