Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond

Abstract

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [<3 years post-HTx, 5-10 years post-HTx, and >14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent <3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the >14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and >14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression.

Figure 1

(A) Brachial artery FMD with placebo and antioxidant supplementation following 5-min cuff occlusion expressed as a percent change from pre-cuff baseline in healthy controls, HFrEF patients, and 3 groups of HTx recipients. (*) Significantly different from Placebo; (†) Significantly different from Controls; (‡) Significantly different from HTx (< 3 yrs). (B) Brachial artery FMD expressed as absolute change in diameter from pre-cuff baseline in healthy controls, HFrEF patients, and 3 groups of HTx recipients. (*) Significantly different from Placebo; (†) Significantly different from Controls; (‡) Significantly different from HTx (< 3 yrs). Values are means ± SE.

Figure 2

Time post-HTx and its influence on FMD (% diameter change).

Figure 3

Placebo FMD broken down by current (HFrEF) or prior (HTx) disease etiology. (*) Significantly different from HTx < 3 yrs non-ischemic; (†) Significantly different from HFrEF ischemic; (‡) Significantly different from HTx < 3 yrs ischemic; (#) Significantly different from HTx 5-10 yrs ischemic. Values are means ± SE.

Figure 4

Resting brachial artery blood flow and RH with placebo and antioxidant supplementation following 5-min cuff occlusion in healthy controls, HFrEF patients, and 3 groups of HTx recipients. There were no significant differences at baseline, peak RH, or AUC for either Placebo (A) or Antioxidant (B).

Figure 5

Quantitative assessment of antioxidant efficacy in healthy controls, HFrEF patients, and 3 groups of HTx recipients. (A) plasma ascorbate; (B) Thiobartituric Acid Reactive Substances (TBARS). Values are means ± SE. (*) Significantly different from Controls; (†) Significantly different from Placebo.

Figure 6

Plasma nitrite (A) and plasma nitrate (B) with placebo and antioxidant supplementation in healthy controls, HFrEF patients, and 3 groups of HTx recipients. Values are means ± SE. (*) Significantly different from Controls; (†) Significantly different from HFrEF; (‡) Significantly different from < 3 yrs post-HTx.