Contribution of α - and β -Adrenergic Mechanisms to the Development of Pulmonary Edema

Abstract

Endogenous or exogenous catecholamines can induce pulmonary edema (PE). This may occur in human pathologic conditions such as in pheochromocytoma or in neurogenic pulmonary edema (NPE) but can also be provoked after experimental administration of adrenergic agonists. PE can result from stimulation with different types of adrenergic stimulation. With α-adrenergic treatment, it develops more rapidly, is more severe with abundant protein-rich fluid in the alveolar space, and is accompanied by strong generalized inflammation in the lung. Similar detrimental effects of α-adrenergic stimulation have repeatedly been described and are considered to play a pivotal role in NPE or in PE in patients with pheochromocytoma. Although β-adrenergic agonists have often been reported to prevent or attenuate PE by enhancing alveolar fluid clearance, PE may also be induced by β-adrenergic treatment as can be observed in tocolysis. In experimental models, infusion of β-adrenergic agonists induces less severe PE than α-adrenergic stimulation. The present paper addresses the current understanding of the possible contribution of α- and β-adrenergic pathways to the development of PE.

Figure 1

Pathogenic mechanisms of the contribution of adrenergic stimulation to the development of pulmonary edema. Pulmonary effects promoting development of edema are presented on the left side (grey box); protective mechanisms are depicted on the right side (white box). Hemodynamic effects (generalized vasoconstriction and increase in the RV output) result in blood overfilling and congestion in pulmonary circulation and consequently, in elevated pulmonary capillary pressure. This is the primary factor in the development of edema. High microvascular pressure causes capillary wall stress and may lead to disruption of the alveolocapillary barrier. Adrenergic stimulation also promotes proinflammatory processes. The resulting inflammation can deteriorate edema by further increasing capillary permeability. On the right-hand side, antiedematous mechanisms of the lung are shown. Reabsorption processes counteract fluid filtration. Excess fluid can be drained from the interstitium into the pleural space, thus forming pleural effusion. Alveolar fluid clearance eliminates fluid from the air space, thus preventing development of alveolar edema. RV: right ventricular, ↑: increase.

Figure 2

(a): Contribution of α-adrenergic stimulation to the development of pulmonary edema. Treatment with α-adrenergic agonists promotes all proedematous effects of adrenoceptor stimulation, particularly pulmonary microvascular congestion. Elevated capillary pressure and capillary wall stress increase fluid filtration. Microvascular permeability can increase due to capillary wall stress and inflammation. This may result in alveolar edema. Protective mechanisms are not advanced by α-adrenergic mechanisms. (b): Contribution of β-adrenergic stimulation to the development of pulmonary edema. Vasodilation mediated by β-adrenergic stimulation may cause blood overfilling in the pulmonary circulation and, consequently, increase pulmonary capillary pressure. This is usually less pronounced than with α-adrenergic stimulation and is not associated with increased capillary wall stress. Although β-adrenergic agonists exert anti-inflammatory effects, prolonged stimulation may induce focal inflammation. In general, with β-adrenergic stimulation edema develops slowly allowing protective mechanisms such as filtration into the pleural space to be more effective. Moreover, compensatory mechanisms such as alveolar fluid clearance are enhanced, thus preventing flooding of the alveoli. Bold arrows and boxes depict the main effects of the respective treatment; thin arrows and boxes characterize slight or less pronounced effects; dashed arrows and boxes with light-grey frames and types mark processes that are not affected or inhibited by this type of stimulation. RV: right ventricular, ↑: increase.