Abstract 10756: Detection of Increased Targeted H₂S Delivery to the Myocardial Microvasculature Using Ultrasound and Intravenous Microbubbles

Abstract

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.