Siva Kumar Panguluri

Supplemental oxygen in critical care patients is associated with increased mortality. We previously reported hyperoxia‐induces cardiac pathophysiology influenced by age, metabolic status, sex, and duration of exposure. The present study investigated the dose‐dependent effects of oxygen on cardiac remodeling in very aged mice (>100 weeks), a model relevant to end‐of‐life physiology and clinical decision‐making. Mice were exposed to graded oxygen concentrations or normal air for 72 h followed by comprehensive assessment of cardiac function and electrophysiology. Exposure to 70% O ₂ led to significant reduction in ejection fraction (82.5% ± 2.1% to 59.8% ± 3.4%) and cardiac output (38.2 ± 1.5 mL/min to 12.8 ± 1.2 mL/min in males and 8.1 ± 0.9 mL/min in females). A significant electrical remodeling (QTc 57.2 ± 1.8 ms to 78.4 ± 2.5 ms) was also observed. Although females exhibited higher baseline cardiac function than males, they demonstrated greater functional decline and earlier onset of electrical abnormalities at lower oxygen concentrations. These findings indicate that oxygen concentration is a critical determinant of cardiac dysfunction in advanced age, with heightened susceptibility in females. Collectively, this study highlights the potential risks of supplemental oxygen and underscores the importance of precision oxygen therapy in end‐of‐life care settings.

Supplemental oxygen is a cornerstone intervention in modern clinical practice, widely used to correct hypoxemia in emergency, perioperative, and critical care settings. While oxygen therapy is lifesaving, accumulating evidence indicates that excessive oxygen exposure can induce significant pathophysiological disturbances, particularly within the cardiovascular and pulmonary systems. Hyperoxia (PaO₂ > 100 mm Hg) promotes the generation of reactive oxygen species (ROS), leading to oxidative stress, mitochondrial dysfunction, and the activation of pro-fibrotic pathways. When combined with mechanical ventilation, these effects are further amplified through alterations in intrathoracic pressure, reduced venous return, and increased pulmonary vascular resistance, collectively imposing hemodynamic stress on the myocardium. These mechanical and biochemical perturbations converge to drive structural, functional, and electrical remodeling of the heart, including conduction abnormalities and arrhythmogenesis. Emerging clinical insights, particularly from critically ill and COVID-19 populations, underscore the importance of titrated oxygen strategies that balance adequate tissue oxygenation with minimization of hyperoxic injury. This review synthesizes current evidence on hyperoxia-induced oxidative stress, heart-lung interactions, and mechanisms underlying myocardial remodeling to provide a comprehensive framework for optimizing oxygen therapy.

Supplemental oxygen is a cornerstone intervention in modern clinical practice, widely used to correct hypoxemia in emergencies, perioperative, and critical care settings. While oxygen therapy is lifesaving, accumulating evidence indicates that excessive oxygen exposure can induce significant pathophysiological disturbances, particularly within the cardiovascular and pulmonary systems. Hyperoxia (PaO₂ > 100 mm Hg) promotes the generation of reactive oxygen species (ROS), leading to oxidative stress, mitochondrial dysfunction, and activation of pro-fibrotic pathways. When combined with mechanical ventilation, these effects are further amplified through alterations in intrathoracic pressure, reduced venous return, and increased pulmonary vascular resistance, collectively imposing hemodynamic stress on the myocardium. These mechanical and biochemical perturbations converge to drive structural, functional, and electrical remodeling of the heart, including conduction abnormalities and arrhythmogenesis. Emerging clinical insights, particularly from critically ill and COVID-19 populations, underscore the importance of titrated oxygen strategies that balance adequate tissue oxygenation with minimization of hyperoxic injury. This review synthesizes current evidence on hyperoxia-induced oxidative stress, heart–lung interactions, and mechanisms underlying myocardial remodeling to provide a comprehensive framework for optimizing oxygen therapy.

Mechanical ventilation often results in hyperoxia, a condition characterized by excess SpO₂ levels (>96%). Hyperoxia results in changes in the physiological parameters, severe cardiac remodeling, arrhythmia development, and alteration of cardiac ion channels, all of which can point toward a gradual increase in the risk of developing cardiovascular disease (CVD). This study extends the analysis of our prior work in young Akita mice, which demonstrated that exposure to hyperoxia worsens cardiac outcomes in a type 1 diabetic murine model as compared to wild-type (WT) mice. Age is an independent risk factor, and when present with a major comorbidity, such as type 1 diabetes (T1D), it can further exacerbate cardiac outcomes. Thus, this research subjected aged T1D Akita mice to clinical hyperoxia and analyzed the cardiac outcomes. Overall, aged Akita mice (60 to 68 weeks) had preexisting cardiac challenges compared to young Akita mice. Aged mice were overweight, had an increased cardiac cross-sectional area, and showed prolonged QTc and JT intervals, which are proposed as major risk factors for CVD like intraventricular arrhythmias. Additionally, exposure to hyperoxia resulted in severe cardiac remodeling and a decrease in Kv 4.2 and KChIP2 cardiac potassium channels in these rodents. Based on sex-specific differences, aged male Akita mice had a higher risk of poor cardiac outcomes than aged females. Aged male Akita mice had prolonged RR, QTc, and JT intervals even at baseline normoxic exposure. Moreover, they were not protected against hyperoxic stress through adaptive cardiac hypertrophy, which, at least to some extent, is due to reduced cardiac androgen receptors. This study in aged Akita mice aims to draw attention to the clinically important yet understudied subject of the effect of hyperoxia on cardiac parameters in the presence of preexisting comorbidities. The findings would help revise the provision of care for older T1D patients admitted to ICUs.

