Increase In PvO2 Research Articles

Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy: A Systematic Review.

Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM. This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO2). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient. We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO2 as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial. Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO2, and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO2, and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments.

Personalized remotely guided preventive exercise therapy for a healthy heart (PRIORITY): protocol for an assessor-blinded, multicenter randomized controlled trial.

A key treatment for patients with varying stages of heart failure with preserved ejection fraction (HFpEF) is exercise. Yet, despite a Class 1A recommendation, only one-third of patients exercise sufficiently. A huge treatment gap exists between guidelines and clinical practice. PRIORITY aims to establish the feasibility, clinical effectiveness and cost-effectiveness of a hybrid centre and home-based personalized exercise and physical activity intervention for patients along the HFpEF continuum. An assessor-blinded, multicenter randomized controlled trial will be conducted among 312 patients along the HFpEF continuum. Participants will be randomized (1:1) to the PRIORITY intervention or a comparator group receiving only a written exercise prescription. Participants in the PRIORITY group will receive 18 supervised centre-based exercise sessions during one year, supplemented with a remotely guided home-based physical activity program. Outcomes will be assessed at baseline, 4 months, one and two years. The primary outcome is the peak oxygen uptake (pVO2) at 1-year. Secondary outcomes include physical activity, other physical fitness parameters, cardiovascular health, echocardiographic parameters, health-related quality of life and costs at 1-year FU. Machine learning algorithms will analyse big data on physical activity collected during the 1-year intervention to develop models that can predict physical activity uptake and adherence as well as changes in fitness and health. A cost-utility analysis will be performed to evaluate the cost-effectiveness of the PRIORITY intervention compared to the control condition. We anticipate that participants in the supervised home-based exercise intervention group will have a greater increase in pVO2 compared to those receiving a written exercise prescription. This trial is registered at ClinicalTrials.gov (NCT04745013) and is currently in the recruitment stage.

High Intensity Exercise Improves Cardiorespiratory Capacity in a Mouse Model of Hypertrophic Cardiomyopathy

IntroductionCardiorespiratory capacity (pVO2) is an important prognostic indicator in patients with HCM. Individuals with HCM that have a lower pVO2 possess a greater risk for heart failure (HF) and mortality. High intensity exercise (HIE) can increase pVO2 to a greater degree compared to other training modalities, including when used for cardiac rehabilitation for in cardiac disease states (e.g., HF and Cardiovascular disease). The effects of HIE on HCM, however, are largely unknown. Our study sought to evaluate the effects of High Intensity Interval Training (HIIT) on pVO2, as well as cardiac structural and functional parameters, in a preclinical mouse model of HCM.MethodsFemale and male C57BL/6J non‐transgenic nTG (n=27) and TG (n=32) mice were subjected to HIIT protocol that mirrored methods used clinically in cardiac rehabilitation. A single treadmill training session included 4‐4 minute high intensity intervals (~80% preVO2 max speed) interspersed by 5‐3 minute recovery intervals (~50% preVO2 max speed) for 31 total minutes. Exercise training sessions were repeated 3 times per week for 6 weeks. Pre and post pVO2 and murine echocardiography were measured and analyzed by a blinded technician.ResultsFollowing 6 weeks of the HIIT, nTG female (+13.5 mL/kg/min ± 3.6, p<0.01), nTG male (+13.5 mL/kg/min ± 3.6, p<0.01) and TG female (+7.06 ± 3.3 mL/kg/min, p<0.05) mice demonstrated an average increase in pVO2. A change in pVO2 observed in TG male mice did not reach statistical significance (+4.34 ± p=0.12). Sedentary female (‐15.9 mL/kg/min ± 3.3, p<0.001) and male (‐13.1 mL/kg/min ± 3.9, p<0.01) TG control mice experienced a significant decrease in pVO2 following the same period, while no change was observed in nTG sedentary controls. Independent of sex, nTG and TG HIIT mice had a significantly greater change in pVO2 compared to sedentary counterparts. HIIT training did not result in changes to the following echocardiography measures in either nTG or TG mice: LV mass, LA volume, cardiac output, or stroke volume.ConclusionOur results indicate that a translationally derived HIIT protocol improved cardiorespiratory capacity in a preclinical HCM mouse model, absent of adverse events or worsening of organ level disease pathology.

