Introduction
The assessment of left‐ and right‐sided cardiac function via closed‐chest pressure‐volume loops is important to understanding and diagnosing a wide range of cardiovascular pathologies. ...In the vast majority of pre‐clinical studies, either left‐ or right‐sided heart function is assessed in isolation, or, more recently, by sequentially right‐ and left‐sided catheterization1. Synchronous biventricular catheterization would offer a significant advancement for pre‐clinical research. To date, closed‐chest synchronous biventricular pressure‐volume loops have only been obtained in a few studies, limited to porcine models2. Here, we describe initial results from what we believe to be the first synchronous biventricular pressure‐volume loops obtained in the rodent using a closed‐chest approach.
Aim
To obtain biventricular pressure‐volume loops in the anesthetized rat using a closed‐chest approach
Methods
A total of 8 Wistar rats were anesthetized with urethane (1.5mg/kg), tracheotomised, ventilated, and subsequently had a solid state catheter placed in the femoral artery to measure blood pressure, and admittance pressure‐volume catheters placed in the right‐ and left‐ventricle to obtain synchronous biventricular pressure‐volume loops. Admittance probes were set to different frequencies to avoid cross‐talk. All catheters were left to stabilize for a minimum of 10 min after which we extracted and averaged 1 minute of basal pressure‐volume indices.
Results
Reliable ventricular pressure waveforms were obtained from both the left (i.e., left‐ventricular end‐systolic pressure = 106±12mmHg) and right (i.e., right‐ventricular end systolic pressure = 28±8mmHg) side in all eight animals, and we were able to obtain standard left‐sided pressure‐volume loops from all eight animals (i.e., stroke work = 22±5mmHg/ml). We were only able to obtain reliable right‐sided pressure‐volume loops in two of eight animals, due to poor volume signals in the remaining 6 animals. In the two animals we were able to obtain synchronous pressure‐volume loops there was clear evidence of ventricular dependence across the respiratory cycle (Fig.1).
Conclusions
Obtaining synchronous biventricular pressure‐volume loops using a closed‐chest approach in rats is possible but technically challenging. Further work is needed to better obtain right‐sided ventricular volumes.
References
Potus F. et al., J. Vis. Exp (160), e61088, doi:10.3791/61088 (2020).
Lyhne MD. et al., J. Vis. Exp.(171), e62661, doi:10.3791/62661 (2021).
Objective
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged as a global pandemic in early 2020 with rapidly evolving approaches to diagnosing the clinical illness called ...coronavirus disease (COVID‐19). The primary objective of this scoping review is to synthesize current research of the diagnostic accuracy of history, physical examination, routine laboratory tests, real‐time reverse transcription–polymerase chain reaction (rRT‐PCR), immunology tests, and computed tomography (CT) for the emergency department (ED) diagnosis of COVID‐19. Secondary objectives included a synopsis of diagnostic biases likely with current COVID‐19 research as well as corresponding implications of false‐negative and false‐positive results for clinicians and investigators.
Methods
A Preferred Reporting Items for Systematic Reviews and Meta‐Analyses–Scoping Review (PRISMA‐ScR)–adherent synthesis of COVID‐19 diagnostic accuracy through May 5, 2020, was conducted. The search strategy was designed by a medical librarian and included studies indexed by PubMed and Embase since January 2020.
Results
A total of 1,907 citations were screened for relevance. Patients without COVID‐19 are rarely reported, so specificity and likelihood ratios were generally unavailable. Fever is the most common finding, while hyposmia and hypogeusia appear useful to rule in COVID‐19. Cough is not consistently present. Lymphopenia is the mostly commonly reported laboratory abnormality and occurs in over 50% of COVID‐19 patients. rRT‐PCR is currently considered the COVID‐19 criterion standard for most diagnostic studies, but a single test sensitivity ranges from 60% to 78%. Multiple reasons for false‐negatives rRT‐PCR exist, including sample site tested and disease stage during which sample was obtained. CT may increase COVID‐19 sensitivity in conjunction with rRT‐PCR, but guidelines for imaging patients most likely to benefit are emerging. IgM and IgG serology levels are undetectable in the first week of COVID‐19, but sensitivity (range = 82% to 100%) and specificity (range = 87% to 100%) are promising. Whether detectable COVID‐19 antibodies correspond to immunity remains unanswered. Current studies do not adhere to accepted diagnostic accuracy reporting standards and likely report significantly biased results if the same tests were to be applied to general ED populations with suspected COVID‐19.
