Biomarkers of Muscle Metabolism in Peripheral Artery Disease: A Dynamic NIRS-Assisted Study to Detect Adaptations Following Revascularization and Exercise Training

Abstract

We assessed whether muscle metabolism biomarkers (MMb) identified by near-infrared spectroscopy (NIRS) are valid for determining adaptations following revascularization or exercise training in peripheral artery disease (PAD). Eighteen patients (males n = 13; 69 ± 7 years) were randomized to receive revascularization (Rev = 6) or pain-free home-based exercise (Ex = 12). MMb were safely collected via a NIRS-assisted treadmill test as area-under-curve for the spectra of oxygenated (-oxy), deoxygenated (-deoxy), differential (-diff) and total (-tot) hemoglobin traces. MMb, ankle–brachial index (ABI), pain-free (PFWD) and 6-min (6MWD) walking distances were assessed at baseline and after four months. MMb were correlated at baseline with ABI (MMb-oxy r = 0.46) and 6MWD (MMb-tot r = 0.51). After treatments, MMb-oxy showed an expected increase, which was more relevant for Rev group than the Ex (56% vs. 20%), with trends towards normalization for the other MMb. These changes were significantly correlated with variations in ABI (MMb-oxy r = 0.71; p = 0.002) and 6MWD (MMb-tot r = 0.58; p = 0.003). The MMb-diff in Rev group and MMb-deoxy in Ex group at baseline predicted clinical outcomes being correlated with PFWD improvements after 4-month (r = −0.94; p = 0.005 and r = −0.57; p = 0.05, respectively). A noninvasive NIRS-based test, feasible in a clinical setting, identified muscle metabolism biomarkers in PAD. The novel MMb were associated with validated outcome measures, selectively modified after different interventions and able to predict long-term functional improvements after surgery or exercise training.

Multispectral optoacoustic tomography of peripheral arterial disease based on muscle hemoglobin gradients—a pilot clinical study

“…Percentage mean changes of Hb (deoxygenated hemoglobin), HbO 2 (oxygenated hemoglobin), THb (total hemoglobin) and SO 2 (oxygen saturation) over time with reference to the baseline during the cuff-induced arterial occlusion measurements for the entire group of volunteers (n 1 =4) Although not fully comparable, the dimension of improvement is in line with other studies using for, e.g., thermal load tests with transcutaneous oxygen tension (tcPO 2 ) measurement observing an improvement of 1.3fold to up to 11-fold(28,29) or of NIRS measurements showing an HbO 2 improvement of about 1.8-fold(30). Thus, MSOT-extracted parameters may well be used for the objective quantification of different therapeutic effects.Nevertheless, even if MSOT offers rich functional information via hemoglobin-based molecular contrast, this information should be evaluated with conventional imaging techniques.…”

Don’t stop walking: the in-home rehabilitation program for peripheral artery disease patients during the COVID-19 pandemic

“…The precise prescription allowed to counteract the progressive decline of mobility [ 24 ] and to maintain functional stability in the whole population, with functional improvement in PAD patients who started rehabilitation immediately before the lockdown and with maintenance of the mobility level among the Veterans. If in the program, early significant aerobic adaptations occur in the most ischemic muscles by walking even in confined spaces [ 28 , 31 ], progressive further adaptations necessary to complete the functional recovery are favored by patient’s spontaneous activity. In Veterans, in absence of this stimulus during the lockdown, the program favored the persistence of the benefits previously achieved.…”

“…One subgroup included patients who started the program within the three months prior to the lockdown (Rookies), whereas the other subgroup included all the other patients who were enrolled more than three months (Veterans) before the lockdown. The cutoff was arbitrarily chosen considering an ideal duration of the program of 6–9 months [ 5 ] and a timeframe possibly associated with physiological adaptations to the program [ 26 , 28 ]. Pre versus Post comparisons of all outcomes were performed by paired samples t tests or Wilcoxon rank tests according to the data distribution.…”

Biomarker Utility for Peripheral Artery Disease Diagnosis in Real Clinical Practice: A Prospective Study

“…As a result, some biomarkers have already found their application in current clinical practice, but several still require more detailed studies to include them in the diagnosing algorithm of PAD [16,[33][34][35]. Therefore, the goal of this research was to investigate the circulating levels of inflammation-related biomarkers and cystatin C and to explore their utility for the diagnosis of PAD.…”