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 T 1 fast field echo imaging at 3.0T with preinjection T 1 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. . Our microvasculature protects organs by tightly regulating tissue perfusion in the presence of changing systemic blood pressure. 1 Furthermore, when microvascular function is normal, perfusion can be altered appropriately in response to changing metabolic and physical demands.However, in a number of ischemic conditions (eg, myocardial ischemia, ischemic stroke, and limb ischemia 2,3 and metabolic syndromes (eg, hypertension, diabetes, and obesity, 4 the microvasculature is dysfunctional. In hypertension, for example, the mechanisms regulating vasomotor tone are abnormal, resulting in enhanced vasoconstriction or reduced vasodilatory response. 4 In ischemia, the ischemic insult and subsequent View this article online at wileyonlinelibrary.com.

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