Hemodynamic Assay of Hind Limb in Multiple Animal Models

Abstract

Introduction Measuring hemodynamic characteristics of injured limbs is paramount to early identification of potentially damaging ischemic conditions, but can often prove difficult attributable to a multitude of factors. Here, we present an in vivo optical imaging technique to characterize pulsatile blood flow quality through the distal extremity in multiple animal models that replicate the signs of distal extremity ischemia. The purpose of this study is to examine the feasibility of the optical imaging technique and relevance to hemodynamic complications such as acute compartment syndrome (ACS) and nonobvious hemorrhage. Materials and Methods In one pig and six mice, three different methods were used to create ischemic conditions in the lower extremity, producing symptoms similar to what is observed in ACS. In each condition, perfusion to the distal extremity was measured with the hemodynamic detection device (HDD; Odin Technologies), an optical assessment tool for perfusion and blood flow quality. Results We observed a profound decrease in extremity perfusion immediately after onset of ischemia in all three models. In the porcine model, the HDD’s measurements demonstrated similar characteristic flow between the various measurement locations. After the tourniquet was applied, the HDD revealed a 95% decrease in normalized perfusion value (npv) while the intracompartmental pressure rose from 5 to 52 mmHg (a 47mmHg increase). After the tourniquet was removed during reperfusion, the normalized blood flow returned to baseline and the intracompartmental pressure dropped from 20 to 6 mmHg in less than 5 minutes. For each mouse, the HDD test leg demonstrated a measurement of 0.97 npv before femoral ligation and 0.05 npv after femoral ligation, an 89% decrease (P < .01) in flow. Pulsed-wave Doppler ultrasound (PWDU) measurements on the test leg had pre-ligation measurement of 0.84 npv and a post-ligation measurement of 0.001 npv, a 99% decrease. These PWDU measurements revealed almost complete stoppage of blood flow during ischemia, followed by a substantial increase after the femoral artery ligation was removed. Conclusions Here, we show that a novel, optics-based sensing system can be used to diagnose and assess ACS in animal models. This technology is comparable to other standards used to monitor ACS and nonobvious hemorrhage and may also be a plausible alternative to prolonged invasive monitoring of patients with sustained extremity trauma.

Animal models in compartment syndrome: a review of existing literature

“…Despite differences in the anatomy and/or physiology of different animals used in the study, multiple authors in this review have demonstrated similar findings using the same methodology in both rat and large animal models. [ 5 , 29 , 41 ] We could not find definitive evidence that anatomic differences associated with small animal models adversely affected compartment syndrome research outcomes. While large animals may provide better anatomic similarity relative to humans, they are associated with significant additional research cost and it is our opinion that authors must weigh the benefits of anatomic similarity with their over-arching research goals when selecting a species.…”

“…Forty-one studies were included in the final review (Tables 1-4). [1–41] A total of 865 animals were included with an average of 22.2 animals per study. Dogs (31.7%) were the most used model species, followed by pigs (26.8%) and rats (24.4%).…”

“…Despite differences in the anatomy and/or physiology of different animals used in the study, multiple authors in this review have demonstrated similar findings using the same methodology in both rat and large animal models. [5,29,41] We could not find definitive evidence that anatomic differences associated with small animal models adversely affected compartment syndrome Heppenstall et al, 1986 [8] Dog 10 Thigh tourniquet vs plasma infusion 3 hours…”

“…Other studies used methods of directly measuring tissue oxygenation and/or glucose, again with promising results. [ 34 , 38 , 39 , 41 ] However, these modalities have not been widely adopted clinically. Overall, no animal model for diagnosis identified in the review outside of intracompartmental pressure monitoring has been successfully translated to clinical use.…”

“…Unfortunately, since that time, a large multicenter study demonstrated that near-infrared spectroscopy was difficult to reliably utilize clinically. Other studies used methods of directly measuring tissue oxygenation and/or glucose, again with promising results [34,38,39,41] . However, these modalities have not been widely adopted clinically.…”