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

J Cardiovasc Magn Reson. 2017 Jul 4;19(1):50. doi: 10.1186/s12968-017-0361-7.

Abstract

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.

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

MeSH terms

  • Animals
  • Contrast Media / administration & dosage
  • Coronary Circulation
  • Disease Models, Animal
  • Edema, Cardiac / diagnostic imaging
  • Edema, Cardiac / pathology
  • Edema, Cardiac / physiopathology
  • Female
  • Gadolinium DTPA / administration & dosage
  • Hemorrhage / diagnostic imaging*
  • Hemorrhage / pathology
  • Hemorrhage / physiopathology
  • Magnetic Resonance Imaging, Cine*
  • Microcirculation
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocarditis / diagnostic imaging*
  • Myocarditis / pathology
  • Myocarditis / physiopathology
  • Myocardium / pathology*
  • Predictive Value of Tests
  • Sus scrofa
  • Time Factors

Substances

  • Contrast Media
  • Gadolinium DTPA