Table 2.
Examples of applying the laws of MI thermodynamics to post-MI inflammation and extracellular matrix responses following matrix metalloproteinase-9 modulation
| Law | Example | Insights gained |
|---|---|---|
| First: post-MI, the cardiac system remodels in an attempt to maintain maximum LV function |
MMP-9 deletion limits early inflammation to reduce macrophage infiltration and ECM turnover, which attenuate later collagen deposition and infarct expansion. |
Early inflammation and ECM turnover status predicts later changes in LV structure or function. |
| Second: post-MI, the LV undergoes unidirectional modifications that lead to irreversible transformation in geometry and function |
Macrophage-specific MMP-9 overexpression blunts pro- inflammatory leukocyte phenotypes and prevents early post-MI LV dysfunction without affecting cell numbers or collagen deposition. |
Cell-to-cell communication and timing of intervention have major effects on MI outcomes. |
| Third: post-MI, the infarct approaches scar equilibrium over time |
While day 28 post-MI inflammation in the infarct is similar between wild-type and MMP-9 null mice, the ECM continues to differentially remodel and the LV operates at different levels of dysfunction. |
End scar quality and LV function is an ultimate outcome measurement. |