Biology subjects

Swiderska, A.

Publications and source records attributed to Swiderska, A..

4 recordsLinked to original sources

bioRxiv2026

Enhanced hypoxic ventilatory response is accompanied by a decrease in carotid body mitochondrial oxygen affinity in heart failure

Carotid bodies (CBs), the main peripheral oxygen sensors, play a significant role in sympathetic overdrive in heart failure (HF), resulting in worse clinical outcomes. Whilst CBs are an attractive therapeutic target, the development of CB focused therapies has been limited as the oxygen sensing mechanism is not fully understood. It has been hypothesised that the oxygen sensor is part of mitochondrial complex IV, and reactive oxygen species (ROS) signalling plays a crucial role in the oxygen sensing cascade. However, changes to CB mitochondrial function have never been determined in HF. Hence, we aimed to address this gap by characterising CB mitochondrial function and ROS production using a rapid pacing ovine model of HF. The hypoxic ventilatory response (HVR) and autonomic function were assessed pre- and post HF induction. Tissue homogenates were prepared from whole CBs from control and HF and utilised to measure kinetics of mitochondrial oxygen affinity, respiration and H2O2 production rates by high-resolution respirometry. In HF, HVR and sympathetic drive were increased, while complex IV oxygen affinity was decreased. Despite an increase in abundance of mitochondrial complexes, no changes in mitochondrial respiration or H2O2 production were observed. However, aconitase activity and lipid peroxidation level were increased in HF. Overall, these results suggest that the CB mitochondrial function is altered in HF, and decreased CB mitochondrial oxygen affinity may suggest a higher complex IV oxygen sensitivity. Higher oxygen sensitivity accompanied by an increased oxidative stress may be key drivers of CB overactivity and therefore autonomic imbalance in HF.

physiology↗

bioRxiv2026

Carotid body mitochondria exhibit normal oxygen affinity despite COX4I2 enrichment

The carotid body (CB) is the key peripheral oxygen sensor. CB mitochondria are hypothesised to be uniquely adapted with unusually low intrinsic oxygen affinity which, in association with nitric oxide (NO) and reactive oxygen species signalling, enables acute responsiveness to hypoxia. However, CB mitochondrial physiology or intrinsic oxygen affinity have never been measured directly. We sought to address this key gap by isolating sheep CB mitochondria and comprehensively characterising their phenotype and contrasting them to a non-oxygen sensing tissue, left ventricular myocardium (LV). High resolution respirometry, liquid chromatography mass spectrometry, enzymatic assays and in silico modelling were used to characterise mitochondrial content, aerobic capacity, oxygen affinity, complex subunit abundance and activity, H2O2 production and NO sensitivity in ovine CB and LV. Mitochondrial oxygen affinity (P50 = 0.089 mmHg) was lower in the CB than the LV (P50 = 0.058 mmHg; p = 0.005). Whilst mitochondrial content was lower in the CB, CB mitochondria had higher respiratory rates and enzymatic activity than LV. H2O2 production and NO sensitivity were similar in the two tissues. While intrinsic mitochondrial oxygen affinity is slightly lower in the oxygen sensing CB than in the non-oxygen sensing LV, this difference is small. Hence, any role of mitochondria in CB oxygen sensing is not due to an intrinsic difference in the O2 affinity of cytochrome oxidase due to differential expression of its subunits. Instead, this work suggests that differences in O2 affinity in vivo are secondary to other factors, perhaps including NO, that alter mitochondrial O2 affinity.

physiology↗

bioRxiv2026

Developmental Hypoxia Increases Susceptibility to Cardiac Ventricular Arrhythmias in Adult Offspring

Ventricular arrhythmias are the leading cause of sudden cardiac death. It is well-established that environmental factors contribute to the origin and penetrance of ventricular arrhythmic disorders. However, to our knowledge, no studies have considered the role of the intrauterine environment. In this study, we investigated the long-term effects of fetal hypoxia on ventricular arrhythmia susceptibility. Pregnant Wistar rats were assigned to normoxia (21% O2) or hypoxia (13% O2 between gestational days 6-20), and offspring were raised to 6 months. Hearts were isolated and loaded with the fluorescent calcium- and voltage-sensitive indicators, Rhod-2 and RH237, respectively. Optical mapping was performed while the left ventricle was burst paced (10-20hz) to induce arrhythmias. Hearts isolated from adult offspring exposed to fetal hypoxia were more susceptible to arrythmia during burst pacing, compared to controls. This phenotype was associated with prolonged Ca2+ transients and action potentials, an increased frequency of Ca2+ waves and delayed after depolarisations, as well as lower gene and protein expression of the sarcoplasmic reticulum Ca2+ ATPase. Collectively, our data shows that fetal hypoxia can programme ventricular arrhythmia sensitivity in adulthood, driven by abnormalities in excitation-contraction coupling. This is the first evidence that some ventricular arrhythmias may have a developmental origin, highlighting pregnancy as a potential window for early preventive intervention.

developmental biology↗

bioRxiv2019

Chronic alcohol abuse affects the clinical course and outcome ofcommunity-acquired bacterial meningitis

BackgroundThe aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM).\n\nMaterials/methodsWe analyzed records of patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland.\n\nResults340 adult patients (211 men and 129 women) were analyzed. Forty-five (13.2%) patients were alcoholics (39 men and 6 women). Compared to non-alcoholics, alcoholics were more likely to present with seizures (33.3% vs 12.6%, p<0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (median 3 vs 2, p<0.001) and lower on the Glasgow Coma Scale (GCS) (median 10 vs 12, p<0.001) and had worse outcome as measured by the Glasgow Outcome Score (GOS) (median 3 vs 5, p<0.001). Furthermore, alcoholics were less likely to complain of headache (23.3% vs 52.3%, p<0.001) and nausea/vomiting (11.4% vs 33.6%, p=0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (median 0,58 mmol/L vs 1,97, p=0.025). In the multiple logistic regression analysis, alcoholism was independently associated with lower GCS (OR 0.716, 95% CI 0.523-0.980, p=0.036), presence of seizures (OR 4.580, 95% CI 1.065-19.706, p=0.041), male gender (OR 4.617, 95% CI 1.060-20.113, p=0.042) and absence of nausea/vomiting (OR 0.205, 95%CI 0.045-0.930, p=0.040). Furthermore, alcoholism (regression coefficient [-0.636], 95% CI [- 1.21] - [-0.06], p=0.031), lower GCS score (regression coefficient 0.144, 95% CI 0.06-0.23, p=0.001) and higher urea blood concentration (regression coefficient [-0.052], 95% CI [-0.10] - [-0.01], p=0.018) were independently associated with worse outcome measured by GOS.\n\nConclusionsCompared to non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.

epidemiology↗