A lateral approach allows accurate and stable total elbow replacement in dogs.

OBJECTIVE: Evaluate whether total elbow replacement (TER) through a lateral approach is accurate and stable. ANIMALS: 12 skeletally mature large-breed dog cadavers were used. METHODS: Limb alignment, elbow joint motion, and collateral ligament laxity were evaluated preoperatively. The order of surgery (left or right) and the approach (lateral or medial) were randomly selected for TER in each dog. The other approach was used in the contralateral elbow. Intraoperative technical difficulties, duration of surgery, and anatomic complications were recorded. Limb alignment, elbow joint motion, collateral ligament laxity, and prosthetic component alignment were evaluated after surgery. Data were collected from June 11 to 15, 2023. RESULTS: The duration of surgery using a lateral or medial approach did not differ (P = .499). Anatomic complications were not observed. The lateral approach resulted in 8° more elbow extension (P = .003), 1.58° less lateral collateral ligament constraint (P = .033), 2.80° less medial collateral ligament constraint (P = .002), 4.38° less frontal plane constraint (P = .004), 8° greater humeral component inclination (P = .033), and 5.6° greater radioulnar component varus (P = .001) than the medial approach. Varus of the radius, mechanical axis deviation, limb supination, elbow flexion, mediolateral humeral component and craniocaudal radioulnar component orientation did not differ among joints operated using a lateral or medial approach. In normal cadaveric elbows, a lateral approach for TER appears feasible, producing equivalent limb alignment, joint laxity, and joint motion to normal elbows and to TER placed using a medial approach. CLINICAL RELEVANCE: In dogs, TER can be performed using a lateral surgical approach.

Habenular volume changes after venlafaxine treatment in patients with major depression.

BACKGROUND: Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement. METHODS: Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant-free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment. RESULTS: A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness. CONCLUSION: Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.

Impaired longitudinal systolic-diastolic coupling and cardiac response to exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S-D coupling may contribute to the impaired cardiac response to exercise in patients with HCM. METHODS: Patients with HCM (n = 25, age = 47 ± 9 years) and healthy adults (n = 115, age = 49 ± 10 years) underwent a cardiopulmonary exercise testing (CPET) and echocardiogram. S-D coupling was defined as the ratio of LV longitudinal excursion of the mitral annulus during early diastole (EDexc) and systole (Sexc) and compared between groups. Peak oxygen uptake (peak V̇O2) (Douglas bags), cardiac index (C2H2 rebreathe), and stroke volume index (SVi) were assessed during CPET. Linear regression was performed between S-D coupling and peak V̇O2, peak cardiac index, and peak SVi. RESULTS: S-D coupling was lower in HCM (Controls: 0.63 ± 0.08, HCM: 0.56 ± 0.10, p < 0.001). Peak V̇O2 and stroke volume reserve were lower in patients with HCM (Peak VO2 Controls: 28.5 ± 5.5, HCM: 23.7 ± 7.2 mL/kg/min, p < 0.001, SV reserve: Controls 39 ± 16, HCM 30 ± 18 mL, p = 0.008). In patients with HCM, S-D coupling was associated with peak V̇O2 (r = 0.47, p = 0.018), peak cardiac index (r = 0.60, p = 0.002), and peak SVi (r = 0.63, p < 0.001). CONCLUSION: Systolic-diastolic coupling was impaired in patients with HCM and was associated with fitness and the cardiac response to exercise. Inefficient S-D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM.

The impact of surgery resident training on the duration of tibial plateau leveling osteotomy surgery.

