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Influence of oxygen tension on myocardial performance. Evaluation by tissue Doppler imaging.
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MedLine Citation:
PMID:  15522119     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Low O2 tension dilates coronary arteries and high O2 tension is a coronary vasoconstrictor but reports on O2-dependent effects on ventricular performance diverge. Yet oxygen supplementation remains first line treatment in cardiovascular disease. We hypothesized that hypoxia improves and hyperoxia worsens myocardial performance.
METHODS: Seven male volunteers (mean age 38 +/- 3 years) were examined with echocardiography at respiratory equilibrium during: 1) normoxia (approximately 21% O2, 79% N2), 2) while inhaling a hypoxic gas mixture (approximately 11% O2, 89% N2), and 3) while inhaling 100% O2. Tissue Doppler recordings were acquired in the apical 4-chamber, 2-chamber, and long-axis views. Strain rate and tissue tracking displacement analyses were carried out in each segment of the 16-segment left ventricular model and in the basal, middle and apical portions of the right ventricle.
RESULTS: Heart rate increased with hypoxia (68 +/- 4 bpm at normoxia vs. 79 +/- 5 bpm, P < 0.001) and decreased with hyperoxia (59 +/- 5 bpm, P < 0.001 vs. normoxia). Hypoxia increased strain rate in four left ventricular segments and global systolic contraction amplitude was increased (normoxia: 9.76 +/- 0.41 vs hypoxia: 10.87 +/- 0.42, P < 0.001). Tissue tracking displacement was reduced in the right ventricular segments and tricuspid regurgitation increased with hypoxia (7.5 +/- 1.9 mmHg vs. 33.5 +/- 1.8 mmHg, P < 0.001). The TEI index and E/E' did not change with hypoxia. Hyperoxia reduced strain rate in 10 left ventricular segments, global systolic contraction amplitude was decreased (8.83 +/- 0.38, P < 0.001 vs. normoxia) while right ventricular function was unchanged. The spectral and tissue Doppler TEI indexes were significantly increased but E/E' did not change with hyperoxia.
CONCLUSION: Hypoxia improves and hyperoxia worsens systolic myocardial performance in healthy male volunteers. Tissue Doppler measures of diastolic function are unaffected by hypoxia/hyperoxia which support that the changes in myocardial performance are secondary to changes in vascular tone. It remains to be settled whether oxygen therapy to patients with heart disease is a consistent rational treatment.
Ole Frøbert; Jacob Moesgaard; Egon Toft; Steen Hvitfeldt Poulsen; Peter Søgaard
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-02
Journal Detail:
Title:  Cardiovascular ultrasound     Volume:  2     ISSN:  1476-7120     ISO Abbreviation:  Cardiovasc Ultrasound     Publication Date:  2004  
Date Detail:
Created Date:  2005-07-19     Completed Date:  2006-04-05     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  101159952     Medline TA:  Cardiovasc Ultrasound     Country:  England    
Other Details:
Languages:  eng     Pagination:  22     Citation Subset:  IM    
Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Denmark.
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MeSH Terms
Heart Ventricles / ultrasonography*
Middle Aged
Myocardial Contraction / physiology*
Oxygen / metabolism*
Oxygen Consumption / physiology*
Stroke Volume / physiology
Ventricular Function*
Ventricular Function, Left / physiology*
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Cardiovasc Ultrasound
ISSN: 1476-7120
Publisher: BioMed Central, London
Article Information
Copyright ? 2004 Fr?bert et al; licensee BioMed Central Ltd.
open-access: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received Day: 26 Month: 8 Year: 2004
Accepted Day: 2 Month: 11 Year: 2004
collection publication date: Year: 2004
Electronic publication date: Day: 2 Month: 11 Year: 2004
Volume: 2First Page: 22 Last Page: 22
ID: 529306
Publisher Id: 1476-7120-2-22
PubMed Id: 15522119
DOI: 10.1186/1476-7120-2-22

Influence of oxygen tension on myocardial performance. Evaluation by tissue Doppler imaging
Ole Fr?bert12 Email:
Jacob Moesgaard1 Email:
Egon Toft3 Email:
Steen Hvitfeldt Poulsen4 Email:
Peter S?gaard1 Email:
1Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Denmark
2Institute of Pharmacology, University of Aarhus, Denmark
3Center for Model-based Medical Decision Support Systems, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
4Skejby University Hospital, Aarhus, Denmark


Low oxygen tension dilates coronary arteries and high oxygen tension is a coronary vasoconstrictor. Yet oxygen supplementation remains first line treatment in cardiovascular disease states such as myocardial infarction and pulmonary oedema.

