Adrenergic control of skeletal muscle blood flow during chronic hypoxia in healthy males.

Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during 1) incremental intra-arterial infusion of phenylephrine to assess α1-adrenergic receptor responsiveness and 2) combined intra-arterial infusion of ß-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-ß-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34 ± 15%, vs. HA; +3 ± 18%; P < 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45 ± 18% vs. HA: -28 ± 11%; P = 0.009) and high (ΔFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%; P = 0.041) doses. Blockade of ß-adrenergic receptors alone had no effect on resting FVC (P = 0.500) and combined α-ß-blockade induced a similar vasodilatory response at SL and HA (P = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA (P = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-ß-blockade at SL (ΔFVC: Control: -27 ± 128 vs. α-ß-blockade: +19 ± 23%; P = 0.0004), but unaffected at HA (ΔFVC: Control: -20 ± 22 vs. α-ß-blockade: -23 ± 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α1-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.

Control of blood pressure in the cold: differentiation of skin and skeletal muscle vascular resistance.

NEW FINDINGS: What is the central question of this study? Why does blood pressure increases during cold air exposure? Specifically, what is the contribution of skin and skeletal muscle vascular resistance during whole body versus isolated face cooling? What is the main finding and its importance? Whole-body cooling caused an increase in blood pressure through an increase in skeletal muscle and cutaneous vascular resistance. However, isolated mild face cooling caused an increase in blood pressure predominately via an increase in cutaneous vasoconstriction. ABSTRACT: The primary aim of this investigation was to determine the individual contribution of the cutaneous and skeletal muscle circulations to the cold-induced pressor response. To address this, we examined local vascular resistances in the cutaneous and skeletal muscle of the arm and leg. Thirty-four healthy individuals underwent three different protocols, whereby cold air to clamp skin temperature (27°C) was passed over (1) the whole-body, (2) the whole-body, but with the forearm pre-cooled to clamp cutaneous vascular resistance, and (3) the face. Cold exposure applied to the whole body or isolated to the face increased mean arterial pressure (all, P < 0.001) and total peripheral resistance (all, P < 0.047) compared to thermal neutral baseline. Whole-body cooling increased femoral (P < 0.005) and brachial artery resistance (P < 0.003) compared to thermoneutral baseline. Moreover, when the forearm was pre-cooled to remove the contribution of cutaneous resistance (P = 0.991), there was a further increase in lower arm vasoconstriction (P = 0.036) when whole-body cooling was superimposed. Face cooling also caused a reflex increase in lower arm cutaneous (P = 0.009) and brachial resistance (P = 0.050), yet there was no change in femoral resistance (P = 0.815) despite a reflex increase in leg cutaneous resistance (P = 0.010). Cold stress causes an increase in blood pressure through a change in total peripheral resistance that is largely due to cutaneous vasoconstriction with face cooling, but there is additional vasoconstriction in the skeletal muscle vasculature with whole-body cooling.

The impact of leg position on muscle blood flow and oxygenation during low-intensity rhythmic plantarflexion exercise.

PURPOSE: Resistance training (RT) is an effective countermeasure to combat physical deconditioning whereby localized hypoxia within the limb increases metabolic stress eliciting muscle adaptation. The current study sought to examine the influence of gravity on muscle oxygenation (SmO2) alongside vascular hemodynamic responses. METHODS: In twelve young healthy adults, an ischemic occlusion test and seven minutes of low-intensity rhythmic plantarflexion exercise were used alongside superficial femoral blood flow and calf near-infrared spectroscopy to assess the microvascular vasodilator response, conduit artery flow-mediated dilation, exercise-induced hyperemia, and SmO2 with the leg positioned above or below the heart in a randomized order. RESULTS: The microvascular vasodilator response, assessed by peak blood flow (798 ± 231 mL/min vs. 1348 ± 290 mL/min; p < 0.001) and reperfusion slope 10 s of SmO2 after cuff deflation (0.75 ± 0.45%.s-1 vs.2.40 ± 0.94%.s-1; p < 0.001), was attenuated with the leg above the heart. This caused a blunted dilatation of the superficial femoral artery (3.0 ± 2.4% vs. 5.2 ± 2.1%; p = 0.008). Meanwhile, blood flow area under the curve was comparable (above the heart: 445 ± 147 mL vs. below the heart: 474 ± 118 mL; p = 0.55) in both leg positions. During rhythmic exercise, the increase in femoral blood flow was lower in the leg up position (above the heart: 201 ± 94% vs. below the heart: 292 ± 114%; p = 0.001) and contributed to a lower SmO2 (above the heart: 41 ± 18% vs. below the heart 67 ± 5%; p < 0.001). CONCLUSION: Positioning the leg above the heart results in attenuated peak vascular dilator response and exercise-induced hyperemia that coincided with a lower SmO2 during low-intensity plantarflexion exercise.

