Intermittent claudication incites systemic neutrophil activation and increased vascular permeability

Area of Science:

• Vascular Biology
• Ischemia-Reperfusion Injury
• Systemic Inflammation

Background:

• Reperfusion following severe ischemia triggers neutrophil activation and vascular injury.
• Intermittent claudication (IC) may induce similar systemic changes, potentially explaining associated cardiovascular mortality.
• Revascularization might reverse these IC-induced changes.

Purpose of the Study:

• To investigate the hypothesis that intermittent claudication induces systemic inflammatory responses and vascular injury.
• To explore the potential link between IC, systemic inflammation, and cardiovascular risk.
• To examine the effects of unilateral hindlimb ischemia and stimulation on systemic parameters.

Main Methods:

• Utilized an in vivo rat model with common iliac artery ligation and repeated hindlimb stimulation.
• Employed intravital fluorescence microscopy to observe postcapillary venules in the tibialis anterior muscle.
• Assessed leucocyte-endothelial adhesion, vascular permeability to albumin, and urinary albumin excretion.

Main Results:

• Unilateral subtotal ischemia and muscle stimulation led to a bilateral increase in leucocyte-endothelial adhesion.
• Increased vascular permeability to albumin was observed bilaterally in postcapillary venules.
• Associated with these findings, increased urinary albumin excretion indicated systemic effects.

Conclusions:

• The study provides evidence supporting the association between intermittent claudication and systemic manifestations.
• These systemic changes, including inflammation and vascular injury, may contribute to the high cardiovascular mortality in IC patients.
• The findings suggest that IC is not merely a localized condition but has broader systemic implications.