Endothelium-dependent vasodilation is reduced in patients with ischemic heart disease [1] and such patients are believed to have a reduced ability to counteract the circulatory consequences of systemic (air line travel, high altitude stay) and regional (coronary artery stenosis) hypoxia. Spontaneous nocturnal hypoxia with desaturation for hours is a frequent phenomenon in patients with severe coronary artery disease [2]. Left atrial, left ventricular (LV), and right ventricular (RV) end-systolic diameter fall during simulated extreme altitude [3] and during moderate altitude exposure [4]. There is controversy concerning myocardial performance during hypoxia; improvement [4], no change [3,5,6]. and worsening [7] of left ventricular systolic function, have been described. One study looked at diastolic function expressed as E/A ratio and found a reduction with hypoxia [3].

Hyperoxia, a condition in which the total oxygen content of the body is increased above that normally existing at sea level, is associated with impairment of cardiac relaxation and increased left ventricular filling pressures in patients with and without congestive heart failure [8].

Tissue Doppler imaging (TDI) objectively derives measurements of contraction and relaxation velocities directly from the myocardium and thus yields information not previously accessible by echocardiography [9]. We used TDI to study myocardial performance in healthy volunteers and we hypothesized that hypoxia increases and hyperoxia reduces myocardial performance.

Material and Methods

Seven healthy men, (age 25?46 (mean 38) years) completed the study. All subjects were normotensive, non-smokers, on no medication, had a normal left ventricular function by 2-D echocardiography, and had no family history of ischemic heart disease. The local ethical committee approved the study.

Ventilation system

We used a system consisting of a ventilator, a gas analyser with pulse oximeter, and a computer. Computer programs control the experimental procedure and continuously collect data from the ventilator and gas analyser [10].


Echocardiography was performed from the apical acoustic window. Tissue Doppler recordings were acquired as digital loops in the apical 4-chamber, 2-chamber, and long-axis views [9]. To avoid aliasing, the settings of the ultrasound equipment and colour-coded area were adjusted to obtain the highest possible frame rate. We measured peak strain in the 16-segment left ventricular model and in 3 segments in the right. From the color-coded tissue tracking image, the motion amplitude toward the apex in systole was recorded in each segment. The global systolic contraction amplitude (GSCA) was calculated as the average shortening amplitude of all 16 segments. The peak E velocity was obtained by pulsed Doppler measurements of the mitral inflow at the tip of the mitral leaflets. We further assessed isovolumetric acceleration, TEI index (spectral and TDI), tricuspid regurgitation and pulmonary ejection time. The tissue E' velocity was obtained by Tissue Doppler at the lateral mitral annulus. E/E' has been proposed as a tool for assessing LV filling pressures that combines the influence of transmitral driving pressure and myocardial relaxation [11]. The TEI index (spectral or TDI), a combined measure of systolic and diastolic function, was assessed by Doppler time intervals from the mitral inflow and LV outflow tract or the time intervals were obtained by TDI at the lateral mitral annulus. The TEI index was calculated by a-b/b where the time interval "a" was measured from cessation to onset of mitral inflow and the time interval "b" was the duration of the LV outflow velocity profile. To minimize the variability of the measurements, all ECHO recordings were performed and analyzed in a blinded fashion by the same author (P.S.).

Study protocol

TDI was performed when the subjects had rested for 15 minutes breathing room air (SpO2 97.9 ? 0.1 %), after 5 minutes of respiratory equilibrium during hypoxia (SpO2 77.6 ? 1.2 %), and after 5 minutes of respiratory equilibrium during hyperoxia (SpO2 99.0 ? 0.2 %). Heart rate was continuously recorded on computer by means of the pulse oximeter. Blood pressure was measured once during each of the three respiratory steady state situations by an automatic blood pressure measuring device based on the oscillometric method.

Statistical analysis

All data are presented as mean ? SEM. Comparisons of the responses to changes in FiO2 (normoxia, hypoxia and hyperoxia) were made with a one-way repeated-measures analysis of variance. The Student-Newman-Keuls test was used post hoc to identify pairwise differences. Differences were considered statistically significant when P < 0.05.

Respiratory parameters and hemodynamics

FiO2 and FeO2 decreased with hypoxia and increased with 100% oxygen breathing (table 1). FeCO2 and tidal volume were unchanged in all three test situations, reflecting that the subjects were in respiratory steady state. There was a small, but statistically significant decrease in respiratory rate from normoxia to hypoxia, which might reflect that the subjects were more accustomed to the test situation at this stage.