OBJECTIVE: To investigate the impact of surgery resident training on surgery duration in tibial plateau leveling osteotomy (TPLO) and evaluate whether surgery duration differs with each year of residency training. STUDY DESIGN: Retrospective medical record review. ANIMALS: A total of 256 client-owned dogs underwent TPLO. METHODS: Records of dogs that underwent TPLO between August 2019 and August 2022 were reviewed. The effects of the surgeon (faculty/resident) and the procedure (arthrotomy/arthroscopy) on TPLO surgery duration were examined with an analysis of variance, and geometric least squares means (GLSM) were compared. A linear mixed effects model (LMM) was fitted to quantify fixed and random effects. RESULTS: Four faculty surgeons performed 74 (29%) TPLOs, while 10 residents performed 182 (71%) TPLOs under the direct supervision of a faculty surgeon. All TPLOs were conducted with arthrotomy (109; 43%) or arthroscopy (147; 57%). Overall, residents (GLSM, 153 min) required 54% more surgery duration than faculty surgeons (GLSM, 99 min). Surgery duration among first-year residents (GLSM, 170 min) was 15% longer than second- (GLSM, 148 min) and third-year (GLSM, 147 min) residents, whereas the duration did not differ statistically between second- and third-year residents. Arthroscopy, meniscal tear treatment, surgery on the right stifle, and increasing patient weight were also associated with longer surgery duration. CONCLUSION: The duration of TPLO surgery significantly decreased after the first year of residency, but did not decrease afterward. CLINICAL SIGNIFICANCE: The results will aid with resource allocation, curricula planning, and cost management associated with resident training.

Respiratory symptom perception during exercise in patients with heart failure with preserved ejection fraction.

We investigated whether central or peripheral limitations to oxygen uptake elicit different respiratory sensations and whether dyspnea on exertion (DOE) provokes unpleasantness and negative emotions in patients with heart failure with preserved ejection fraction (HFpEF). 48 patients were categorized based on their cardiac output (Q̇c)/oxygen uptake (V̇O2) slope and stroke volume (SV) reserve during an incremental cycling test. 15 were classified as centrally limited and 33 were classified as peripherally limited. Ratings of perceived breathlessness (RPB) and unpleasantness (RPU) were assessed (Borg 0-10 scale) during a 20 W cycling test. 15 respiratory sensations statements (1-10 scale) and 5 negative emotions statements (1-10) were subsequently rated. RPB (Central: 3.5±2.0 vs. Peripheral: 3.4±2.0, p=0.86), respiratory sensations, or negative emotions were not different between groups (p>0.05). RPB correlated (p<0.05) with RPU (r=0.925), "anxious" (r=0.610), and "afraid" (r=0.383). While DOE provokes elevated levels of negative emotions, DOE and respiratory sensations seem more related to a common mechanism rather than central and/or peripheral limitations in HFpEF.

Kinematic performance of a novel temporomandibular joint replacement prosthesis under bite-force conditions in dogs and cats.

OBJECTIVE: To evaluate the kinematics and stability of the temporomandibular joint (TMJ) of cats and dogs with and without a TMJ replacement (TMJR) prosthesis under simulated bite forces and mouth opening. ANIMALS: Sixteen cadaver skulls from domestic cats (n = 8) and medium- to large-breed dogs (n = 8). METHODS: Intact TMJs were tested. Following condylectomy and coronoidectomy, the skulls were fitted with a TMJR prosthesis unilaterally and retested. Prosthesis was similarly implanted in the contralateral TMJ in 4 cats and 4 dogs before retesting. Left and right bite motions were evaluated before bite contact to peak bite force (200 N in dogs, 63 N in cats). Mouth opening motion was recorded. Mandibular displacement under load was evaluated in 3 orthogonal planes. Maximal displacement was compared between TMJR groups and native TMJ. Prosthesis-bone motion of the temporal and mandibular components was evaluated during simulated bites and mouth opening. RESULTS: TMJR resulted in joint motion not demonstrably different from the native TMJ, with the ability to fully open and close the mouth and with minimal laterotrusion. The TMJR prosthesis demonstrated similar stability after unilateral and bilateral replacement during bite force and with an open mouth. Mean implant-bone motion during bite simulations for the temporal and mandibular TMJR components was ≤ 60 µm in cats and ≤ 30 µm in dogs. CLINICAL RELEVANCE: A novel TMJR can be implanted and allows normal jaw motion. Joint stability is maintained after TMJR implantation in the TMJ of dogs and cats TMJ that is devoid of muscular support.

Effects of decongestion on nasal cavity air conditioning efficiency: a CFD cohort study.

