It is with interest that we read the review by Biccard and Rodesth [1] entitled “The pathophysiology of peri-operative myocardial infarction,” wherein the authors draw on data derived from pre-operative testing, troponin surveillance, peri-operative haemodynamic predictors, and post-mortem studies to postulate that flow stagnation and thrombus formation are the predominant mechanisms associated with peri-operative myocardial infarction.

While we find the authors’ review timely, we wish to emphasize that flow stagnation and thrombus formation are likely to be secondary events which are highly dependent on the inflammatory responses at microvascular level, and thus dependent on residual microvascular endothelial cell function during the peri-operative course. Furthermore, while peri-operative macrovascular events (e.g. myocardial infarction, stroke etc.) are readily evident their absolute incidence remains relatively low. Given the ubiquitous presence of endothelium, it is likely that this microvascular dysfunction, which is aggravated by peri-operative systemic inflammation, is likely to have a greater impact, through impaired perfusion in multiple organs. This often presents as prolonged postoperative recovery through a multitude of non-cardiovascular complications (e.g. end organ dysfunction, impaired wound healing).

The fundamental change involved in this process of microvascular dysfunction is a switch in signaling from nitrous oxide-mediated silencing of cellular processes toward activation by redox signaling [2]. Studies have shown that risk factors such as hypercholesterolemia, hypertension, and diabetes, as well as other inflammatory conditions, such as peridontitis, lead to endothelial dysfunction on the basis of a chronic dysregulation of nitrous oxide and reactive oxygen species production [3-4]. Prolonged and/or repeated exposure to cardiovascular risk factors can ultimately exhaust the protective effect of endogenous anti-inflammatory systems within endothelial cells [5]. Endothelial activation occurs in the face of acute stressors (inflammation from surgical trauma or infection) and represents a switch from a quiescent phenotype, to an adaptive host defense with vasoconstriction and thus a prothrombotic, proinflammatory state. We argue that inadequate basal (pre-operative) endothelial function, or excessive adaptive host response results in deterioration of endothelial reserve below a ‘physiologic threshold’ needed to sustain perfusion (Figure). A maladaptive endothelium response system, characterized by endothelial cell dysfunction ensues, which clinically leads to microcirculatory hypoperfusion and end-organ dysfunction, with secondary consequences such as myocardial infarction.

Improved pre-operative and peri-operative surveillance techniques of microvascular endothelial cell dysfunction (e.g. non-invasive measurements of vascular reactivity: brachial artery reactivity testing (BART) [6] or digital thermal monitoring [7] hold promise of improving prediction of those patients at risk of peri-operative cardiovascular events, thereby providing timely opportunity for (pre-operative or peri-operative) modulation of microvascular endothelial cell function. Current clinical strategies applicable to the peri-operative setting that improve microvascular health include pre-operative exercise therapy and pharmacologic interventions (e.g. statins, newer ß-blockers,) and future promise of regenerative cell therapy with bone-marrow derived endothelial progenitor cells. Many of these strategies are still in their infancy and large prospective trials that investigate the impact of these therapeutic options on postoperative outcome are eagerly awaited.