Graduation Year

2021

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Medical Sciences

Major Professor

Siva Kumar Panguluri, Ph.D.

Committee Member

Mark Kindy, MSc, Ph.D.

Committee Member

Srinivas Tipparaju, Ph.D.

Keywords

Arrhythmia, Electrocardiogram, Hyperoxia, Hypertrophy

Abstract

Hyperoxia, is regularly introduced to critically ill patients in ICU. Nevertheless, recent studies have shown the negative effects of this treatment on patients in critical care, including increased rates of lung and cardiac injury and thereby high in-hospital mortality. Large part of the literature related to hyperoxia was majorly focused on lung injury, with no or minimal investigations on cardiac injury. Our lab is the first to investigate the effect of hyperoxia on cardiac pathophysiology in mice and showed that mice exposed to hyperoxia for 3 days demonstrated brady-arrhythmia, cardiac hypertrophy, QTc prolongation along with other electrical remodeling and functional abnormalities due to dysregulation of important ion channels and other genes. Although, rodents are widely used animal model for research studies, guinea pigs are well known for its close similarity with human physiology. Therefore, to bring more clinical relevance to this study, we have utilized guinea pigs and investigated effect of hyperoxia on cardiac remodeling. For this study we exposed male guinea pigs (n=12) of one-year old age to hyperoxia or normoxia for three days and investigated physical and electrical parameters. Similar to our previous reports in mice, hyperoxia treated guinea pigs also showed significant reduction in body weight compared to normoxia controls. We also observed lung edema in hyperoxia treated guinea pigs, as evident by lung wet weight to dry weight ratio. Surprisingly in guinea pigs there are no significant changes in heart weight after hyperoxia treatment which is different from our previous studies in mice. Whereas we observed significant differences in left ventricle (LV), right ventricle (RV) and septum cardiomyocytes size in hyperoxia treated hearts compared to normoxia control hearts. ECG analysis revealed significant increase in RR intervals as a result of bradycardia, similar to what we reported in mice. Whereas significant decrease in P duration, QTc interval, R amplitude and T amplitude, which is distinct from what we observed in mice. From qRT-PCR data results we found marginal difference in key ion channel Kv 1.4 and Kv 4.2 whereas in Kv 4.3 and Kv 2.1 showed significant difference between normoxia and hyperoxia group which may be the reason of arrythmias in hyperoxia guinea pigs. Overall, our data indicated that hyperoxia-induced cardiac pathophysiology in guinea pigs are distinct from mice, despite of we similarities in physical parameters.

The data obtained from this study will not only improve our understanding on hyperoxia related in-hospital mortality, but also help us to understand possible mechanisms through which hyperoxia induce cardiac pathophysiology. This will also open new avenues for targeted therapy

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