Increased tissue endothelin-1-like immunoreactivity in the internal mammary artery of patients with diabetes or hypercholesterolemia modulates the graft flow in the peri-operative period

Objective: Peri-operative ischemic episodes following coronary artery bypass grafting with the internal mammary artery (IMA) are thought to be due to a vasospasm of this conduit. Endothelin-1 (ET-1) is a potent vasoconstrictor by itself and increases the response to other vasoconstrictor stimuli. This study focused on the possible role of an enhanced tissue ET-1-like immunoreactivity in the perioperative reaction of the IMA in patients with diabetes or hypercholesterolemia. Methods: Specimens of the distal part of the IMA from 46 patients (mean age 58.5 years, four women, 42 men) were studied prospectively. Nine of those patients were diabetic and 26 had evidence of hypercholesterolemia. Another cohort of 20 IMA specimens was stained retrospectively; 10 of those biopsies were from patients that had experienced transient ischemic events peri-operatively in the myocardial area supplied by the IMA. The biopsies were examined histologically and immunohistochemically (rabbit polyclonal ET-1 antiserum, three-step avidin-biotin complex) with regard to their immunoreactivity to tissue ET-1. Results: An immunoreactivity to ET-1 (graded 0-3) was present in 89% of the biopsies. The reactivity was significantly higher in patients with hypercholesterolemia (1.92 +/- 0.74) when compared to controls (1.0 +/- 0.63) (P = 0.04). The reactivity was also increased in patients with non-insulin-dependent diabetes mellitus (2.1 +/- 0.79), when compared to controls (P = 0.02). Mostly transient ischemic events in the area supplied by the IMA seemed to occur mon frequently when the biopsies revealed a higher immunoreactivity to ET-1. They showed an increased reactivity to ET-1 (2.27 +/- 0.76) compared to 10 patients with an uneventful peri-operative course (1.66 +/- 0.71) (P = 0.04). Conclusions: This study provides evidence that the internal mammary artery is not a passive conduit. Vasospasm or vasoconstriction, in particular at its distal end, may occur more frequently in patients with hypercholesterolemia or diabetes, and may lead to post-operative ischemic events. (C) 1998 Elsevier Science B.V. All rights reserved.