Oxygen supplementation, although a cornerstone of emergency and cardiovascular medicine, often results in hyperoxia, a condition characterized by excessive tissue oxygen which results in adverse cardiac remodeling and subsequent injurious effects to physiological function. Cardiac remodeling is further influenced by various risk factors, including pre-existing conditions and sex. Thus, the purpose of this experiment was to investigate cardiac remodeling in Type I Diabetic (Akita) mice subjected to hyperoxic treatment. Overall, we demonstrated that Akita mice experience distinct challenges from wild type (WT) mice. Specifically, Akita males at both normoxia and hyperoxia showed significant decreases in body and heart weights, prolonged PR, QRS, and QTc intervals, and reduced %EF and %FS at normoxia compared to WT controls. Moreover, Akita males largely resemble female mice (both WT and Akita) with regards to the parameters studied. Finally, statistical analysis revealed hyperoxia to have the greatest influence on cardiac pathophysiology, followed by sex, and finally genotype. Taken together, our data suggest that Type I diabetic patients may have distinct cardiac pathophysiology under hyperoxia compared to uncomplicated patients, with males being at high risk. These findings can be used to enhance provision of care in ICU patients with Type I diabetes as a comorbid condition.

Oxygen supplementation, although a cornerstone of emergency and cardiovascular medicine, often results in hyperoxia, a condition characterized by excessive tissue oxygen which results in adverse cardiac remodeling and subsequent injurious effects to physiological function. Cardiac remodeling is further influenced by various risk factors, including pre-existing conditions and sex. Thus, the purpose of this experiment was to investigate cardiac remodeling in Type I Diabetic (Akita) mice subjected to hyperoxic treatment. Overall, we demonstrated that Akita mice experience distinct challenges from wild type (WT) mice. Specifically, Akita males at both normoxia and hyperoxia showed significant decreases in body and heart weights, prolonged PR, QRS, and QTc intervals, and reduced %EF and %FS at normoxia compared to WT controls. Moreover, Akita males largely resemble female mice (both WT and Akita) with regards to the parameters studied. Finally, statistical analysis revealed hyperoxia to have the greatest influence on cardiac pathophysiology, followed by sex, and finally genotype. Taken together, our data suggest that Type I diabetic patients may have distinct cardiac pathophysiology under hyperoxia compared to uncomplicated patients, with males being at high risk. These findings can be used to enhance provision of care in ICU patients with Type I diabetes as a comorbid condition.

Clinical reports suggest a high incidence of ICU mortality with the use of hyperoxia during mechanical ventilation in patients. Our laboratory is pioneer in studying effect of hyperoxia on cardiac pathophysiology. In this study for the first time, we are reporting the sequence of cardiac pathophysiological events in mice under hyperoxic conditions in time‐dependent manner. C57BL/6J male mice, aged 8–10 weeks, were treated with either normal air or >90% oxygen for 24, 48, and 72 h. Following normal air or hyperoxia treatment, physical, biochemical, functional, electrical, and molecular parameters were analyzed. Our data showed that significant reduction of body weight observed as early as 24 h hyperoxia treatment, whereas, no significant changes in heart weight until 72 h. Although we do not see any fibrosis in these hearts, but observed significant increase in cardiomyocyte size with hyperoxia treatment in time‐dependent manner. Our data also demonstrated that arrhythmias were present in mice at 24 h hyperoxia, and worsened comparatively after 48 and 72 h. Echocardiogram data confirmed cardiac dysfunction in time‐dependent manner. Dysregulation of ion channels such as Kv4.2 and KChIP2; and serum cardiac markers confirmed that hyperoxia‐induced effects worsen with each time point. From these observations, it is evident that electrical remodeling precedes structural remodeling, both of which gets worse with length of hyperoxia exposure, therefore shorter periods of hyperoxia exposure is always beneficial for better outcome in ICU/critical care units.

Drug delivery to the anterior and posterior segment of eye remains a challenge. Nanoparticle-mediated drug delivery has indicated some promise. The presented review aims to summarize recent advancements in chitosan-based nanotherapies for ocular drug delivery and the challenges encountered during the process. Significant research using chitosan, a cationic linear polymer, is being conducted for ocular drug delivery. A vast number of publications exploit the mucoadhesive properties of the polymer, which arise due to interactions between the amino acids of chitosan and the sialic acid residues in mucous. The high degree of crosslinking in chitosan nanoparticles facilitates a dramatic increase in ocular drug retention of the desired drug, which subsequently helps in ocular penetration and improving the bioavailability of the drugs. A noted decrease in the initial burst of the drug is the basis for developing sustained drug release formulation using biodegradable and biocompatible chitosan polymer. In vitro as well as in vivo studies have indicated enhancement in the uptake, accumulation, and removal of chitosan nanoparticles from the site of delivery. In summary, chitosan- or modified-chitosan-based nanoparticles are being widely tested as drug carriers for treatment of bacterial and viral infections, glaucoma, age-related macular degeneration, and diabetic retinopathy.