Global REACH 2018: increased adrenergic restraint of blood flow preserves coupling of oxygen delivery and demand during exercise at high-altitude.

Chronic exposure to hypoxia (high-altitude, HA; >4000 m) attenuates the vasodilatory response to exercise and is associated with a persistent increase in basal sympathetic nerve activity (SNA). The mechanism(s) responsible for the reduced vasodilatation and exercise hyperaemia at HA remains unknown. We hypothesized that heightened adrenergic signalling restrains skeletal muscle blood flow during handgrip exercise in lowlanders acclimatizing to HA. We tested nine adult males (n = 9) at sea-level (SL; 344 m) and following 21-28 days at HA (∼4300 m). Forearm blood flow (FBF; duplex ultrasonography), mean arterial pressure (MAP; brachial artery catheter), forearm vascular conductance (FVC; FBF/MAP), and arterial and venous blood sampling (O2 delivery ( DO2${D}_{{{\rm{O}}}_{\rm{2}}}$ ) and uptake ( V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ )) were measured at rest and during graded rhythmic handgrip exercise (5%, 15% and 25% of maximum voluntary isometric contraction; MVC) before and after local α- and ß-adrenergic blockade (intra-arterial phentolamine and propranolol). HA reduced ΔFBF (25% MVC: SL: 138.3 ± 47.6 vs. HA: 113.4 ± 37.1 ml min-1 ; P = 0.022) and Δ V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ (25% MVC: SL: 20.3 ± 7.5 vs. HA: 14.3 ± 6.2 ml min-1 ; P = 0.014) during exercise. Local adrenoreceptor blockade at HA restored FBF during exercise (25% MVC: SLα-ß blockade : 164.1 ± 71.7 vs. HAα-ß blockade : 185.4 ± 66.6 ml min-1 ; P = 0.947) but resulted in an exaggerated relationship between DO2${D}_{{{\rm{O}}}_{\rm{2}}}$ and V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ( DO2${D}_{{{\rm{O}}}_{\rm{2}}}$ / V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ slope: SL: 1.32; HA: slope: 1.86; P = 0.037). These results indicate that tonic adrenergic signalling restrains exercise hyperaemia in lowlanders acclimatizing to HA. The increase in adrenergic restraint is necessary to match oxygen delivery to demand and prevent over perfusion of contracting muscle at HA. KEY POINTS: In exercising skeletal muscle, local vasodilatory signalling and sympathetic vasoconstriction integrate to match oxygen delivery to demand and maintain arterial blood pressure. Exposure to chronic hypoxia (altitude, >4000 m) causes a persistent increase in sympathetic nervous system activity that is associated with impaired functional capacity and diminished vasodilatation during exercise. In healthy male lowlanders exposed to chronic hypoxia (21-28 days; ∼4300 m), local adrenoreceptor blockade (combined α- and ß-adrenergic blockade) restored skeletal muscle blood flow during handgrip exercise. However, removal of tonic adrenergic restraint at high altitude caused an excessive rise in blood flow and subsequently oxygen delivery for any given metabolic demand. This investigation is the first to identify greater adrenergic restraint of blood flow during acclimatization to high altitude and provides evidence of a functional role for this adaptive response in regulating oxygen delivery and demand.

Global Reach 2018: sympathetic neural and hemodynamic responses to submaximal exercise in Andeans with and without chronic mountain sickness.

