Differential responses in human subcutaneous and skeletal muscle vascular beds to critical limb ischaemia.

Abstract

To investigate the effects of chronic ischaemia on the subcutaneous and the skeletal muscle resistance vasculature. To understand the redistribution of available blood in the ischaemic limb. Human subcutaneous and skeletal muscle resistance arteries were obtained from limbs amputated for critical limb ischaemia and studied under isobaric conditions using pressure myography. Morphological measurements of wall and lumen were analysed using light microscopy and image analysis. Vasoconstrictor responses to potassium and adrenoceptor agonists were used to measure functional status. Noradrenaline re-uptake mechanisms and alpha(1)-selectivity were investigated. Both human skeletal muscle and subcutaneous resistance arteries undergo a severe atrophy of the arterial wall in ischaemic conditions. However, whereas subcutaneous resistance arteries become less able to vasoconstrict to adrenoceptor stimulation, the response of skeletal muscle resistance arteries becomes exaggerated and significantly augmented. This is true in response to both the endogenous vasoconstrictor noradrenaline and the alpha(1)-selective adrenoceptor agonist phenylephrine. Hypersensitivity to circulating catecholamines in the skeletal muscle vascular resistance bed may contribute to the progression of ischaemic disease by differentially diverting available blood to the subcutaneous tissue to the detriment of skeletal muscle perfusion.