Altered central and peripheral haemodynamics during rhythmic handgrip exercise in young adults with SARS-CoV-2.

NEW FINDINGS: What is the central question of this study? Are central and peripheral haemodynamics during handgrip exercise different in young adults 3-4 weeks following infection with of SARS-CoV-2 compared with young healthy adults. What is the main finding and its importance? Exercising heart rate was higher while brachial artery blood flow and vascular conductance were lower in the SARS-CoV-2 compared with the control group. These findings provide evidence for peripheral impairments to exercise among adults with SARS-CoV-2, which may contribute to exercise limitations. ABSTRACT: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a profound impact on vascular function. While exercise intolerance may accompany a variety of symptoms associated with SARS-CoV-2 infection, the impact of SARS-CoV-2 on exercising blood flow (BF) remains unclear. Central (photoplethysmography) and peripheral (Doppler ultrasound) haemodynamics were determined at rest and during rhythmic handgrip (HG) exercise at 30% and 45% of maximal voluntary contraction (MVC) in young adults with mild symptoms 25 days after testing positive for SARS-CoV-2 (SARS-CoV-2: n = 8M/5F; age: 21 ± 2 years; height: 176 ± 11 cm; mass: 71 ± 11 kg) and were cross-sectionally compared with control subjects (Control: n = 8M/5F; age: 27 ± 6 years; height: 178 ± 8 cm; mass: 80 ± 25 kg). Systolic blood pressure, end systolic arterial pressure and rate pressure product were higher in the SARS-CoV-2 group during exercise at 45% MVC compared with controls. Brachial artery BF was lower in the SARS-CoV-2 group at both 30% MVC (Control: 384.8 ± 93.3 ml min-1 ; SARS-CoV-2: 307.8 ± 105.0 ml min-1 ; P = 0.041) and 45% MVC (Control: 507.4 ± 109.9 ml min-1 ; SARS-CoV-2: 386.3 ± 132.5 ml min-1 ; P = 0.002). Brachial artery vascular conductance was lower at both 30% MVC (Control: 3.93 ± 1.07 ml min-1  mmHg-1 ; SARS-CoV-2: 3.11 ± 0.98 ml min-1  mmHg-1 ; P = 0.022) and 45% MVC (Control: 4.74 ± 1.02 ml min-1  mmHg-1 ; SARS-CoV-2: 3.46 ± 1.10 ml min-1  mmHg-1 ; P < 0.001) in the SARS-CoV-2 group compared to control group. The shear-induced dilatation of the brachial artery increased similarly across exercise intensities in the two groups, suggesting the decrease in exercising BF may be due to microvascular impairments. Brachial artery BF is attenuated during HG exercise in young adults recently diagnosed with mild SARS-CoV-2, which may contribute to diminished exercise capacity among those recovering from SARS-CoV-2 like that seen in severe cases.

Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units.

BACKGROUND: COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients. METHODS: This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio). RESULTS: Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies. CONCLUSION: Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477 . Retrospectively registered 30 December 2020.

The short external rotators dissection during the posterior approach in total hip arthroplasty did not change the blood flow.

OBJECTIVES: The posterior approach in total hip arthroplasty (THA) often requires dissection of the short external rotators (SERs), which could increase the postoperative dislocation rate. The reattachment of the dissected SERs has been reported to reduce the dislocation rate, while such repair generally causes progression of muscle atrophy. 1 of the suggested causes of atrophy is reduced blood flow to the repaired SERs. The present study aimed to measure the blood flow of the SERs before dissection (pre-tenotomy) and after reattachment (post-reattachment) during the posterior approach in THA. METHODS: This prospective study included 26 patients who underwent THA via the posterior approach. A laser-Doppler rheometer was used to measure the blood flow in the following SERs at the time of pre-tenotomy and post-reattachment: the piriformis muscle (PM), superior gemellus (SG), inferior gemellus (IG), obturator internus (OI), and subcutaneous tissue as a control. RESULTS: The average pre-tenotomy and post-reattachment blood flows (mL/minutes/100 g) were: 1.90 ± 0.28 and 1.92 ± 0.40 in the PM, 1.94 ± 0.20 and 1.99 ± 0.39 in the SG, 1.91 ± 0.21 and 1.94 ± 0.30 in the IG, 1.93 ± 0.22 and 1.98 ± 0.36 in the OI, and 1.94 ± 0.24 and 1.87 ± 0.38 in the subcutaneous tissue. The pre-tenotomy and post-reattachment blood flows did not show significant difference in any muscle. CONCLUSIONS: Laser-Doppler blood flow measurements showed that the blood flow is preserved, even when the SERs are dissected and reattached in THA via the posterior approach.

Direct reprogramming induces vascular regeneration post muscle ischemic injury.

Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFß, DN-Wnt8a, and acid ceramidase (AC)-to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival, and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.

First, do no harm: bilateral radial artery occlusion in a COVID-19 patient.

OBJECTIVE: Objective of this case report is to draw attention to a less known thrombotic complication associated with COVID-19, i.e., thrombosis of both radial arteries, with possible (long-term) consequences. THE CASE: In our COVID-19 ICU a 49-year-old male patient was admitted, with past medical history of obesity, smoking and diabetes, but no reported atherosclerotic complications. The patient had been admitted with severe hypoxemia and multiple pulmonary emboli were CT-confirmed. ICU-treatment included mechanical ventilation and therapeutic anticoagulation. Preparing the insertion of a new radial artery catheter for invasive blood pressure measurement and blood sampling, we detected that both radial arteries were non-pulsating and occluded: (a) Sonography showed the typical anatomical localization of both radial and ulnar arteries. However, Doppler-derived flow-signals could only be obtained from the ulnar arteries. (b) To test collateral arterial supply of the hand, a pulse-oximeter was placed on the index finger. Thereafter, the ulnar artery at the wrist was compressed. This compression caused an immediate loss of the finger's pulse-oximetry perfusion signal. The effect was reversible upon release of the ulnar artery. (c) To test for collateral perfusion undetectable by pulse-oximetry, we measured regional oxygen saturation (rSO2) of the thenar muscle by near-infrared spectroscopy (NIRS). Confirming our findings above, ulnar arterial compression demonstrated that thenar rSO2 was dependent on ulnar artery flow. The described development of bilateral radial artery occlusion in a relatively young and therapeutically anticoagulated patient with no history of atherosclerosis was unexpected. CONCLUSIONS: Since COVID-19 patients are at increased risk for arterial occlusion, it appears advisable to meticulously check for adequacy of collateral (hand-) perfusion, avoiding the harm of hand ischemia if interventions (e.g., catheterizations) at the radial or ulnar artery are intended.