Abstract 14346: High Intensity Exercise Increases Cardiorespiratory Capacity in a Preclinical Hypertrophic Cardiomyopathy Mouse Model

Introduction: Patients with Hypertrophic Cardiomyopathy (HCM) who possess greater cardiorespiratory capacity (pVO 2 ) are at lower risk for heart transplant and mortality. High intensity exercise (HIE) training used in cardiac rehabilitation for heart failure and cardiovascular disease results in superior increases in pVO 2. The purpose of this investigation was to evaluate the effects of high intensity interval training (HIIT) on pVO 2 , as well as cardiac structural and functional parameters known to be altered by exercise in a transgenic cardiac troponin T (TG) HCM mouse model. Methods: Female and male C57BL/6J non-transgenic nTG (n=27) and TG (n=32) mice underwent a translationally parallel cardiac rehabilitation HIIT protocol. One treadmill training bout included 4-4 minute high intensity intervals (~80% preVO2 max speed) interspersed by 5-3 minute recovery intervals (~50% preVO2 max speed) for 31 total minutes. Bouts were repeated 3 times/wk for 6 wks. Pre and post HIIT pVO 2 and murine echocardiography were measured and analyzed by a blinded technician. Results: Following 6 weeks of the HIIT, nTG female (+13.5 mL/kg/min ± 3.6, p<0.01), nTG male (+13.5 mL/kg/min ± 3.6, p<0.01) and TG female (+7.06 ± 3.3 mL/kg/min, p<0.05) mice demonstrated an average increase in pVO 2 . TG male mice did not reach statistical significance (+4.34 ± p=0.12). Sedentary female (-15.9 mL/kg/min ± 3.3,p<0.001) and male (-13.1 mL/kg/min ± 3.9, p<0.01) TG control mice experienced a significant decrease in pVO 2 following the same period, while no change was observed in nTG sedentary controls. Independent of sex, nTG and TG HIIT mice had a significantly greater change in pVO 2 compared to sedentary counterparts. HIIT training did not result in changes to the following echocardiography measures in either nTG or TG mice: LV mass, LA volume, cardiac output, or stroke volume. Conclusions: Our results indicate that a translationally derived HIIT protocol improves cardiorespiratory capacity in HCM mice, absent of any adverse events or worsening of organ level disease pathology.

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial

Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (-36 mm Hg, 95% CI -43·2 to -28·1; p<0·0001), greater increase in pVO2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB -1·8, -2·4 to -1·2; p<0·0001). 34% more patients in the mavacamten group improved by at least one NYHA class (80 of 123 patients in the mavacamten group vs 40 of 128 patients in the placebo group; 95% CI 22·2 to 45·4; p<0·0001). Safety and tolerability were similar to placebo. Treatment-emergent adverse events were generally mild. One patient died by sudden death in the placebo group. Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy. The results of this pivotal trial highlight the benefits of disease-specific treatment for this condition. MyoKardia.

