Abstract : The current study attempts to assess how short-term, occasional reoxygenation affects cardiac alterations brought on by hypoxia. The current study is experimental/quantitative study during the period of 1 year from 2023 January to January 2024. For Human Experimental Work, Samples of the ultra-structural and histological alterations in the heart in the aftermath of hypoxia were gathered. Eight patients' left atrial myocardium and one patient's left ventricular myocardium were extracted from the specimens. Male mice were kept in a light-dark cycle for 12 hours and randomly assigned to controls and hypoxia groups. They were exposed to various treatments, including altitude, pressure, and re-oxygenation. Cardiac tissue homogenate was used to measure IL-6 and TNF-α levels. Heart specimens were preserved, fixed, and analyzed using SPSS version 23. The data was then analyzed using an electron microscope. There were total 8 human subjects were count, in which 75% male and 25% females. In human model, Electron microscopy of human heart samples revealed hypoxia-associated changes, with no differences in gender or life histories. Changes worsened after occlusion, suggesting adaptation to aerobic metabolism. Myofibrils separated after atrial clamping. In animal model, Hypoxia significantly elevated pro-inflammatory cytokines and oxidative stress indicators, but these levels were reduced by re-oxygenation. Cardiac muscle fibers in hypoxic groups showed disruption, degeneration, and disarray, while mitochondrial changes were observed, but desmosomal intercellular connections remained unaltered. It was concluded that, in the human model, several steady could be readily detected following hypoxia for varied lengths of time. Our results indicate that intermittent short-duration re-oxygenation in animals mitigates the changes in heart architecture brought on by hypoxia by reducing pro-inflammatory cytokines and oxidative stress.