Effect of free radical scavengers on myocardial function and Na+, K+-ATPase activity in stunned rabbit myocardium.
OBJECTIVE
The role of reactive oxygen species (ROS) in the mechanism of myocardial stunning was investigated.


METHODS
Isolated Langendorff-perfused rabbit hearts were subjected to 15 min normothermic ischemia followed by 10 min reperfusion with Krebs-Henseleit solution+/-mannitol or histidine.


RESULTS
In hearts reperfused without free radical scavenger the left ventricular developed pressure as well as its maximal positive and negative first derivatives (+dP/dt, -dP/dt) was significantly depressed, whereas end diastolic pressure (LVEDP) increased when compared to preischemic values. Treatment with mannitol had little protective effects, whereas singlet oxygen scavenger histidine significantly improved the recovery of LVEDP and -dP/dt. Sarcolemmal Na+, K+-ATPase activity (control, 400+/-41 nmol Pi.min-1.mg-1) was depressed in untreated stunned hearts (260+/-27 nmol Pi.min-1.mg-1), but was almost completely recovered in hearts pretreated with histidine (364+/-27 nmol Pi.min-1.mg-1). The inhibition of Na+, K+-ATPase was only slightly prevented by mannitol (302+/-29 nmol Pi.min-1.mg-1l).


CONCLUSIONS
The results suggest that ROS-induced inhibition of Na+, K+-ATPase activity is involved in the mechanism of postischemic contractile dysfunction and support the view that singlet oxygen may be one of the major causes of oxidative injury during ischemia and reperfusion.
Kaplan
Peter
P
Centre for Experimental Surgery and Anaesthesiology, Katholieke Universiteit Leuven, Provisorium I, Minderbroedersstraat 17, B-3000, Leuven, Belgium.
Matejovicova
Milena
M
Herijgers
Paul
P
Flameng
Willem
W
D000818:Animals; D004195:Disease Models, Animal; D004234:Diuretics, Osmotic / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006639:Histidine / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000378:metabolism* / Q000503:physiopathology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism*; D013318:Stroke Volume / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D004234:Diuretics, Osmotic; D016166:Free Radical Scavengers; D008353:Mannitol; D006639:Histidine; D000254:Sodium-Potassium-Exchanging ATPase