Response of large and small coronary arteries of pigs to intracoronary injection of acetylcholine: angiographic and histologic analysis.
With coronary arteriography we examined the effect of acetylcholine (ACh) on large and small coronary arteries. ACh (12.5 to 200 micrograms) was injected into the right coronary arteries of 10 pigs during left ventricular pacing. The percentage of narrowing of the epicardial major coronary artery was used as an indicator of the constriction of the large coronary arteries, and the time required for the contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery (blood-flow delay) was used as an indicator of the constriction of the same coronary arteries. A small dose of ACh (12.5 to 100 micrograms) induced mild narrowing (14 to 41%) of the epicardial major coronary artery and a marked blood-flow delay of over 7.0 sec (control: less than or equal to 1.8 sec) in all 10 pigs. A large dose of ACh (100 to 200 micrograms) caused over 75% narrowing of the epicardial major coronary artery and a marked blood-flow delay in 4 of the 10 pigs. When the marked blood-flow delay appeared, the perfused right ventricular myocardium became macroscopically anemic (ischemic). The constriction of large and small coronary arteries was not prevented by diphenhydramine (H1 blocker: 100 mg i.v.), but was prevented by pretreatment with atropine (1.0 mg i.v.). The intracoronary injection of histamine (1.5 mg) in 5 pigs constricted the epicardial major coronary artery over 75% in 2 pigs, 50 to 75% in 1 pig, and 25 to 50% in 2 pigs, but there was no evidence of blood-flow delay. Neither methoxamine nor norepinephrine caused any significant coronary artery narrowing. The histology of the large and small coronary arteries was examined quantitatively with an image analyzer. The coronary artery showed no intimal thickening, and the endothelium was intact on light microscopic examination. The % area of the smooth muscle layer (media) to the calculated total vascular area, and the ratio of the calculated medial thickness to the calculated inner radius (h/Ri) were 64 +/- 7% (mean +/- SD) and 0.69 +/- 0.16, respectively, in the small coronary arteries less than 100 microns in external diameter, 47 +/- 9% and 0.39 +/- 0.12 in the small coronary arteries 100 to 2000 microns in external diameter, and 34 +/- 4% and 0.24 +/- 0.03 in the large right coronary arteries over 2000 microns in external diameter; the % area of the media and the h/Ri showed a negative correlation with the size of the coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
Kawamura
A
A
Department of Internal Medicine, Kyoto University, Japan.
Fujiwara
H
H
Onodera
T
T
Wu
D J
DJ
Matsuda
M
M
Ishida
M
M
Takemura
G
G
Fujiwara
Y
Y
Kawai
C
C
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D006632:Histamine; D008729:Methoxamine; D000109:Acetylcholine; D009638:Norepinephrine