Lowered pulmonary arterial pressure prevents edema after endotoxin in sheep

Abstract

Escherichia coli endotoxin causes increased capillary membrane permeability and increased pulmonary arterial pressure (PAP) in sheep. If the pulmonary hypertension extends to the level of the microvasculature, then the increased microvascular pressure may contribute to the pulmonary edema caused by endotoxin. We tested the hypothesis that reducing the pulmonary hypertension would reduce the amount of edema caused by endotoxin. Twelve sheep were chronically instrumented with catheters to measure PAP, left atrial pressure, and central venous pressure. The sheep were divided into two groups. One group (E) of six sheep received an intravenous infusion of 4 micrograms/kg of E. coli endotoxin. The second group (E + SNP) received the same dose of endotoxin as well as a continuous infusion of sodium nitroprusside (SNP) to reduce PAP. Three hours after the endotoxin infusions, the sheep were terminated and the extravascular fluid-to-blood-free dry weight ratios of the lungs were determined (EVF). The base-line PAP was 17.5 +/- 2.7 mmHg. A two-way analysis of variance demonstrated a significant difference (P less than 0.01) in PAP between the E and E + SNP groups. Although PAP in each group varied as a function of time, the difference between the two groups did not. The mean PAP for the E + SNP group (20.9 +/- 1.5 mmHg) was lower than the E group PAP of 27.3 +/- 2.1 mmHg after the endotoxin spike. Furthermore, the E + SNP group EVF (3.9 +/- 0.2) was significantly less than the EVF of the E group (4.7 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…28 In an experimental setting, a rising pulmonary arterial pressure is an early initial event followed by right ventricular failure; hence control of associated pulmonary hypertension can protect against edema. 24,29 In the clinical setting, lowered pulmonary arterial pressure and improved right ventricular function is a distinctive pattern in septic shock survivors. 30 Thus, addition of pressure-supporting drugs sharing different pharmacological and physiological targets and pathways could influence the "physiological low-pressure pulmonary circulation".…”

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“…Some of them could limit pulmonary edema, such as the immunomodulatory properties of hypertonic saline 7,8 or its vasodilator properties on pulmonary circulation. 14,15 Others may potentiate edema, such as the increase in endothelial permeability induced by blood hyperosmolarity, [11][12][13] the effect of sodium input on lung water accumulation, 16 or the increase in cardiac output. 17,18 In the present study, we evaluated the effects of a pre-treatment by intravenous hypertonic saline in a clinically reliable model of ischemia-reperfusion such as encountered during lung transplantation.…”

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“…In the pigs, lungs were significantly heavier in the high versus normal tidal volume group, whereas in the rats, they were significantly heavier in the normal versus high tidal volume group. However, this surprising result in the rats may be a methodological artefact, since the blood pressure was not measured in this species, and alveolar overdistension in the high volume group may have led to hemodynamic compromise, lung hypoperfusion, and a smaller perfused lung vascular surface [15], hence reducing the formation of lung oedema, which primarily requires lung circulation. In contrast, arterial blood pressure was monitored in the pigs, and hemodynamic alterations were detected and immediately treated with volume infusion and inotropes when necessary, ensuring that a effective lung circulation was always maintained.…”