Unexplained exertional intolerance associated with impaired systemic oxygen extraction
Purpose The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE). Method...
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| Veröffentlicht in: | European journal of applied physiology 2019-10, Vol.119 (10), p.2375-2389 |
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| container_title | European journal of applied physiology |
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| creator | Melamed, Kathryn H. Santos, Mário Oliveira, Rudolf K. F. Urbina, Mariana Faria Felsenstein, Donna Opotowsky, Alexander R. Waxman, Aaron B. Systrom, David M. |
| description | Purpose
The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).
Methods
We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO
2
)/[Hb] ≤ 0.8 and
V
O
2max
0.8,
V
O
2max
≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO
2
|
| doi_str_mv | 10.1007/s00421-019-04222-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2286921689</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2285412821</sourcerecordid><originalsourceid>FETCH-LOGICAL-c418t-f46b87b513ebf556766958b2f7c8b3da6d74782418588d3697c1df711c9fa1063</originalsourceid><addsrcrecordid>eNp9kMlOwzAQhi0EoqXwAhxQJC5cAh478XJEFZtUiQvlajmOU1xlKXYq2rfHXSgSB04ea7757fkQugR8Cxjzu4BxRiDFINNYEJKyIzSEjMqUUcKPDzXIAToLYY4xFgTEKRpQyCTFNB-i92lrV4tau9aWiV1Z37uu1XXi2r6rrdetsYkOoTNO95H4cv1H4pqFdj7ewjr0tnEm6VbrmW3jfO-12SSco5NK18Fe7M8Rmj4-vI2f08nr08v4fpKaDESfVhkrBC9yoLao8pxxxmQuClJxIwpaalbyjAsS2VyIkjLJDZQVBzCy0oAZHaGbXe7Cd59LG3rVuGBsXevWdsugCBFMEmBCRvT6Dzrvlj7uuqXyDEiUEymyo4zvQvC2UgvvGu3XCrDaWFc76ypaV1vravOLq330smhseRj50RwBugNCbLUz63_f_if2G35QjTo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2285412821</pqid></control><display><type>article</type><title>Unexplained exertional intolerance associated with impaired systemic oxygen extraction</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Melamed, Kathryn H. ; Santos, Mário ; Oliveira, Rudolf K. F. ; Urbina, Mariana Faria ; Felsenstein, Donna ; Opotowsky, Alexander R. ; Waxman, Aaron B. ; Systrom, David M.</creator><creatorcontrib>Melamed, Kathryn H. ; Santos, Mário ; Oliveira, Rudolf K. F. ; Urbina, Mariana Faria ; Felsenstein, Donna ; Opotowsky, Alexander R. ; Waxman, Aaron B. ; Systrom, David M.</creatorcontrib><description>Purpose
The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).
Methods
We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO
2
)/[Hb] ≤ 0.8 and
V
O
2max
< 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO
2
)/[Hb] > 0.8,
V
O
2max
≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO
2
< [1.5 × HCO
3
+ 6].
Results
Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs. 7.38 ± 0.05 vs. 7.32 ± 0.02,
p
< 0.001), which was explained by relative hypocapnia (PaCO
2
= 29.9 ± 5.4 mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4,
p
< 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO
2
nadir (28 ± 2 mmHg vs. 26 ± 4,
p
= 0.627) but increased SvO
2
at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0,
p
< 0.001).