Relation of Pretransplant Peak Oxygen Consumption to Outcomes After Heart Transplantation

Peak exercise oxygen consumption (pVO2) is an important predictor of prognosis in patients with heart failure (HF). The association between pretransplant pVO2 and post-transplantation outcomes in HF patients has not been previously studied. We identified adult OHT recipients with available pVO2 in the United Network for Organ Sharing registry (2000 to 2015). Patients were divided into 3 categories using Weber classification: class B (pVO2 16 to 20 ml/kg/min), class C (pVO2 10 to 16 ml/kg/min), and class D (pVO2 <10 ml/kg/min). Postoperative outcomes (mortality, renal failure, rejection) were compared between the groups. A total of 9,623 patients were included in this analysis; the mean age was 54 ± 11 years, 74% were male, 75% were white and 59% had nonischemic etiology of HF. The mean pVO2 was 11.7 ± 3.6 ml/kg/min: 1,202 (12.5%) in class B, 6,055 (62.9%) in class C, and 2,366 (24.6%) were in class D. At a median follow-up of 6.1 years, 2,730 (28.4%) died. Post-transplantation survival decreased with decreasing pVO2; 1 and 5-year survival: B (92%, 80%), C (90%, 79%), and D (87%, 75%), p <0.001 by log-rank. After multiple adjustments, patients in class D had significantly higher post-transplantation mortality compared with class C (Hazard Ratio (HR) 1.21 [1.03 to 1.43], p = 0.02). When analyzed as a continuous variable, each 1 ml/kg/min increase in pVO2 was associated with 2% decrease in mortality during follow-up (adjusted HR 0.98 [0.96 to 0.99], p <0.001). Patients in class D had significantly prolonged (>14 days) hospitalization (adjusted Odds Ratio (OR) 1.42 [1.20 to 1.68], p <0.001) and a trend toward increased need for dialysis (adjusted OR 1.36 [1.00 to 1.84], p = 0.05) compared with patients in class B. In this large cohort, lower pretransplant pVO2 was associated with greater mortality and morbidity after OHT. These results suggest that earlier transplantation might improve post-transplantation outcomes in advanced HF patients.

Different outcomes of acardiac rehabilitation programme in functional parameters among myocardial infarction survivors according to ejection fraction.

IntroductionExercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO2) and exercise duration, of an EBCR programme in AMI survivors.MethodsObservational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test.ResultsA total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO2 and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO2 and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO2 (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO2.ConclusionA phase II EBCR programme was associated with significant improvements in pVO2 and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

Cardiac rehabilitation after acute coronary syndrome: Do all patients derive the same benefit?

IntroductionCardiac rehabilitation (CR) has been demonstrated to improve exercise capacity in acute coronary syndrome (ACS), but not all patients derive the same benefit. Careful patient selection is crucial to maximize resources. ObjectiveTo identify in a heterogeneous ACS population which patients would benefit the most with CR, in terms of functional capacity (FC), by using cardiopulmonary exercise testing (CPET). MethodsA retrospective analysis of consecutive ACS patients who underwent CR and CPET was undertaken. CPET was performed at baseline and after 36 sessions of exercise. Peak oxygen uptake (pVO2), percentage of predicted pVO2, minute ventilation/CO2 production (VE/VCO2) slope, VE/VCO2 slope/pVO2 and peak circulatory power (PCP) (pVO2 times peak systolic blood pressure) were assessed in two moments. The differences in pVO2 (ΔpVO2), %pVO2, PCP and exercise test duration were calculated. Patients were classified according to baseline pVO2 (group 1, <20 ml/kg/min vs. group 2, ≥20 ml/kg/min) and left ventricular ejection fraction (group A, <50% vs. group B, ≥50%). ResultsWe analyzed 129 patients, 86% male, mean age 56.3±9.8 years. Both group 1 (n=31) and group 2 (n=98) showed significant improvement in FC after CR, with a more significant increase in pVO2, in group 1 (ΔpVO2 4.4±7.3 vs. 1.6±5.4; p=0.018). Significant improvement was observed in CPET parameters in group A (n=34) and group B (n=95), particularly in pVO2 and test duration. ConclusionPatients with lower baseline pVO2 (<20 ml/kg/min) presented more significant improvement in FC after CR. CPET which is not routinely used in assessement before CR in context of ACS, could be a valuable tool to identify patients who will benefit the most.

Cardiac rehabilitation after acute coronary syndrome: Do all patients derive the same benefit?

