title: Why is the subendocardium more vulnerable to ischemia? A new paradigm.
abstract: Myocardial ischemia is transmurally heterogeneous where the subendocardium is at higher risk. Stenosis induces reduced perfusion pressure, blood flow redistribution away from the subendocardium, and consequent subendocardial vulnerability. We propose that the flow redistribution stems from the higher compliance of the subendocardial vasculature. This new paradigm was tested using network flow simulation based on measured coronary anatomy, vessel flow and mechanics, and myocardium-vessel interactions. Flow redistribution was quantified by the relative change in the subendocardial-to-subepicardial perfusion ratio under a 60-mmHg perfusion pressure reduction. Myocardial contraction was found to induce the following: 1) more compressive loading and subsequent lower transvascular pressure in deeper vessels, 2) consequent higher compliance of the subendocardial vasculature, and 3) substantial flow redistribution, i.e., a 20% drop in the subendocardial-to-subepicardial flow ratio under the prescribed reduction in perfusion pressure. This flow redistribution was found to occur primarily because the vessel compliance is nonlinear (pressure dependent). The observed thinner subendocardial vessel walls were predicted to induce a higher compliance of the subendocardial vasculature and greater flow redistribution. Subendocardial perfusion was predicted to improve with a reduction of either heart rate or left ventricular pressure under low perfusion pressure. In conclusion, subendocardial vulnerability to a acute reduction in perfusion pressure stems primarily from differences in vascular compliance induced by transmural differences in both extravascular loading and vessel wall thickness. Subendocardial ischemia can be improved by a reduction of heart rate and left ventricular pressure.
authors.affiliation: Faculty of Biomedical Engineering, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Dotan
authors.initials: D
authors.lastname: Algranati
authors.forename: Ghassan S
authors.initials: GS
authors.lastname: Kassab
authors.forename: Yoram
authors.initials: Y
authors.lastname: Lanir
mesh_terms: D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology; D004699:Endocardium / Q000503:physiopathology*; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*