Decongestion reduces blood flow in the nasal turbinates, enlarging the airway lumen. Although the enlarged airspace reduces the trans-nasal inspiratory pressure drop, symptoms of nasal obstruction may relate to nasal cavity air-conditioning. Thus, it is necessary to quantify the efficiency of nasal cavity conditioning of the inhaled air. This study quantifies both overall and regional nasal air-conditioning in a cohort of 10 healthy subjects using computational fluid dynamics simulations before and after nasal decongestion. The 3D virtual geometry model was segmented from magnetic resonance images (MRI). Each subject was under two MRI acquisitions before and after the decongestion condition. The effects of decongestion on nasal cavity air conditioning efficiency were modelled at two inspiratory flowrates: 15 and 30 L min-1 to represent restful and light exercise conditions. Results show inhaled air was both heated and humidified up to 90% of alveolar conditions at the posterior septum. The air-conditioning efficiency of the nasal cavity remained nearly constant between nostril and posterior septum but dropped significantly after posterior septum. In summary, nasal cavity decongestion not only reduces inhaled air added heat by 23% and added moisture content by 19%, but also reduces the air-conditioning efficiency by 35% on average.

The Test-retest Reliability of Pain Outcome Measures in People with Phantom Limb Pain.

OBJECTIVES: To quantify the test-retest reliability of three patient-reported outcome measures of pain for people living with phantom limb pain (PLP) and assess impact of test-retest errors on future research and clinical decisions. METHODS: Thirty-nine participants (30 males), mean (SD) age: 55 (16), mean (SD) years post amputation: 6.8 (8.3), reported their PLP levels on a Visual Analogue Scale (VAS) for pain intensity, the revised Short Form McGill Pain Questionnaire (SF-MPQ-2), and a pain diary, on two occasions 7-14 days apart. Mean systematic change, within-subjects SD, limits of agreement (LOA), coefficient of variation and the intraclass correlation coefficient (ICC) were quantified alongside their respective 95% confidence intervals (95%CI). RESULTS: Systematic learning effects (mean changes) were not clinically relevant across the VAS, SF-MPQ-2 and pain diary. Within-subjects SDs (95%CI) were 11.8 (9.6-15.3), 0.9 (0.7-1.2), and 8.6 (6.9-11.5), respectively. LOA (95%CI) were 32.6 (26.5-42.4), 2.5 (2-3.3), and 23.9 (19.2-31.8), respectively. ICCs (95%CI) were 0.8 (0.6-0.9), 0.8 (0.7-0.9), and 0.9 (0.8-0.9), respectively, but may have been inflated by sample heterogeneity. The test-retest errors allowed detection of clinically relevant effect sizes with feasible sample sizes in future studies, but individual errors were large. DISCUSSION: For people with PLP, a pain intensity VAS, the SF-MPQ-2, and a pain diary show an acceptable level of inter-session reliability for use in future clinical trials with feasible sample sizes. Nevertheless, the random error observed for all three of the pain outcome measures suggests they should be interpreted with caution in case studies and when monitoring individuals' clinical status and progress.

Review of the genus Eotilla Schuster, 1949 (Hymenoptera: Typhoctinae, Eotillini) 2: species from Chile.

The Eotillini primarily occur in Argentina, Bolivia and Chile. This paper treats the Chilean species of Eotilla Schuster, 1949. In addition to E. mickeli Schuster, 1949, six new species are described, based on males: E. ferruginea Brothers & Torrns sp. nov., E. punctata Brothers & Torrns sp. nov., E. setosa Brothers & Torrns sp. nov., E. fidalgoi Brothers & Torrns sp. nov., E. packeri Brothers & Torrns sp. nov. and E. pallidipes Brothers & Torrns sp. nov.. The previously unknown female of E. mickeli is also described. The distributions of both genera of Eotillini and their possible evolutionary history and zoogeography as related to the uplift of the Andes Mountains are briefly discussed.

Practices and Outcomes Associated With Sublingual Buprenorphine Use in a Critically Ill Population.

