Effect of coronary stenosis on adjacent bed flow reserve - Assessment of microvascular mechanisms using myocardial contrast echocardiography

Background - During coronary stenosis, flow reserve in the adjacent nonstenotic bed decreases, but the microvascular mechanisms are unknown. Because myocardial contrast echocardiography ( MCE) assesses microvascular physiology, we used it to relate flow reserve to intramyocardial blood volume in the adjacent bed. Methods and Results - A noncritical left anterior descending ( LAD) stenosis was created in 10 dogs. MCE was performed and myocardial blood flow was measured with neutron-activated microspheres and flow probes. Data were collected at baseline, hyperemia, and hyperemia and stenosis. Hyperemia was induced with an A(2A) receptor agonist. MCE acoustic intensity in the LAD and left circumflex ( LCx) regions were fit to the following: y = A( 1-e(-beta t)), where A, beta, and A x beta reflect intramyocardial blood volume, red cell velocity, and flow, respectively. During hyperemia alone, LCx probe and microsphere flows and MCE-derived red cell velocity increased from baseline ( 30 +/- 14 versus 125 +/- 62 mL/min, P < 0.0005; 1.5 +/- 0.5 versus 6.6 +/- 2.0 mL . min(-1) . g(-1), P < 0.0005; and 0.53 +/- 0.14 versus 0.96 +/- 0.45 second(-1), P = 0.030, respectively); intramyocardial blood volume was unchanged. LAD stenosis during hyperemia decreased LCx probe flow ( 125 +/- 62 versus 110 +/- 57 mL/min; P < 0.05), microsphere flow ( 6.6 +/- 2.0 versus 4.2 +/- 2.1 mL . min(-1) . g(-1); P < 0.0005), and MCE-derived flow ( 0.57 +/- 0.29 versus 0.45 +/- 0.33 second(-1); P = 0.032). LCx bed intramyocardial blood volume concurrently increased ( 0.61 +/- 0.14 versus 0.70 +/- 0.15; P < 0.01). Conclusions - Coronary stenosis impairs flow reserve in the adjacent nonstenotic bed, in which intramyocardial blood volume increases. MCE suggests compensatory recruitment of microvascular anastomotic collateral networks that augment stenotic bed flow reserve, but at the expense of the adjacent bed. Adjacent bed collateral microcirculation thus participates in the regulation of collateral flow and appears functionally significant during coronary stenosis.