Mechanisms of increased right and left ventricular oxygen uptake during inotropic stimulation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Low cardiorespiratory fitness (CRF) is associated with high mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis, different cancers, renal impairment and, in particular, for heart failure. Further, higher Gal-3 levels are associated with increased cardiovascular mortality. Whether Gal-3 is related with the protective effects of a high CRF is unclear. Purpose The present study examined the relation between Gal-3 and CRF as determined by body weight adjusted peak oxygen uptake (VO2peak/kg), oxygen uptake at the anaerobic threshold (VO2@AT) and maximal workload (Wmax). Methods We used data of the population-based Study of Health in Pomerania (SHIP-TREND) from Northeast Germany. A total of n = 1,483 participants with a median age of 49 (IQR: 39 – 59 years, male 48%) were included in the analysis. CRF parameters were measured using standardized cardiopulmonary exercise testing on a bicycle ergometer. Plasma galectin-3 concentrations were determined using a quantitative sandwich enzyme immunoassay. Individuals with left ventricular ejection fraction < 40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (eGFR < 30 ml/min/mm2), a history of cancer, and extreme values for Gal-3 were excluded. Linear regression models adjusted for age, sex and lean mass were used to analyze the association between Gal-3 and CRF. Results A one ml/min/kg greater VO2peak was related to a 0.32 ng/ml (95% confidence interval [CI] -0.45 to -0.18, p <.001) lower Gal-3. Further, a one Watt larger power output was also associated with a 1.32 ng/ml (95% CI -2.10 to – 0.54, p <.001) lesser Gal-3. VO2@AT was not related to Gal-3 (β: -3.31 95% CI -8.68 to 2.05, p = .23). Conclusions In the general population Gal-3 is inversely associated with CRF. Further studies should investigate whether lower Gal-3, beyond its importance as a biomarker for heart disease, may even play a role in the protective effect of the CRF.

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Central and peripheral adaptations of the gas transport system to one-leg training

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y81-177 ◽

1981 ◽

Vol 59 (11) ◽

pp. 1146-1154 ◽

Cited By ~ 5

Author(s):

S. G. Thomas ◽

D. A. Cunningham ◽

M. J. Plyley ◽

D. R. Boughner ◽

R. A. Cook

Keyword(s):

Cardiac Output ◽

Oxygen Uptake ◽

Endurance Training ◽

Maximal Oxygen Uptake ◽

Enzyme Activities ◽

Cardiovascular Responses ◽

Cycle Ergometer ◽

Left Ventricular ◽

Enzyme Analysis ◽

Ergometer Exercise

The role of central and peripheral adaptations in the response to endurance training was examined. Changes in cardiac structure and function, oxygen extraction, and muscle enzyme activities following one-leg training were studied.Eleven subjects (eight females, three males) trained on a cycle ergometer 4 weeks with one leg (leg 1), then 4 weeks with the second leg (leg 2). Cardiovascular responses to exercise with both legs and each leg separately were evaluated at entry (T1), after 4 weeks of training (T2), and after a second 4 weeks of training (T3). Peak oxygen uptake ([Formula: see text] peak) during exercise with leg 1 (T1 to T2 increased 19.8% (P < 0.05) and during exercise with leg 2 (T2 to T3 increased 16.9% (P < 0.05). Maximal oxygen uptake with both legs increased 7.9% from T1 to T2 and 9.4% from T2 to T3 (P < 0.05). During exercise at 60% of [Formula: see text] peak, cardiac output [Formula: see text] was increased significantly only when the trained leg was exercised. [Formula: see text] increased 12.2% for leg 1 between T1 and T2 and 13.0% for leg 2 between T2 and T3 (P < 0.05). M-mode echocardiographic assessment of left ventricular internal diameter at diastole and peak velocity of circumferential fibre shortening at rest or during supine cycle ergometer exercise at T1 and T3 revealed no training induced changes in cardiac dimensions or function. Enzyme analysis of muscle biopsy samples from the vastus lateralis (At T1, T2, T3) revealed no consistent pattern of change in aerobic (malate dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase) or anaerobic (phosphofructokinase, lactate dehydroginase, and creatine kinase) enzyme activities. Increases in cardiac output and maximal oxygen uptake which result from short duration endurance training can be achieved, therefore, without measurable central cardiac adaptation. The absence of echocardio-graphically determined changes in cardiac dimensions and contractility and the absence of an increase in cardiac output during exercise with the nontrained leg following training of the contralateral limb support this conclusion.

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How to Be 80 Year Old and Have a VO2maxof a 35 Year Old

Case Reports in Medicine ◽

10.1155/2015/909561 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Trine Karlsen ◽

Ingeborg Megård Leinan ◽

Fredrik Hjulstad Bækkerud ◽

Kari Margrethe Lundgren ◽

Atefe Tari ◽

...

