Analysis of Endotoxin Effects on Pulmonary Circulation in Terms of Pressure-Flow Characteristics

in Circulatory Shock (1993), 39(4), 285-92

The purpose of the present work was to explore the hypothesis that pulmonary vasoconstriction secondary to endotoxin insult results mainly from an increase in the critical closing pressure of the ... [more ▼]

The purpose of the present work was to explore the hypothesis that pulmonary vasoconstriction secondary to endotoxin insult results mainly from an increase in the critical closing pressure of the pulmonary vessels. Specifically, we reasoned that in the face of a Starling resistor located between pulmonary arteries and left atrium, upstream transmission of increased left atrial pressure (Pla) would be inversely related to the level of the pressure intercept (Pi) obtained by extrapolation from the linear pulmonary arterial pressure (Ppa)--flow (Q degrees) plot. Six dogs (group E) were infused with Escherichia coli endotoxin (0.25 microgram/kg/min) for 2 hr, whereas six additional dogs (group C) served as control. During baseline conditions, Pi approximated LAP in both groups. In group C dogs, increasing LAP at constant Q degrees led to a proportional augmentation of Ppa. In group E dogs, endotoxin resulted in a shift of the Ppa-Q relationships to higher pressures due to both increases in Pi and slope. In addition, changes in Pla over the same range as in control dogs affected Ppa only at the highest levels of Pla. We conclude that endotoxin insult increases the critical closing pressure that exceeds Pla and induces the occurrence of a Starling resistor responsible for the production of an effective vascular waterfall. [less ▲]

Effect of Positive End-Expiratory Pressure on Pulmonary Vascular Pressure-Flow Characteristics in Canine Endotoxin Shock

in Circulatory Shock (1992), 37(3), 189-97

The vascular pulmonary pressure-flow (P-Q degree) relationships were studied in anesthetized dogs in order to characterize the distribution of total resistance in the pulmonary bed with respect to ... [more ▼]

The vascular pulmonary pressure-flow (P-Q degree) relationships were studied in anesthetized dogs in order to characterize the distribution of total resistance in the pulmonary bed with respect to incremental resistance and critical closure prior to and after endotoxin insult. Incremental resistance was computed as the slope of the P-Q degree relation, whereas critical closure was referred to as the extrapolated pressure intercept at zero flow. P-Q degree coordinates were obtained by varying Q degree through graded inflation of right atrial balloon. The gradients across the arterial segment (Pa = Ppa - Pc) and across the venous segment (Pv = Pc - Pw) of the pulmonary vasculature were defined by the computation of effective capillary pressure (Pc) obtained from the analysis of the transient decay of pulmonary artery pressure (Ppa) toward wedge pressure (Pw) after arterial occlusion. Six group E dogs were infused with endotoxin at a rate of 0.25 microgram/kg min, while six additional animals served as control (group C). Endotoxin induced increases in flow resistance from 0.056 to 0.096 mm Hg/ml/min/kg due to arterial vasoconstriction and increases in critical closure from 2.3 to 8.4 mm Hg due to a venous waterfall. Before and after endotoxin insult, we assessed effects of each of three levels of static lung inflation (PEEP) on P-Q degree relationships.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Lung Fluid Dynamics and Supply Dependency of Oxygen Uptake During Experimental Endotoxic Shock and Volume Resuscitation

in Critical Care Medicine (1991), 19(7), 955-62

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr ... [more ▼]

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion. RESULTS: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg. CONCLUSIONS: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion. [less ▲]

Neuroendocrine-Immune Interactions in T Cell Ontogeny

in Thymus (1989), 13(3-4), 131-40