There was a significant increase in heart rate with hypoxia and a decrease with hyperoxia (figure 1). Neither systolic (126 ? 6, 123 ? 8, 122 ? 12 mmHg, respectively, P = ns) nor diastolic blood pressure (80 ? 5, 78 ? 8, 81 ? 6 mmHg, respectively, P = ns) changed significantly with test situation.

TDI and spectral echocardiography, hypoxia

A significant increase in strain rate was found in 4 segments (figure 2). GSCA increased with hypoxia (9.76 ? 0.41 vs. 10.87 ? 0.42, P < 0.001, figure 3). Tissue tracking displacement was reduced in all three right ventricular segments (figure 4) and systolic tricuspid regurgitation increased with hypoxia (figure 5). The TEI index (spectral or TDI) and E/E' did not change with hypoxia.

TDI and spectral echocardiography, hyperoxia

Hyperoxia worsened left ventricular function. Strain rate was reduced in 10 segments (figure 2) with preponderance in the lateral and anterior segments. GSCA was reduced (8.83 ? 0.38, P < 0.001 vs. normoxia). Tissue tracking displacement did not change in the right ventricular segments (figure 4) and systolic tricuspid regurgitation was unchanged compared with normoxia (figure 5)). The TDI TEI index was significantly increased with hyperoxia (0.32 ? 0.04 vs. 0.45 ? 0.05, P < 0.001) and the spectral TEI index showed similar changes. E/E' did not change with hyperoxia.


The main findings of the present study of healthy volunteers are: 1) hypoxia increased strain rate and tissue tracking displacement. 2) Hypoxia increased tricuspid regurgitation and reduced right ventricular tissue tracking displacement. 3) Hyperoxia reduced strain rate and tissue tracking displacement and increased the TEI index. The novelty of our findings, when compared to the literature, is the demonstration that longitudinal myocardial function, and thus the function of the subendocardium, is sensitive to moderate changes in inspired oxygen.

Patients with ischemic heart disease and heart failure frequently encounter hypoxia but the consequences of hypoxia on left ventricular function remain a matter of controversy, in part because of differences in methodology and the measured parameters. In early studies using roentgenkymograms [12] and dye injection [13] hypoxia was shown to increase cardiac output at rest despite reduced [13] or unchanged [12] stroke volume. The authors explained the increase in cardiac output by increased heart rate [12,13] Myocardial blood flow in the left and right ventricles increased at high altitude in dogs studied with radioactive microspheres [14] and in healthy controls using positron emission tomography [15]. In a study using M-mode echocardiography at high altitude [4] percent fractional shortening and velocity of circumferential fiber shortening remained normal while LV isovolumetric contraction time shortened. Echocardiography was also employed in a simulated ascent of Mount Everest [3] and an insignificant increase in fractional shortening and ejection fraction was found. It is generally accepted that right-sided pressures increase with hypoxia [3,14] We speculate that the improvement in tissue tracking displacement in our study reflects the systemic vasodilation which is another consequence of hypoxia [16]. On the other hand, RV-systolic function decreased which is likely to be correlated to the increased systolic pulmonary pressure reflecting the increased pulmonary vascular resistance during hypoxia.

Hemoglobin saturation in healthy persons increase very little from breathing room air to breathing 100% oxygen. Nevertheless, profound cardiovascular effects were found. This is probably because of an anticipated increase in oxygen dissolved into plasma from 0.32% to 2.09% [17]. Hyperoxia is a possible product of oxygen therapy when administered to patients with heart disease during acute illness. Hyperoxia reduces cardiac output as documented with roentgenkymograms [12], dye injection [18,19]., echocardiography [20] heart catheterisation [8] and indirectly by measurement of isometric systolic tension by means of strain gauge in dogs [21]. Reduced cardiac output with hyperoxia has even been demonstrated in patients with myocardial infarction using dye injection [22]. Some of the reduction in cardiac output may be explained by the observation that hyperoxia reduces heart rate as seen in our study and previously [19,23-25] Reduced heart rate is, however, not an entirely consistent finding [8,20,22,26] but in these four studies this could be because of high sympathetic tone (stay in a hyperbaric chamber [20], acute myocardial infarction [22], open heart surgery [26], heart catheterisation [8]). We found that heart rate increased with hypoxia and decreased with hyperoxia. This might have affected our measures of LV systolic and diastolic function but we consider this unlikely on the basis of our previous studies [11,27] demonstrating that TEI index, strain rate and the tissue tracking was unrelated to heart rate. During hypoxia as well as hyperoxia no change in LV filling pressure was noted as the E/E' ratio was unchanged. The individual parameters in the E/E' ratio are known to be influenced by heart rate but as a ratio it seems independent of heart rate and load conditions [11,27]. Therefore, we did not perform any adjustments for heart rate in the evaluation of LV diastolic function.

