Diminished Circulating Monocytes after Peripheral Bypass Surgery for Critical Limb Ischemia
Mononuclear cells (MNCs) have been shown to increase neovascularization and ulcer
healing after direct injection into the ischemic limbs of patients with unreconstructable
peripheral vascular disease (PVD). Circulating MNCs are composed of lymphocytes (85%),
monocytes (15%) and endothelial progenitor cells (EPCs; 0.03%). It is thought that MNCs
may be effective in ameliorating ischemia since EPCs are a component of the monocyte
fraction, and EPCs have been shown to participate in vascular healing.
We hypothesized that ischemic areas secrete paracrine signals such as cytokines and growth
factors that recruit bone marrow-derived monocytes into the circulation in order to augment
vascular healing. For this reason we predicted that patients with critical limb ischemia (CLI)
undergoing bypass surgery would have elevated preoperative monocyte counts compared to
control subjects without CLI. In addition, since a successful surgical bypass procedure
relieves ischemia, we expected a postoperative decrease in circulating monocyte numbers.
We reviewed the records of all patients at the VA Connecticut Healthcare System undergoing
lower extremity peripheral bypass surgery between 2002 and 2007. Patients were excluded if
they did not have both preoperative and postoperative complete blood counts with
differentials within a given time frame. Subjects were divided into two groups: those with
preoperative critical limb ischemia (CLI) and those without. ANOVA and Chi-Square were used to compare counts, and multivariable logistic regression was used to determine risk
Patients with CLI (n=24) had elevated preoperative monocyte counts compared to control
patients (n=8) undergoing bypass for claudication or asymptomatic popliteal aneurysm
(0.753 ± 0.04 vs. 0.516 ± 0.05; p=0.0046), but the preoperative lymphocyte count was not
significantly different (1.979 ± 0.14 vs. 1.912 ± 0.22; p=0.814). After revascularization,
ischemic patients had decreased monocyte counts compared to control patients (-20% vs.
+55%; p=.0003) although lymphocyte ratios were unchanged in both groups (-10% vs. +1%;
p=0.404). Diabetic patients also had reduced postoperative monocyte counts (-32% vs.
+13%; p=0.035), however multivariable analysis demonstrated that the only factor that
independently predicted reduced postoperative monocyte count was preoperative critical
limb ischemia (p=0.038).
Diminished numbers of circulating monocytes correlate with relief of ischemia after surgical
revascularization. Circulating monocytes may be a clinically useful surrogate marker of
circulating stem cells for patients undergoing vascular surgery.
School Location:USA - Connecticut
Source Type:Master's Thesis
Keywords:surgery va connecticut healthcare system military veterans blood cells ischemia peripheral vascular disease
Date of Publication:05/06/2009