Euler–Liljestrand mechanism

Of the Euler Liljestrand mechanism or Euler Liljestrand reflex clinically as hypoxic pulmonary vasoconstriction denotes (HPV), describes the relationship between the ventilation (ventilation) and the blood flow ( perfusion ) of the lung are described as ventilation / perfusion ratio (or V / Q quotient ). The term reflex is misleading because reflexes are strictly mediated neurally. It is better to use the term hypoxic pulmonary vasoconstriction (HPV).

History

It was founded in 1946 discovered by Ulf von Euler and Göran Liljestrand, although already the British explorer John Rose Bradford, and Henry Percy Dean in 1894 in animal experiments on dogs a rise in pulmonary arterial pressure (PAP ) observed under asphyxia (see also this Pulmonary hypertension).

Physiology

Takes in a part of the ventilation of the lungs from - also known as alveolar hypoventilation - this leads to a local lack of oxygen (hypoxia) and reflex constriction ( constriction ) of the blood vessels in the lung portion. Through selective vasoconstriction of the pulmonary vessels in corresponding areas of alveolar hypoxia, the lung or the lung sections can adjust the perfusion of local ventilation. This prevents that blood can pass through the lungs without being oxygenated (shunt). One can differentiate between a physiologically acute phase of HPV and a protracted phase. The HPV is a matter of seconds and reaches a plateau after about 15 minutes.

By HPV, there is a homogenization of the ventilation-perfusion ratio. The partial pressure difference between alveoli and arterioles, ie, the alveolar- arterial oxygen pressure difference ( AaDO2 ) decreases. Pulmonary shunt decreases, that is, the admixture of venous blood supply, but not ventilated areas decreases. The arterial partial pressure of oxygen ( PaO2 ) increased in terms of normalization.

Phylogenetically hypoxic pulmonary vasoconstriction likely plays an important role in the evolutionary adaptation of the local blood flow of the lung portions to the regional ventilation. The mechanism plays an important role in adjusting the height or in the onset of altitude sickness. Thus, a high altitude pulmonary edema occur when it comes by progressive hypoxia to a vasoconstriction of the pulmonary vessels. This increases the pressure in the pulmonary circulation, resulting in damage to the capillary endothelium. Thus, the capillaries more permeable, and there is a lower air pressure. As a result, fluid is forced from the intravascular space into the alveoli ( high altitude pulmonary edema ).

Pathophysiology and clinical significance

In principle, the hypoxic pulmonary vasoconstriction (HPV ) in all diseases of great importance, which are due to alveolar hypoxia - thus decreasing the oxygen content in the alveoli - a redistribution of blood flow from these same hypoxic areas in better oxygenated portions of the lung, and thus leads to an optimization of the ventilation-perfusion ratio. Such disorders are, for example, pneumonia, chronic obstructive pulmonary disease, acute respiratory pulmonary failure (ARDS ), and altitude sickness.

Molecular Mechanisms

The question is how to pulmonary artery smooth muscle cells, an oxygen difference is perceived (oxygen sensing and signal transduction) and through which molecular mechanisms it comes to HPV of the smooth muscle of pulmonary vessels.

The study of HPV carried in and on various experimental set-ups or models, such as the animal model, isolated lung preparations or pulmonary arteries and endothelfreien Pulmonalarterienringen as well as in isolated smooth muscle cells of the pulmonary arteries ( pulmonary artery PASMC = smooth muscle cells ). First, could the smooth Pulmonalarterienmuskelzellen ( PASMC ) than the actual histological location of HPV or the location of the oxygen sensor, which then leads to vasoconstriction, were identified. Thus, the PASMC both the sensor and the effector of HPV.

There seems to be evidence that a cytosolic increase in calcium concentration to the constriction of the PASMC leads. At issue is so far the origin of increasing cytosolic calcium. One hypothesis sees the influx of calcium through so-called voltage-dependent L -type calcium channels ( VOCC = voltage - operated calcium channel) or storage - gated 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.

Also seems to be a sensitization of PASMC to calcium on the RhoKinase pathway for the sustained phase of HPV possible.

In addition to calcium channels, whether voltage-dependent L-type channel to play ( VOCC ) or memory - controlled calcium channel ( SOCC ), but also seem potassium channels play an important role in the HPV ( synergism ). If there is to waste the oxygen partial pressure - hypoxia - the Pulmonalarterienmuskelzellen ( PASMC ), the potassium channel is blocked, leading to depolarization of the cell. Voltage-dependent L -type calcium channels are activated and there is an influx of Ca2 across the plasma membrane and the release of calcium from the sarcoplasmic reticulum. The increase of the calcium concentration causes contraction of vascular smooth muscle cell.

Conclusion: The decrease of the oxygen partial pressure leads to inhibition of potassium channels, which resulted in the cell membrane is depolarized - ie change in membrane potential toward more positive (or less negative ) values ​​- and ultimately to the opening of L- type calcium channels.

Negative influence

The following factors cause a lifting of the Euler - Liljestrand mechanism or act against him. This is not clinically desirable in certain cases ( thoracic surgery or anesthesia ).

• Vasodilators, such as volatile, ie gaseous anesthetics, nitroglycerin, sodium nitroprusside, aminophylline
• Hypocapnia - ie a reduction in the Kohlenstoffdioxidpartialdruckes ( pCO2 ) in the blood - and alkalosis

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