Dipyridamole, cold pressor test, and demonstration of endothelial dysfunction: a PET study of myocardial perfusion in diabetes.
Much evidence suggests endothelial dysfunction to be present in non-insulin-dependent diabetes mellitus (NIDDM) and to be important for the development of myocardial ischemia. Endothelial function in the coronary vessels may be studied in various ways. We compared the effect of cold pressor testing (CPT) with that of dipyridamole, a pharmacologic vasodilator, on coronary blood flow (CBF) measured by PET in NIDDM patients and healthy volunteers. In addition, we studied the effect of acute angiotensin-converting enzyme (ACE) inhibition on the flow response.


METHODS
Ten NIDDM patients and 10 control subjects participated. Myocardial perfusion was determined at baseline, during CPT, and after dipyridamole infusion by PET using intravenous (13)N-ammonia.


RESULTS
Resting CBF was similar in NIDDM patients and in control subjects. CPT increased CBF by 20% in the control group, whereas no increase was observed in the patients. After dipyridamole infusion, CBF increased 2- to 3-fold in patients and 3- to 4-fold in control subjects. The increase and maximal CBF were significantly higher in control subjects than in patients. During ACE-inhibitor infusion, which had no influence on resting CBF in patients or control subjects (n = 5), CPT increased CBF by 14% in the NIDDM group. After dipyridamole, CBF increased 3- to 4-fold in both groups. The increase in CBF and maximal CBF in the 2 groups were not different during ACE-inhibitor infusion.


CONCLUSIONS
In these NIDDM patients without evidence of epicardial coronary disease, endothelial dysfunction is strongly suggested by an impaired increase in CBF both to dipyridamole and to CPT. This dysfunction was reversed by infusion of an ACE inhibitor. Although ACE inhibition during CPT did induce significant increases in CBF in the patients, the changes during ACE inhibition were small compared with the dipyridamole response, and the absence of CBF increase during CPT in 3 of the 10 control subjects further limits the value of CPT for the study of coronary endothelial dysfunction.
Kjaer
Andreas
A
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. kjaer@mfi.ku.dk
Meyer
Christian
C
Nielsen
Flemming S
FS
Parving
Hans-Henrik
HH
Hesse
Birger
B
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D003080:Cold Temperature; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000000981:diagnostic imaging; D004176:Dipyridamole; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000187:drug effects; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed; D014665:Vasodilator Agents
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; C053500:perindoprilat; D004176:Dipyridamole