Conclusions
With the exception of fever and disorders of smell/taste, history and physical examination findings are unhelpful to distinguish COVID‐19 from other infectious conditions that mimic SARS‐CoV‐2 like influenza. Routine laboratory tests are also nondiagnostic, although lymphopenia is a common finding and other abnormalities may predict severe disease. Although rRT‐PCR is the current criterion standard, more inclusive consensus‐based criteria will likely emerge because of the high false‐negative rate of PCR tests. The role of serology and CT in ED assessments remains undefined.
Obesity poses a challenge to thromboembolic prophylaxis following total joint arthroplasty (TJA). The purpose of this study is to evaluate a weight-based aspirin dosing regimen for prevention of ...venous thromboembolism (VTE) following TJA.
This is a retrospective observational study of 2403 patients who underwent primary total hip or knee arthroplasty at one institution. A weight-based aspirin dosing regimen for VTE prophylaxis was administered to 1247 patients: patients weighing ≥120 kg received 325 mg aspirin twice daily (BID) and those weighing <120 kg received 81 mg aspirin BID for 4 weeks. In total, 1156 patients in the comparison cohort received 81 mg aspirin BID. VTE and gastrointestinal bleeding events were identified through chart review at 42 days and 6 months postoperatively. A multivariable logistic regression was performed to adjust for covariates.
The weight-based aspirin cohort had a significantly lesser incidence of VTE at 42 days (P = .03, relative risk RR 0.31, 95% confidence interval 0.12-0.82) and 6 months (P = .03, RR 0.38, 95% confidence interval 0.18-0.80). There was no difference in VTE incidence between total hip arthroplasty and total knee arthroplasty cases (P = .8). There was no difference in gastrointestinal bleeding events between the cohorts at 42 days (P = .69) or 6 months (P = .92). Subanalysis of patients weighing ≥120 kg demonstrated a significant difference between the cohorts with a VTE incidence of 3.48% and 0% in the 81 mg and weight-based cohorts, respectively (P = .02).
Patients prescribed a weight-based aspirin regimen had significantly fewer VTEs after TJA compared to historical controls with an RR reduction of 69% at 6 weeks and 62% at 6 months postoperatively. This suggests the need to factor patient weight when determining postoperative VTE prophylaxis with aspirin.
Key points
Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance.
Women may be more resistant to DF ...compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure‐threshold loading (PTL) performed to task failure.
At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men.
For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men.
Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance.
Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n = 9, age = 24 ± 3 years) and women (n = 9, age = 24 ± 3 years). Subjects performed isocapnic inspiratory pressure‐threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat‐by‐beat throughout PTL via photoplethysmography, and low‐frequency systolic pressure (LFSBP; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw; P = 0.33). However, time to task failure was significantly longer in women than in men (27 ± 11 vs. 16 ± 11 min, respectively; P = 0.02). Women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm; P = 0.02) and MAP (10 ± 8 vs. 14 ± 9 mmHg; P = 0.01), and significantly lower LFSBP (23 ± 11 vs. 34 ± 8 mmHg2; P = 0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance.
Key points
Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance.
Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure‐threshold loading (PTL) performed to task failure.
At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men.
For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men.
Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance.
To describe the process and outcomes of using a new evidence base to develop scientific guidelines that specify the type and minimum dose of exercise necessary to improve fitness and cardiometabolic ...health in adults with spinal cord injury (SCI).
International.
