Abstract
Pulmonary edema (PE) is an issue widely noted in acute exposure to hypoxia as seen in high altitude climbers, yet the etiology of this is not defined. Previous studies in rats showed that both hypoxia and strong sympathetic activation may induce PE. As acute exposure to hypoxia is accompanied by sympathetic activation, we assume that this may impair pulmonary circulation and contribute to the development of hypoxic PE. The aim of the present study was to investigate the effects of adrenergic agonists and antagonists as models for overstimulation and suppression, respectively, of sympathetic activity on cardiovascular function and formation of PE in hypoxic rats. Norepinephrine or adrenergic blockers were infused to rats exposed to normobaric hypoxia with 10% O2 over time intervals up to 24 h. Normoxic and hypoxic controls received 0.9% NaCl infusion. We evaluated hemodynamic function and lung histology. A significant decrease of left ventricular systolic function was observed after 6 h of hypoxia. This effect was less pronounced with α-adrenergic blockade but was more severe with combined α-plus β-adrenergic blockade. Norepinephrine delayed the onset of hypoxic left ventricular depression but did not reduce its degree. Significant PE developed after 16 h of hypoxia. It regressed under α- but not with β-adrenergic blockade, and was aggravated by combining hypoxia with norepinephrine. Almost half of the animals exposed to hypoxia over 16–24 h suffered cardiorespiratory arrest during the experiment and presented with signs of acute right ventricular failure. They had significantly elevated serum catecholamine concentrations and significantly stronger PE than the others. Notably, most of them had received norepinephrine or combined adrenergic blockade. Mild changes in serum catecholamine concentrations indicated that hypoxic sympathoadrenergic activation was only weak. Hence, it was not sufficient to prevent left ventricular depression. However, the results show that α-adrenergic mechanisms contribute to the formation of hypoxic PE. Adrenergic blockade but also sympathetic overactivity may induce pulmonary congestion, PE and acute right ventricular failure indicating that a fine balance of sympathetic activation under hypoxic conditions is crucial. This has important implications for climbers to high altitude as well as for patients suffering from hypoxia.
Highlights
Acute exposure to hypoxia may induce development of pulmonary edema (PE) as can often be observed after rapid ascents to high altitude (Bärtsch et al, 2005; Korzeniewski et al, 2015)
As a consequence of the depression of left ventricle (LV) systolic function and the decrease in diastolic aortic pressure, mean aortic pressure was significantly reduced in hypoxia (Table 2 and Figure 1C)
The main results of this study were: (a) Hypoxia induced a depression in LV systolic function that was deteriorated with β-adrenergic or, even more, with combined α- and β-adrenergic blockade and was not fully compensated with NE administration; (b) Hypoxia induced an interstitial PE that was slightly attenuated with α-adrenergic blockade and increased with NE application; (c) Under prolonged hypoxia exposure, both combined adrenergic blockade and NE application may induce acute right ventricle (RV) failure
Summary
Acute exposure to hypoxia may induce development of pulmonary edema (PE) as can often be observed after rapid ascents to high altitude (Bärtsch et al, 2005; Korzeniewski et al, 2015). High-altitude pulmonary edema (HAPE) is initiated by an increase in pulmonary capillary pressure and is considered a hydrostatic-type PE. Elevated pulmonary capillary pressure results from hypoxic pulmonary vasoconstriction that occurs in arterial vessels and has a considerable venous component (Maggiorini et al, 2001). Pulmonary venoconstriction may significantly increase pulmonary capillary pressure and promote edema formation. In a number of species including the human, pulmonary veins are more sensitive to vasoconstrictor stimuli than pulmonary arteries (Gao and Raj, 2005). A significantly greater vasoconstrictor effect of hypoxia was found in rat pulmonary veins than in arteries (Zhao et al, 1993)
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