Andeans with chronic mountain sickness (CMS) and polycythemia have similar maximal oxygen uptakes to healthy Andeans. Therefore, this study aimed to explore potential adaptations in convective oxygen transport, with a specific focus on sympathetically mediated vasoconstriction of nonactive skeletal muscle. In Andeans with (CMS+, n = 7) and without (CMS-, n = 9) CMS, we measured components of convective oxygen delivery, hemodynamic (arterial blood pressure via intra-arterial catheter), and autonomic responses [muscle sympathetic nerve activity (MSNA)] at rest and during steady-state submaximal cycling exercise [30% and 60% peak power output (PPO) for 5 min each]. Cycling caused similar increases in heart rate, cardiac output, and oxygen delivery at both workloads between both Andean groups. However, at 60% PPO, CMS+ had a blunted reduction in Δtotal peripheral resistance (CMS-, -10.7 ± 3.8 vs. CMS+, -4.9 ± 4.1 mmHg·L-1·min-1; P = 0.012; d = 1.5) that coincided with a greater Δforearm vasoconstriction (CMS-, -0.2 ± 0.6 vs. CMS+, 1.5 ± 1.3 mmHg·mL-1·min-1; P = 0.008; d = 1.7) and a rise in Δdiastolic blood pressure (CMS-, 14.2 ± 7.2 vs. CMS+, 21.6 ± 4.2 mmHg; P = 0.023; d = 1.2) compared with CMS-. Interestingly, although MSNA burst frequency did not change at 30% or 60% of PPO in either group, at 60% Δburst incidence was attenuated in CMS+ (P = 0.028; d = 1.4). These findings indicate that in Andeans with polycythemia, light intensity exercise elicited similar cardiovascular and autonomic responses compared with CMS-. Furthermore, convective oxygen delivery is maintained during moderate-intensity exercise despite higher peripheral resistance. In addition, the elevated peripheral resistance during exercise was not mediated by greater sympathetic neural outflow, thus other neural and/or nonneural factors are perhaps involved.NEW & NOTEWORTHY During submaximal exercise, convective oxygen transport is maintained in Andeans suffering from polycythemia. Light intensity exercise elicited similar cardiovascular and autonomic responses compared with healthy Andeans. However, during moderate-intensity exercise, we observed a blunted reduction in total peripheral resistance, which cannot be ascribed to an exaggerated increase in muscle sympathetic nerve activity, indicating possible contributions from other neural and/or nonneural mechanisms.

Global Reach 2018 Heightened α-Adrenergic Signaling Impairs Endothelial Function During Chronic Exposure to Hypobaric Hypoxia.

RATIONALE: Chronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined. OBJECTIVE: To determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE. METHODS AND RESULTS: We tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+ß adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: -52.7±19.6%, ACh2: -25.4±38.7%, ACh3: -35.1±34.7%, all P≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: -36.4%, P=0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade (P=0.012), but this effect was not observed in the EE Andeans. CONCLUSIONS: These data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.

Scoping review of interventions to support families with preterm infants post-NICU discharge.

BACKGROUND: A successful transition from the NICU to home is fundamental for the long-term health and well-being of preterm infants. Post-NICU discharge, parents may experience a lack of support and resources during the transition to home. The purpose of this scoping review was to identify post-NICU discharge interventions that may reduce parental stress and provide support to families with preterm infants. METHOD: Systematic searches of databases, i.e., PubMed, Web of Science, and CINAHL. Inclusion criteria were data-based articles: 1) published in English between 2011 and 2021, 2) published in peer-reviewed journals, (3) focused on families with preterm infants, and (4) focused on interventions to reduce parental stress and provide support to families with preterm infants post-NICU discharge. RESULTS: 26 articles were included and synthesized. We identified the following face-to-face and remote communication interventions: in-person home visits, phone/video calls, text messages, periodic email questionnaires, mobile/website apps, and online social networking sites. DISCUSSION: Families may highly benefit from a comprehensive family-focused post-NICU discharge follow-up intervention that includes face-to-face and remote communication and support. Post-NICU discharge interventions are imperative to provide education related to infant care and health, increase parental confidence and competency, increase parent-infant relationship, promote emotional and social support, reduce unplanned hospital visits, parental stress, and maternal post-partum depression.

Global REACH 2018: the adaptive phenotype to life with chronic mountain sickness and polycythaemia.

