Grant: Operating Grant

Life expectancy is increasing and therefore the number of elderly patients presenting for surgery is also increasing. The aging process is associated with numerous physiological changes that can present challenges for the anesthesiologist. Propofol is the most commonly used anesthetic agent in the world, but its use is associated with low blood pressure, and this effect is exaggerated with aging. Prolonged low blood pressure can lead to organ injury and delayed postsurgical recovery. Therefore, it is important to understand why low blood pressure occurs with propofol, so that better prevention and interventions strategies can be tested. In the proposed experiments, we will use an aged rat model to investigate the mechanisms by which propofol causes low blood pressure. We will study two mediators involved in blood vessel function: nitric oxide (NO) and endothelin-1 (ET-1), because the activity of these mediators change as we age, and play a key role in the blood pressure-lowering effects of propofol. We will also test the potential use of novel intervention strategies to reverse the low blood pressure caused by propofol. A second aim of this proposal is to study the effects of propofol in a model of accelerated aging. Accelerated aging occurs when an individual is born to a complicated pregnancy (e.g. fetal anemia); offspring from such pregnancies show age-related cardiovascular damage at an accelerated rate. How the accelerated aging individual copes with anesthetic agents such as propofol has not been explored. We therefore propose to investigate whether the blood pressure decrease from propofol is exaggerated in these offspring and if it is also due to the NO and ET-1 systems. By completing this study, we will establish important mechanisms as to how propofol causes a decrease in blood pressure in an aging animal model and potential new treatment for this decrease in blood pressure. This important information will lead to clinical applications in humans.