The effects of the antiarrhythmic drugs lidocaine and bretylium tosylate on myocardial necrosis were studied in anesthetized pigs subjected to 60-min coronary occlusion followed by 3-h reperfusion. Group A (n = 7) received lidocaine (average dose +/- SD = 1,828 +/- 515 mg) before and during coronary occlusion and after reperfusion; the other series (group B, n = 7) received bretylium tosylate (3,457 +/- 1,323 mg). Infarct size was 16.3 +/- 14.7% in the lidocaine group as compared with 68.6 +/- 12.6% (p less than 0.01) in the bretylium group. In vitro release of superoxide anion from porcine granulocytes was studied using the lucigenin-dependent chemiluminescence technique. Lidocaine significantly reduced the peak chemiluminescence response to zymosan from 3.34 +/- 0.44 without lidocaine to 2.23 +/- 0.46 (p less than 0.01) and 1.06 +/- 0.17 mV (p less than 0.001), with lidocaine concentrations of 20 and 200 micrograms/ml, respectively. Bretylium had no effect on the chemiluminescence response. Adherence of porcine granulocytes to plastic was also reduced from 332 +/- 32 cells/mm2 (no lidocaine) to 247 +/- 35 and 206 +/- 26 cells/mm2 with lidocaine concentrations of 20 and 200 micrograms/ml, respectively (p less than 0.001). Bretylium had no significant effect. Eight additional bretylium-treated pigs received either rabbit antiporcine granulocyte serum (group C, n = 4) to reduce circulating granulocytes or nonimmune serum (group D, n = 4). Infract size in the granulocyte-depleted pigs was 26.6 +/- 5.6% as compared with 51.4 +/- 5.5% in pigs that received nonimmune serum (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)