Abstract 12706: Peripheral Venous Congestion Causes Time- and Dose-Dependent Release of Endothelin-1 in Humans
Background: Venous congestion (VC) is typically viewed as a consequence of heart failure (HF) and renal failure (RF) although it is possible that hypervolemia itself might be a critical intermediate in the pathophysiology of these diseases. This study aimed to characterize whether peripheral VC promotes a time- and dose-dependent increase in plasma endothelin-1 (ET-1) (a critical mediator of vasoconstriction and inflammation) similar to that observed in HF and RF.
Methods: To experimentally model peripheral VC, we developed a new method where the venous pressure in one arm (congested) was increased by inflating a tourniquet cuff, while the other arm served as the control (non-congested). We used a randomized, cross-over design to measure plasma ET-1 on two separate encounters at two levels of VC (15 and 30 mmHg) in 19 healthy subjects (18 males, age 30±7 years). Blood was sampled at baseline; after 20, 60 and 120 minutes of VC; and finally at 180 minutes (60 minutes after cuff release - decongestion).
Results: No adverse event was observed. Plasma ET-1 levels progressively and significantly increased over 120 minutes of VC in the congested arm (Figure). At a VC dose of 15 mmHg, plasma ET-1 increased from 1.821pg/ml to 2.632pg/ml after 120 minutes of VC. At a VC dose of 30 mmHg, plasma ET-1 increased from 1.585 pg/ml to 3.160 pg/ml after 120 minutes of VC. Overall, the percent increase in plasma ET-1 was significantly higher (67.7% vs. 28.1%) at 30 mmHg than at 15 mmHg after 120 minutes of VC.
Conclusion: Peripheral VC causes time- and dose-dependent release of ET-1. These findings further support the concept that VC might be a causal contributor to (as opposed to a consequence of) the pathophysiology of HF and RF through release of vasoconstrictive and inflammatory mediators.
- © 2013 by American Heart Association, Inc.