CIRCUIT FACTORS IN THE HIGH CARDIAC-OUTPUT OF SEPSIS

Purpose: The increase of cardiac output (GO) in sepsis must be matched by an increase in venous return. Our goal was to determine which of t he determinants of venous return are responsible in volume-loaded and nonvolume-loaded pigs with endotoxemia. The determinants include stres sed volume, venous compliance (C-v), venous resistance (RVR) and right atrial pressure (Pra). We also tested the effect of the nitric oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine-methyl ester (L-NAME ) after the hemodynamics with endotoxin stabilized. Methods: Pigs were anesthetized and mechanically ventilated. We measured CO by thermodil ution, mean circulatory filling pressure (MCFP) by inflating a balloon in the right atrium, blood volume by dye dilution, and C-v by rapid b lood infusions. RVR was calculated from MCFP - Pra/CO). After baseline measurements, we infused 10 mu g/(kg x h(-1)) of Escherichia coli end otoxin. Eight animals also received 30 mL x kg(-1) of dextran over the 2 hours (volume treated), and seven did not (no volume). After 2 hour s we injected 25 mg x kg(-1) of the NO synthase inhibitor, L-NAME, and repeated the measurements. Results: In volume treated animals, CO inc reased from 3.9 +/- 0.7 to 5.4 +/- 0.8 L x min(-1) (P < .05), and bloo d pressure (BP) fell from 118 +/- 9 to 76 +/- 12 mmHg. MCFP rose, and there was no change in RVR or C-v, whereas capacitance increased (ie, right shift of pressure-volume curve). Cardiac function (ie, Starling curve) did not change, In no-volume animals, CO fell from 4.47 +/- 0.6 4 to 2.50 +/- 0.86 L x min(-1), BP from 114 +/- 10 to 9 +/- 13 mmHg an d MCFP fell. Systemic vascular resistance did not change. Cardiac func tion was markedly depressed, and the heart rate increased from 143 +/- 13 to 203 +/- 30 beats x min(-1). L-NAME restored BP in both groups b ut also increased RVR and depressed cardiac function. Conclusion: Chan ges in vascular tone during endotoxemia are dependent on volume status . The increased cardiac output in volume-treated septic animals occurr ed because of an increase in stressed volume due to the volume given i n combination with a dilated vasculature. L-NAME restored arterial ton e but decreased CO because of a rise in EVE and decrease in cardiac fu nction. Copyright (C) 1996 by W.B. Saunders Company