Assessment of microvascular dysfunction in acute limb ischemia-reperfusion injury

Abstract

Background: Ischemia-reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast-enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function.

Purpose: To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury.

Study type: Prospective, longitudinal.

Animal model: Twenty-three healthy male adult Sprague-Dawley rats.

Field strength/sequence: Dynamic T₁ fast field echo imaging at 3.0T with preinjection T₁ mapping.

Assessment: Injury in the left hindlimb was induced using a 3-hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters K^trans and v_e were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas-mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored.

Statistical tests: Two-way analysis of variance with Tukey-Kramer post-hoc analysis was used to determine significant changes in vasomodulatory response, K^trans , and v_e .

Results: This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05). However, DCE-MRI measured K^trans and v_e were significantly (P < 0.05) different from baseline only during acute inflammation (Day 3), with severe inflammation noted on histology.

Data conclusion: While conventional DCE-MRI shows normalization after the acute phase, our new approach reveals sustained functional impairment in muscle microvasculature following I/R injury, with compromised response in vasomotor tone present for at least 21 days.

Level of evidence: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1174-1185.

Keywords: hypercapnia; ischemia-reperfusion injury; microvascular dysfunction; skeletal muscle; vascular reactivity; vasomodulation.