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The Journal of Cardiovascular Surgery 2002 December;43(6):761-71

language: English

Pharmacological studies on internal mammary artery bypass grafts. Action of endogenous and exogenous vasodilators and vasoconstrictors

Evora P. R. B. 1,2, Pearson P. J. 1, Discigil B. 1, Oeltjen M. R. 1, Schaff H. V. 1

1 Car­diac Sur­gical ­Research and the Sec­tion of Car­di­o­vas­cular Sur­gery, ­Mayo ­Clinic and ­Mayo Foun­da­tion, Roch­ester, MN, USA
2 Di­vi­sion of Experi­mental Sur­gery - ­Ribeirão ­Preto ­School of Med­i­cine - Uni­ver­sity of São ­Paulo, and ­UNAERP Med­ical ­School, ­Ribeirão ­Preto, SP, ­Brazil


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Back­ground. The pur­pose of ­this experi­ment was ­four-­fold: 1) to deter­mine the ­effect of cur­rently ­used car­di­o­vas­cular ­drugs on ­internal mam­mary ­artery (IMA) vas­cular ­tone, 2) to ­examine IMA reac­tivity to auta­coids and prod­ucts ­released ­from aggre­gating plate­lets, 3) to com­pare the vas­cular reac­tivity of the ­right ­versus ­left IMA, and 4) to deter­mine ­whether the ­canine IMA was an accept­able phys­io­log­ical ­model as ­regards its sim­i­larity to the ­human IMA, ­which is ­used rou­tinely for cor­o­nary ­artery ­bypass ­grafting.
­Methods. To ­study fac­tors ­that mod­ulate the ­tone of IMA, ­bypass ­grafts, ­right and ­left ­canine ­IMAs ­were ­studied in ­vitro in ­organ cham­bers (95% O2/5% CO2, pH=7.4).
­Results. ­Increasing con­cen­tra­tions (10-9 to 10-4M) of the neu­ro­trans­mitter ace­tyl­cho­line (ACH) and the ­platelet-­derived prod­ucts aden­o­sine diph­os­phate (ADP) or serot­onin (5-HT) ­induced vas­o­dil­a­ta­tion of con­tracted ­right and ­left ­IMAs. The vasod­i­la­tion ­caused by ACH and ADP was endo­the­lium-depen­dent ­while serot­onin ­acted ­directly on the vas­cular ­smooth ­muscle. His­ta­mine and bra­dy­kinin ­also ­induced IMA vasod­i­la­tion, his­ta­mine via a ­direct ­action on the ­smooth ­muscle, and bra­dy­kinin ­through the ­release of ­nitric ­oxide (NO). In ­canine ­IMAs, the cal­cium ion­o­phore A23187 pro­duced endo­the­lium-depen­dent vasod­i­la­tion of con­tracted ­blood ves­sels; ­this vasod­i­la­tion was ­blocked by NG-­nitro-L-argi­nine (10-4M), a com­pet­i­tive inhib­itor of ­nitric ­oxide syn­thesis ­from L-argi­nine, and by hemo­globin (10-5M). Dop­a­mine, dobu­ta­mine, and papav­e­rine ­induced vasod­i­la­tion of the IMA regard­less of the pres­ence or ­absence of an ­intact ­intima, ­while nor­epi­neph­rine ­induced pro­found IMA vaso­con­stric­tion, ­which was com­par­able to con­trac­tion to potas­sium ­ions or the con­strictor pep­tide endo­thelin.
Con­clu­sions. ­These experi­ments estab­lish a phar­mac­o­log­ical pro­file of IMA and dem­on­strate ­that endog­e­nous and exog­e­nous com­pounds can sig­nif­i­cantly ­alter its vas­cular ­tone.

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