KEY POINTS: Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity. During exercise, several circulatory adaptations are observed, especially involving adrenergic and non-adrenergic mechanisms within non-active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models. Despite profound circulatory stress, i.e. polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology. Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. ABSTRACT: Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high-altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea-level inhabitants residing at high altitude. By studying this unique population, which has adapted through natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity and characterizing the transport of oxygen through blood rheology, including haemoglobin mass, blood and plasma volume and blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances through pharmacological dissection of α-adrenergic signalling pathways within non-active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non-active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity.

6-week High-intensity Interval Training (HIIT) of the Lower Extremities Improves VO2max of the Upper Extremities.

High intensity interval training (HIIT) is widely used to improve VO2max. The purpose of this study was to examine if lower extremity HIIT resulted in improved maximal oxygen uptake (VO2max) and peak power output (PPO) of the upper extremities. Twenty healthy and trained participants (11 female and 9 male, VO2max 3160±1175 ml/min) underwent a 6-week HIIT program of the lower extremities on a cycle ergometer. Before and after the training period a maximal cycle ergometry (CE) and a maximal hand crank ergometry (HCE) were conducted to determine VO2max and PPO. Additionally, hematological parameters were determined. Increases in VO2max of the lower extremities (3160±1175 to 3449±1231 ml/min, p<0.001, η2p=0.779) as well as of the upper extremities (2255±938 to 2377±1015 ml/min, p=0.010, η2p=0.356) from pre- to post-test were found. PPO of the lower extremities increased (243±95 to 257±93 W, p<0.001, η2p=0.491), whereas it remained unchanged for the upper extremities (103±50 to 108±54 W, p=0.209, η2p=0.150). All hematological parameters increased. The results demonstrate that VO2max of the upper extremities increased after 6-weeks of cycling HIIT. However, upper body PPO was unchanged.

Functional Vs. Running Low-Volume High-Intensity Interval Training: Effects on VO2max and Muscular Endurance.

The purpose of the study was to assess if high-intensity interval training (HIIT) using functional exercises is as effective as traditional running HIIT in improving maximum oxygen uptake (VO2max) and muscular endurance. Fifteen healthy, moderately trained female (n = 11) and male (n= 4) participants (age 25.6 ± 2.6 years) were assigned to either running HIIT (HIIT-R; n = 8, 6 females, 2 males) or functional HIIT (HIIT-F; n = 7, 5 females, 2 males). Over a four-week period, both groups performed 14 exercise sessions of either HIIT-R or, HIIT-F consisting of 3-4 sets of low-volume HIIT (8x 20 s, 10 s rest; set rest: 5 min). Training heart rate (HR) data were collected throughout all training sessions. Mean and peak HR during the training sessions were significantly different (p = 0.018 and p = 0.022, respectively) between training groups, with HIIT-F eliciting lower HR responses than the HIIT-R. However, despite these differences in exercise HR, VO2max improved similarly (~13% for the HIIT-R versus ~11% for the HIIT-F, p=0.300). Muscular endurance (burpees and toes to bar) significantly improved (p =0.004 and p = 0.001, respectively) independent of training modality. These findings suggest that classic running HIIT and functional HIIT both improve VO2max and affect muscular endurance to the same extent despite a lower cardiovascular strain in the functional protocol.

Acute Kidney Injury Impairs Postnatal Renal Adaptation and Increases Morbidity and Mortality in Very Low-Birth-Weight Infants.

OBJECTIVE: This study aims to estimate the impact of acute kidney injury (AKI) on postnatal renal adaptation, morbidity, and mortality in very low-birth-weight (VLBW) infants. DESIGN: We conducted a retrospective study of 457 VLBW infants admitted to a tertiary level neonatal intensive care unit (NICU) between July 2009 and April 2015. We compared patient characteristics, risk factors, serum creatinine trends, and adverse outcomes in infants with and without AKI using multivariate logistic regression analysis. RESULTS: Incidence of AKI was 19.5%. On multivariate analysis, postnatal risk factors such as patent ductus arteriosus and vancomycin use were significantly associated with AKI. Infants with AKI had significantly higher mortality; 25/89 (28%) versus 15/368 (4%) (p < 0.001). Among survivors with AKI, bronchopulmonary dysplasia (BPD) was more prevalent (52.8 vs. 23.9%, p < 0.001), serum creatinine remained elevated for a longer duration and median length of stay extended by 38 days. CONCLUSION: Presence of AKI was associated with impaired postnatal renal adaptation, BPD, significantly longer stay in the NICU and higher mortality.