IMPORTANCE: Buprenorphine for opioid use disorder (OUD) is commonly used in the outpatient setting with increasing use in hospitalized patients. However, there is limited literature describing its use in critically ill populations. OBJECTIVES: The primary objective was to report the practices of buprenorphine prescribing among ICU teams. We also assessed the effect of a novel initiation strategy on opioid requirements in the ICU and the incidence of precipitated withdrawal. DESIGN SETTING PARTICIPANTS: Single-center, retrospective, descriptive study of patients receiving buprenorphine in the ICU. MAIN OUTCOMES AND MEASURES: The main outcome was to describe the use of buprenorphine in ICU patients through indication, initiation strategy, dosing information, and time from ICU admission to the first dose. We also detailed the incidence of precipitated withdrawal overall and the difference in opioid requirements before and after a low-dose induction strategy (buprenorphine initiated while receiving full agonist opioids [5-d titration from 150 µg to 4 mg four times daily]). RESULTS: A total of 153 patients were included. Most patients (86.3%) received buprenorphine for treatment of OUD. Of the 75 patients taking buprenorphine before admission, 46 (61%) had it restarted within 24 hours of ICU admission. Among 95 patients requiring buprenorphine induction, 57 (60%) underwent standard induction and 38 (40%) underwent low-dose induction, with only one instance of precipitated withdrawal. Median morphine milligram equivalents (MMEs) of concomitant full agonist opioids in patients completing low-dose induction decreased from 1057.5 mg to 262.5 mg in the 24 hours before initiation compared with the 24 hours after target buprenorphine dose was reached (p < 0.005). CONCLUSIONS AND RELEVANCE: Use of sublingual buprenorphine was most often in patients with OUD. Timely continuation of home buprenorphine in the ICU was suboptimal. Both standard and low-dose induction strategies appear to be safe with a low risk of precipitating withdrawal. When implemented appropriately, low-dose buprenorphine induction may lead to significant reduction in full agonist opioids in critically ill patients.

K-wire is more damaging than standard or acrylic drill bits when evaluating torsional properties of rabbit (Oryctolagus cuniculi) femurs.

OBJECTIVE: The objective of this study is to compare drilling variables and torsional mechanical properties of rabbit femora after bicortical drilling with a 1.5-mm standard surgical drill bit, acrylic drill bit, and K-wire. SAMPLES: 24 pairs of rabbit femora. METHODS: After drilling under controlled axial displacement rate, each bone was biaxially loaded in compression followed by rapid external torsion to failure. Maximum axial thrust force, maximum drill torque, integral of force and displacement, change in temperature, maximum power spectral density of the torque signal, torque vibration, and torque and angle at the yield and failure points were collected. Pre- and postyield stiffness, yield and failure energies, and postyield energy were calculated. RESULTS: The work required to drill through the cis- and transcortices (integral of force and displacement) was greater for the K-wire, followed by the acrylic and then standard drill bits, respectively. The K-wire demonstrated higher maximum torque than the drill bits at the ciscortex, and the force of drilling was significantly greater. The vibration data was greater with the acrylic and standard drill bits than the K-wire. There was no difference in torsional strength between drilling types. CLINICAL RELEVANCE: Mechanical differences exist between different drill bits and K-wire and demonstrate that the K-wire is overall more damaging than the surgical drill bit.

The effect of chronic habitual exercise on oxygen carrying capacity and blood compartment volumes in older adults.

