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

• Published in: Journal of cardiovascular magnetic resonance Vol. 19; no. 1; p. 50
• Main Authors: Ghugre, Nilesh R, Pop, Mihaela, Thomas, Reuben, Newbigging, Susan, Qi, Xiuling, Barry, Jennifer, Strauss, Bradley H, Wright, Graham A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.07.2017; BioMed Central; Elsevier
• Subjects: Animals; Care and treatment; Contrast Media - administration & dosage; Coronary Circulation; Damage assessment; Diagnosis; Disease Models, Animal; Edema; Edema, Cardiac - diagnostic imaging; Edema, Cardiac - pathology; Edema, Cardiac - physiopathology; Electrocardiography; Female; Gadolinium; Gadolinium DTPA - administration & dosage; Heart; Heart attack; Heart attacks; Hemorrhage; Hemorrhage - diagnostic imaging; Hemorrhage - pathology; Hemorrhage - physiopathology; Incidence; Inflammation; Inflammatory response; Ischemia; Magnetic resonance; Magnetic resonance imaging; Magnetic Resonance Imaging, Cine; Mapping; Microcirculation; Microvascular obstruction; Myocardial infarction; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocarditis - diagnostic imaging; Myocarditis - pathology; Myocarditis - physiopathology; Myocardium - pathology; NMR; Nuclear magnetic resonance; Occlusion; Patients; Predictive Value of Tests; Risk factors; Staining; Stroke; Sus scrofa; Time Factors; Myocardial infarction; Ischemia reperfusion injury; Microvascular obstruction; Inflammation; cardiovascular magnetic resonance; Hemorrhage; T2
• ISSN: 1097-6647; 1532-429X
• DOI: 10.1186/s12968-017-0361-7

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). 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. 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. 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.