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We sought to determine the physiological relevance of pannexin/purinergic‐dependent signaling in mediating conducted vasodilation elicited by capillary stimulation through skeletal muscle contraction. Using hamster cremaster muscle and intravital microscopy we stimulated capillaries through local muscle contraction while observing the associated upstream arteriole. Capillaries were stimulated with muscle contraction at low and high contraction (6 and 60CPM) and stimulus frequencies (4 and 40 Hz) in the absence and presence of pannexin blocker mefloquine (MEF; 10−5 M), purinergic receptor antagonist suramin (SUR 10−5 M) and gap‐junction uncoupler halothane (HALO, 0.07%) applied between the capillary stimulation site and the upstream arteriolar observation site. Conducted vasodilations elicited at 6CPM were inhibited by HALO while vasodilations at 60CPM were inhibited by MEF and SUR. The conducted response elicited at 4 Hz was inhibited by MEF while the vasodilation at 40 Hz was unaffected by any blocker. Therefore, upstream vasodilations resulting from capillary stimulation via muscle contraction are dependent upon a pannexin/purinergic‐dependent pathway that appears to be stimulation parameter‐dependent. Our data highlight a physiological importance of the pannexin/purinergic pathway in facilitating communication between capillaries and upstream arteriolar microvasculature and, consequently, indicating that this pathway may play a crucial role in regulating blood flow in response to skeletal muscle contraction. [ABSTRACT FROM AUTHOR]

We sought to determine if a pannexin/purinergic-dependent intravascular communication pathway exists in skeletal muscle microvasculature that facilitates capillary communication with upstream arterioles that control their perfusion. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries and observed the vasodilatory response in the associated upstream 4A arteriole. We stimulated capillaries with vasodilators relevant to muscle contraction: 10-6 M S-nitroso-N-acetyl-dl-penicillamine (SNAP; nitric oxide donor), 10-6 M adenosine, 10 mM potassium chloride, 10-5 M pinacidil, as well as a known initiator of gap-junction-dependent intravascular communication, acetylcholine (10-5 M), in the absence and the presence of the purinergic membrane receptor blocker suramin (10-5 M), pannexin blocker mefloquine (2 × 10-5 M), or probenecid (5 × 10-6 M) and gap-junction inhibitor halothane (0.07%) applied in the transmission pathway, between the capillary stimulation site and the upstream 4A observation site. Potassium chloride, SNAP, and adenosine-induced upstream vasodilations were significantly inhibited by suramin, mefloquine, and probenecid but not halothane, indicating the involvement of a pannexin/purinergic-dependent signaling pathway. Conversely, SNAP-induced upstream vasodilation was only inhibited by halothane indicating that communication was facilitated by gap junctions. Both pinacidil and acetylcholine were inhibited by suramin but only acetylcholine was inhibited by halothane. These data demonstrate the presence of a pannexin/purinergic-dependent communication pathway between capillaries and upstream arterioles controlling their perfusion. This pathway adds to the gap-junction-dependent pathway that exists at this vascular level as well. Given that vasodilators relevant to muscle contraction can use both of these pathways, our data implicate the involvement of both pathways in the coordination of skeletal muscle blood flow. NEW & NOTEWORTHY Blood flow control during increased metabolic demand in skeletal muscle is not fully understood. Capillaries have been implicated in controlling blood flow to active skeletal muscle, but how capillaries communicate to the arteriolar vascular network is not clear. Our study uncovers a novel pathway through which capillaries can communicate to upstream arterioles to cause vasodilation and therefore control perfusion. This work implicates a new vascular communication pathway in blood flow control in skeletal muscle. [ABSTRACT FROM AUTHOR]