Absolute total hemoglobin mass (tHbmass) and blood compartment volumes are often considered to be higher in endurance athletes compared with nonathletes, yet little data support a fitness effect in older age. Therefore, we measured tHbmass and blood compartment volumes (carbon monoxide rebreathing) in 77 healthy individuals (23% female; aged, 60-87 yr). Participants were recruited into groups based upon their lifelong (>25 yr) exercise "dose": 1) 15 sedentary individuals, <2 sessions/wk; 2) 25 casual exercisers, 2-3 sessions/wk; 3) 24 committed exercisers, 4-5 sessions/wk; and 4) 13 competitive Masters athletes, 6-7 sessions/wk, plus regular competitions. Absolute (L/min) and relative (mL/kg/min) V̇o2peak were higher with increasing exercise "dose" (P = 0.0005 and P < 0.0001, respectively). Hemoglobin concentration, hematocrit, and absolute tHbmass and blood compartment volumes were not significantly different between groups (all, P > 0.1328). When scaled to body mass, tHbmass (Sedentary, 9.2 ± 1.7 mL/kg; Casual, 9.2 ± 1.3; Committed, 10.2 ± 1.4; Competitive, 11.5 ± 1.4, ANOVA P < 0.0001) and blood volume were significantly different between groups [Sedentary, 63.4 (59.2-68.5) mL/kg; Casual, 67.3 (64.4-72.6); Committed, 73.5 (67.5-80.2); Competitive, 83.4 (78.9-88.6), ANOVA P < 0.0001], whereby all values were highest in Masters athletes. However, when scaled to fat-free mass (FFM), tHbmass and blood compartment volumes were greater in Competitive compared with Casual exercisers (all, P < 0.0340) and tHbmass and erythrocyte volume were also higher in Committed compared with Casual exercisers (both, P < 0.0134). In conclusion, absolute tHbmass and blood compartment volumes are not different between groups, with dose-dependent differences only among exercisers when scaled for FFM, with the highest tHbmass and blood compartment volumes in competitive Masters athletes.NEW & NOTEWORTHY We observed that absolute oxygen carrying capacity (total hemoglobin mass, tHbmass) and blood compartment volumes were not associated with lifelong exercise dose. However, hematological adaptations associated with lifelong habitual exercise are only present among exercisers, whereby competitive Masters athletes have a greater oxygen carrying capacity (tHbmass) and expanded blood compartment volumes when scaled to fat-free mass.

Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Mice.

BACKGROUND: Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, PTSD, dementia, and age-related cognitive decline. While BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis (AHN), its significance as a pharmacological target has not been tested. METHODS: In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis. One compound with a favorable profile, RO6871135, was then tested in BPS in mice. RESULTS: Chronic treatment with RO6871135, 7.5 mg/kg increased AHN and improved BPS in a fear discrimination task in both young and aged mice. RO6871135 treatment also lowered innate anxiety-like behavior, which was more apparent in mice exposed to chronic corticosterone. Ablation of AHN by hippocampal irradiation supported a neurogenesis-dependent mechanism for RO6871135-induced improvements in BPS. To identify possible mechanisms of action, in vitro and in vivo kinase inhibition and chemical proteomics assays were performed. These tests indicated that RO6871135 inhibited CDK8, CDK11, CaMK2a, CaMK2b, MAP2K6, and GSK3b. An analog compound also demonstrated high affinity for CDK8, CaMK2a, and GSK3b. CONCLUSIONS: These studies demonstrate a method for empirical identification and preclinical testing of novel neurogenic compounds that can improve BPS, and points to possible novel mechanisms that can be interrogated for the development of new therapies to improve specific endophenotypes such as impaired BPS.

Disparities in resource utilisation by families of children with cardiac conditions.

OBJECTIVES: There are limited data documenting sources of medical information that families use to learn about paediatric cardiac conditions. Our study aims to characterise these resources and to identify any disparities in resource utilisation. We hypothesise there are significant variations in the resources utilised by families from different educational and socio-economic backgrounds. METHODS: A survey evaluating what resources families use (websites, healthcare professionals, social media, etc.) to better understand paediatric cardiac conditions was administered to caretakers and paediatric patients at Morgan Stanley Children's Hospital. Patients with a prior diagnosis of CHD, cardiac arrhythmia, and/or heart failure were included. Caretakers' levels of education (fewer than 16 years vs. 16 years or more) and patients' medical insurance types (public vs. private) were compared with regard to the utilisation of resources. RESULTS: Surveys completed by 137 (91%) caretakers and 27 (90%) patients were analysed. Websites were utilised by 72% of caretakers and 56% of patients. Both private insurance and higher education were associated with greater reported utilisation of websites, healthcare professionals, and personal networks (by insurance p = 0.009, p = 0.001, p = 0.006; by education p = 0.022, p < 0.001, p = 0.018). They were also more likely to report use of electronic devices (such as a computer) compared to those with public medical insurance and fewer than 16 years of education (p < 0.001, p < 0.001, respectively). CONCLUSION: Both levels of education and insurance status are associated with the utilisation of informative resources and digital devices by families seeking to learn more about cardiac conditions in children.