IntroductionCardiac rehabilitation (CR) has been demonstrated to improve exercise capacity in acute coronary syndrome (ACS), but not all patients derive the same benefit. Careful patient selection is crucial to maximize resources. ObjectiveTo identify in a heterogeneous ACS population which patients would benefit the most with CR, in terms of functional capacity (FC), by using cardiopulmonary exercise testing (CPET). MethodsA retrospective analysis of consecutive ACS patients who underwent CR and CPET was undertaken. CPET was performed at baseline and after 36 sessions of exercise. Peak oxygen uptake (pVO2), percentage of predicted pVO2, minute ventilation/CO2 production (VE/VCO2) slope, VE/VCO2 slope/pVO2 and peak circulatory power (PCP) (pVO2 times peak systolic blood pressure) were assessed in two moments. The differences in pVO2 (ΔpVO2), %pVO2, PCP and exercise test duration were calculated. Patients were classified according to baseline pVO2 (group 1, <20 ml/kg/min vs. group 2, ≥20 ml/kg/min) and left ventricular ejection fraction (group A, <50% vs. group B, ≥50%). ResultsWe analyzed 129 patients, 86% male, mean age 56.3±9.8 years. Both group 1 (n=31) and group 2 (n=98) showed significant improvement in FC after CR, with a more significant increase in pVO2, in group 1 (ΔpVO2 4.4±7.3 vs. 1.6±5.4; p=0.018). Significant improvement was observed in CPET parameters in group A (n=34) and group B (n=95), particularly in pVO2 and test duration. ConclusionPatients with lower baseline pVO2 (<20 ml/kg/min) presented more significant improvement in FC after CR. CPET which is not routinely used in assessement before CR in context of ACS, could be a valuable tool to identify patients who will benefit the most.

Observed change in peak oxygen consumption after aortic valve replacement and its predictors

ObjectiveTo assess the change in peak oxygen consumption (pVO2) and determine its outcome predictors after aortic valve replacement (AVR) for aortic stenosis (AS).MethodsPatients with AS and preserved left ventricular ejection...

Structured exercise program prior to major cancer surgery improves cardiopulmonary fitness: a retrospective cohort study.

To determine if cardiopulmonary exercise testing (CPET) was useful in predicting response to exercise in cancer patients preoperatively. A secondary aim was to explore if exercise was associated with improved postoperative outcomes. A retrospective cohort study was performed on consecutive cancer patients from 2012 to 2014, referred for exercise prehabilitation and had two CPET preoperatively. Twenty-six patients were analysed. There was a significant overall increase in oxygen uptake at anaerobic threshold (AT) from 10.4 to 11.6 ml kg(-1) min(-1) (ΔAT = 1.2 ± 3.0 ml kg(-1) min(-1) [9 %]; p = 0.046); peak oxygen uptake (pVO2) from 16.0 to 17.7 ml kg(-1) min(-1) (ΔpVO2 = 1.7 ± 2.4 ml kg(-1) min(-1) [9 %]; p = 0.002); and pVO2/BSA from 658 to 726 ml min(-1) m(-2); (ΔpVO2/BSA = 68 ± 112.3 mL min(-1) m(2) [10 %]; p = 0.004). Fifty percent of patients were responders to exercise, defined as having >10 % increase in AT. Responders had a median increase in AT of 26 % [IQR 7 %, 45 %] with an absolute increase in AT of 2.5 ml kg(-1) min(-1) [IQR 1.1, 3.9] (p = 0.002) and a median increase in pVO2 of 22 % [IQR 11.5, 32.5 %] with an absolute increase in pVO2 of 3.8 ml.kg(-1).min(-1) [IQR 2.0, 5.7] (p < 0.001). Responders were more likely to have a lower baseline AT (9.1 ml kg(-1) min(-1); p = 0.002). Exercise improved cardiorespiratory fitness prior to major cancer surgery. Not all patients responded the same, with only 50 % of the study cohort being responders to exercise. A low AT, pVO2 and ratio of AT/pVO2 at baseline were good predictors of response to exercise, with a tendency for responders to suffer fewer major postoperative complications.

