Euler-Liljestrand mechanism

The Euler-Liljestrand mechanism or Euler Liljestrand reflex (according to Paul H. Rossier also alveolar-vascular reflex called), clinically as hypoxic pulmonary vasoconstriction (HPV) refers, describes the relationship between the ventilation ( ventilation ) and circulation ( Perfusion ) of the lungs , described as the ventilation / perfusion ratio (or V / Q quotient ). The term reflex is misleading because, strictly speaking , reflexes are mediated by neurons. It is better to use the term hypoxic pulmonary vasoconstriction (HPV) .

history

It was discovered by Ulf von Euler and Göran Liljestrand in 1946 , although the British researchers John Rose Bradford and Henry Percy Dean observed an increase in pulmonary artery pressure (PAP) under asphyxia in animal experiments on dogs in 1894 (see also pulmonary hypertension ).

physiology

If the ventilation in a part of the lungs decreases - also known as alveolar hypoventilation - this leads to a local lack of oxygen ( hypoxia ) and a reflex narrowing ( constriction ) of the blood vessels in this lung segment. By targeted vasoconstriction of the corresponding pulmonary vessels in areas of alveolar hypoxia, the lungs or the sections of the lungs can adapt the perfusion to the local ventilation. This prevents blood from passing through the lungs without being oxygenated ( shunt ). Physiologically, one can differentiate between an acute phase of HPV and a protracted phase. The HPV sets in within a few seconds and reaches a plateau after about 15 minutes.

The HPV homogenizes the ventilation-perfusion ratio. The partial pressure difference between alveoli and arterioles, i.e. the alveolo-arterial oxygen pressure difference (AaDO ₂ ), decreases. The pulmonary shunt decreases, that is, the venous admixture from perfused but not ventilated areas decreases. The arterial oxygen partial pressure (p _a O ₂ ) increases in the sense of normalization.

Phylogenetically , hypoxic pulmonary vasoconstriction probably plays an important role in the evolutionary adaptation of the regional blood flow in lung sections to regional ventilation. The mechanism also plays an important role in the adaptation to altitude or in the development of altitude sickness . So progressive is hypoxia , a high altitude pulmonary edema cause.

Pathophysiology and Clinical Significance

In principle, hypoxic pulmonary vasoconstriction (HPV) is of great importance in all diseases in which, due to alveolar hypoxia - i.e. a decrease in the oxygen content in the alveoli - there is a redistribution of blood flow from these hypoxic areas into better oxygenated sections of the lungs and thus the ventilation-perfusion ratio is optimized. Such diseases are e.g. B. pneumonia , chronic obstructive pulmonary disease , acute respiratory lung failure (ARDS) and altitude sickness .

Molecular Mechanisms

The question is how an oxygen difference is perceived in the pulmonary arterial smooth muscle cells (oxygen sensing and signal transduction ) and what molecular mechanisms lead to HPV in the smooth muscles of the pulmonary vessels.

HPV was investigated in and on various experimental set-ups or models, such as the animal model, isolated lung preparations or pulmonary arteries and endothelial-free pulmonary artery rings, as well as on isolated smooth muscle cells of the pulmonary arteries (PASMC = pulmonary artery smooth muscle cells ). First, the smooth pulmonary artery muscle cells (PASMC) could be identified as the actual histological location of the HPV or the localization of the oxygen sensors, which then lead to vasoconstriction. This makes the PASMC both the sensor and the effector cells of HPV.

It seems to be proven that a cytosolic increase in calcium concentration leads to constriction of the PASMC. The origin of the rising cytosolic calcium has been disputed so far. One hypothesis sees the influx of calcium via so - called voltage - dependent L-type calcium channels (VOCC = voltage-operated calcium channel ) or via memory-controlled calcium channels (SOCC = store-operated calcium channel ) from the extracellular space. Other hypotheses postulate the origin of calcium from intracellular stores, such as the sarcoplasmic reticulum or from the mitochondria .

A sensitization of the PASMC to calcium via the RhoKinase signaling pathway for the protracted phase of HPV also appears to be possible.

In addition to the calcium channels, whether voltage-dependent L-type channel (VOCC) or memory-controlled calcium channel (SOCC), potassium channels also seem to play an important role in HPV (synergism). If the oxygen partial pressure drops - a hypoxia - in the pulmonary artery muscle cells (PASMC), the potassium channel is blocked, which leads to the depolarization of the cell. Voltage- dependent L-type calcium channels are activated and an influx of Ca ^{2+ occurs} across the plasma membrane and calcium is released from the sarcoplasmic reticulum . The increase in calcium concentration causes the vascular smooth muscle cells to contract.

Conclusion: The drop in oxygen partial pressure leads to an inhibition of potassium channels, as a result of which the cell membrane is depolarized - i.e. a change in membrane potential towards positive (or less negative) values - and ultimately to the opening of L-type calcium channels.

Negative influence

The following factors cause or counteract the Euler-Liljestrand mechanism. This is clinically undesirable in certain cases ( thoracic surgery or anesthesia).

Vasodilators , e.g. B. volatile, i.e. gaseous anesthetics, glycerol trinitrate , nitroprusside sodium , aminophylline
Hypocapnia - a reduction in the partial pressure of carbon dioxide (pCO2) in the blood - and alkalosis

It should be mentioned that acidosis would cause pulmonary vasoconstriction, and HPV would increase.

literature

Yale Enson, Carlo Giuntini, et al. a .: The Influence of Hydrogen Ion Concentration and Hypoxia on the Pulmonary Circulation. In: The Journal of clinical investigation. Volume 43, June 1964, pp. 1146-1162, doi: 10.1172 / JCI104999 . PMID 14171792 , PMC 289596 (free full text).
Markus Rupp: Oxygen sensors and signal transduction pathways of hypoxic pulmonary vasoconstriction - the role of diacylglycerol, voltage-dependent Ca ²⁺ -activated potassium channel (BK) and haem oxygenase 2 . Inaugural dissertation . Giessen 2010. uni-giessen.de (PDF)
N. Weißmann: Vascular effects of alveolar hypoxia - sensor and signal transduction mechanisms. In: Pneumology. 56, 2002, pp. 511-513. doi: 10.1055 / s-2002-33311

Individual evidence

↑ Ulf von Euler, Göran Liljestrand: Observations on the Pulmonary Arterial Blood Pressure in the Cat . In: Acta Physiologica Scandinavica . No. 12 , 1946, pp. 301-320 , doi : 10.1111 / j.1748-1716.1946.tb00389.x .
↑ John Rose Bradford, Henry Percy Dean: The Pulmonary Circulation . In: The Journal of Physiology . No. 16 (1-2) , March 22, 1894, pp. 34-158 , PMID 16992161 , PMC 1514499 (free full text).
^ R. Larsen, T. Ziegenfuß: Ventilation . Springer, Berlin / Heidelberg 1997.

[1] Ulf von Euler, Göran Liljestrand: Observations on the Pulmonary Arterial Blood Pressure in the Cat . In: Acta Physiologica Scandinavica . No. 12 , 1946, pp. 301-320 , doi : 10.1111 / j.1748-1716.1946.tb00389.x .

[2] John Rose Bradford, Henry Percy Dean: The Pulmonary Circulation . In: The Journal of Physiology . No. 16 (1-2) , March 22, 1894, pp. 34-158 , PMID 16992161 , PMC 1514499 (free full text).

[3] R. Larsen, T. Ziegenfuß: Ventilation . Springer, Berlin / Heidelberg 1997.