M Yan* and Y L Lim.

National Heart Centre of Singapore and Department of Cardiology, Box Hill Hospital, Vic.

Spasm of the coronary bypass grafts using the radial artery (RA), internal mammary artery (IMA) and saphenous vein (SV) occurs in clinic. It appears that Alpha₁-adrenoceptor (AR) is the main mediator of spasm in the human RA, IMA and SV.  We aimed to study the distribution of Alpha₁-AR subtypes in these vessels since this information may have clinical significance in designing potential therapeutic targets for preventing spasm of coronary grafts.

The segments of blood vessels were obtained from 8 patients undergoing the bypass surgery. These patients were selected because they were not receiving any Alpha-AR agonists or antagonists. We examined the Alpha₁-AR subtypes in RA, IMA and SV using reverse transcription polymerase chain reaction (RT-PCR), DNA-DNA hybridization analysis and functional affinities experiments. Using Alpha_1A-, Alpha _1B- or Alpha_1D-AR subtypes oligonucleotide primers sets to amplify human RA, IMA and SV cDNAs, DNA-DNA Hybridization was used to analyze PCR products. Cumulative concentration-response curves were constructed for noradrenaline Alpha-AR agonist)-induced contraction, and the effects of competitive antagonists were examined versus the potency in RA, IMA and SV.

The results are as follows: (1) The PCR products for Alpha_1A-AR in RA and SV and Alpha_1B-AR in IMA were observed, but Alpha_1D-AR was not detectable in RA, IMA and SV. DNA-DNA hybridization confirmed the presence of Alpha_1A-, Alpha_1B- and Alpha_1D-AR in RA, IMA and SV. (2) Prazosin, the a₁-AR antagonist, phentolamine, a₁- and a₂-AR antagonist, 5-MU and WB4101, a_1A-AR antagonists, were competitively antagonized the noradrenaline-induced contraction. The selective Alpha_1D-AR antagonist BMY 7378 had a low affinity in RA, IMA and SV. Chloroethylclonidine, a a_1B and a_1D-AR antagonist, inhibited the noradrenaline-induced contraction in IMA and SV, but no effect in RA. Functional and binding affinities in RA, IMA and SV correlated well (Alpha_1A r = 0.96 in RA; Alpha_1B r = 0.91 in IMA; Alpha_1A r = 0.89 and Alpha_1B r = 0.98 in SV).

The results suggest that the Alpha_1A-AR in RA, Alpha_1B-AR in IMA and Alpha_1A-and Alpha_1B-ARs in SV is the main functional and expressed receptor subtypes.  These data emphases the need for prevention of catecholamine induced vasospasm, reinforcing consideration of Alpha_1A antagonists to RA, Alpha_1B antagonists to IMA, and Alpha_1A and Alpha_1B antagonists to SV, respectively, during and after coronary artery bypass surgery.

[ Back to 48th ASM Abstract Index ]