A robust workforce of locum tenens (LT) physicians is imperative for health service stability. A systematic review was conducted to synthesize current evidence on the strategies used to facilitate the recruitment and retention of LT physicians. English articles up to October 2023 across five databases were sourced. Original studies focusing on recruitment and retention of LT's were included. An inductive content analysis was performed to identify strategies used to facilitate LT recruitment and retention. A separate grey literature review was conducted from June–July 2023. 12 studies were retained. Over half (58%) of studies were conducted in North America. Main strategies for facilitating LT recruitment and retention included financial incentives (83%), education and career factors (67%), personal facilitators (67%), clinical support and mentorship (33%), and familial considerations (25%). Identified subthemes were desire for flexible contracts (58%), increased income (33%), practice scouting (33%), and transitional employment needs (33%). Most (67%) studies reported deterrents to locum work, with professional isolation (42%) as the primary deterrent-related subtheme. Grey literature suggested national physician licensure could enhance license portability, thereby increasing the mobility of physicians across regions. Organizations employ five main LT recruitment facilitators and operationalize these in a variety of ways. Though these may be incumbent on local resources, the effectiveness of these approaches has not been evaluated. Consequently, future research should assess LT the efficacy of recruitment and retention facilitators. Notably, the majority of identified LT deterrents may be mitigated by modifying contextual factors such as improved onboarding practices. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We hypothesized that CO2 and H+ stimulate capillaries and arterioles to produce local and conducted vasodilations required to coordinate the distribution of blood flow to contracting skeletal muscle fibers. Methods: CO2 and H+ independently and in combination were applied to 2A arterioles (first branch order from the 1A feed arteriole) and capillaries of the in situ, blood‐perfused hamster cremaster muscle. The resulting local and conducted vasodilations were measured. Results: H+ (pH: 7.2‐6.6) and CO2 (5% and 10%) applied to the vascular network induced 2A arteriolar vasodilations, while 15% CO2 produced vasoconstriction. Localized application of H+ produced 2A arteriolar vasodilation, while 15% CO2 resulted in a variable response. Simultaneous application of CO2 and H+ did not result in the predicted additive effects. Application of CO2 and H+ alone or combined on arterioles or capillaries did not induce a conducted response. Conclusions: CO2 and H+ produce arteriolar vasodilation but, critically, cannot stimulate the spread of vasodilation throughout the network, thus limiting their ability to coordinating blood flow to contracting skeletal muscle fibers. Given their potential for interaction, the importance of CO2 and H+ may lie in their ability to modify the effects of other vasodilators. [ABSTRACT FROM AUTHOR]

Key points: The current theory behind matching blood flow to metabolic demand of skeletal muscle suggests redundant interactions between metabolic vasodilators. Capillaries play an important role in blood flow control given their ability to respond to muscle contraction by causing conducted vasodilatation in upstream arterioles that control their perfusion. We sought to determine whether redundancies occur between vasodilators at the level of the capillary by stimulating the capillaries with muscle contraction and vasodilators relevant to muscle contraction. We identified redundancies between potassium and both adenosine and nitric oxide, between nitric oxide and potassium, and between adenosine and both potassium and nitric oxide. During muscle contraction, we demonstrate redundancies between potassium and nitric oxide as well as between potassium and adenosine. Our data show that redundancy is physiologically relevant and involved in the coordination of the vasodilator response during muscle contraction at the level of the capillaries. Abstract: We sought to determine if redundancy between vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between vasodilators are indicative of redundancy, we tested whether vasodilators implicated in mediating active hyperaemia (potassium (K+), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10−7 m S‐nitroso‐N‐acetylpenicillamine (SNAP), 10−7 m ADO, 10 m m KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP‐ and ADO‐induced vasodilatations by ∼49.7% and ∼128.0% respectively and ADO significantly attenuated KCl‐ and SNAP‐induced vasodilatations by ∼94.7% and ∼59.6%, respectively. NO significantly attenuated KCl vasodilatation by 93.8%. Further, during muscle contraction we found that inhibition of NO production using l‐NG‐nitroarginine methyl ester and inhibition of ADO receptors using xanthine amine congener was effective at inhibiting contraction‐induced vasodilatation but only in the presence of K+ release channel inhibition. Thus, only when the inhibiting vasodilator K+ was blocked was the second vasodilator, NO or ADO, able to produce effective vasodilatation. Therefore, we show that there are inhibitory interactions between specific vasodilators at the level of the capillary. Further, these inhibitions can be observed during muscle contraction indicating that redundancies between vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia. [ABSTRACT FROM AUTHOR]

In this invited review, we explore the burgeoning possibility of capillary endothelial cells as coordinators of skeletal muscle blood flow in response to muscle contraction. The idea that the capillary is an active vascular unit in skeletal muscle microcirculation starkly diverges from the traditional dogma that seats arterioles as the central controllers of blood flow during exercise. This review aims to incite discussion as we revisit and rethink the role of capillary endothelial cells in skeletal muscle. We discuss the potential for a mismatch in the architectural relationships between the arteriolar microvasculature and contracting motor units that would negate consistent communication between them. We review the data from the past two decades demonstrating that capillaries are ideally located architecturally to communicate with skeletal muscle fibers and are mechanistically capable of signaling upstream arterioles that control their own perfusion. We show that the orchestration of a coordinated vascular response necessary to support active skeletal muscle fibers cannot be achieved by the arterioles, but rather it is the capillaries that drive the blood flow response to muscle contraction. Thus, capillaries need to be seriously considered as critical in the coordination of skeletal muscle blood flow during active hyperemia. [ABSTRACT FROM AUTHOR]

