Compartment Syndrome: Evaluation of Skeletal Muscle Ischemia and Physiologic Biomarkers in Controlled Conditions Within Ex Vivo Isolated Muscle Bundles

Abstract

Objectives: To identify potential physiologic markers of muscle ischemia to serve as diagnostic indicators of compartment syndrome. We hypothesize that muscle bundles in hypoxic conditions will elicit decreases in potential hydrogen (pH) and increases in lactate and potassium that correlates with decreased muscle twitch forces. Methods: We performed an ex vivo evaluation of individual skeletal muscle bundles obtained from a swine's diaphragm that were exposed to hypoxic conditions and compared with control groups. Over a 4-hour period, we evaluated the following parameters for each muscle bundle: muscle twitch forces and levels of potassium, lactate, and pH. Comparisons between the hypoxic and control groups were calculated at each time point using the 2-tailed Wilcoxon rank sum test for nonparametric data. Longitudinal associations between biomarkers and muscle twitch forces were tested using repeated measures analyses. Results: The hypoxic group elicited more significant decreases in normalized muscle twitch forces than the control group at all time points (0.15 g vs. 0.55 g at 4 hours, P < 0.001). Repeated measures analyses of the hypoxic group demonstrated a statistically significant association between potassium, lactate, and normalized peak force over the course of time. Potassium demonstrated the strongest association with a 1 mmol/L unit increase in potassium associated with a 2.9 g decrease in normalized peak force (95% confidence interval −3.3 to −2.4, P < 0.001). The pH of all muscle baths increased over the course of time at similar rates between the study groups. Conclusions: This study used an ex vivo ischemic skeletal muscle model as a representation for pathophysiologic pathways associated with compartment syndrome. In this experimental approach we were unable to evaluate the pH of the muscle bundles due to continuous applied gassing. Our findings support further evaluations of potassium and lactate levels as potential diagnostic markers.

The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers

“…Fig. 6 could mimic application of tourniquets ( MacDonald et al, 2021 ) and compartment syndrome ( Tatman et al, 2020 ). Depending on the severity of vascular constriction in compartment syndrome, ischemic and anoxic fibers’ rundown to firing threshold would vary enormously, consistent with reports, in compartment syndrome, of the unpredictable timing of lethal threshold events ( Johnstone and Ball, 2019 ).…”

Reaming the intramedullary canal during tibial nailing does not affect in vivo intramuscular pH of the anterior tibialis

“…This research was performed in healthy, uninjured subjects with a tourniquet and offers us little new knowledge about the state or fragility of muscle in the setting of traumatic injury. Tatman et al 45 established in an elegant ex vivo study that muscle fibers in a hypoxic environment lose contractile power and exhibit increases in markers of cellular injury and anerobic metabolism including increases in potassium and lactate concentrations. However, this research was unable to comment on changes in hydrogen ion concentration (pH) as a function of muscular ischemia because of limitations in the model (self-described: “nonphysiologic gaseous concentrations”).…”

“… 44 Other studies have directly measured markers of tissue physiology in ex vivo models of acute compartment syndrome, although technical factors have prevented the measurement of IpH. 45 To the best of our knowledge, there are no published data that describe the invasive measurement of IpH in vivo in the setting of fracture.…”

Donnan dominated ion homeostasis and the longevity of ischemic Na+-loaded dystrophic skeletal muscle

“…In compartment syndrome, similar issues arise, albeit far more rapidly than for DMD. Commonalities include profound ischemia, muscle damage and the imperative to avoid irreversible thresholds (Johnstone & Ball 2019; Tatman et al 2020). Dooley and Chiasson (2014; see too, Siegel 1992) argue, interestingly, that DMD patients’ sustained limb contractures can secondarily produce (fasciotomy-relieved) compartment syndrome.…”