Because of the finding of no change [19] or a discrete rise [18,22] in blood pressure, a reduction in cardiac output results in an increased systemic vascular resistance during hyperoxia [18,19,22] Regardless of the fact that sympathetic tone may be affected by hyperoxia, even after complete sympathetic blockade myocardial contractile force remains reduced [26]. In the present study both tissue tracking displacement and strain rate worsened during hyperoxia. It seems plausible that this deterioration could be explained by systemic vasoconstriction [21] increasing afterload.

In conclusion, hypoxia improves and hyperoxia worsens systolic myocardial performance in healthy male volunteers. TDI measures of diastolic function are unaffected by hypoxia/hyperoxia which support that the changes in myocardial performance are secondary to changes in vascular tone. It remains to be settled whether oxygen therapy to patients with heart disease is a rational treatment that may sometimes be harmful or whether supplemental oxygen consistently results in an overall gain in delivered oxygen.


The study was supported by The Danish Heart Foundation (no 03-1-2-12-22050), the John and Birthe Meyer Foundation, Karen Elise Jensens Fond, the Novo Nordisk Foundation, and the Danish Medical Research Council.

Adams MR,McCredie R,Jessup W,Robinson J,Sullivan D,Celermajer DS. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery diseaseAtherosclerosis 1997;129:261–269. [pmid: 9105569] [doi: 10.1016/S0021-9150(96)06044-3]
Smith HL,Sapsford DJ,Delaney ME,Jones JG. The effect on the heart of hypoxaemia in patients with severe coronary artery diseaseAnaesthesia 1996;51:211–218. [pmid: 8712318]
Boussuges A,Molenat F,Burnet H,Cauchy E,Gardette B,Sainty JM,Jammes Y,Richalet JP. Operation Everest III (Comex '97): modifications of cardiac function secondary to altitude-induced hypoxia. An echocardiographic and Doppler studyAm J Respir Crit Care Med 2000;161:264–270. [pmid: 10619830]
Fowles RE,Hultgren HN. Left ventricular function at high altitude examined by systolic time intervals and M-mode echocardiographyAm J Cardiol 1983;52:862–866. [pmid: 6624678] [doi: 10.1016/0002-9149(83)90429-0]
Alexander JK,Grover RF. Mechanism of reduced cardiac stroke volume at high altitudeClin Cardiol 1983;6:301–303. [pmid: 6872373]
Reeves JT,Groves BM,Sutton JR,Wagner PD,Cymerman A,Malconian MK,Rock PB,Young PM,Houston CS. Operation Everest II: preservation of cardiac function at extreme altitudeJ Appl Physiol 1987;63:531–539. [pmid: 3654411]
Maruyama J,Tobise K,Kawashima E. The effect of acute hypoxia on left ventricular function with special reference to diastolic function ? an analysis using ultrasonic methodJpn Circ J 1992;56:998–1011. [pmid: 1433826]
Mak S,Azevedo ER,Liu PP,Newton GE. Effect of hyperoxia on left ventricular function and filling pressures in patients with and without congestive heart failureChest 2001;120:467–473. [pmid: 11502645] [doi: 10.1378/chest.120.2.467]
Isaaz K. Tissue Doppler imaging for the assessment of left ventricular systolic and diastolic functionsCurr Opin Cardiol 2002;17:431–442. [pmid: 12357118] [doi: 10.1097/00001573-200209000-00001]
Rees SE,Kjaergaard S,Perthorgaard P,Malczynski J,Toft E,Andreassen S. The automatic lung parameter estimator (ALPE) system: non-invasive estimation of pulmonary gas exchange parameters in 10?15 minutesJ Clin Monit Comput 2002;17:43–52. [pmid: 12102249] [doi: 10.1023/A:1015456818195]
Poulsen SH,Nielsen JC,Andersen HR. The influence of heart rate on the Doppler-derived myocardial performance indexJ Am Soc Echocardiogr 2000;13:379–384. [pmid: 10804435] [doi: 10.1067/mje.2000.104061]
