Hemorrhage promotes inflammation and myocardial damage following acute myocardial infarction: insights from a novel preclinical model and cardiovascular magnetic resonance

Journal of Cardiovascular Magnetic Resonance

Research

Jennifer Barry¹  Reuben Thomas¹  Xiuling Qi¹  Graham A. Wright²  Nilesh R. Ghugre²  Mihaela Pop²  Bradley H. Strauss³  Susan Newbigging⁴ 

[1] Physical Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Room M7-510, M4N 3M5, Toronto, ON, Canada;Physical Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Room M7-510, M4N 3M5, Toronto, ON, Canada;Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada;Schulich Heart Research Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada;Schulich Heart Research Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada;The Toronto Centre for Phenogenomics, Mount Sinai Hospital, Toronto, ON, Canada;

关键词: Myocardial infarction;    Hemorrhage;    Inflammation;    Microvascular obstruction;    T2;    T2*;    Ischemia reperfusion injury;    cardiovascular magnetic resonance;   

DOI  :  10.1186/s12968-017-0361-7

 received in 2016-12-20, accepted in 2017-05-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMyocardial hemorrhage is a frequent complication following reperfusion in acute myocardial infarction and is predictive of adverse outcomes. However, it remains unsettled whether hemorrhage is simply a marker of a severe initial ischemic insult or directly contributes to downstream myocardial damage. Our objective was to evaluate the contribution of hemorrhage towards inflammation, microvascular obstruction and infarct size in a novel porcine model of hemorrhagic myocardial infarction using cardiovascular magnetic resonance (CMR).MethodsMyocardial hemorrhage was induced via direct intracoronary injection of collagenase in a novel porcine model of ischemic injury. Animals (N = 27) were subjected to coronary balloon occlusion followed by reperfusion and divided into three groups (N = 9/group): 8 min ischemia with collagenase (+HEM); 45 min infarction with saline (I-HEM); and 45 min infarction with collagenase (I+HEM). Comprehensive CMR was performed on a 3 T scanner at baseline and 24 h post-intervention. Cardiac function was quantified by cine imaging, edema/inflammation by T2 mapping, hemorrhage by T2* mapping and infarct/microvascular obstruction size by gadolinium enhancement. Animals were subsequently sacrificed and explanted hearts underwent histopathological assessment for ischemic damage and inflammation.ResultsAt 24 h, the +HEM group induced only hemorrhage, the I-HEM group resulted in a non-hemorrhagic infarction, and the I+HEM group resulted in infarction and hemorrhage. Notably, the I+HEM group demonstrated greater hemorrhage and edema, larger infarct size and higher incidence of microvascular obstruction. Interestingly, hemorrhage alone (+HEM) also resulted in an observable inflammatory response, similar to that arising from a mild ischemic insult (I-HEM). CMR findings were in good agreement with histological staining patterns.ConclusionsHemorrhage is not simply a bystander, but an active modulator of tissue response, including inflammation and microvascular and myocardial damage beyond the initial ischemic insult. A mechanistic understanding of the pathophysiology of reperfusion hemorrhage will potentially aid better management of high-risk patients who are prone to adverse long-term outcomes.

【 授权许可】

CC BY   
© The Author(s). 2017