Nosocomial Infections in the Neonatal Intensive Care Unit.

Nosocomial infections are relatively common in the NICU. These infections increase morbidity and mortality, particularly in the smallest and most fragile infants. The impact of these infections on long-term outcomes and health-care costs is devastating. Worldwide efforts to decrease the incidence of nosocomial infections have focused on implementing specific prevention protocols such as handwashing, central line teams, care bundles, and antimicrobial stewardship. This review summarizes common nosocomial infections in patients in the NICU.

Correction: Ruchaya et al. Transplantation of Skeletal Muscle-Derived Sca-1+/PW1+/Pax7- Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction. Cells2022, 11, 4050.

In the original publication [...].

Neonatal Hypocalcemia: Common, Uncommon, and Rare Etiologies.

Calcium homeostasis in the neonatal period is a reflection of the transition from placental regulation to hormonal maturation in the newborn. Hypocalcemia occurring within the first 72 hours after birth, termed early-onset hypocalcemia (EOH), is more common and often asymptomatic. Hypocalcemia occurring beyond 72 hours of age is termed late-onset hypocalcemia (LOH). LOH is less common than EOH, and affected patients are more likely to be symptomatic. To prevent and treat hypocalcemia in the newborn, neonatal clinicians should be familiar with the common, uncommon, and rare etiologies of EOH and LOH, as summarized in this review.

Neonatal serial creatinine levels as an adjunct biomarker in timing of fetal neurologic injury.

Objective: To investigate the rise and clearance of newborn creatinine in perinatal asphyxia as an adjunct biomarker to support or refute allegations of acute intrapartum asphyxia. Study design: In this retrospective chart review, newborns > 35 weeks gestational age were evaluated from closed medicolegal cases of confirmed perinatal asphyxia and reviewed for causation. Data collected included newborn demographic data, patterns of hypoxic ischemic encephalopathy, brain magnetic resonance imaging, Apgar scores, cord and initial newborn blood gases, and serial newborn creatinine levels during the first 96 h of life. Newborn serum creatinine values were collected at 0-12, 13-24, 25-48, and 49-96 h. Newborn brain magnetic resonance imaging was used to define 3 patterns of asphyxial injury: acute profound, partial prolonged, or Both. Results: Two hundred and eleven cases of neonatal encephalopathy from multiple institutions were reviewed from 1987 to 2019 with only 76 cases having serial creatinine values during the first 96 h of life. A total of 187 creatinine values were collected. Partial prolonged and Both had significantly greater degree of metabolic acidosis in the first newborn arterial blood gas in comparison to acute profound. Acute profound and Both had significantly lower 5- and 10- minute Apgar scores in comparison to partial prolonged. Newborn creatinine values were stratified by asphyxial injury. Acute profound injury showed minimally elevated creatinine trends with rapid normalization. Partial prolonged and Both demonstrated higher creatinine trends with delayed normalization. Mean creatinine values were significantly different between the three types of asphyxial injuries within 13-24 h of life at the time when creatinine values peaked (p = 0.01). Conclusion: Serial newborn serum creatinine levels taken within the first 96 h of life can provide objective data of timing and duration of perinatal asphyxia.

High-intensity exercise and passive hot water immersion cause similar postintervention changes in peripheral and cerebral shear.