Keys A,Stapp JP,Violante A. Responses in size, output and efficiency of the human heart to acute alteration in the composition of inspired airAm J Physiol 2004;138:763–771.
Asmussen E,Nielsen M. The cardiac output in rest and work at low and high oxygen pressuresActa Physiol Scand 1955;35:73–83. [pmid: 13301852]
Jones DP,Damiano R,Cox JL,Wolfe WG. The effect of altitude-induced hypoxia on regional myocardial blood flowJ Thorac Cardiovasc Surg 1981;82:216–220. [pmid: 6789010]
Wyss CA,Koepfli P,Fretz G,Seebauer M,Schirlo C,Kaufmann PA. Influence of altitude exposure on coronary flow reserveCirculation 2003;108:1202–1207. [pmid: 12939217] [doi: 10.1161/01.CIR.0000087432.63671.2E]
Taggart MJ,Wray S. Hypoxia and smooth muscle function: key regulatory events during metabolic stressJ Physiol 1998;509:315–325. [pmid: 9575282] [doi: 10.1111/j.1469-7793.1998.315bn.x]
Grim PS,Gottlieb LJ,Boddie A,Batson E. Hyperbaric oxygen therapyJAMA 1990;263:2216–2220. [pmid: 2181162] [doi: 10.1001/jama.263.16.2216]
Daly WJ,Bondurant S. Effects of oxygen breathing on the heart rate, blood pressure, and cardiac index of normal men ? resting, with reactive hyperemia, and after atropineJ Clin Invest 1962;41:126–132. [pmid: 13883265]
Kenmure AC,Murdoch WR,Hutton I,Cameron AJ. Hemodynamic effects of oxygen at 1 and 2 Ata pressure in healthy subjectsJ Appl Physiol 1972;32:223–226. [pmid: 5007874]
Molenat F,Boussuges A,Grandfond A,Rostain JC,Sainty JM,Robinet C,Galland F,Meliet JL. Hemodynamic effects of hyperbaric hyperoxia in healthy volunteers: An Echocardiographic and Doppler studyClin Sci (Lond). 2003
Crawford P,Good PA,Gutierrez E,Feinberg JH,Boehmer JP,Silber DH,Sinoway LI. Effects of supplemental oxygen on forearm vasodilation in humansJ Appl Physiol 1997;82:1601–1606. [pmid: 9134910]
Kenmure AC,Murdoch WR,Beattie AD,Marshall JC,Cameron AJ. Circulatory and metabolic effects of oxygen in myocardial infarctionBr Med J 1968;4:360–364. [pmid: 5683582]
Benedict FG,Higgins HL. Effects on men at rest of breathing oxygen-rich gas mixturesAm J Physiol 1911;28:1–28.
Barratt-Boyes BG,Wood EH. Cardiac output and related measurements and pressure values in the right heart and associated vessels, together with an analysis of the hemo-dynamic response to the inhalation of high oxygen mixtures in healthy subjectsJ Lab Clin Med 1958;51:72–90. [pmid: 13514210]
Alveryd A,Brody S. Cardiovascular and respiratory changes in man during oxygen breathingActa Physiol Scand 1948;15:140–149.
Daniell HB,Bagwell EE. Effects of high oxygen on coronary flor and heart forceAm J Physiol 1968;214:1454–1459. [pmid: 5649501]
Andersen NH,Poulsen SH. Evaluation of the longitudinal contraction of the left ventricle in normal subjects by Doppler tissue tracking and strain rateJ Am Soc Echocardiogr 2003;16:716–723. [pmid: 12835657] [doi: 10.1016/S0894-7317(03)00325-0]


[Figure ID: F1]
Figure 1 

Bar graph depicting heart rate during normoxia, hypoxia and hyperoxia. ** P < 0.01 vs. normoxia.

[Figure ID: F2]
Figure 2 

Comparison of peak systolic strain in the 16-segment left ventricular model illustrating the effects of hypoxia and hyperoxia. A, Anterior; B, basal; D, distal; I, inferior; L, lateral; M, mid; P, posterior; S, septal. * P < 0.05, ** P < 0.01 vs. normoxia.

[Figure ID: F3]
Figure 3 

Tissue tracking score index on the basis of the 16-segment left ventricular model illustrating the effects of hypoxia and hyperoxia.

[Figure ID: F4]
Figure 4 

Comparison of peak systolic strain in the right ventricle model illustrating the effects of hypoxia and hyperoxia. * P < 0.05.

[Figure ID: F5]
Figure 5 

Bar graph depicting systolic tricuspid regurgitation during normoxia, hypoxia and hyperoxia. ** P < 0.01 vs. normoxia.

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