Scott M. Moore, Matthew R. Waters, James E. Faber
Surgery, UNC Chapel Hill, Chapel Hill, NC.
OBJECTIVES: Collaterals are an important determinant of the capacity for compensation in occlusive disease. In mice, advanced age (>16 months) is accompanied by anatomic loss, or rarefaction, of native (pre-existing) collaterals, resulting in worse ischemic injury. Targeted deletion of eNOS greatly accelerates collateral loss, implicating eNOS deficiency in age-associated collateral rarefaction. To determine whether other CV risk factors in addition to aging that are known to associate with eNOS deficiency also cause collateral rarefaction, we examined 7-8-month-old mice with hypertension (renin transgene; MAP 139±3 mm Hg) and other genetically imposed CV risk factors.
METHODS: Functional assessment of collateral capacity in skeletal muscle was obtained by measurement of hindlimb perfusion, limb use and ischemic appearance scores after femoral artery ligation, and in brain by determining infarct volume after middle cerebral artery occlusion. Collateral extent (number and diameter) was determined by filling the arterial circulation with a silicone-based casting agent (Microfil™).
RESULTS: Hypertensive mice had greater reduction in hindlimb flow immediately after ligation (depends on native collateral extent) and impaired recovery of perfusion during 21 days thereafter (depends on native extent plus collateral remodeling), worse ischemia and use impairment, increased cerebral infarct volume, reduced native collateral extent and impaired collateral remodeling. Mice with metabolic syndrome showed similar collateral rarefaction and functional impairments. In contrast, hyperlipidemia, type-1 diabetes and obesity were not accompanied by collateral rarefaction.
CONCLUSIONS: Chronic hypertension leads to rarefaction of the native collateral circulation and worse ischemia and tissue necrosis following acute arterial obstruction. Ongoing experiments are examining the molecular mechanisms underlying hypertension-induced collateral rarefaction.
AUTHOR DISCLOSURES: J. E. Faber: Nothing to disclose; S. M. Moore: Nothing to disclose; M. R. Waters: Nothing to disclose.
Posted April 2013