Key points Multiple vasodilators have been identified as being important in matching blood flow to the metabolism of contracting skeletal muscle and it has been hypothesized that this process is governed by redundancy between vasodilators, where one vasodilator can compensate for the loss of another., In the present study, we aimed to determine whether redundancy between vasodilators exists by investigating whether vasodilators relevant to skeletal muscle contraction can inhibit the effects of other vasodilators., We show that potassium can inhibit vasodilatations induced by adenosine and nitric oxide, and also that adenosine and nitric oxide can interact in a way that changes over time., Furthermore, we show that inward rectifying potassium channels and Na+/K+ATPase are partially mechanistically responsible for the interaction between potassium and adenosine and nitric oxide., Our data provide proof of principle that vasodilators relevant to muscle contraction interact and also that redundancy may govern the processes of active hyperaemia., Abstract Redundancy, in active hyperaemia, where one vasodilator can compensate for another if the first is missing, would require that one vasodilator inhibits the effects of another; therefore, if the first vasodilator is inhibited, its inhibitory influence on the second vasodilator is removed and the second vasodilator exerts a greater vasodilatory effect. We aimed to determine whether vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl), adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to investigate the mechanisms for this interaction. We used the hamster cremaster muscle and intravital microscopy to directly visualize 2A arterioles when exposed to a range of concentrations of one vasodilator [10−8 to 10−5 m S-nitroso- N-acetyl penicillamine (SNAP), 10−8 to 10−5 m ADO, 10 and 20 m m KCl] in the absence and then in the presence of a second vasodilator (10−7 m ADO, 10−7 m SNAP, 10 m m KCl). We found that KCl significantly attenuated SNAP-induced vasodilatations by ∼65.8% and vasodilatations induced by 10−8 to 10−6 m ADO by ∼72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by antagonizing either Na+/K+ ATPase using ouabain or inward rectifying potassium channels using barium chloride, could restore the SNAP-induced vasodilatation by up to ∼53.9% and 30.6%, respectively, and also restore the ADO-induced vasodilatations by up to ∼107% and 76.7%, respectively. Our data show that vasodilators relevant to muscle contraction can interact in a way that alters the effectiveness of other vasodilators. These data suggest that active hyperaemia may be the result of complex interactions between multiple vasodilators via a redundant control paradigm. [ABSTRACT FROM AUTHOR]

The article focuses on characterization of endothelial-dependent vasodilator signaling sympatholytic role during handgrip exercise. Topics include modulation of sympathetic vasoconstriction from vasoactive compounds present during muscle contraction such as adenosine triphosphate (ATP), reduction of forearm vascular conductance (FVC) and blood flow from infusion of phenylephrine-mediated vasoconstriction (PE) and endothelium-derived hyperpolarization (EDH) as a powerful signaling mechanism.

Purpose: Navigated total knee arthroplasty (TKA) improves implant alignment by providing feedback on resection parameters based on femoral and tibial cutting guide positions. However, saw blade thickness, deflection, and cutting guide motion may lead to final bone cuts differing from planned resections, potentially contributing to suboptimal component alignment. We used an imageless navigation device to intraoperatively quantify the magnitude of error between planned and actual resections, hypothesizing final bone cuts will differ from planned alignment. Materials and methods: A retrospective study including 60 consecutive patients undergoing primary TKA using a novel imageless navigation device was conducted. Device measurements of resection parameters were obtained via attachment of optical trackers to femoral and tibial cutting guides prior to resection. Following resection, optical trackers were placed directly on the bone cut surface and measurements were recorded. Cutting guide and bone resection measurements of both femoral and tibial varus/valgus, femoral flexion, tibial slope angles, and both femoral and tibial medial and lateral resection depths were compared using a Student’s t-test. Results: Femoral cutting guide position differed from the actual cut by an average 0.6 ± 0.5° (p = 0.85) in the varus/ valgus angle and 1.0 ± 1.0° (p = 0.003) in the flexion/extension angle. The difference between planned and actual cut measurements for medial and lateral femoral resection depth was 1.1 ± 1.1 mm (p = 0.32) and 1.2 ± 1.0 mm (p = 0.067), respectively. Planned cut measurements based on tibial guide position differed from the actual cut by an average of 0.9 ± 0.8° (p = 0.63) in the varus/valgus angle and 1.1 ± 1.0° (p = 0.95) in slope angle. Measurement of medial and lateral tibial resection depth differed by an average of 0.1 ± 1.8 mm (p = 0.78) and 0.2 ± 2.1 mm (p = 0.85), respectively. Conclusions: Significant discrepancies between planned and actual femoral bone resection were demonstrated for flexion/extension angle, likely the result of cutting error. Our data highlights the importance of cut verification postresection to confirm planned resections are achieved, and suggests imageless navigation may be a source of feedback that would allow surgeons to intraoperatively adjust resections to achieve optimal implant alignment. [ABSTRACT FROM AUTHOR]