Influence of the beta-blocker therapy on neutrophil superoxide generation and platelet aggregation in experimental myocardial ischemia and reflow

Abstract

The beneficial effect of beta-blockade has been reported in acute myocardial ischemia as well as in the postinfarction period. Recent interest focused on the special effect of beta-blocking agents regarding the changes of lipid metabolism, free radical mediated reactions and arachidonic acid cascade. In previous experiments on dogs we have shown that ultrashort-acting beta-blocker (Brevibloc) could modify production of prostacyclin and thromboxane in ischemic heart tissue. The purpose of this study was to investigate the effect of Brevibloc on the function of isolated neutrophils and platelets during myocardial ischemia and reperfusion. In mongrel dogs the left descending coronary artery (LAD) was ligated for 1 or 2 hours followed by one hour reperfusion. Animals were divided into two groups: Group I control dogs (n = 21) no drugs were given; in Group II. (n = 20) short half-life beta-blocker esmolol HCl (Brevibloc) was administered intravenously. Polymorphonuclear leukocytes (PMN) were isolated from venous blood before and after LAD ligature and following reperfusion. Spontaneous and phorbol myrystate acetate (PMA) stimulated superoxide radical generation of isolated PMN was measured. Platelets were separated at the same periods and maximal aggregation was determined in platelet rich plasma (PRP) after stimulation with collagen, adrenaline and ADP. There was no spontaneous radical production of PMN neither in the control, nor in the Brevibloc treated animals. Neutrophil superoxide production after activation in Group I was 9.54 +/- 0.3 O2-/min/1.5 x 10(6) before LAD ligature, and significant elevation was present following one hour reperfusion (14.8 +/- 0.8 O2-/min/1.5 x 10(6)). Increased production of neutrophils was inhibited by beta-blocker therapy (9.32 +/- 1.05, 8.25 +/- 0.82 respectively). Collagen and ADP stimulated platelet aggregation increased more than 20% during ischemia in Group I, which elevated further after reperfusion. Administration of Brevibloc diminished maximal aggregation in both cases, after 1-2 hours of LAD ligature and after reperfusion, compared to the initial value. Our findings suggested that ultrashort-acting beta-blocker has in vivo inhibitory action on neutrophil superoxide generation and platelet aggregation influencing the pathological cellular interactions.