This study aimed to determine the importance of repeated increases in blood flow to conduit artery adaptation, using an exercise-independent repeated episodic stimulus. Recent studies suggest that exercise training improves vasodilator function of conduit arteries via shear stress-mediated mechanisms. However, exercise is a complex stimulus that may induce shear-independent adaptations. Nine healthy men immersed their forearms in water at 42°C for three 30-min sessions/wk across 8 wk. During each session, a pneumatic pressure cuff was inflated around one forearm to unilaterally modulate heating-induced increases in shear. Forearm heating was associated with an increase in brachial artery blood flow (P Ͻ 0.001) and shear rate (P Ͻ 0.001) in the uncuffed forearm; this response was attenuated in the cuffed limb (P Ͻ 0.005). Repeated episodic exposure to bilateral heating induced an increase in endothelium-dependent vasodilation in response to 5-min ischemic (P Ͻ 0.05) and ischemic handgrip exercise (P Ͻ 0.005) stimuli in the uncuffed forearm, whereas the 8-wk heating intervention did not influence dilation to either stimulus in the cuffed limb. Endothelium-independent glyceryl trinitrate responses were not altered in either limb. Repeated heating increases blood flow to levels that enhance endothelium-mediated vasodilator function in humans. These findings reinforce the importance of the direct impacts of shear stress on the vascular endothelium in humans.

The endothelium, a single layer of cells lining the entire circulatory system, plays a key role in maintaining vascular health. Endothelial dysfunction independently predicts cardiovascular events and improvement in endothelial function is associated with decreased vascular risk. Previous studies have suggested that exercise training improves endothelial function in macrovessels, a benefit mediated via repeated episodic increases in shear stress. However, less is known of the effects of shear stress modulation in microvessels. In the present study we examined the hypothesis that repeated skin heating improves cutaneous microvascular vasodilator function via a shear stress-dependent mechanism. We recruited 10 recreationally active males who underwent bilateral forearm immersion in warm water (42 • C), 3 times per week for 30 min. During these immersion sessions, shear stress was manipulated in one arm by inflating a pneumatic cuff to 100 mmHg, whilst the other arm remained uncuffed. Vasodilatation to local heating, a NO-dependent response assessed using laser Doppler, improved across the 8 week intervention period in the uncuffed arm (cutaneous vascular conductance week 0 vs. week 4 at 41• C: 1.37 ± 0.45 vs. 2.0 ± 0.91 units, P = 0.04; 42 • C: 2.06 ± 0.45 vs. 2.68 ± 0.83 units; P = 0.04), whereas no significant changes were evident in the cuffed arm. We conclude that increased blood flow, and the likely attendant increase in shear stress, is a key physiological stimulus for enhancing microvascular vasodilator function in humans.

Several neurological manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported, including cerebral venous sinus thrombosis (CVST). In this report, we discuss two cases of cerebral venous thrombosis in young patients with a recent SARS-CoV-2 infection and otherwise unrevealing workup. Case 1 was a 35-year-old man who was found unresponsive with urinary incontinence and vomitus on the floor. Computed tomography (CT) angiogram of the head revealed evidence of extensive venous thrombosis. Extensive workup for thrombotic disease was unrevealing and SARS-CoV-2 was detected via polymerase chain reaction. Anticoagulation was immediately initiated, and the patient made a good clinical recovery. Case 2 was a 31-year-old man who presented with severe decreased level of consciousness and was found to have extensive cerebral sinus thrombosis. Past medical history was significant for a recent SARS-CoV-2 infection diagnosed 12 days prior. The patient was treated with intravenous heparin and eventually oral anticoagulation with good clinical outcome. CVST is a potential cerebrovascular complication of SARS-CoV-2. We advise clinicians to consider this diagnosis in patients with a recent SARS-CoV-2 infection in the appropriate clinical setting.