Altered Vascular Endothelium-Dependent Responsiveness in Frail Elderly Patients Recovering from COVID-19 Pneumonia: Preliminary Evidence

We evaluated vascular dysfunction with the single passive leg movement test (sPLM) in 22 frail elderly patients at 84 + 31 days after hospitalization for COVID-19 pneumonia, compared to 22 age-, sex- and comorbidity-matched controls (CTRL). At rest, all COVID-19 patients were in stable clinical condition without severe comorbidities. Patients (aged 72 ± 6 years, 73% male) had moderate disability (Barthel index score 77 ± 26), hypoxemia and normocapnia at arterial blood gas analysis and mild pulmonary restriction at spirometry. Values of circulating markers of inflammation (C-reactive protein: CRP; erythrocyte sedimentation rate: ESR) and coagulation (D-dimer) were: 27.13 ± 37.52 mg/dL, 64.24 ± 32.37 mm/1 h and 1043 ± 729 ng/mL, respectively. At rest, femoral artery diameter was similar in COVID-19 and CTRL (p = 0.16). On the contrary, COVID-19 infection deeply impacted blood velocity (p = 0.001) and femoral blood flow (p < 0.0001). After sPLM, peak femoral blood flow was dramatically reduced in COVID-19 compared to CTRL (p = 0.001), as was blood flow ∆peak (p = 0.05) and the area under the curve (p < 0.0001). This altered vascular responsiveness could be one of the unknown components of long COVID-19 syndrome leading to fatigue, changes in muscle metabolism and fibers’ composition, exercise intolerance and increased cardiovascular risk. Impact of specific treatments, such as exercise training, dietary supplements or drugs, should be evaluated.

Systemic and regional hemodynamic response to activation of the exercise pressor reflex in patients with peripheral artery disease

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2–12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation ([Formula: see text]) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, [Formula: see text] of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD. NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Reptile-like physiology in Early Jurassic stem-mammals

There is uncertainty regarding the timing and fossil species in which mammalian endothermy arose, with few studies of stem-mammals on key aspects of endothermy such as basal or maximum metabolic rates, or placing them in the context of living vertebrate metabolic ranges. Synchrotron X-ray imaging of incremental tooth cementum shows two Early Jurassic stem-mammals, Morganucodon and Kuehneotherium, had lifespans (a basal metabolic rate proxy) considerably longer than comparably sized living mammals, but similar to reptiles. Morganucodon also had femoral blood flow rates (a maximum metabolic rate proxy) intermediate between living mammals and reptiles. This shows maximum metabolic rates increased evolutionarily before basal rates, and that contrary to previous suggestions of a Triassic origin, Early Jurassic stem-mammals lacked the endothermic metabolism of living mammals.One Sentence SummarySurprisingly long lifespans and low femoral blood flow suggest reptile-like physiology in key Early Jurassic stem-mammals.

Effects of bone cement filling in rabbit proximal femoral medullary cavity on distal femoral blood flow and metabolism

Objective A rabbit model was used to evaluate the effects of bone-cemented hip arthroplasty on distal femoral blood flow and metabolism relative to that of the non-cemented contralateral leg. Methods The marrow cavity of the right hind femur was filled with bone cement. At each of the following time points, rabbits were randomly selected to receive an injection of one dose of 99mTc-methylene diphosphonate and then immediately scanned using a gamma camera: immediately postoperatively and at 4 and 8 weeks postoperatively. A BL-410 model biofunction experimental system was used to analyze the acquired images and determine the radioactive counts of each hind leg. Results The X-ray and photographic images of the right femoral bones confirmed successful filling of the marrow cavity with bone cement. The radioactive counts were significantly lower in the experimental than control legs at each time point. The ratio of the radioactive count of the experimental to control leg increased considerably at each time point, but each ratio was <1. Conclusion Blocking the proximal femoral medullary cavity with bone cement was associated with significant lowering of the blood circulation of the femur and marrow, decreasing the distal femoral blood flow and bone metabolic rate.