Abstract 17519: Exercise Capacity Increase, Obesity, and Statin Therapy Are the Key Factor for Decrease C-Reactive Protein through Exercise Training after Acute Myocardial Infarction

Backgrounds: Cardiac rehabilitation with exercise training (CR/ET) has been reported to be associated with reduction in C-reactive protein (CRP) levels in patients with coronary artery disease. However, determinants of reduction in CRP through CR/ET after acute myocardial infarction (AMI) are not fully understood. Methods: We studied 490 consecutive AMI patients (age 63±11 years, male 83%) who participated in our CR/ET program and underwent measurements for serum CRP and peak oxygen uptake (PVO2) by symptom-limited cardiopulmonary exercise test at the beginning and the end of the 3-month CR program. Patients with abnormally high CRP (&gt;= 20mg/L at baseline, &gt;=10mg/L at 3 months) or on hemodialysis were excluded. Results: After the 3-month CR/ET, body mass index (BMI, 23.3 to 23.1, P&lt;0.001) and CRP (4.7mg/L to 1.1mg/L, P&lt;0.001) significantly decreased, and normalized PVO2 increased (77.4% to 84.9% P&lt;0.001). The magnitude of changes in CRP (ΔCRP) were greater in patients with statin therapy than in patients without statin therapy (-2.9 +/- 0.4mg/L vs -3.9,+/- 0.3mg/L p&lt;0.05). There were significant positive correlation between ΔCRP and HDL-cholesterol (r=0.14), and inverse correlations between ΔCRP and BMI (r=-0.09) and changes in %PVO2 (%ΔPVO2, r=-0.16). Multiple linear regression analysis (incorporating age, sex, baseline ejection fraction, BMI, Brain natriuretic peptide, Hemoglobin A1c, HDL-cholesterol, LDL-cholesterol, statin use, and %ΔPVO2) demonstrated that higher BMI, greater increase in PVO2, higher HDL-cholesterol, and statin use were the independent determinants (all p&lt;0.05) of greater decrease in CRP. Diabetes and smoking status were not the independent determinants of CRP decrease. Conclusion: A greater increase in exercise capacity, in combination with obesity and statin use, significantly associated with a greater reduction in CRP in patients after AMI participating in CR/ET.

Physical activity is associated with improved aerobic exercise capacity over time in adults with congenital heart disease

BackgroundImpaired exercise capacity is common in adults with congenital heart disease (ACHD). This impairment is progressive and is associated with increased morbidity and mortality. We studied the influence of the frequency of at least moderately strenuous physical activity (PhysAct) on changes in exercise capacity of ACHD patients over time. MethodsWe studied ACHD patients ≥21years old who had repeated maximal (RER≥1.09) cardiopulmonary exercise tests within 6 to 24months. On the basis of data extracted from each patient's clinical records, PhysAct frequency was classified as (1) Low: minimal PhysAct, (2) Occasional: moderate PhysAct <2 times/week, or (3) Frequent: moderate PhysAct ≥2 times/week. ResultsPhysAct frequency could be classified for 146 patients. Those who participated in frequent exercise tended to have improved pVO2 (∆pVO2=+1.63±2.67ml/kg/min) compared to those who had low or occasional activity frequency (∆pVO2=+0.06±2.13ml/kg/min, p=0.003) over a median follow-up of 13.2months. This difference was independent of baseline clinical characteristics, time between tests, medication changes, or weight change. Those who engaged in frequent PhysAct were more likely to have an increase of pVO2 of ≥1SD between tests as compared with sedentary patients (multivariable OR=7.4, 95%CI 1.5–35.7). Aerobic exercise capacity also increased for patients who increased activity frequency from baseline to follow-up; 27.3% of those who increased their frequency of moderately strenuous physical activity had a clinically significant (at least +1SD) increase in pVO2 compared to only 11% of those who maintained or decreased activity frequency. ConclusionsACHD patients who engage in frequent physical activity tend to have improved exercise capacity over time.

