PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction.
OBJECTIVE
We investigated whether a myocardial perfusion gradient during pharmacologically induced hyperemia also occurred during sympathetic stimulation with cold pressor testing (CPT), which commonly induces a paradoxical coronary vasoconstriction in individuals with coronary risk factors.


METHODS
Myocardial blood flow (MBF) was measured in absolute units (ml/g/min) with 13N-ammonia and PET at rest, during CPT, and during pharmacologic vasodilation in 59 participants with coronary risk factors ("at risk") and in 43 healthy individuals (controls). MBF was assessed globally as mean MBF, and in the mid and mid-distal myocardium of the left ventricle (LV). A decrease in MBF from mid to mid-distal LV myocardium was defined as MBF difference indicative of a perfusion gradient.


RESULTS
The change in mean MBF to CPT (DeltaMBF) in the at-risk group was significantly reduced compared with controls (0.05+/-0.19 vs 0.31+/-0.20 ml/g/min, p<0.0001), whereas mean MBF during pharmacologic vasodilation in the at-risk group tended to be lower than in controls (1.72+/-0.71 vs 2.00+/-0.64 ml/g/min, p=NS). Absolute MBFs during CPT and pharmacologic vasodilation were significantly lower in the mid-distal than in the mid LV myocardium, resulting in a significant MBF difference in the at-risk group (0.15+/-0.06 and 0.27+/-0.12 ml/g/min, p<0.0001) that was not observed in controls (0.007+/-0.05 and 0.014+/-0.10 ml/g/min, p=NS). In the at-risk group there was a significant correlation between the difference of mid to mid-distal MBF during CPT and that during pharmacologic vasodilation (r=0.43, p<0.004), suggesting functional alterations of epicardial vessels as the predominant cause for the observed MBF difference.


CONCLUSIONS
The relative decrease in MBF from the mid to the mid-distal left-ventricular myocardium suggests an intracoronary pressure decline during CPT and pharmacologic vasodilation, which is likely to reflect an impairment of flow-mediated epicardial vasomotor function.
Schindler
Thomas H
TH
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Ave, 23-120 CHS, P.O. Box 173517, Los Angeles, CA 90095-1735, USA.
Facta
Alvaro D
AD
Prior
John O
JO
Campisi
Roxana
R
Inubushi
Masayuki
M
Kreissl
Michael C
MC
Zhang
Xiao-Li
XL
Sayre
James
J
Dahlbom
Magnus
M
Schelbert
Heinrich R
HR
D000328:Adult; D000641:Ammonia; D001783:Blood Flow Velocity; D002250:Carbon Radioisotopes; D003080:Cold Temperature; D003326:Coronary Circulation; D005080:Exercise Test / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D010496:Pericardium / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014665:Vasodilator Agents; D014666:Vasomotor System / Q000000981:diagnostic imaging*
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; D000641:Ammonia