Conclusions
We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.</description><identifier>ISSN: 1439-6319</identifier><identifier>EISSN: 1439-6327</identifier><identifier>DOI: 10.1007/s00421-019-04222-6</identifier><identifier>PMID: 31493035</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Anaerobic Threshold ; Biomedical and Life Sciences ; Biomedicine ; Carbon dioxide ; Cardiorespiratory Fitness ; Exercise - physiology ; Exercise Tolerance ; Female ; Heart ; Heart Rate ; Human Physiology ; Humans ; Hyperventilation ; Intolerance ; Male ; Middle Aged ; Occupational Medicine/Industrial Medicine ; Original Article ; Oxygen ; Pulmonary Gas Exchange ; Pulmonary Ventilation ; Skeletal muscle ; Sports Medicine</subject><ispartof>European journal of applied physiology, 2019-10, Vol.119 (10), p.2375-2389</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>European Journal of Applied Physiology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-f46b87b513ebf556766958b2f7c8b3da6d74782418588d3697c1df711c9fa1063</citedby><cites>FETCH-LOGICAL-c418t-f46b87b513ebf556766958b2f7c8b3da6d74782418588d3697c1df711c9fa1063</cites><orcidid>0000-0003-0837-3488</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00421-019-04222-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00421-019-04222-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31493035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Melamed, Kathryn H.</creatorcontrib><creatorcontrib>Santos, Mário</creatorcontrib><creatorcontrib>Oliveira, Rudolf K. F.</creatorcontrib><creatorcontrib>Urbina, Mariana Faria</creatorcontrib><creatorcontrib>Felsenstein, Donna</creatorcontrib><creatorcontrib>Opotowsky, Alexander R.</creatorcontrib><creatorcontrib>Waxman, Aaron B.</creatorcontrib><creatorcontrib>Systrom, David M.</creatorcontrib><title>Unexplained exertional intolerance associated with impaired systemic oxygen extraction</title><title>European journal of applied physiology</title><addtitle>Eur J Appl Physiol</addtitle><addtitle>Eur J Appl Physiol</addtitle><description>Purpose
The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).
Methods
We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO
2
)/[Hb] ≤ 0.8 and
V
O
2max
< 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO
2
)/[Hb] > 0.8,
V
O
2max
≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO
2
< [1.5 × HCO
3
+ 6].
Results
Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs. 7.38 ± 0.05 vs. 7.32 ± 0.02,
p
< 0.001), which was explained by relative hypocapnia (PaCO
2
= 29.9 ± 5.4 mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4,
p
< 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO
2
nadir (28 ± 2 mmHg vs. 26 ± 4,
p
= 0.627) but increased SvO
2
at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0,
p
< 0.001).
Conclusions
We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.</description><subject>Adult</subject><subject>Aged</subject><subject>Anaerobic Threshold</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carbon dioxide</subject><subject>Cardiorespiratory Fitness</subject><subject>Exercise - physiology</subject><subject>Exercise Tolerance</subject><subject>Female</subject><subject>Heart</subject><subject>Heart Rate</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hyperventilation</subject><subject>Intolerance</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Original Article</subject><subject>Oxygen</subject><subject>Pulmonary Gas Exchange</subject><subject>Pulmonary Ventilation</subject><subject>Skeletal muscle</subject><subject>Sports Medicine</subject><issn>1439-6319</issn><issn>1439-6327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kMlOwzAQhi0EoqXwAhxQJC5cAh478XJEFZtUiQvlajmOU1xlKXYq2rfHXSgSB04ea7757fkQugR8Cxjzu4BxRiDFINNYEJKyIzSEjMqUUcKPDzXIAToLYY4xFgTEKRpQyCTFNB-i92lrV4tau9aWiV1Z37uu1XXi2r6rrdetsYkOoTNO95H4cv1H4pqFdj7ewjr0tnEm6VbrmW3jfO-12SSco5NK18Fe7M8Rmj4-vI2f08nr08v4fpKaDESfVhkrBC9yoLao8pxxxmQuClJxIwpaalbyjAsS2VyIkjLJDZQVBzCy0oAZHaGbXe7Cd59LG3rVuGBsXevWdsugCBFMEmBCRvT6Dzrvlj7uuqXyDEiUEymyo4zvQvC2UgvvGu3XCrDaWFc76ypaV1vravOLq330smhseRj50RwBugNCbLUz63_f_if2G35QjTo</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Melamed, Kathryn H.