The use of ultrapurified bovine hemoglobin solution in the treatment of two cases of presumed red maple toxicosis in a miniature horse and a pony

AbstractObjective: To report the use of ultrapurified bovine hemoglobin (PBHg) in the treatment of red maple toxicosis in horses.Summary: The use of PBHg in a miniature horse and a pony with clinical signs of red maple toxicosis is described. Initial treatment of the horses included blood transfusion in Case 1, and intravenous crystalloid fluids, nasogastrically administered mineral oil, and activated charcoal in both cases. Both cases received PBHg (16 and 11 ml/kg, respectively) when the hematocrit dropped below 10%. Clinical stabilization of the horses (reflected by improved vital signs and mucous membrane color, increase in PvO2, and increase in plasma hemoglobin) was temporary, lasting 12 and 42 hours, respectively. A whole blood transfusion was given 16 hours after the infusion of PBHg in Case 1 and 42 hours after the infusion of PBHg in Case 2. The horses were discharged on days 15 and 17, respectively. Both were stable on discharge and were reported to be doing well 1 month after discharge. New information provided: Ultrapurified bovine hemoglobin is shown to be safe in the treatment of red maple toxicosis. Ultrapurified bovine hemoglobin infusion resulted in temporary improvement in oxygen (O2) delivery as assessed by clinical and laboratory parameters. The use of PBHg may provide an ‘oxygen bridge’ in an acute hemolytic crisis in the horse. It may allow additional time in the treatment of red maple toxicity for the acute hemolysis to subside and for metabolism of the toxin to occur, thus providing a more optimal environment for an effective whole blood transfusion.

Influence of continuous haemofiltration-related hypothermia on haemodynamic variables and gas exchange in septic patients

To investigate the influence of continuous haemofiltration (CHF) on haemodynamics, gas exchange and core temperature in critically ill septic patients with acute renal failure. In 20 patients (17 male, 3 female) ultrafiltration rate, core temperature, gas exchange and haemodynamic variables were measured at regular intervals during the first 48 h of haemofiltration. Baseline data were compared to those obtained 30 min after initiating CHF and also to those during hypothermia (if observed). Haemodynamic variables remained remarkably constant throughout the study period. In patients with a relatively low ultrafiltration rate (855 +/- 278 ml/h) temperature did not change, while in patients with a high ultrafiltration rate (1468 +/- 293 ml/h) core temperature significantly decreased from 37.6 +/- 0.9 degrees C to 34.8 +/- 0.8 degrees C (p < 0.001). There was a statistically significant correlation between temperature decrease and ultrafiltration rate (r = -0.68, Y = 1.8-0.003 X, p < 0.01). Hypothermic patients also showed a mean decrease in VO2 from 141 +/- 22 ml/min/m2 to 112 +/- 22 ml/min/m2 (p < 0.01) with a concomitant increase in PaO2 from 103 +/- 37 mmHg to 140 +/- 42 mmHg (p < 0.001) and in PvO2 from 35 +/- 4 mmHg to 41 +/- 5 mmHg (p < 0.001). 1) Continuous haemofiltration does not cause significant alternations in haemodynamic variables. 2) Hypothermia frequently occurs in patients undergoing continuous haemofiltration with high ultrafiltration rates. These hypothermic patients show a reduction in VO2 leading to an increase in PvO2 and PaO2. This mild hypothermia in these circumstances has no evident deleterious effects.

