In vivo studies of the therapeutic effects of argon in traumatic brain injury (TBI) are limited, and their results are contradictory. The aim of this study was to evaluate the effect of a three-hour inhalation of argon (70%Ar/30%O₂) after an open TBI on the severity of the neurological deficit and the degree of brain damage in rats. The experiments were performed on male Wistar rats (n = 35). The TBI was simulated by the dosed open brain contusion injury. The animals were divided into three groups: sham-operated (SO, n = 7); TBI + 70%N2/30%O₂ (TBI, n = 14); TBI + 70%Ar/30%O₂ (TBI + iAr, n = 14). The Neurological status was assessed over a 14-day period (using the limb-placing and cylinder tests). Magnetic resonance imaging (MRI) scans and a histological examination of the brain with an assessment of the volume of the lesions were performed 14 days after the injury. At each of the time points (days 1, 7, and 14), the limb-placing test score was lower in the TBI and TBI + iAr groups than in the SO group, while there were no significant differences between the TBI and TBI + iAr groups. Additionally, no differences were found between these groups in the cylinder test scores (day 13). The volume of brain damage (tissue loss) according to both the MRI and histological findings did not differ between the TBI and TBI + iAr groups. A three-hour inhalation of argon (70%Ar/30%O₂) after a TBI had no neuroprotective effect.

Cardiac arrest remains one of the leading causes of death worldwide. Even with successful resuscitation, patient outcomes are often poor due to post-resuscitation syndrome, which includes cerebral hypoxia, myocardial dysfunction, microcirculatory disorders, coagulation abnormalities, and systemic inflammation. Argon, an inert noble gas, has neuroprotective and cardioprotective properties, making it a promising candidate for early post-resuscitation therapy. The aim of the study was to evaluate the organoprotective properties of an argon-oxygen mixture when inhaled in the early post-resuscitation period for 2 hours after asphyxial circulatory arrest in rats. Materials and methods. A prospective randomized controlled experimental study was conducted on male Wistar rats ( n = 43) using an asphyxial circulatory arrest model. The animals were divided into three groups: sham-operated (SO, n = 12), circulatory arrest with resuscitation (CAR, n = 13), and circulatory arrest with resuscitation and two-hour inhalation of a 70%/30% argon-oxygen mixture in the post-resuscitation period (CAR + iAr, n = 18). Hemodynamics, microcirculation, blood gas composition, coagulation (low-frequency piezothromboelastography), neurological status, and biomarkers of organ damage were evaluated. Beclin-1 and caspase-3 expression was analyzed immunohistochemically. Results. Argon inhalation did not have a significant effect on systemic hemodynamics, but it was accompanied by improved tissue oxygenation and metabolism: a decrease in blood lactate ( p = 0.043), an increase in the p/F oxygenation index ( p = 0.001), and stabilization of microcirculation variability (Kv, σ). Statistically significantly increased expression of the Beclin-1 protein in the lungs, myocardium, and hippocampus reflected activation of autophagy. In the CAR + iAr group, there was an improvement in neurological status compared to CAR ( p = 0.02), a decrease in serum neuron-specific enolase ( p = 0.011), and a decrease in the number of caspase-3-positive cells ( p = 0.011), indicating a reduction in apoptosis and damage to the nervous tissue. Argon had a moderate anticoagulant and antiplatelet effect (coagulation drive intensity — CDI, and maximum clot firmness-MCF reduction), while maintaining normal processes of clot retraction and lysis. The electrophysiological parameters of the heart (QRS, QTc) varied within the physiological range, indicating the absence of pro-arrhythmic effects in argon. Conclusion. Early inhalation of argon-oxygen mixture after circulatory arrest has a multisystem protective effect: improves oxygenation and microcirculation, promotes activation of autophagy mechanisms in vital organs, reduces the severity of neuronal damage, and modulates blood clotting in some measure. Argon can be considered a promising therapeutic agent for post-resuscitation syndrome. Further clarification is needed to assess argon’s molecular mechanisms of action and long-term outcomes after its use.