Metabolomic profiles of 38 acylcarnitines in major depressive episodes before and after treatment.

BACKGROUND: Major depression is associated with changes in plasma L-carnitine and acetyl-L-carnitine. But its association with acylcarnitines remains unclear. The aim of this study was to assess metabolomic profiles of 38 acylcarnitines in patients with major depression before and after treatment compared to healthy controls (HCs). METHODS: Metabolomic profiles of 38 plasma short-, medium-, and long-chain acylcarnitines were performed by liquid chromatography-mass spectrometry in 893 HCs from the VARIETE cohort and 460 depressed patients from the METADAP cohort before and after 6 months of antidepressant treatment. RESULTS: As compared to HCs, depressed patients had lower levels of medium- and long-chain acylcarnitines. After 6 months of treatment, increased levels of medium- and long-chain acyl-carnitines were observed that no longer differed from those of controls. Accordingly, several medium- and long-chain acylcarnitines were negatively correlated with depression severity. CONCLUSIONS: These medium- and long-chain acylcarnitine dysregulations argue for mitochondrial dysfunction through fatty acid ß-oxidation impairment during major depression.

The Wood equation allows consistent fitting of individual antibody-response profiles of Zika virus or SARS-CoV-2 infected patients.

Antibody kinetic curves obtained during a viral infection are often fitted using aggregated patient data, hiding the heterogeneity of individual humoral immune responses. Individual antibody responses can be modeled using the Wood equation and grouped according to their profile. Such modeling takes into account several important kinetic parameters, such as the day when antibody detection becomes positive [daypos], the day of the maximal response [daymax], the maximum antibody level [levelmax], and the day when antibody detection becomes negative [dayneg]. Potential associations between these profiles and studied factors can then be tested.

Effects of Synchronizing Foot Strike and Cardiac Phase on Exercise Hemodynamics in Patients With Cardiac Resynchronization Therapy: A Within-Subjects Pilot Study to Fine-Tune Cardio-Locomotor Coupling for Heart Failure.

BACKGROUND: Despite advances in medical and cardiac resynchronization therapy (CRT), individuals with chronic congestive heart failure (CHF) have persistent symptoms, including exercise intolerance. Optimizing cardio-locomotor coupling may increase stroke volume and skeletal muscle perfusion as previously shown in healthy runners. Therefore, we tested the hypothesis that exercise stroke volume and cardiac output would be higher during fixed-paced walking when steps were synchronized with the diastolic compared with systolic portion of the cardiac cycle in patients with CHF and CRT. METHODS: Ten participants (58±17 years of age; 40% female) with CHF and previously implanted CRT pacemakers completed 5-minute bouts of walking on a treadmill (range, 1.5-3 mph). Participants were randomly assigned to first walking to an auditory tone to synchronize their foot strike to either the systolic (0% or 100±15% of the R-R interval) or diastolic phase (45±15% of the R-R interval) of their cardiac cycle and underwent assessments of oxygen uptake (V̇o2; indirect calorimetry) and cardiac output (acetylene rebreathing). Data were compared through paired-samples t tests. RESULTS: V̇o2 was similar between conditions (diastolic 1.02±0.44 versus systolic 1.05±0.42 L/min; P=0.299). Compared with systolic walking, stroke volume (diastolic 80±28 versus systolic 74±26 mL; P=0.003) and cardiac output (8.3±3.5 versus 7.9±3.4 L/min; P=0.004) were higher during diastolic walking; heart rate (paced) was not different between conditions. Mean arterial pressure was significantly lower during diastolic walking (85±12 versus 98±20 mm Hg; P=0.007). CONCLUSIONS: In patients with CHF who have received CRT, diastolic stepping increases stroke volume and oxygen delivery and decreases afterload. We speculate that, if added to pacemakers, this cardio-locomotor coupling technology may maximize CRT efficiency and increase exercise participation and quality of life in patients with CHF.