A model of multivessel coronary artery disease using conscious, chronically instrumented dogs

The present investigation was undertaken to develop a reproducible model of multivessel coronary artery disease including a total occlusion of one vessel and a stenosis of an adjacent vessel in chronically instrumented dogs. Utilizing sterile techniques, we surgically prepared dogs for measurement of heart rate, arterial pressure, left ventricular pressure, and blood flow velocity in the left anterior descending (LAD) and left circumflex (LCCA) coronary arteries. A hydraulic occluder and Ameroid constrictor were implanted around the LAD and LCCA, respectively. Pairs of piezoelectric crystals were implanted within the subendocardium of the LAD and LCCA perfusion territories to measure regional contractile function (segment shortening). A catheter was placed in the left atrial appendage for injection of radioactive microspheres to measure regional myocardial perfusion. Beginning on the second day following implantation, 25, 50, and 100 micrograms bolus injections of adenosine were administered daily via the left atrium to evaluate LAD and LCCA coronary reserve. Although LAD reserve remained intact, the hyperemic response of the LCCA was progressively attenuated as stenosis severity increased during slow closure of the Ameroid constrictor. When the LCCA vasodilator response to adenosine was reduced by 50% (moderate stenosis; no change in resting flow velocity) or 70% (severe stenosis; 20% reduction in resting flow velocity), the LAD was acutely occluded (via inflation of the hydraulic occluder) to simulate multivessel coronary artery disease. After a hemodynamic steady state was established during coronary occlusion, radioactive microspheres were administered to compare regional perfusion within normal myocardium to flow in myocardium supplied by the occluded or stenotic coronary arteries. In dogs with a stenosis of moderate severity, transmural myocardial blood flow was significantly decreased (-83%) only in the occluded zone. However, in dogs with a severe coronary artery stenosis, reductions in perfusion in both stenotic (-31%) and occluded (-87%) regions were demonstrated. Subendocardial/subepicardial flow ratios were significantly reduced in both stenotic and totally occluded regions in the presence of severe stenosis, but this occurred only in the occluded (LAD) zone of dogs with a moderate LCCA stenosis. This preparation provides a model whereby the vasodilator reserve of a progressively constricted coronary artery can be quantified and simultaneously compared to the reserve of a normal vessel. With acute occlusion of the normal artery, a multivessel disease state can be simulated and verified by measurement of regional myocardial perfusion. The model is reproducible, free of the influence of anesthesia and acutely performed surgery, and the degree of stenosis is easily varied over time.