Structural and electrophysiological changes in atherosclerotic radial artery grafts account for impairment of vessel reactivity
Introduction
The radial artery (RA) is increasingly being used as a conduit for coronary artery bypass grafting (CABG) surgeries [1], [2]. Easy harvesting and handling characteristics, adaptability to higher pressures, easy accessibility to any coronary target and less post-operative wound complications has allowed the RA to gain popularity as a bypass conduit [2], [3]. However, one of the drawbacks associated with the RA is that it is significantly predisposed towards development of atherosclerosis [4]. Histologically, the internal elastic lamina of the RA has multiple fenestrations which makes it vulnerable to the development of atherosclerotic lesions [5], [6]. The propensity for the RA to develop atherosclerosis (5–10%) has been shown to be significantly higher compared to the gold standard, the internal thoracic artery (ITA) (<1%) [4], [7], [8], [9], [10].
There is an obvious need for the CABG graft to be free of disease. Screening and pre-operative diagnosis for conduit atherosclerosis are not performed as part of pre-surgical work up for CABG patients. In fact, there is no established screening and diagnostic methodology or criteria available to date. Typically, the arterial conduits are inspected and assessment of their suitability is made intra-operatively on the basis of macroscopic appearance [11], [12]. Potential shortcomings of such practice are many. First, intra-operative inspections are arbitrary, subjective and imprecise and not supported by evidence-based data. Secondly, unsuitable conduits (RAs with gross calcification) are rejected after harvesting, which leads to excess incisions for the patients and, potentially, shortage of conduits for the surgeons.
The atherosclerotic plaque is a potent source of inflammatory mediators, reactive oxygen species and other vasoactive molecules including isoprostanes, all of which are known to dramatically alter vascular function [13], [14]. Therefore, using a borderline atherosclerotic RA as a graft could have significant implications on the clinical outcome of surgery. While there is a wealth of data documenting the histopathological evidence for the development of atherosclerosis in the RA [7], [8], [9], [12], there is relatively limited information available regarding the functional properties of atherosclerotic arteries. Therefore, we decided to investigate the vasoreactivity of mildly and severely atherosclerotic RAs using the pressurized vessel technique. We also used patch clamp electrophysiology to study K+ currents in the atherosclerotic smooth muscle cells.
Section snippets
Methods
All experimental procedures were approved by the ethics committee of St. Joseph's Healthcare and Hamilton Health Sciences. Patients (∼50 to 70 years in age) provided consent for the use of their radial arteries in these studies, but no demographic data were collected, neither were there any specific selection criteria such as age, gender or medical history (including risk factors for atherosclerosis).
RA tissues were harvested as pedicles (with veins and peri-arterial fat) using the traditional
Histology
Fatty streaks, loss of arterial wall elasticity and intimal thickening were used as diagnostic criteria for sclerosis. The atherosclerotic arteries were categorized by the surgeons as mild or severe based on visual inspection (Fig. 1A), and were later also assessed histologically by a pathologist (Fig. 1B). Plaques, fibrosis and focal mild calcification were noted in the mild cases. These findings were limited to the subendothelium and tunica intima with mild involvement of tunica media. In
Discussion
In this study we investigated the pharmacological and electrophysiological properties of atherosclerotic RA. We found that pressure-induced dilation in both mildly and severely atherosclerotic arteries was attenuated, significantly so in the latter group. Vasoconstrictor responses to a variety of agonists were also compromised. A possible explanation for these observations could be the increased stiffness of atherosclerotic arteries and significantly greater K+ currents in atherosclerotic SMCs
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