Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

Hydrogen sulfide (H(2)S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H(2)S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H(2)S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H(2)S/C(3)F(8) ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H(2)S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H(2)S/C(3)F(8) ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H(2)S loading capability. Ultrasound targeted hs-MB destruction triggered H(2)S release and increased the concentration of H(2)S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H(2)S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects.