- Meeting abstract
Release of endothelin in an experimental model of shock and ARDS in sheep
Critical Care volume 2, Article number: P026 (1998)
The Endothelins (ETs) are a class of 21 amino-acid peptides, which were first described in 1988 as vasoactive peptides produced in the endothelial cells of the porcine aorta. Meanwhile three different subtypes have been identified. ETs act as potential vasocontrictors in the cardiovascular system. In the lungs, ETs induce bronchospasm and via vasoconstriction pulmonary hypertension followed by severe edema formation. It is well known, that ETs are synthesized and present in the lung. Additionally a high number of ET-receptors has been identifed in the lung. Recent studies show elevated ET-plasma concentration in various diseases like cardiogenic shock, subarachnoidal bleeding, COPD, sepsis and trauma. This study was performed to evaluate the ET-plasma concentration after induced hypovolemic shock states and ARDS.
The experiment was performed in 14 anesthesized, and mechanically ventilated sheep (21–28 kg BW) during two different consecutive shock models (A: 3.5% BW ultrafiltrate withdrawal by hemofiltration; B: Blood withdrawal up to 3.5% of BW) and after lung lavage induced ARDS. A 4 F catheter was placed in the A. carotis to obtain blood pressure. Cardiac output was determinated by a 7.5 F fiberoptic thermodilution catheter placed into the main pulmonary artery. Blood samples from the A. carotis (CAR) and the A. pulmonalis (PUL) and urine samples were taken at baseline, 15 min after hemofiltration, 15 min after blood withdrawal and 5, 20, 60 min after lung lavage. ET-concentrations were measured by RIA (Nichols, Bad Homburg, FRG). Transpulmonary flux was calculated by the equation: (ET - concentration [A. pulmonalis] - [A. carotis])/cardiac output. Statistical analysis was performed using Wilcoxon sign rank test.
A significant increase of plasma-ET concentrations from baseline levels in the A. carotis and A. pulmonalis (CAR 7.89 ± 3.9 μg/ml; PUL 8.22 ± 4.1 μg/ml) was observed during hypovolemia with ultrafiltration (CAR 14.9 ± 7.8 μg/ml, P < 0.01; PUL 15.4 ± 7.1 μg/ml, P < 0.01), and during hypovolemia with blood-withdrawal (CAR 14.4 ± 6.6 μg/ml, P < 0.01; PUL 13.6 ± 6.4 μg/ml, P < 0.01), and 60 min after ARDS (CAR 10.6 ± 5.0 μg/ml, P < 0.05). No significant difference was found between plasma-ET concentration in CAR and PUL at any state. Urine-ET concentration showed a slight, but not significant increase after ARDS, but no alterations in hypovolemic states. Flux calculation did not indicate significant changes.
The presented data show a significant increase in plasma-ET concentration after induced hypovolemic shock. It can be speculated that the potential vasoconstrictory effects of ETs act as a paracrine regulator of vascular tone. In contrast to other studies we could not find a significant change in the early state of induced ARDS. In a saline lavage model desquamation of bronchial and bronchialar epithelium, hyaline membranes and accumulations of pyknotic cells in peterminal airspaces can be observed. These pathological changes may explain the lack of an early response due to partial destruction of endothelium cells.
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Friess, U., Quintel, M., Roth, H. et al. Release of endothelin in an experimental model of shock and ARDS in sheep. Crit Care 2 (Suppl 1), P026 (1998). https://doi.org/10.1186/cc156
- Pulmonary Hypertension
- Main Pulmonary Artery
- Hypovolemic Shock
- Flux Calculation
- Lung Lavage