Abstract 10756: Detection of Increased Targeted H2S Delivery to the Myocardial Microvasculature Using Ultrasound and Intravenous Microbubbles
Background: Studies have demonstrated that the gaseous signaling molecule hydrogen sulfide (H2S) may have clinical benefit in preventing myocardial ischemic-reperfusion injury. However, systemic delivery of H2S is hampered by cytotoxicity. We hypothesized that encapsulation of H2S gas into perflourocarbon filled microbubbles (PESDA), combined with ultrasound mediated targeted release, would permit the safe local release of H2S.
Methods: A 1:1 mixture of the H2S (4ml) and perfluorocarbons (4ml) was encapsulated into PESDA (H2S-PESDA), Ultrasound-triggered H2S release from H2S-PESDA (versus regular PESDA containing 8 ml perfluorocarbon) was evaluated in an in vitro flow system, as well as in three open chest pigs, where a 200 micron H2S sensor (World Precision Instruments, Sarasota, FL) was placed in the coronary sinus for continuous sampling. Measurements were made following H2S-PESDA or regular PESDA injections with or without intermittent high mechanical index (MI) impulses (1.0 MI; 1.6 MHz S5-1 transducer; Philips Medical) applied to the short axis of the left ventricle through a 3 centimeter thick tissue mimiking phantom.
Results: The amount of H2S released from H2S-PESDA treated with ultrasound targeted microbubble destruction in vitro was 59 + 7 % (compared to 13.9 + 3.5% from microbubbles alone; p=0.005). Coronary sinus H2S concentration did not change following reg PESDA injections with intermittent high MI ultrasound or with H2S-PESDA injections in the absence of high MI ultrasound, but increased up to five fold with H2S-PESDA injections with intermittent high ultrasound (Figure 1; p<0.0001). No significant hemodynamic differences between reg PESDA and H2S-PESDA were observed.
Conclusions: Targeted intramyocardial delivery of the therapeutic H2S signaling molecule is possible with a diagnostic ultrasound system. This technqiue may be a method of safely delivering this gas to prevent ischemia-reperfusion injury in multiple clinical settings.
- © 2012 by American Heart Association, Inc.