title: Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury.
abstract: Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S 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 H2S 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 H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S 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 H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S 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 H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects.
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Gangbin
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Division of Cardiology, University of Nebraska College of Medicine, Children's Hospital &Medical Center, Omaha, Nebraska, USA.
authors.forename: Shelby
authors.initials: S
authors.lastname: Kutty
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Yuegang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Xiu
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pathophysiology, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Juefei
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Panyu Central Hospital, Guangzhou, P.R. China.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D008168:Lung / Q000737:chemistry; D045423:Microbubbles; D017202:Myocardial Ischemia / Q000150:complications*; D009206:Myocardium / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods*
chemical_list: D006862:Hydrogen Sulfide