Perfusion Versus Function: The Ischemic Cascade in Demand Ischemia

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Abstract
Background— We hypothesized that during demand ischemia, abnormal perfusion will precede abnormal function, the spatial extent of perfusion abnormality will be greater than that of functional abnormality, and the spatiotemporal disparity between abnormal perfusion and abnormal function will be more marked in the presence of single-vessel stenosis (SVS) versus multivessel stenosis (MVS). Methods and Results— Nine dogs each underwent either SVS or MVS placement. These noncritical stenoses were classified as mild, moderate, or severe on the basis of the transstenotic pressure gradient (10 to 14, 15 to 20, or >20 mm Hg). Dobutamine was infused starting at 10 and reaching 40 μg/kg−1 · min−1. Wall thickening (WT) and myocardial perfusion (myocardial contrast echocardiography) were assessed at each stage. Resting perfusion and function were normal in all dogs. In SVS, abnormal perfusion (delayed rate of microbubble replenishment) was seen at the lowest dose of dobutamine irrespective of the stenosis severity, whereas WT abnormality was seen only at high doses of dobutamine and was influenced by the stenosis severity. The spatial extent of abnormal perfusion exceeded that of WT abnormality at all but the highest dobutamine dose. This spatiotemporal discordance between abnormal perfusion and function was significantly less in MVS, where it was possible to identify separate regions with abnormal function at lower doses of dobutamine. Conclusions— These data support the occurrence of the ischemic cascade during demand ischemia. They also explain the higher sensitivity of abnormal perfusion compared with abnormal function for the detection of coronary stenosis as well as the higher sensitivity of dobutamine echocardiography for MVS compared with SVS.

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