Microvascular transport model predicts oxygenation changes in the infarcted heart after treatment.
Chronic heart failure is most commonly due to ischemic cardiomyopathy after a previous myocardial infarction (MI). Rebuilding lost myocardium to prevent heart failure mandates a neovasculature able to nourish new cardiomyocytes. Previously we have used a series of novel techniques to directly measure the ability of the scar neovasculature to deliver and exchange oxygen at 1-4 wk after MI in rats following left coronary artery ligation. In this study, we have developed a morphologically realistic mathematical model of oxygen transport in cardiac tissue to help in deciding what angiogenic strategies should be used to rebuild the vasculature. The model utilizes microvascular morphology of cardiac tissue based on available morphometric images and is used to simulate experimentally measured oxygen levels after MI. Model simulations of relative oxygenation match experimental measurements closely and can be used to simulate distributions of oxygen concentration in normal and infarcted rat hearts. Our findings indicate that both vascular density and vascular spatial distribution play important roles in cardiac tissue oxygenation after MI. Furthermore, the model can simulate relative changes in tissue oxygen levels in infarcted tissue treated with proangiogenic compounds such as losartan. From the minimum oxygen concentration myocytes need to maintain their normal function, we estimate that 2 wk after MI 29% of the myocardium is severely hypoxic and that the vascular density of the infarcted tissue should reach 75% of normal tissue to ensure that no areas of the myocardium are critically hypoxic.
Wang
Bin
B
Department of Mechanical Engineering, Temple University, 1947 North 12th Street, Philadelphia, PA 19122, USA.
Scott
Robert C
RC
Pattillo
Christopher B
CB
Prabhakarpandian
Balabhaskar
B
Sundaram
Shankar
S
Kiani
Mohammad F
MF
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003198:Computer Simulation; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019808:Losartan / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors
D043925:Angiogenesis Inducing Agents; D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan; D010100:Oxygen