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Systemic vasodilating agents like nitroglycerin (NG) or iloprost (Ilo) show beneficial effects on intestinal microcirculation during sepsis, which could be attenuated by activation of the sympathetic nervous system or systemic side effects of vasodilating agents. This exploratory study aimed to investigate the effects of topically administered vasodilators and the parasympathetic drug carbachol on colonic microcirculatory oxygenation (µHbO2), blood flow (µFlow) and mitochondrial respiration. A total of 120 male Wistar rats were randomly assigned to twelve groups and underwent either colon ascendens stent peritonitis (CASP) or sham surgery. After 24 h, animals received the following therapeutic regimes: (1) balanced full electrolyte solution, (2) carbachol, (3) NG, (4) Ilo, (5) NG + carbachol, and (6) Ilo + carbachol. Mitochondrial respiration was measured in colon homogenates by respirometry. In sham animals, NG (−13.1%*) and Ilo (−10.5%*) led to a decrease in µHbO2. Additional application of carbachol abolished this effect (NG + carbachol: −4.0%, non-significant; Ilo + carbachol: −1.4%, non-significant). In sepsis, carbachol reduced µHbO2 when applied alone (−10.5%*) or in combination with NG (−17.6%*). Thus, the direction and degree of this effect depend on the initial pathophysiologic condition. [ABSTRACT FROM AUTHOR]

Recent studies observed, despite an anti-hyperlipidaemic effect, a positive impact of fibrates on septic conditions. This study evaluates the effects of gemfibrozil on microcirculatory variables, mitochondrial function, and lipid peroxidation levels with regard to its potential role as an indicator for oxidative stress in the colon and liver under control and septic conditions and dependencies on PPARα-mediated mechanisms of action. With the approval of the local ethics committee, 120 Wistar rats were randomly divided into 12 groups. Sham and septic animals were treated with a vehicle, gemfibrozil (30 and 100 mg/kg BW), GW 6471 (1 mg/kg BW, PPARα inhibitor), or a combination of both drugs. Sepsis was induced via the colon ascendens stent peritonitis (CASP) model. Then, 24 h post sham or CASP surgery, a re-laparotomy was performed. Measures of vital parameters (heart rate (HR), mean arterial pressure (MAP), and microcirculation (µHbO2)) were recorded for 90 min. Mitochondrial respirometry and assessment of lipid peroxidation via a malondialdehyde (MDA) assay were performed on colon and liver tissues. In the untreated sham animals, microcirculation remained stable, while pre-treatment with gemfibrozil showed significant decreases in the microcirculatory oxygenation of the colon. In the CASP animals, µHbO2 levels in the colon and the liver were significantly decreased 90 min after laparotomy. Pre-treatment with gemfibrozil prevented the microcirculatory aberrations in both organs. Gemfibrozil did not affect mitochondrial function and lipid peroxidation levels in the sham or CASP animals. Gemfibrozil treatment influences microcirculation depending on the underlying condition. Gemfibrozil prevents sepsis-induced microcirculatory aberrances in the colon and liver PPARα-independently. In non-septic animals, gemfibrozil impairs the microcirculatory variables in the colon without affecting those in the liver. [ABSTRACT FROM AUTHOR]

Introduction: Acute hemorrhage results in perfusion deficit and regional hypoxia. Since failure of intestinal integrity seem to be the linking element between hemorrhage, delayed multi organ failure, and mortality, it is crucial to maintain intestinal microcirculation in acute hemorrhage. During critical bleeding physicians increase FiO 2 to raise total blood oxygen content. Likewise, a systemic hypercapnia was reported to maintain microvascular oxygenation (μHbO 2 ). Both, O 2 and CO 2 , may have adverse effects when applied systemically that might be prevented by local application. Therefore, we investigated the effects of local hyperoxia and hypercapnia on the gastric and oral microcirculation., Methods: Six female foxhounds were anaesthetized, randomized into eight groups and tested in a cross-over design. The dogs received a local CO 2 -, O 2 -, or N 2 -administration to their oral and gastric mucosa. Hemorrhagic shock was induced through a withdrawal of 20% of estimated blood volume followed by retransfusion 60 min later. In control groups no shock was induced. Reflectance spectrophotometry and laser Doppler were performed at the gastric and oral surface. Oral microcirculation was visualized by incident dark field imaging. Systemic hemodynamic parameters were recorded continuously. Statistics were performed using a two-way-ANOVA for repeated measurements and post hoc analysis was conducted by Bonferroni testing ( p < 0.05)., Results: The gastric μHbO 2 decreased from 76 ± 3% to 38 ± 4% during hemorrhage in normocapnic animals. Local hypercapnia ameliorated the decrease of μHbO 2 from 78 ± 4% to 51 ± 8%. Similarly, the oral μHbO 2 decreased from 81 ± 1% to 36 ± 4% under hemorrhagic conditions and was diminished by local hypercapnia (54 ± 4%). The oral microvascular flow quality but not the total microvascular blood flow was significantly improved by local hypercapnia. Local O 2 -application failed to change microvascular oxygenation, perfusion or flow quality. Neither CO 2 nor O 2 changed microcirculatory parameters and macrocirculatory hemodynamics under physiological conditions., Discussion: Local hypercapnia improved microvascular oxygenation and was associated with a continuous blood flow in hypercapnic individuals undergoing hemorrhagic shock. Local O 2 application did not change microvascular oxygenation, perfusion and blood flow profiles in hemorrhage. Local gas application and change of microcirculation has no side effects on macrocirculatory parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hof, Truse, Weber, Herminghaus, Schulz, Weber, Maleckova, Bauer, Picker and Vollmer.)