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ATP gated potassium channels in acute myocardial hibernation and reperfusion
J Offstad1, K A Kirkebøen, A Ilebekk
1Institute for Experimental Medical Research, Ullevål Hospital, Oslo, Norway.
Insights
Opening ATP-gated potassium (KATP) channels and stimulating adenosine receptors are vital for regulating coronary blood flow. This study found KATP channels do not influence perfusion-contraction matching or recovery after reperfusion in piglet and rabbit hearts.
Area of Science:
- Cardiovascular Physiology
- Cardiac Metabolism
- Pharmacology
Background:
- ATP-gated potassium (KATP) channels and adenosine play critical roles in regulating coronary blood flow.
- Activation of KATP channels and adenosine receptor stimulation offer protection against myocardial infarction and stunning.
Purpose of the Study:
- To investigate the involvement of KATP channels and adenosine receptors in perfusion-contraction matching.
- To determine the role of KATP channels and adenosine receptors in acute myocardial hibernation.
- To assess the impact of KATP channels and adenosine receptors on functional recovery after reperfusion.
Main Methods:
- Isolated piglet and rabbit hearts were perfused with modified Krebs Henseleit solutions.
- The effects of KATP channel opener (aprikalim) and antagonist (glibenclamide), and adenosine receptor antagonist (SPT) were examined during low-flow ischemia and reperfusion.
- Measurements included perfusion pressure and left ventricular systolic pressure.
Main Results:
- KATP channel modulation significantly altered coronary vascular tone in both piglet and rabbit hearts.
- Left ventricular systolic pressure decreased in parallel with coronary flow reductions across all treatment groups.
- Functional recovery after reperfusion was not significantly modulated by KATP channel activity or adenosine receptor blockade.
Conclusions:
- Coronary vascular tone is highly sensitive to KATP channel modulation and adenosine receptor blockade.
- KATP channels do not appear to play a role in perfusion-contraction matching, acute hibernation, or functional recovery during reperfusion in these models.
- Adenosine receptor antagonism also did not affect these functional parameters in piglet hearts.
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.