Localized and systemic variations in central motor drive at different local skin and muscle temperatures

This study investigated the ability to sustain quadriceps central motor drive while subjected to localized heat and metaboreceptive feedback from the contralateral leg. Eight active males each completed two counter-balanced trials, in which muscle temperature (Tm) of a single-leg (TEMP-LEG) was altered to 29.4°C (COOL) or 37.6°C (WARM), while the contralateral leg (CL-LEG) remained thermoneutral: 35.3°C and 35.2°C Tm in COOL and WARM, respectively. To activate metaboreceptive feedback, participants first performed one 120-s isometric maximal voluntary contraction (MVC) of the knee extensors in the TEMP-LEG, immediately followed by postexercise muscle ischemia (PEMI) via femoral blood flow occlusion. To assess central motor drive of a remote muscle group immediately following PEMI, another 120-s MVC was subsequently performed in the CL-LEG. Voluntary muscle activation (VA) was assessed using the twitch interpolation method. Perceived mental effort and limb discomfort were also recorded. In a cooled muscle, a significant increase in mean force output and mean VA (force, P < 0.001; VA, P < 0.05), as well as a significant decrease in limb discomfort ( P < 0.05) occurred during the sustained MVC in the TEMP-LEG. However, no differences between Tm were observed in mean force output, mean VA, or limb discomfort during the sustained MVC in the CL-LEG (force, P = 0.33; VA, P > 0.68; and limb discomfort, P = 0.73). The present findings suggest that elevated local skin temperature and Tm can increase limb discomfort and decrease central motor drive, but this does not limit systemic motor activation of a thermoneutral muscle group.

Postexercise Hemodynamics in Patients With Type 2 Diabetes: Effect of Exercise Intensity and Duration

Background: For individuals with type 2 diabetes (T2D), the hemodynamic response to regular exercise is critical for regulating blood glucose, protecting vascular function, and reducing cardiovascular disease risk, but the hemodynamic responses to differing doses of acute exercise in T2D are unclear. We aimed to compare postexercise (PE) hemodynamics in patients with T2D in response to 4 doses of dynamic exercise. Methods: Eight subjects with well-controlled T2D (42–64 years old.; hemoglobin A1c: 6.6% ± 0.9%) participated in 4 study days, during which they exercised on a cycle ergometer at 4 different combinations of exercise duration and intensity: 30 min at 40% V˙O2peak (30@40), 30 min at 60% V˙O2peak (30@60), 60 min at 40% V˙O2peak (60@40), and 60 min at 60% V˙O2peak (60@60). Heart rate, arterial pressure, and femoral blood flow (Doppler ultrasound) were measured pre-exercise and every 15 min through 120 min PE. Femoral vascular conductance was calculated as flow/pressure. Results: Compared with pre-exercise baseline, femoral blood flow and femoral vascular conductance were higher through at least 105 min of recovery in all conditions (all P &lt; .05), except for the 30@40 trial. Compared with the pre-exercise measures, systolic blood pressure was lower through at least 75 min of recovery in all conditions (all P &lt; .05), except for the 30@40 trial. Conclusion: These results suggest that exercise must be at least moderate in intensity or prolonged in duration (&gt;30 min) to promote sustained PE elevations in skeletal muscle blood flow and reductions in systolic blood pressure in patients with T2D.

Central and peripheral responses to static and dynamic stretch of skeletal muscle: mechano- and metaboreflex implications

Passive static stretching (SS), circulatory cuff occlusion (CCO), and the combination of both (SS + CCO) have been used to investigate the mechano- and metaboreflex, respectively. However, the effects of dynamic stretching (DS) alone or in combination with CCO (DS + CCO) on the same reflexes have never been explored. The aim of the study was to compare central and peripheral hemodynamic responses to DS, SS, DS + CCO, and SS + CCO. In 10 participants, femoral blood flow (FBF), heart rate (HR), cardiac output (CO), and mean arterial pressure (MAP) were assessed during DS and SS of the quadriceps muscle with and without CCO. Blood lactate concentration [La−] in the lower limb undergoing CCO was also measured. FBF increased significantly in DS and SS by 365 ± 98 and 377 ± 102 ml/min, respectively. Compared with baseline, hyperemia was negligible during DS + CCO and SS + CCO (+11 ± 98 and +5 ± 87 ml/min, respectively). DS generated a significant, sustained increase in HR and CO (∼40s), while SS induced a blunted and delayed cardioacceleration (∼20 s). After CCO, [La−] in the lower limb increased by 135%. Changes in HR and CO during DS + CCO and SS + CCO were similar to DS and SS alone. MAP decreased significantly by ∼5% during DS and SS, did not change in DS + CCO, and increased by 4% in SS + CCO. The present data indicate a reduced mechanoreflex response to SS compared with DS (i.e., different HR and CO changes). SS evoked a hyperemia similar to DS. The similar central hemodynamics recorded during stretching and [La−] accumulation suggest a marginal interaction between mechano- and metaboreflex. NEW & NOTEWORTHY Different modalities of passive stretching administration (dynamic or static) in combination with circulatory cuff occlusion may reduce or amplify the mechano- and metaboreflex. We showed a reduced mechanoreflex response to static compared with dynamic stretching. The lack of increase in central hemodynamics during the combined mechano- and metaboreflex stimulation implicates marginal interactions between these two pathways.