The majority of asphyxial circulatory arrest (CA) models have a number of disadvantages, such as the lack of uniform criteria for fixing CA and recovery of spontaneous circulation, short duration of CA episode and limited volume of post-resuscitation intensive care, poor similarity with resuscitation measures in current clinical anesthesiology/intensive care settings.The aim of the study: to improve the experimental model of asphyxicial CA by standardizing experimental procedures and using a complex of resuscitation measures replicating current CA management in clinical anesthesiology-intensive care.Materials and methods. The experiments were conducted on 34 male Wistar rats, distributed into 2 groups: Group I included animals subjected to sham procedure (SP, N=12) and Group II – animals subjected to asphyxial circulatory arrest (CA, N=22) and subsequent resuscitation. Asphyxia in anesthetized rats was induced by rocuronium bromide injection, followed by recording of electrocardiogram (ECG), parameters of invasive blood pressure (BP) measurement and laser Doppler fluxmetry (LDF) to assess skin perfusion. CA episode was maintained for 2 min, followed by a series of resuscitation measures and intensive therapy for 2 h. Circulatory parameters (ECG, BP, LDF), gas composition and arterial blood acid-base state (ABS) dynamics were evaluated.Results. Monitored parameters were comparable in both groups at baseline after stabilization period. After exclusion criteria were applied 11 animals from SP group and 18 — from CA were included in the analysis. Tachycardia (heart rate, beats/min–1, SP vs CA) was documented in the CA group: 218 [205; 236] vs 286 [272; 305], P⩽0.0001), as well as recovery of skin perfusion to subnormal parameters in the first minutes after successful resuscitation. At minute 10 in the post-resuscitation period worsening of skin perfusion (M, perfusion units, SP vs CA): 14.7 [12.1; 16.5] vs 10.1 [7.0; 12.5], P=0.0014), and decompensated mixed acidosis (pH, SP vs CA): 7.42 [7.40; 7.43] vs 7.20 [7.13; 7.23], P⩽0.0001) were documented in the CA group, however BP values were comparable (BP, mmHg, SP vs CA): 60 [58; 72] vs 67 [62; 82], P=0.482). At minute 120 post-resuscitation and at the end of intensive care period, both groups demonstrated similar values of the monitored parameters. Three out of 18 animals in the CA group died after resuscitation.Conclusion. Electromechanical dissociation underlies CA in rats subjected to asphyxia. The use of LDF to assess peripheral blood flow makes it possible to standardize the severity of ischemic reperfusion injuries and improve reproducibility of the model. Series of resuscitation measures in experimental setting is justified from a bioethical point of view, and makes it possible to improve repeatability of preclinical research results in clinical practice.

Background: Despite successful resuscitation from cardiac arrest (CA), patients often develop a fatal post-resuscitation syndrome due to ischemia-reperfusion injury. The disruption of hemodynamic coherence, where restored macrocirculation fails to improve microcirculation, leads to persistent tissue hypoperfusion and organ failure, making early non-invasive assessment of the microvasculature crucial for detecting these post-resuscitation disturbances. This study aimed to identify markers of peripheral circulatory disturbances in the early post-resuscitation period after asphyxial CA in rats. Methods: The study was performed on adult male Wistar rats randomized into two groups: group I—sham operated animals (Sham group), group II—asphyxial CA followed by resuscitation (CA group). Asphyxial CA was induced by cessation of ventilation. Resuscitation was performed 2 minutes after actual CA. Invasive blood pressure, skin perfusion (M) assessed by laser Doppler flowmetry and cutaneous vascular conductance (CVC) were measured at baseline, 10 and 120 min after return of a spontaneous circulation (ROSC). In addition, the variables of cutaneous post-occlusive reactive hyperemia (PORH) were calculated. Results: At 10 minutes after ROSC, there were no differences in mean arterial pressure (MAP) values in the “CA” group compared to the “Sham” group [MAP 67.3 (61.52, 82.35) vs. 60.39 (58.54, 72.03), P=0.47, respectively]. M and CVC were decreased in the “CA” group compared to the “Sham” group [M 10.1 (7.0, 12.5) vs. 14.7 (12.1, 16.5) PU, P=0.001; CVC 0.12 (0.11, 0.21) vs. 0.21 (0.19, 0.24), P=0.005, respectively]. 120 min after ROSC, the studied groups did not differ in hemodynamic parameters and in basic microcirculatory parameters. The groups also did not differ (P>0.05) in the values of PORH variables. Conclusions: Microcirculatory disturbances in the first minutes after ROSC are manifested by a decrease in M and CVC. These pathological alterations largely reversed 2 hours after resuscitation. The use of LDF with an occlusion test did not reveal specific changes in skin PORH variables at this time. We suggests that microcirculatory assessment might have its greatest diagnostic value in the very early phase (first minutes to hours) after ROSC, while its prognostic value might require later assessments (beyond 2 hours).