Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation

Abstract

Argon exerts neuroprotection. Thus, it might improve patients’ neurological outcome after cerebral disorders or cardiopulmonary resuscitation. However, limited data are available concerning its effect on pulmonary vessel and airways. We used rat isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of rats and humans to assess this topic. IPL: Airway and perfusion parameters, oedema formation and the pulmonary capillary pressure (Pcap) were measured and the precapillary and postcapillary resistance (Rpost) was calculated. In IPLs and PCLS, the pulmonary vessel tone was enhanced with ET-1 or remained unchanged. IPLs were ventilated and PCLS were gassed with argon-mixture or room-air. IPL: Argon reduced the ET-1-induced increase of Pcap, Rpost and oedema formation (p < 0.05). PCLS (rat): Argon relaxed naïve pulmonary arteries (PAs) (p < 0.05). PCLS (rat/human): Argon attenuated the ET-1-induced contraction in PAs (p < 0.05). Inhibition of GABAB-receptors abolished argon-induced relaxation (p < 0.05) in naïve or ET-1-pre-contracted PAs; whereas inhibition of GABAA-receptors only affected ET-1-pre-contracted PAs (p < 0.01). GABAA/B-receptor agonists attenuated ET-1-induced contraction in PAs and baclofen (GABAB-agonist) even in pulmonary veins (p < 0.001). PLCS (rat): Argon did not affect the airways. Finally, argon decreases the pulmonary vessel tone by activation of GABA-receptors. Hence, argon might be applicable in patients with pulmonary hypertension and right ventricular failure.

Update of the organoprotective properties of xenon and argon: from bench to beside

“…Fixed argon-oxygen mixtures used in animal experiments will be less comfortable for use in critically ill patients. As we have no clinical experience with argon application in humans, new insights into the pulmonary vascular tone in rats and humans have been reported by Suleiman et al [127]. These cell culture experiments present the first evidence that unlike xenon, argon will not be irritating to the airways.…”

Argon Attenuates Multiorgan Failure in Relation with HMGB1 Inhibition

“…During the previous study, the mechanical ventilation led to a positive end-expiratory pressure (~3–5 cmH 2 O), which was not the case in the current experiment with zero end-expiratory pressure. This difference could have hampered the vasodilatory effect of argon on pulmonary vessels, which might contribute to the cardiac output increase in the present study [ 20 ]. Obviously, this is still only a hypothesis that deserves further investigation but that could open perspectives for argon use during cardiogenic shock.…”

Ventilation with the noble gas argon in an in vivo model of idiopathic pulmonary arterial hypertension in rats

“…Suleiman et al 2 for the first time described the vasodilating effects of 74% Ar in rat isolated perfused lungs and precision-cut lung slices from both rats and humans. In this ex vivo and in vitro study, the authors showed that treatment with Ar attenuates ET-1 induced vasoconstriction.…”

“…As previously described, 3 pulsed-wave Doppler of pulmonary outflow was recorded in parasternal short-axis view at the level of the great vessels and pulmonary artery acceleration time was measured as the time of systolic flow to peak pulmonary outflow velocity. The RV stroke volume (RVSV) and cardiac output (RVCO) were calculated by the formulas: RVSV = π × (RV outflow tract/2) 2 × RV outflow tract velocity time, RVCO = SV × heart rate. RV catheterization (Millar SPR71, AD Instruments Ltd., Oxford, UK) was performed through the right jugular vein during 70% Ar inhalation delivered by a nose mask.…”

“…No Ar-induced pulmonary vasodilating properties were shown, despite encouraging data from earlier investigations in ex vivo models. 2 …”