Pulsatility Index as a Novel Parameter for Perfusion in Mouse Model of Hindlimb Ischemia

Abstract

Background/Aims: In clinical settings, the pulsatility index (PI) has become a widely used tool for monitoring obstetrics or other vascular diseases. It is based on the maximum Doppler shift waveform derived from ultrasonography. However, it remains unclear whether the PI levels are correctly predicted from the perfusion in mouse model of hindlimb ischemia. Methods: To explore the relationship between PI and perfusion, we generated a unilateral hindlimb ischemia model in 8-week-old C57BL/6 male mice by ligation of the right common iliac artery and femoral artery. These mice were monitored with laser Doppler perfusion imaging (LDPI) and an ultrasound system (Vevo2100). Vessel densities in ischemic skeletal muscles were measured with vWF staining, which functions as a marker for endothelial cells. In order to further verify PI evaluation in other conditions, we performed therapeutic experiments using hindlimb ischemic mouse with PBS or FGF2 treatment. Results: In the mouse model of hindlimb ischemia, the PI levels were continuously elevated and were accompanied by an increased ratio of perfusion to blood flow. 1 and 4 weeks after ischemia, the densities of vWF staining were correlated with PI values. Moreover, the PI index exactly reflected the perfusion in hindlimb ischemic mice after FGF2 treatment, while it indicated the condition of angiogenesis after therapeutic treatment based on the association between PI values and the number of vWF-positive stained cells in muscles. Conclusion: This study confirms the utility of a noninvasive and reproducible ultrasound index for a rapid evaluation of perfusion and blood recovery after hindlimb ischemia in vivo. PI, as one stable and comparable parameter, is correlated with angiogenesis in hindlimb ischemic mouse. Moreover, PI can exactly reflect perfusion and angiogenesis in therapeutic hindlimb ischemic mouse models. This study suggested that PI can serve as a novel index for relatively reproducible and repeatable blood flow recovery in the evaluation of emerging ischemic therapies and disease development in mouse models of hindlimb ischemia.