Detection of Intestinal Tissue Perfusion by Real-Time Breath Methane Analysis in Rat and Pig Models of Mesenteric Circulatory Distress

Abstract

Objectives: Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. Design: Randomized, controlled in vivo animal study. Setting: University research laboratory. Subjects: Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). Interventions: In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. Measurements and Main Results: Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson’s r = 0.669 or r = 0.632, respectively). Conclusions: we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.

Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation

“…In our earlier proof of principle study, we provided evidence that the exhaled methane levels change in association with changes in superior mesenteric arterial blood flow (13). It has been demonstrated that arterial occlusions and reperfusions and the accompanying mucosal microcirculatory cycles correlated significantly with parallel changes in methane concentration in the exhaled air (13). Therefore, the aim of the present study was to investigate the diagnostic value of real-time detection of exhaled methane levels to recognize internal bleeding in a clinicallyrelevant large animal model.…”

“…The average for baseline exhaled methane was 60.9-90.1 ppm, which corresponds to the higher range of values measured in methane-producing humans (9). The individual baseline data were subtracted from the test values to increase the comparability of measurements even in the case of larger individual variances (13). The exhaled methane concentration decreased significantly after 5% blood loss, already at T 1 , similarly to the SMA flow changes.…”

Methane Production and Bioactivity-A Link to Oxido-Reductive Stress

“…Here it should be noted that the intra- and inter-subject variability is usually very large (Pitt et al, 1980; Peled et al, 1985; Minocha and Rashid, 1997; Levitt et al, 2006; Roccarina et al, 2010; Sahakian et al, 2010), partly because the pulmonary route is not exclusive and the production is manifested not only in the exhaled air but also through other body surfaces (Nose et al, 2005). Besides, the production of CH 4 is dependent from the age, the health condition and the physical activity of the subjects (Polag et al, 2014; Szabó et al, 2015; Tuboly et al, 2017; Polag and Keppler, 2018), and the breath output is influenced by splanchnic microcirculatory factors as well (Szücs et al, 2019). In accordance with the above findings the exhaled CH 4 level in humans is always above the inhaled CH 4 concentration (Keppler et al, 2016).…”

Methane, a gut bacteria-produced gas, does not affect arterial blood pressure in normotensive anaesthetized rats

“…[10] The intraluminally generated CH4 enters the splanchnic circulation and is then released in the breath if the partial pressure is higher than in the atmosphere. [11] Considering the physicochemical properties and the favorable distribution properties of methane, it is assumed that it can also be excreted through other body surfaces. [12] Due to methane's flammable and explosive nature, its use by inhalation route in research is limited.…”