</creator><creator>Santos, Mário</creator><creator>Oliveira, Rudolf K. F.</creator><creator>Urbina, Mariana Faria</creator><creator>Felsenstein, Donna</creator><creator>Opotowsky, Alexander R.</creator><creator>Waxman, Aaron B.</creator><creator>Systrom, David M.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0837-3488</orcidid></search><sort><creationdate>20191001</creationdate><title>Unexplained exertional intolerance associated with impaired systemic oxygen extraction</title><author>Melamed, Kathryn H. ; Santos, Mário ; Oliveira, Rudolf K. F. ; Urbina, Mariana Faria ; Felsenstein, Donna ; Opotowsky, Alexander R. ; Waxman, Aaron B. ; Systrom, David M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-f46b87b513ebf556766958b2f7c8b3da6d74782418588d3697c1df711c9fa1063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anaerobic Threshold</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Carbon dioxide</topic><topic>Cardiorespiratory Fitness</topic><topic>Exercise - physiology</topic><topic>Exercise Tolerance</topic><topic>Female</topic><topic>Heart</topic><topic>Heart Rate</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hyperventilation</topic><topic>Intolerance</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Occupational Medicine/Industrial Medicine</topic><topic>Original Article</topic><topic>Oxygen</topic><topic>Pulmonary Gas Exchange</topic><topic>Pulmonary Ventilation</topic><topic>Skeletal muscle</topic><topic>Sports Medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Melamed, Kathryn H.</creatorcontrib><creatorcontrib>Santos, Mário</creatorcontrib><creatorcontrib>Oliveira, Rudolf K. F.</creatorcontrib><creatorcontrib>Urbina, Mariana Faria</creatorcontrib><creatorcontrib>Felsenstein, Donna</creatorcontrib><creatorcontrib>Opotowsky, Alexander R.</creatorcontrib><creatorcontrib>Waxman, Aaron B.</creatorcontrib><creatorcontrib>Systrom, David M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of applied physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Melamed, Kathryn H.</au><au>Santos, Mário</au><au>Oliveira, Rudolf K. F.</au><au>Urbina, Mariana Faria</au><au>Felsenstein, Donna</au><au>Opotowsky, Alexander R.</au><au>Waxman, Aaron B.</au><au>Systrom, David M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unexplained exertional intolerance associated with impaired systemic oxygen extraction</atitle><jtitle>European journal of applied physiology</jtitle><stitle>Eur J Appl Physiol</stitle><addtitle>Eur J Appl Physiol</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>119</volume><issue>10</issue><spage>2375</spage><epage>2389</epage><pages>2375-2389</pages><issn>1439-6319</issn><eissn>1439-6327</eissn><abstract>Purpose
The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).
Methods
We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO
2
)/[Hb] ≤ 0.8 and
V
O
2max
< 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO
2
)/[Hb] > 0.8,
V
O
2max
≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO
2
< [1.5 × HCO
3
+ 6].
Results
Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs. 7.38 ± 0.05 vs. 7.32 ± 0.02,
p
< 0.001), which was explained by relative hypocapnia (PaCO
2
= 29.9 ± 5.4 mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4,
p
< 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO
2
nadir (28 ± 2 mmHg vs. 26 ± 4,
p
= 0.627) but increased SvO
2
at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0,
p
< 0.001).
Conclusions
We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31493035</pmid><doi>10.1007/s00421-019-04222-6</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-0837-3488</orcidid></addata></record> |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adult Aged Anaerobic Threshold Biomedical and Life Sciences Biomedicine Carbon dioxide Cardiorespiratory Fitness Exercise - physiology Exercise Tolerance Female Heart Heart Rate Human Physiology Humans Hyperventilation Intolerance Male Middle Aged Occupational Medicine/Industrial Medicine Original Article Oxygen Pulmonary Gas Exchange Pulmonary Ventilation Skeletal muscle Sports Medicine |
| title | Unexplained exertional intolerance associated with impaired systemic oxygen extraction |
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