Role of intramural platelet thrombus in the pathogenesis of wall rupture and intra-ventricular thrombosis following acute myocardial infarction.
Left ventricular thrombus (LVT) and rupture are important mechanical complications following myocardial infarction (MI) and are believed to be due to unrelated mechanisms. We studied whether, in fact, wall rupture and LVT are closely related in their pathogenesis with intramural platelet thrombus (IMT) playing a pivotal role. Male 129sv and C57Bl/6 mice underwent operation to induce MI, and autopsy was performed to confirm rupture deaths. Haemodynamic features of rupture events were monitored by telemetry in conscious mice. Detailed histological examination was conducted with special attention to the presence of IMT in relation to rupture location and LVT formation. IMT was detected in infarcted hearts of 129sv (82%) and C57Bl/6 (39%) mice with rupture in the form of a narrow streak spanning the wall or an occupying mass dissecting the infarcted myofibers apart. IMT often contained dense inflammatory cells and blood clot, indicating a dynamic process of thrombus formation and destruction. Notably, IMT was found extending into the cavity to form LVT. Haemodynamic monitoring by telemetry revealed that rupture occurred either as a single event or recurrent episodes. Importantly, the anti-platelet drug clopidogrel, but not aspirin, reduced the prevalence of rupture (10% vs. 45%) and IMT, and suppressed the degree of inflammation. Thus, IMT is a key pathological element in the infarcted heart closely associated with the complications of rupture and LVT. IMT could be either triggered by a wall tear or act as initiator of rupture. IMT may propagate towards the ventricular chamber to trigger LVT.
Baker IDI Heart and Diabetes Institute, St Kilda Road Central, Melbourne, Victoria 8008, Australia. xiao-jun.du@bakeridi.edu.au
Xiao-Jun
XJ
Du
Leonard
L
Shan
Xiao-Ming
XM
Gao
Helen
H
Kiriazis
Yang
Y
Liu
Abhirup
A
Lobo
Geoffrey A
GA
Head
Anthony M
AM
Dart
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology*; D000077144:Clopidogrel; D004195:Disease Models, Animal; D006439:Hemodynamics; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013686:Telemetry; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D018658:Ventricular Septal Rupture / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin