Recent studies have shown that blood flow through the internal mammary artery graft is inadequate for maximal exercise and that hypoperfusion may be worsened by high-dose vasopressor therapy that could further reduce arterial graft flow. Histologic studies have suggested that the human internal mammary artery is an elastic "passive conduit" along the majority of its length. However, although the pharmacologic reactivity at the distal section of the internal mammary artery has been extensively studied, this evaluation has never been done at the middle and proximal sections. It is extremely important to understand the contractility at the midsection of the internal mammary artery because, in a critical situation, any contraction may further reduce the internal mammary artery flow. The present study was designed to investigate the following: (1) Is it true that the pharmacologic reactivity of the human internal mammary artery is different among various sections? and (2) Is the human internal mammary artery a nonreactive "passive conduit" at its most important area used as the graft--the middle and the proximal sections? One hundred six human internal mammary artery ring segments taken from patients who underwent internal mammary artery grafting procedures (29 from the proximal, 38 from the middle, and 39 from the distal sections) were studied in the organ bath under a physiologic pressure. Concentration-response curves were established for norepinephrine, endothelin-1, U46619, potassium, and glyceryl trinitrate (precontracted with 10 nmol/L U46619). Contraction forces were standardized (in grams per millimeter circumference) at a pressure of 100 mm Hg. The contraction force was greater in the distal section than in other sections for norepinephrine (p = 0.002) and endothelin-1 (p = 0.04). No differences were seen for potassium, U46619, or glyceryl trinitrate, whereas the effective concentration inducing 50% of maximal response for U46619 was 100-fold lower in the distal than in the middle section (9.06 +/- 0.34 versus 7.06 +/- 0.48 -log M; p = 0.01) indicating higher sensitivity in the distal section. This study for the first time shows various reactivity along the full length of the human internal mammary artery and shows that the distal section is the most reactive part of the graft. However, although the middle and the proximal sections are less reactive to some vasoconstrictors (norepinephrine and endothelin-1), it is not a "passive conduit" and it contracts with all four vasoconstrictors tested.(ABSTRACT TRUNCATED AT 400 WORDS)