Effect of endothelial dysfunction on regional perfusion in myocardial territories supplied by normal and diseased vessels in patients with coronary artery disease.

BACKGROUND: Endothelium-dependent regulation of coronary tone affects both conduit and resistance coronary arteries. However, little is known about the usefulness of myocardial perfusion imaging in evaluating coronary endothelial function. We evaluated the relation between invasive angiographic measurements of coronary vasomotion in response to intracoronary acetylcholine and the presence of regional perfusion abnormalities assessed by technetium 99m sestamibi imaging. METHODS AND RESULTS: We studied 11 patients (9 men and 2 women) with suspected coronary artery disease (48 +/- 8 years, mean +/- standard deviation). We used quantitative coronary angiography to delineate the vasomotor response to increasing doses of acetylcholine given intracoronary. Regional myocardial perfusion was assessed by planar Tc-99m sestamibi imaging during and after the administration of acetylcholine. In the 11 patients, 23 coronary artery territories were analyzed: 13 were angiographically normal, and 10 showed varying degrees of luminal narrowing. Four (31%) of 13 angiographically normal coronary arteries had a positive vasomotor response to acetylcholine (> or =20% reduction in luminal diameter) that was associated with a regional perfusion defect. Acetylcholine induced a positive vasomotor response, which was also associated with a regional perfusion defect in 1 of 3 coronary arteries with stenoses of intermediate severity (50% to 69%). Likewise, acetylcholine induced a positive vasomotor response in 6 of 7 coronary arteries with significant luminal narrowing (> or =70%), 5 of which showed a corresponding regional perfusion defect. CONCLUSIONS: In patients with coronary artery disease, noninvasive measurements of regional myocardial perfusion by Tc-99m sestamibi correlate well with invasive measurements of coronary endothelial function. These findings may have implications for monitoring the effects of interventions designed to improve endothelial function and microvascular function in patients with coronary artery disease.

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.