Comparison of endothelium-dependent vasoactivity of internal mammary arteries from hypertensive, hypercholesterolemic, and diabetic patients.
BACKGROUND
Endothelium-dependent relaxation is abnormal in a variety of diseased states. Despite the widespread use of the internal mammary artery (IMA) in coronary artery bypass grafting, there is a lack of comparative studies on IMA endothelial-dependent function in patients with major cardiovascular risk factors.


METHODS
An IMA segment from 48 selected patients undergoing coronary artery bypass grafting was harvested intraoperatively and assigned to one of four groups (n = 12): diabetics requiring therapy, hypertensives, hypercholesterolemic, and nondiabetic-normotensive-normocholesterolemic patients. Internal mammary artery specimens were cut into rings and suspended in organ bath chambers, and the isometric tension of vascular tissues was recorded. The IMA rings were (1) precontracted with norepinephrine, and the endothelium-derived relaxation was evaluated by cumulative addition of acetylcholine, (2) contracted with cumulative concentrations of endothelin-1, and (3) contracted with the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine. Furthermore, the release of prostacyclin by the IMA rings was directly measured during basal tone conditions and at the end of the various pharmacologic interventions. Histology of IMA rings was randomly performed.


RESULTS
The results obtained in these experiments showed that IMA rings harvested from hypertensive patients have the greatest impairment of endothelium-dependent response to relaxant and contracting stimuli (p < 0.01 versus nondiabetic-normotensive-normocholesterolemic tissues; p < 0.05 versus hypercholesterolemic and diabetic tissues) and prostacyclin release in normal and stimulated conditions. To a lesser extent, hypercholesterolemic and diabetic tissues show similar depression (diabetic > hypercholesterolemic) both of relaxation and prostacyclin production, with respect to nondiabetic-normotensive-normocholesterolemic specimens (p < 0.05). Histology findings (scanning electron microscopy) did not differ in multiple sections from vessel studies.


CONCLUSIONS
Major cardiovascular risk factors affect the endothelium-dependent vasoactive homeostasis of human IMA differently. Depression of relaxation is highest in patients with a history of hypertension. These findings may be pertinent to early and long-term treatment of patients undergoing coronary artery bypass grafting.
Pompilio
G
G
Department of Cardiovascular Surgery, Centro Cardiologico I. Monzino Foundation IRCCS, Milan, Italy. giulio.pompilio@cardiologicomonzino.it
Rossoni
G
G
Alamanni
F
F
Tartara
P
P
Barajon
I
I
Rumio
C
C
Manfredi
B
B
Biglioli
P
P
D000368:Aged; D001026:Coronary Artery Bypass; D046508:Culture Techniques; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007387:Internal Mammary-Coronary Artery Anastomosis; D008297:Male; D008323:Mammary Arteries / Q000503:physiopathology*; D008875:Middle Aged; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*