Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine.
OBJECTIVE
The aim as to compare the responses of intracoronary infusions of ATP, an endothelium dependent vasodilator, with adenosine following brief ischaemia (10 min) and reperfusion in a model of myocardial stunning.


METHODS
In group 1 (n = 6), coronary blood flow and endocardial (endo) and epicardial (epi) percent segment length shortening were measured in the distribution of the left anterior descending coronary artery before and during maximal intracoronary infusions of either adenosine or ATP (20 micrograms.kg-1.min-1). Measurements were obtained before and after myocardial stunning both at control heart rate and during atrial pacing (150 beats.min-1). In group 2 (n = 6), myocardial blood flows by microspheres and arterial-venous lactate and oxygen differences were determined following the same ischaemia-reperfusion protocol to characterise transmural changes in blood flow and metabolism in this model of stunning.


METHODS
The experiments were done on 12 anaesthetised swine, weight 25-39 kg.


RESULTS
In group 1, baseline endo and epi segment length shortening were 16(SD 3)% and 14(6)% and following reperfusion were reduced to 10(4)% and 8(6)% respectively (p less than 0.05). Prior to stunning, minimal coronary resistances during adenosine and ATP were 0.81(0.40) and 0.76(0.25) mm Hg.min.ml-1 respectively and following reperfusion were 0.86(0.31) (NS) and 0.85(0.23) (NS) mm Hg.min.ml-1 respectively. Infusion of either vasodilator enhanced function by 30% following reperfusion whereas no such effect was observed prior to ischaemia. In group 2, no maldistribution of blood flow was observed following the same ischaemia-reperfusion protocol to account for this vasodilator enhancement in function. Percent lactate extraction values were 29(11)% and 25(14)% at preischaemic control and paced heart rates respectively, and following reperfusion were lowered to 0(12)% without pacing (p less than 0.05) and -1(34)% during pacing (p less than 0.05).


CONCLUSIONS
Brief ischaemia and reperfusion in swine induces myocardial stunning without altering the vasodilator responses of either ATP, an endothelium dependent vasodilator, or adenosine. Recruitment in postischaemic segment length shortening was observed during infusions of both vasodilators at a time when maldistribution of flow was not observed. Possible mechanisms include either enhanced washout of lactate from the reperfused myocardium or greater utilisation of substrates during higher blood flows.
McFalls
E O
EO
Laboratory for Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
Duncker
D J
DJ
Krams
R
R
Ward
H
H
Gornick
C
C
Verdouw
P D
PD
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods; D010138:Pacemaker, Artificial; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000255:Adenosine Triphosphate; D000241:Adenosine