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

Background: myocardial 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). methods: myocardial 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. results: at 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. conclusions: hemorrhage 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. © 2017 the author(s).