Keyword(s):

Physical Activity ◽

Oxygen Uptake ◽

Maximal Oxygen Uptake ◽

Left Ventricular ◽

Left Ventricular Filling ◽

Maximal Heart Rate ◽

Cardiopulmonary Fitness ◽

Systolic And Diastolic Function ◽

High Level ◽

Ventricular Filling

Background. To discuss the cardiovascular and pulmonary physiology and common risk factors of an 80-year-old man with a world record maximal oxygen uptake of 50 mL·kg−1·min−1.Methods. Case report.Results. His maximal oxygen uptake of 3.31 L·min−1, maximal heart rate of 175 beats·min−1, and maximal oxygen pulse of 19 mL·beats−1are high. He is lean (66.6 kg) and muscular (49% skeletal muscle mass). His echo parameters of mitral flow (left ventricular filling,E= 82 cm·s−1andE/A= 1.2) were normal for 40- to 60-year-old men. Systolic and diastolic function increased adequately during exercise, with no increase in left ventricular filling pressure. He has excellent pulmonary function (FVC = 4.31 L, FEV1 = 3.41, FEV1/FVC = 0.79, and DLCO = 12.0 Si1) and normal FMD and blood volumes (5.8 L). He has a high level of daily activity (10,900 steps·day−1and 2:51 hours·day−1of physical activity) and a lifelong history of physical activity.Conclusion. The man is in excellent cardiopulmonary fitness and is highly physically active. His cardiac and pulmonary functions are above expectations for his age, and his VO2maxis comparable to that of an inactive 25-year-old and of a normal, active 35-year-old Norwegian man.

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Obesity and hemoglobin content impact peak oxygen uptake in human heart failure

European Journal of Preventive Cardiology ◽

10.1177/2047487318802695 ◽

2018 ◽

Vol 25 (18) ◽

pp. 1937-1946 ◽

Cited By ~ 9

Author(s):

Erik H Van Iterson ◽

Chul-Ho Kim ◽

Katelyn Uithoven ◽

Thomas P Olson

Keyword(s):

Heart Failure ◽

Body Mass Index ◽

Oxygen Uptake ◽

Left Ventricular ◽

Exercise Intolerance ◽

Left Ventricular Ejection ◽

Peak Exercise ◽

Ventricular Ejection Fraction ◽

Group 4 ◽

Group 1

Background Exercise intolerance, obesity, and low hemoglobin (hemoglobin<13 and <12 g/dl, men/women, respectively) are common features of heart failure. Despite serving as potent contributors to metabolic dysfunction, the impact of obesity and low hemoglobin on exercise intolerance is unknown. This study tested the hypotheses, compared with non-obese (NO) heart failure with normal hemoglobin, (a) counterparts with low hemoglobin and obesity or non-obesity will demonstrate reduced peak exercise oxygen uptake; (b) obese with normal hemoglobin will demonstrate decreased peak exercise oxygen uptake; (c) compared across stratifications, obese with low hemoglobin will demonstrate the sharpest decrement in peak exercise oxygen uptake. Methods Adults with heart failure ( n = 315; left ventricular ejection fraction≤40%; 77% men) (Group 1: normal hemoglobin and non-obese, n = 137; Group 2: low hemoglobin and non-obese, n = 51; Group 3: normal hemoglobin+obesity, n = 89; Group 4, n = 38: low hemoglobin+obesity; body mass index = 26 ± 3, 26 ± 2, 34 ± 4, 34 ± 4 kg/m2, respectively) completed treadmill cardiopulmonary exercise testing as part of routine clinical management. Peak exercise oxygen uptake was measured via standard metabolic system. Results There were no group-wise differences for heart failure class, gender, left ventricular ejection fraction, and resting cardiopulmonary function. Group 1 demonstrated increased peak exercise oxygen uptake versus Groups 2–4 (20 ± 6 versus 17 ± 6, 17 ± 5, 13 ± 4 ml/kg/min, respectively; all p < 0.001); whereas Group 4 peak exercise oxygen uptake was reduced versus all groups ( p < 0.001). Additionally, both body mass index (R2 = 0.10) and hemoglobin (R2 = 0.12) were significant predictors of peak exercise oxygen uptake in Group 1; which were relationships not mirrored for Groups 2–4. Conclusion These data suggest obesity together with low hemoglobin are potent contributors to impaired peak exercise oxygen uptake and, hence, oxidative metabolic capacity. In diverse populations of heart failure where obesity and/or low hemoglobin are present, it is important to consider these features together when interpreting peak exercise oxygen uptake and underlying exercise limitations.

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Oxygen delivery and myocardial function in rabbit hearts perfused with cell-free hemoglobin

Journal of Applied Physiology ◽

10.1152/jappl.1992.72.2.476 ◽

1992 ◽

Vol 72 (2) ◽

pp. 476-483 ◽

Cited By ~ 21

Author(s):

V. W. MacDonald ◽

R. M. Winslow

Keyword(s):