Relationship Between Mixed Venous Oxygen Saturation and Cardiac Index in Patients with Chronic Congestive Heart Failure

The use of mixed venous oxygen saturation (SvO2) in patients with chronic congestive heart failure (CHF) has been advocated to analyze the action of therapy on cardiac index (CI). To evaluate the relationship between CI and SvO2, ten CHF patients (mean age 65 years) were studied before and one, two, three, four (T4), six, eight and 24 hours after oral administration of an angiotensin converting enzyme (ACE) inhibitor (perindopril, 4 mg). At T4, a 12 percent increase in CI (p less than 0.01) was associated with a 16 percent decrease in arteriovenous oxygen difference (p less than 0.01), a 13 percent increase in mixed venous oxygen pressure (PvO2) (p less than 0.01), and a 9 percent increase in SvO2 (p less than 0.05) with no significant change in arterial oxygen pressure. There was no correlation between CI and SvO2 (r = 0.22) and between CI and PvO2 (r = 0.23). Individual analyses were performed and patients were divided into two groups based on CI versus SvO2 r value; group 1, n = 6, r greater than 0.65 (0.65-0.90), group 2, n = 4, r less than 0.65 (0.14-0.20). The lack of correlation in group 2 was due to a drug-dependent increase in oxygen consumption (VO2) +18 percent vs -3 percent in group 1 (p less than 0.05) associated with a lack of increase in PvO2 +3 percent vs +14 percent in group 1 (p less than 0.05) despite a similar increase in oxygen availability +19 percent versus +16 percent. It was concluded that (1) a correlation between CI and SvO2 is not found in every patient with CHF; (2) the lack of correlation in four out of our ten patients was due to an associated and significant increase in CI and VO2 in group 2; (3) group 2 patients probably had an important oxygen debt before treatment; (4) SvO2 cannot be used instead of CI to determine the hemodynamic consequences of the use of cardiovascular drugs.

Early physiologic changes in canine fecal peritonitis.

Oxygen delivery (DO2) and related variables were studied in eight dogs during severe untreated peritonitis induced by cecal ligation and perforation. The development of peritonitis was accompanied by abdominal fluid sequestration and significant increases in hemoglobin (Hgb), arterial oxygen content (CaO2), and P50. Changes in mixed venous PO2 (P-vO2), mixed venous saturation (S-vO2), DO2, oxygen uptake (VO2), cardiac index (CI), and arteriovenous O2 difference (C[a--v]O2) were not significant. When blood volume was returned to normal levels with dextran, CI rose and C(a--v)O2 decreased; P-vO2 increased and Hgb returned to baseline levels. In this animal model, sepsis and fluid sequestration produced an increase in blood O2 capacity and CaO2, which sustained DO2 and VO2. No changes were observed in P-vO2 or S-vO2. The hyperdynamic state of severe sepsis became evident only after reversing hemoconcentration by colloid infusion. The increase in P-vO2 and S-vO2 after volume loading is possibly related to primary septic mechanisms and/or to changes in DO2.

Correlation of changes in oxygenation, lung water and hemodynamics after oleic acid-induced acute lung injury in dogs.

Changes in oxygenation after oleic acid (OA)-induced acute lung injury were correlated to changes in extravascular lung water (EVLW) and hemodynamics in 19 mongrel dogs. Three patterns seemed apparent. In group 1 (seven dogs) EVLW increased by 88% from control values but PaO2 fell only 15%. The change in PaO2 in this group was related directly to the change in mixed venous O2 tension (PvO2) after the OA-induced fall in cardiac output. In group 2 (eight dogs), EVLW rose by 120% and PaO2 fell 53%, 90 min after OA administration. In this group, there was a subsequent spontaneous improvement of PaO2 to 75% of control values, without any measured change in EVLW. In group 3 (four dogs), the fall in PaO2 was comparable to that of group 2, but the increase in EVLW was greater (148%) and there was no spontaneous improvement in oxygenation. Cardiac index fell in all three groups. A small but significant increase in PvO2 partially explains the improvement in oxygenation in group 2. We conclude that changes in oxygenation are a poor index of injury during this model of acute lung injury and that the course of oxygenation is directly related to measured changes in EVLW and hemodynamics.

