Relation between graded, subcritical impairments of coronary flow reserve and regional myocardial dysfunction induced by isoproterenol infusion in dogs.

Isoproterenol has been used experimentally and clinically to elicit ischemia. The usefulness of this approach, however, in eliciting regional dysfunction in the presence of mild to moderate single-vessel coronary disease quantitated on the basis of coronary flow reserve measurements has not been previously defined. Open-chest, anesthetized dogs were instrumented with an electromagnetic flow probe, high-fidelity micromanometers, and subendocardial ultrasonic crystals. A rigid, screw occluder was used to produce five subcritical coronary stenoses in each dog associated with varying impairment of postocclusion reactive hyperemia at rest but no impairment of resting coronary blood flow. Regional function at rest and in response to the isoproterenol challenge (0.25 micrograms/kg/min) in nonstenotic and stenotic conditions was assessed. Relative regional function was maintained during the infusion until nearly total loss of coronary flow reserve. With this near-critical stenosis, function was lower than in the nonstenotic state but remained greater than resting control values. Moderate impairments of coronary flow reserve were not associated with isoproterenol-induced deterioration of regional function. In conclusion, detection of impaired coronary flow reserve at rest is a more sensitive index of the severity of a coronary stenosis than is detection of regional dysfunction during isoproterenol challenge. Failure to maintain the expected isoproterenol-induced increase in regional function is manifested only when stenoses are associated with nearly total loss of resting coronary flow reserve. This suggests that the clinical use of isoproterenol challenge is not effective in eliciting regional dysfunction when mild coronary disease is present.