Oxygen Uptake ◽

Myocardial Function ◽

Oxygen Affinity ◽

Left Ventricular ◽

Rate Of Change ◽

Free Hemoglobin ◽

Langendorff Preparation ◽

Oxygen Gradients ◽

Developed Pressure ◽

Krebs Henseleit Buffer

Isolated rabbit hearts were perfused with Krebs-Henseleit buffer that contained 1.5 g/dl hemoglobin Ao [HbAo; PO2 at which half-saturation of hemoglobin occurs = 12 Torr], human hemoglobin cross-linked between alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha-Hb; PO2 at which half-saturation of hemoglobin occurs = 30 Torr), or fatty acid-free bovine serum albumin (BSA). Myocardial performance and oxygen uptake were determined at different aortic PO2's [arterial PO2 (PaO2)] by use of an isovolumic Langendorff preparation. Function and oxygen uptake were comparable among the three different groups of hearts at an average mean PaO2 of 557 Torr. As PaO2 decreased, myocardial function was preserved better in hearts perfused with hemoglobin than in hearts perfused with Krebs-Henseleit buffer alone or with BSA. Hearts perfused with either HbAo or alpha alpha-Hb exhibited similar 10% decreases in left ventricular developed pressure and rate of change in left ventricular developed pressure at PaO2 of 141 Torr compared with a 58% decrease with BSA. However, corresponding venous PO2's were lower with HbAo (20 Torr) than with alpha alpha-Hb (35 Torr), and oxygen uptake decreased by 36% with HbAo but remained constant with alpha alpha-Hb. These data suggest that although myocardial function can be sustained over a fairly broad range of hemoglobin oxygen affinities, tissue oxygen gradients and myocardial oxygen uptake are maintained better by cell-free hemoglobin with an oxygen affinity in the normal physiological range.

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Contractile function of heterogeneously perfused myocardium in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.256.2.h352 ◽

1989 ◽

Vol 256 (2) ◽

pp. H352-H360 ◽

Cited By ~ 1

Author(s):

M. Nagata ◽

M. Lavallee

Keyword(s):

Contractile Function ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Left Ventricular ◽

Ischemic Myocardium ◽

Conscious Dogs ◽

Base Line ◽

Circumflex Coronary Artery ◽

Ventricular Afterload ◽

Inotropic Stimulation

The contractile function of heterogeneously perfused segments (HET) after circumflex coronary artery occlusion (CAO) was examined in conscious dogs. At 1 h after CAO, regional shortening (SH) in nonischemic segments did not change from pre-CAO base line, and regional endocardial blood flow (REBF) increased (P less than 0.05) to 1.52 +/- 0.20 from 1.06 +/- 0.08 ml.min-1.g of tissue-1. In ischemic segments, SH was replaced by paradoxical bulging, and REBF averaged 0.07 +/- 0.02 ml.min-1.g of tissue-1. In HET with one crystal of each pair in nonischemic myocardium and the other in severely ischemic myocardium, SH at 1 h after CAO was reduced (P less than 0.01) by 53.2 +/- 3.4%. REBF maps constructed with serial sections of ventricular rings containing the crystals revealed that in HET 50 +/- 5% of the myocardium was ischemic. Therefore, in the acute phase of ischemia, the reductions in SH in HET were proportional to the amount of ischemic myocardium between recording sites. In HET, SH significantly recovered (P less than 0.01) over 4 wk after CAO but remained depressed by 26.8 +/- 5.1%. In contrast, SH in ischemic segments did not improve after CAO. In HET, the effects of inotropic stimulation and changes in left ventricular afterload on SH (as percent of base line) were similar before and at 1-4 wk after CAO. Thus, in HET, the level of dysfunction is acutely determined by the amount of ischemic myocardium between recording sites. Over 4 wk after CAO, SH improved substantially in these segments, and contractile function was not adversely influenced by an inotropic stimulation or an increase in ventricular afterload.

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Cardiac adjustments to left-side inotropic stimulation of in situ pig hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.252.6.h1164 ◽

1987 ◽

Vol 252 (6) ◽

pp. H1164-H1174

Author(s):

O. A. Vengen ◽

K. Lande ◽

O. Ellingsen ◽

A. Ilebekk

Keyword(s):

Right Ventricular ◽

Systemic Circulation ◽

Left Ventricular ◽

Segment Length ◽

Ventricular Afterload ◽

Computer Based ◽

The Right ◽

Isoproterenol Infusion ◽

Inotropic Stimulation ◽

Stimulation Of

Cardiac adjustments to inotropic stimulation of the left side of the heart by continuous infusions of isoproterenol (0.6-0.8 microgram/min) and calcium chloride (240 mumol/min) into the left coronary artery were examined in open-chest pigs (17-36 kg) anesthetized with pentobarbital sodium. Both agents caused a reduction in the left ventricular (LV) preload and preejection segment length (PESL). Stroke volume (SV) rose by only 1.2 ml from 15.9 ml (P less than 0.01) during isoproterenol infusion, but when the reduction in LV PESL of 3.2% (P less than 0.01) was restored by saline infusion, SV increased by 27%. The LV PESL reduction was less at hypervolemia than at normovolemia. A computer-based model of the circulation predicted most of these changes and suggested redistribution of blood from the pulmonary to the systemic circulation. During isoproterenol infusion, the pulmonary arterial pressure fell, and the right ventricular end-ejection segment length declined. Reduced right ventricular afterload thus appears to be an important mechanism by which right ventricular output is increased during a selective increase in LV inotropy.

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