Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication

Abstract

To review possible mechanisms and therapeutics for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide (NO) through the inducible NO synthase (iNOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In conscious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Keywords: Acute lung injury; Acute respiratory distress syndrome; Inducible nitric oxide synthase; Nitric oxide; Pathogenetic mechanisms; Therapeutic regimen.

Figure 1

The gross inspection of the lung following cerebral compression in anesthetized rats. The normal lung in a rat without cerebral compression appears pink color and small size (left); Severe pulmonary edema and hemorrhage occur after cerebral compression. The lung is swollen and dark red in color (right).

Figure 2

Schematical representation of the neural and hemodynamic mechanisms involved in the pulmonary edema and hemorrhage following cerebral compression. The hypothalamic “pulmonary edemagenic center” and vagal pathway are not important. Activation of the medullary sympathetic mechanism causes vasoconstriction of the systemic resistance and capacitance vessels, resulting in blood shift from the systemic to pulmonary circulation. A dramatic decrease in the left ventricular output produces pulmonary volume loading. Subsequently, pulmonary arterial and venous hypertension ensue, and finally, severe lung edema and hemorrhage.

Figure 3

The isolated perfused lung in situ preparation. A roller pump provides constant flow. The pulmonary arterial pressure (PAP) and venous pressure (PVP) are monitored by pressure transducers. The change in body weight is determined by a balance platform. The increase in body weight reflects the lung weight gain.