JT Granton, CM Goddard, MF Allard, S van Eeden and KR Walley
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.

We hypothesized that leukocytes contribute to decreased myocardial contractility following endotoxin infusion. To test this hypothesis, we administered endotoxin (1 mg/kg intravenously) to intact, anesthetized rabbits whose arterial blood perfused two isolated hearts at a constant pressure (75 mm Hg). One heart was perfused with blood passed through a leukocyte filter, whereas the other received unfiltered blood. Contractility of both hearts was measured every 30 min for 6 h, using the slope of the end-systolic pressure-volume relationship (Emax) and the maximum rate of change of intraventricular pressure (dP/dt(max)). In the unfiltered hearts at 6 h, Emax decreased to 81 +/- 6% (mean +/- SEM) of baseline (p < 0.05). In the hearts perfused with leukocyte- filtered blood there was no change in Emax. Similarly, dP/dt(max) decreased 74 +/- 9% of baseline in the hearts receiving unfiltered blood (p < 0.05) but did not decrease in the hearts receiving leukocyte- filtered blood. The leukocyte filter significantly reduced the number of neutrophils in perfusing blood (p < 0.01), decreased the number of neutrophils in the heart by 77% (p < 0.01), and decreased myocardial morphometric changes (p < 0.05). A 55 +/- 18% reduction in neutrophil L- selectin expression after endotoxin infusion (p < 0.01) suggests that the neutrophils were significantly activated. We conclude that leukocytes, notably activated neutrophils, may contribute to decreased myocardial contractility during septic shock.

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