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 the determinants of venous return are responsible in volume-loaded and nonvolume-loaded pigs with endotoxemia. The determinants include stressed 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 thermodilution, mean circulatory filling pressure (MCFP) by inflating a balloon in the right atrium, blood volume by dye dilution, and C-v by rapid blood infusions. RVR was calculated from MCFP - Pra/CO). After baseline measurements, we infused 10 mu g/(kg x h(-1)) of Escherichia coli endotoxin. 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 hours we injected 25 mg x kg(-1) of the NO synthase inhibitor, L-NAME, and repeated the measurements. Results: In volume treated animals, CO increased from 3.9 +/- 0.7 to 5.4 +/- 0.8 L x min(-1) (P < .05), and blood 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 +/- 0.64 to 2.50 +/- 0.86 L x min(-1), BP from 114 +/- 10 to 9 +/- 13 mmHg and MCFP fell. Systemic vascular resistance did not change. Cardiac function 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 but also increased RVR and depressed cardiac function. Conclusion: Changes in vascular tone during endotoxemia are dependent on volume status. The increased cardiac output in volume-treated septic animals occurred because of an increase in stressed volume due to the volume given in combination with a dilated vasculature. L-NAME restored arterial tone but decreased CO because of a rise in EVE and decrease in cardiac function. Copyright (C) 1996 by W.B. Saunders Company