Using Appraisal of Guidelines, Research and Evaluation (AGREE) II reporting criteria, steps included (a) determining the guidelines' scope; (b) conducting a systematic review of relevant literature; (c) holding three consensus panel meetings (European, Canadian and International) to formulate the guidelines; (d) obtaining stakeholder feedback; and (e) process evaluation by an AGREE II consultant. Stakeholders were actively involved in steps (c) and (d).
For cardiorespiratory fitness and muscle strength benefits, adults with a SCI should engage in at least 20 min of moderate to vigorous intensity aerobic exercise 2 times per week AND 3 sets of strength exercises for each major functioning muscle group, at a moderate to vigorous intensity, 2 times per week (strong recommendation). For cardiometabolic health benefits, adults with a SCI are suggested to engage in at least 30 min of moderate to vigorous intensity aerobic exercise 3 times per week (conditional recommendation).
Through a systematic, rigorous, and participatory process involving international scientists and stakeholders, a new exercise guideline was formulated for cardiometabolic health benefits. A previously published SCI guideline was endorsed for achieving fitness benefits. These guidelines represent an important step toward international harmonization of exercise guidelines for adults with SCI, and a foundation for developing exercise policies and programs for people with SCI around the world.
Pressure injuries, also known as pressure ulcers, are regions of localized damage to the skin and/or underlying tissue. Repeated rounds of ischemia-reperfusion (I/R) have a major causative role for ...tissue damage in pressure injury. Ischemia prevents oxygen/nutrient supply, and restoration of blood flow induces a burst of reactive oxygen species that damages blood vessels, surrounding tissues and can halt blood flow return. Minimizing the consequences of repeated I/R is expected to provide a protective effect against pressure injury. Sulfaphenazole (SP), an off patent sulfonamide antibiotic, is a potent CYP 2C6 and CYP 2C9 inhibitor, functioning to decrease post-ischemic vascular dysfunction and increase blood flow. The therapeutic effect of SP on pressure injury was therefore investigated in apolipoprotein E knockout mice, a model of aging susceptible to ischemic injury, which were subjected to repeated rounds of I/R-induced skin injury. SP reduced overall severity, improved wound closure and increased wound tensile strength compared to vehicle-treated controls. Saliently, SP restored tissue perfusion in and around the wound rapidly to pre-injury levels, decreased tissue hypoxia, and reduced both inflammation and fibrosis. SP also demonstrated bactericidal activity through enhanced M1 macrophage activity. The efficacy of SP in reducing thermal injury severity was also demonstrated. SP is therefore a potential therapeutic option for pressure injury and other ischemic skin injuries.
To determine whether spinal cord perfusion pressure (SCPP) as measured with a lumbar intrathecal catheter is a more predictive measure of neurologic outcome than the conventionally measured mean ...arterial pressure (MAP).
A total of 92 individuals with acute spinal cord injury were enrolled in this multicenter prospective observational clinical trial. MAP and CSF pressure (CSFP) were monitored during the first week postinjury. Neurologic impairment was assessed at baseline and at 6 months postinjury. We used logistic regression, systematic iterations of relative risk, and Cox proportional hazard models to examine hemodynamic patterns commensurate with neurologic outcome.
We found that SCPP (odds ratio 1.039,
= 0.002) is independently associated with positive neurologic recovery. The relative risk for not recovering neurologic function continually increased as individuals were exposed to SCPP below 50 mm Hg. Individuals who improved in neurologic grade dropped below SCPP of 50 mm Hg fewer times than those who did not improve (
= 0.012). This effect was not observed for MAP or CSFP. Those who were exposed to SCPP below 50 mm Hg were less likely to improve from their baseline neurologic impairment grade (
= 0.0056).
We demonstrate that maintaining SCPP above 50 mm Hg is a strong predictor of improved neurologic recovery following spinal cord injury. This suggests that SCPP (the difference between MAP and CSFP) can provide useful information to guide the hemodynamic management of patients with acute spinal cord injury.
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