Intravenous isosorbide dinitrate inhibits neutrophil aggregation and plasma-mediated stimulation of superoxide anion production.

Polymorphonuclear neutrophils are known to be activated during myocardial ischaemia causing release of free oxygen radicals and capillary plugging by cell aggregates and therefore to exacerbate ischaemic myocardial injury. Nitric oxide has been shown to modulate neutrophil activation within the ischaemic myocardium and therefore reduce myocardial injury during ischaemia. Drugs that act as nitric oxide donors may therefore modify neutrophil activation. We evaluated the effect of intravenous treatment with isosorbide dinitrate on neutrophil aggregation and plasma-mediated stimulation of neutrophil superoxide anion production in patients with ischaemic heart disease. Samples were obtained from patients before treatment and 15 and 30 min after receiving intravenous isosorbide dinitrate. Isosorbide dinitrate decreased neutrophil aggregation visualized in whole blood (25.3 +/- 3.6, 19.0 +/- 2.6 and 18.5 +/- 2.6 per 300 cells, respectively, P < 0.01). When patient's plasma was incubated with neutrophils obtained from healthy donors, superoxide anion release was 18.99 +/- 6.23, 11.38 +/- 2.79 and 11.49 +/- 3.15 nmol O2-/10(6) cells, respectively (P < 0.01). Therefore, intravenous isosorbide dinitrate inhibited both plasma-mediated stimulation of neutrophil superoxide anion production and neutrophil aggregation.

Evidence for plasma-mediated neutrophil superoxide anion production during myocardial infarction.

The participation of polymorphonuclear neutrophils (PMN) in the development of free-oxygen-mediated myocardial injury is well documented, but direct evidence that PMN-oriented stimuli released to the peripheral blood are able to stimulate PMN free oxygen radical production is missing. We have previously reported that peripheral blood plasma obtained from patients with acute myocardial infarction has chemotactic activity for neutrophils and augments PMN adherence. To investigate whether neutrophilic stimuli released to peripheral blood may induce PMN superoxide anion (O2-) production, we incubated PMN from healthy donors with plasma from patients with acute transmural infarction. PMN O2- production was measured by cytochrome c reduction. PMN O2- was higher under the influence of plasma obtained on the day of admission (24.66 +/- 12.41) and 1 day after onset of acute ischemia (22.91 +/- 10.37) as compared with those observed after incubation with saline (4.18 +/- 1.37; negative control) or zymosan-activated plasma (11.07 +/- 3.4; activated complement cascade positive control). In the following days, plasma-mediated PMN O2- decreased: 13.27 +/- 1.96; 12.37 +/- 3.54 and 8.18 +/- 1.56 after incubation with plasma obtained 2, 3 and 7 days after onset of symptoms, respectively. The results indicate an additional possibility of monitoring the inflammatory response to myocardial necrosis.