Cardiovascular diseases are major cause of deaths in United States and Worldwide. According to the American Heart Association (AHA), more than 2200 deaths reported every day with an average of 1 in every 39 seconds. Arrhythmias and cardiomyopathy is also reported in many diseased conditions including acute lung injury, diabetes, obesity, hypertension and cancer. Patients in critical care or intensive care unit (ICU) are often administered with hyperoxia (PaO2 > 100 mmHg) for treatment with acute lung injury, congestive heart failure, cardiac fibrosis. However, recent studies indicate that dysfunctional lung and compromised pulmonary functioning cause increased workload on the heart and therefore lead to cardiac remodeling resulting in arrhythmias, heart failure and death. Among all the ventilated patients, early estimates of mortality rates in mechanical ventilation was as high as 40-45%. Additionally, existing reports suggests that more than 50% of the population admitted to ICU are older adults with ages more than 60 years. Studies also reported significantly higher in-hospital mortality in older adult population in ICU than younger population without differences in the duration of mechanical ventilation. The exact nature of this problem remains unknown. In this study we will investigate the genes involved in ventricular remodeling and electrical remodeling in hyperoxia induced aged (older adult) mice hearts using molecular, and biochemical methods and compared with young adult mice. These changes will be further investigated for their roles in physiological changes occur in aged mice heart using echocardiography, ECG and whole-cell patch-clamping techniques and will be compared with young adult mice. Our preliminary data also suggests that exposure of mice to hyperoxia for 24h is enough to initiate cardiac remodeling. Therefore, in this proposal we will identify the optimum time of exposure for hyperoxia at which most of the pathophysiology induced by hyperoxia in aged mice hearts can be reversed. We will also investigate the molecular mechanisms of ventricular remodeling and electrical remodeling in hyperoxia conditions, knowing which not only important to understand the disease development and progression, but also to develop targeted therapy for the disease cure.
Heart diseases accounts for 25% of deaths in United States, which is a leading cause of deaths for both men and women. Recent reports suggest that hyperoxia is directly associated with in-hospital deaths in mechanical ventilated patients in Care Units or ICU. The exact mechanism of which is yet to be investigated.
