Abstract
AimsPost-infarction remodelling (PIR) determines left-ventricular (LV) function and prognosis after myocardial infarction. The aim of this study was to evaluate transthoracic ultrasound-mediated microbubble stimulation (UMS) as a novel gene- and cell-free therapeutic option after acute myocardial infarction and reperfusion (AMI/R) in mice.Methods and ResultsFor myocardial delivery of UMS, a novel therapeutic ultrasound-system (TIPS, Philips Medical) and commercially available microbubbles (BR1, Bracco Suisse SA) were utilized in a closed-chest mouse model. UMS was performed as myocardial post-conditioning (PC) on day four after 30 minutes of coronary occlusion and reperfusion. LV-morphology, as well as global and regional function were measured repeatedly with reconstructive 3-dimensional echocardiography applying an additional low-dose dobutamine protocol after two weeks. Scar size was quantified by means of histomorphometry. A total of 41 mice were investigated; 17 received PC with UMS. Mean ejection fraction (EF) prior UMS was similar in both groups 53%±10 (w/o UMS) and 53%±14 (UMS, p = 0.5), reflecting comparable myocardial mass at risk 17%±8 (w/o UMS), 16%±13 (UMS, p = 0.5). Two weeks after AMI/R, mice undergoing UMS demonstrated significantly better global LV-function (EF = 53%±7) as compared to the group without PC (EF = 39%±11, p<0.01). The fraction of akinetic myocardial mass was significantly lower among mice undergoing UMS after AMI/R [27%±10 (w/o UMS), 13%±8 (UMS), p<0.001)]. Our experiments showed a fast onset of transient, UMS-induced upregulation of vascular-endothelial and insulin-like growth factor (VEGF-a, IGF-1), as well as caveolin-3 (Cav-3). The mice undergoing PC with UMS after AMI/R showed a significantly lower scar size. In addition, the microvascular density was significantly higher in the borderzone of UMS-treated animals.ConclusionUMS following AMI/R ameliorates PIR in mice via up-regulation of VEGF-a, IGF-1 and Cav-3, and consecutive improvement of myocardial borderzone vascularization.
Highlights
Acute myocardial infarction (AMI) and its sequelae are some of the most common causes of death in the western world, even worldwide
We investigated the time course of expression patterns with three primers: 1. vascular-endothelial growth factor-a (VEGF-a), 2. insulin-like growth factor-1 (IGF-1) and 3. caveolin-3 (Cav-3) (Applied Biosystems, Foster City, CA, USA)
A total of 41 C57BL6 mice undergoing AMI/R were randomized into two treatment groups receiving either ultrasound-mediated microbubble stimulation (UMS) (n = 17) or control procedure (n = 24)
Summary
Acute myocardial infarction (AMI) and its sequelae are some of the most common causes of death in the western world, even worldwide. The cicatrization of the infarcted left-ventricular (LV) myocardium leads to morphological and functional changes of the contractile tissue, referred to as post-infarction remodelling (PIR) [1]. This process is progressive and comprises: a) LVdilatation, b) deterioration of global and regional LV-function, c) progression of scar size and d) loss of viable myocardial tissue [1,2]. The main objective of our study is to test the functional impact of a novel, non-gene, non-cell based intervention to ameliorate both, morphological and functional changes after AMI and reperfusion in mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
