Abstract 323: Acute Reduction of Ambient Air Pressure Lowers Systemic Vascular Resistance and Improves Cardiac Output in Mice in-vivo

Abstract

Background: Humans have lower risk for myocardial infarction and stroke at higher altitudes. The mechanism is unknown. We previously demonstrated that acute reductions in ambient air pressure result in enhanced arterial vasodilation ex vivo using a myograph model of murine resistance arteries. Enhanced vasodilation might increase effective arterial compliance in vivo , thus we further hypothesized a reduction in systemic vascular resistance in vivo as a result of lowered ambient air pressure. Methods: In-vivo Pressure Volume Loops: A novel hypobaric chamber was designed and constructed with the capacity to hold a single anaesthetized mouse and simulate a variety of lowered air pressures within the chamber. The design of the chamber allowed for monitoring of murine heart rate, respiratory rate, & blood oxygen saturation at all times. Using inhaled isoflurane to anesthetize the animal, a closed-chest left-ventricular catheterization procedure was performed within the chamber on free-breathing adult male C57-WT mice (n=8) during consecutive acute exposures to the three air pressure steps: 754 mmHg (control or room atmospheric pressure), 714 mmHg (p1) and 674 mmHg (p2). Results: In-vivo : Total systemic vascular resistance was reduced by acute exposure to lower air pressure (10.09±0.15 mmHg*min/μL at control vs. 8.11±1.45 and 8.18±1.24 mmHg*min/μL at p1 and p2, respectively; p<0.05). Cardiac output was significantly improved by lowering atmospheric pressure below room pressure (7.36±0.15 mL/min at control versus 9.71±1.45 mL/min and 9.59±1.77 mL/min at p1 and p2, respectively; p<0.05). Significant increases in stroke volume with a reduction in air pressure were also observed (p<0.05 for p1 and p2 vs. control). We did not note significant changes in heart rate, mean arterial pressure, or contractility of the mice with lowered atmospheric pressure. Conclusion: Acute reductions in ambient air pressure lower systemic vascular resistance, and increase cardiac output and stroke volumes in vivo .