Effects of pulmonary blood flow and mixed venous O2 tension on gas exchange in dogs.

The authors investigated whether the increases in venous admixture and intrapulmonary shunt which occur with increases in cardiac output (Qt) results from an effect mediated by mixed venous PO2 (PVO2) or an effect mediated by the increase in pulmonary blood flow. Using a veno-venous bypass system thay were able to alter PVO2 independent of variations in Qt and vice versa. During room air ventilation of dogs with normal lungs at constant Qt, an increase in PVO2 from 33 +/- 7 (mean +/- SD) to 54 +/- 9 mmHg (P less than 0.05) resulted in a decrease in venous admixture from 22 +/- 11 to 13 +/- 4% (P less than 0.05). During room air ventilation of normal dogs at a constant PVO2, raising Qt from 2.16 +/- .53 to 3.49 +/- 0.91 l/min (P less than 0.05) increased venous admixture from 10 +/- 5 to 16 +/- 5% (P less than 0.05). During oxygen ventilation in these two groups of dogs, changes in PVO2 and Qt had no effect on shunt. During oxygen ventilation of dogs with significant shunts from oleic-acid-induced pulmonary edema, independent increases in either PVO2 or pulmonary blood flow resulted in increased shunt. At constant Ot, an increase in PVO2 from 30 +/- 8 to 52 +/- 3 mmHg (P less than 0.05) resulted in an increase in shunt from 39 +/- 12 to 43 +/- 12% (P less than 0.05). When PVO2 remained constant, increasing Qt from 1.97 pm 0.42 to 3.61 +/- 0.50 l/min (P less than 0.05) resulted in an increase in shunt from 47 +/- 17 to 53 +/- 15% (P less than 0.05). The authors conclude that during oxygen ventilation, normal dogs have shunts which are unaffected by changes in blood flow or PVO2. Increases in pulmonary blood flow increase venous admixture during room air ventilation, while increases in PVO2 decrease venous admixture during air ventilation. In edematous lungs, increases in either PVO2 or pulmonary blood flow increase shunt.

866 RELATIVE EFFECT OF BLOOD OXYGEN (O2) TRANSPORT CHARACTERISTICS ON OPTIMAL OXYGEN DELIVERY TO THE TISSUES

The present study investigates the relative importance of altering O2 content and/or hemoglobin O2 affinity (P50) in changing cardiac output (C.O.) and O2 delivery to the tissues. 18 newborn (NB) lambs were divided into 3 groups. Blood gases, [Hb], P50 (mm Hg), regional blood flow (ml/min/100g tissue) and C.O. (ml/min/kg) were measured before and 2 hrs after alteration of O2 affinity and/or content by means of exchange transfusing the lambs with fetal or maternal blood of varying Hct. O2 content was increased 38% in Gr 1 (n=6) with no change in P50. O2 content and P50 were increased 9% and 32% in Gr 2 (n=5), and 38% and 32% in Gr 3 (n=7), respectively. C.O. decreased 39% (364-221), 45% (324-177) and 48% (318-166) in groups 1,2 and 3, respectively. Systemic O2 delivery decreased 22% in Gr 2 (52.9-32.4) and 26% in Gr 3 (45-33) and was unchanged in Gr 1. PVO2 increased in Gr 2 from 31.8 to 34.6 and in Gr 3 from 23.4 to 32.3. O2 consumption was unchanged in all groups. These data suggest that in the NB lamb an increased P50 associated with increased Hct provides the same reduction of C.O. as a 4-fold increased Hct without change in P50. Higher increase in O2 content provides no further reduction in C.O. but a greater increase in PVO2, suggesting enhanced O2 availability to the tissues. These data suggest that the combined effect of increased P50 and increased O2 content achieves optimal O2 delivery, presumably at the greatest economy of the cardiovascular system.