Passive hot water immersion (PHWI) provides a peripheral vasculature shear stimulus comparable to low-intensity exercise within the active skeletal muscle, whereas moderate- and high-intensity exercise elicit substantially greater shear rates in the peripheral vasculature, likely conferring greater vascular benefits. Notably, few studies have compared postintervention shear rates in the peripheral and cerebral vasculature after high-intensity exercise and PHWI, especially considering that the postintervention recovery period represents a key window in which adaptation occurs. Therefore, we aimed to compare shear rates in the internal carotid artery (ICA), vertebral artery (VA), and common femoral artery (CFA) between high-intensity exercise and whole body PHWI for up to 80 min after intervention. Fifteen healthy (27 ± 4 yr), moderately trained individuals underwent three time-matched interventions in a randomized order that included 30 min of whole body immersion in a 42°C hot bath, 30 min of treadmill running and 5 × 4-min high-intensity intervals (HIIE). There were no differences in ICA (P = 0.4643) and VA (P = 0.1940) shear rates between PHWI and exercise (both continuous and HIIE) after intervention. All three interventions elicited comparable increases in CFA shear rate after intervention (P = 0.0671); however, CFA shear rate was slightly higher 40 min after threshold running (P = 0.0464) and slightly higher, although not statistically, for HIIE (P = 0.0565) compared with PHWI. Our results suggest that time- and core temperature-matched high-intensity exercise and PHWI elicit limited changes in cerebral shear and comparable increases in peripheral vasculature shear rates when measured for up to 80 min after intervention.NEW & NOTEWORTHY The study aimed to compare shear rates in lower limb and extracranial cerebral blood vessels for up to 80 min after high-intensity exercise and whole body passive hot water immersion (PHWI). Time- and core temperature-matched high-intensity exercise and whole body PHWI both elicited minimal, but comparable, postintervention changes in cerebral artery shear rate. Furthermore, 30 min of PHWI caused a postintervention increase in femoral shear rate similar to high-intensity exercise; however, femoral shear remained slightly elevated for a longer period after high-intensity exercise. These results suggest that PHWI provides postintervention changes in lower limb peripheral shear rates comparable to intense exercise and is likely a therapeutic alternative in individuals unable to perform exercise.

Transplantation of Skeletal Muscle-Derived Sca-1+/PW1+/Pax7- Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction.

We have previously shown that skeletal muscle-derived Sca-1+/PW1+/Pax7- interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 105 eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (p < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (p < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (p < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (p < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapies.

Effects of Regular Long-Term Circuit Training (Once per Week) on Cardiorespiratory Fitness in Previously Sedentary Adults.

The purpose of the study was (1) to investigate the effects of regular long-term circuit training (once per week) on cardiorespiratory fitness (CRF) in sedentary adults and (2) to compare training progress with the effects of continued exercise participation by regularly active age-matched individuals. Ten sedentary, middle-aged (51 ± 6 years) individuals (sedentary group, SG) of both sexes performed 32 weeks (1 training session/week) of supervised circuit training and 10 weeks of self-managed training. Effects were compared to an age-matched group (51 ± 8 years; n = 10) of regularly active individuals (active group, AG). CRF (expressed as peak oxygen uptake: VO2peak; peak power output: PPO) and systemic blood pressure (BP) during the incremental test were measured at the start and after the training intervention. CRF decreased significantly within the AG (VO2peak: 43.1 ± 7.3 vs. 40.3 ± 6.5 mL/min/kg, p < 0.05; PPO: 3.3 ± 0.6 vs. 3.1 ± 0.6; p < 0.05) but was maintained in the SG. In addition, significant improvements in restoration of the oxygen level in leg muscles after exercise and reduced systolic BP (180 ± 14 vs. 170 ± 17 mmHg, p = 0.01) at submaximal exercise were found within the SG. However, differences in changes from pre to post did not reach significance between groups. In contrast to the regularly active individuals, circuit training once per week over 32 weeks prevented the aging-related decline of CRF in previously sedentary subjects and reduced systolic BP during submaximal exercise, indicating improved exercise tolerance.

Acetaminophen Therapy for Persistent Patent Ductus Arteriosus.

Persistence of a left-to-right shunt caused by a patent ductus arteriosus (PDA) leads to significant sequelae in extremely premature infants as a result of pulmonary overcirculation and systemic steal. Although timing and duration of treatment for a persistent clinically significant PDA differ among institutions, standard pharmacologic interventions are the nonsteroidal anti-inflammatory drugs indomethacin and ibuprofen. Acetaminophen has emerged as an alternative to indomethacin and ibuprofen with less significant adverse effects, but there is no consensus regarding its use. This review summarizes the most recent evidence for the use of acetaminophen in PDA treatment.