Can human myocardium be remotely preconditioned? The results of a randomized controlled trial

Abstract OBJECTIVES No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for e...

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Published in:European journal of cardio-thoracic surgery 2019-06, Vol.55 (6), p.1086-1094
Main Authors: Deja, Marek A, Piekarska, Magda, Malinowski, Marcin, Wiaderkiewicz, Ryszard, Czekaj, Piotr, Machej, Leszek, Węglarzy, Andrzej, Kowalówka, Adam, Kołodziej, Tadeusz, Czech, Ewa, Plewka, Danuta, Mizia, Magdalena, Latusek, Tomasz, Szurlej, Bartosz
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container_title European journal of cardio-thoracic surgery
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creator Deja, Marek A
Piekarska, Magda
Malinowski, Marcin
Wiaderkiewicz, Ryszard
Czekaj, Piotr
Machej, Leszek
Węglarzy, Andrzej
Kowalówka, Adam
Kołodziej, Tadeusz
Czech, Ewa
Plewka, Danuta
Mizia, Magdalena
Latusek, Tomasz
Szurlej, Bartosz
description Abstract OBJECTIVES No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study. RESULTS The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3–48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1–53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0–13.5) to 19.1% (13.2–23.8) (P 
doi_str_mv 10.1093/ejcts/ezy441
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The results of a randomized controlled trial</title><source>Oxford Journals Online</source><creator>Deja, Marek A ; Piekarska, Magda ; Malinowski, Marcin ; Wiaderkiewicz, Ryszard ; Czekaj, Piotr ; Machej, Leszek ; Węglarzy, Andrzej ; Kowalówka, Adam ; Kołodziej, Tadeusz ; Czech, Ewa ; Plewka, Danuta ; Mizia, Magdalena ; Latusek, Tomasz ; Szurlej, Bartosz</creator><creatorcontrib>Deja, Marek A ; Piekarska, Magda ; Malinowski, Marcin ; Wiaderkiewicz, Ryszard ; Czekaj, Piotr ; Machej, Leszek ; Węglarzy, Andrzej ; Kowalówka, Adam ; Kołodziej, Tadeusz ; Czech, Ewa ; Plewka, Danuta ; Mizia, Magdalena ; Latusek, Tomasz ; Szurlej, Bartosz</creatorcontrib><description>Abstract OBJECTIVES No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study. RESULTS The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3–48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1–53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0–13.5) to 19.1% (13.2–23.8) (P &lt; 0.001) after 1 h of ischaemia and 2 h of reperfusion in vitro. The amount of activated Caspase 3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells also significantly increased. No difference was observed between the remotely preconditioned and sham-treated myocardium. In the in vivo trial, the area under the curve for postoperative concentration of troponin T over 72 h was 16.4 ng⋅h/ml (95% confidence interval 14.2–18.9) for the remote ischaemic preconditioning and 15.5 ng⋅h/ml (13.4–17.9) for the control group in the intention-to-treat analysis. This translated into an area under the curve ratio of 1.06 (0.86–1.30; P = 0.586). CONCLUSIONS Remote ischaemic preconditioning with 3 cycles of 5-min ischaemia/reperfusion of the upper limb before cardiac surgery does not make human myocardium more resistant to ischaemia/reperfusion injury. Clinical trial registration number NCT01994707.</description><identifier>ISSN: 1010-7940</identifier><identifier>EISSN: 1873-734X</identifier><identifier>DOI: 10.1093/ejcts/ezy441</identifier><identifier>PMID: 30649238</identifier><language>eng</language><publisher>Germany: Oxford University Press</publisher><ispartof>European journal of cardio-thoracic surgery, 2019-06, Vol.55 (6), p.1086-1094</ispartof><rights>The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. 2019</rights><rights>The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-2482113015a5545559047bd320c09598695a8b9ef767df7f28733ca3e1bac0d33</citedby><cites>FETCH-LOGICAL-c361t-2482113015a5545559047bd320c09598695a8b9ef767df7f28733ca3e1bac0d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30649238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deja, Marek A</creatorcontrib><creatorcontrib>Piekarska, Magda</creatorcontrib><creatorcontrib>Malinowski, Marcin</creatorcontrib><creatorcontrib>Wiaderkiewicz, Ryszard</creatorcontrib><creatorcontrib>Czekaj, Piotr</creatorcontrib><creatorcontrib>Machej, Leszek</creatorcontrib><creatorcontrib>Węglarzy, Andrzej</creatorcontrib><creatorcontrib>Kowalówka, Adam</creatorcontrib><creatorcontrib>Kołodziej, Tadeusz</creatorcontrib><creatorcontrib>Czech, Ewa</creatorcontrib><creatorcontrib>Plewka, Danuta</creatorcontrib><creatorcontrib>Mizia, Magdalena</creatorcontrib><creatorcontrib>Latusek, Tomasz</creatorcontrib><creatorcontrib>Szurlej, Bartosz</creatorcontrib><title>Can human myocardium be remotely preconditioned? The results of a randomized controlled trial</title><title>European journal of cardio-thoracic surgery</title><addtitle>Eur J Cardiothorac Surg</addtitle><description>Abstract OBJECTIVES No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study. RESULTS The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3–48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1–53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0–13.5) to 19.1% (13.2–23.8) (P &lt; 0.001) after 1 h of ischaemia and 2 h of reperfusion in vitro. The amount of activated Caspase 3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells also significantly increased. No difference was observed between the remotely preconditioned and sham-treated myocardium. In the in vivo trial, the area under the curve for postoperative concentration of troponin T over 72 h was 16.4 ng⋅h/ml (95% confidence interval 14.2–18.9) for the remote ischaemic preconditioning and 15.5 ng⋅h/ml (13.4–17.9) for the control group in the intention-to-treat analysis. This translated into an area under the curve ratio of 1.06 (0.86–1.30; P = 0.586). CONCLUSIONS Remote ischaemic preconditioning with 3 cycles of 5-min ischaemia/reperfusion of the upper limb before cardiac surgery does not make human myocardium more resistant to ischaemia/reperfusion injury. 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The results of a randomized controlled trial</atitle><jtitle>European journal of cardio-thoracic surgery</jtitle><addtitle>Eur J Cardiothorac Surg</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>55</volume><issue>6</issue><spage>1086</spage><epage>1094</epage><pages>1086-1094</pages><issn>1010-7940</issn><eissn>1873-734X</eissn><abstract>Abstract OBJECTIVES No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study. RESULTS The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3–48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1–53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0–13.5) to 19.1% (13.2–23.8) (P &lt; 0.001) after 1 h of ischaemia and 2 h of reperfusion in vitro. The amount of activated Caspase 3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells also significantly increased. No difference was observed between the remotely preconditioned and sham-treated myocardium. In the in vivo trial, the area under the curve for postoperative concentration of troponin T over 72 h was 16.4 ng⋅h/ml (95% confidence interval 14.2–18.9) for the remote ischaemic preconditioning and 15.5 ng⋅h/ml (13.4–17.9) for the control group in the intention-to-treat analysis. This translated into an area under the curve ratio of 1.06 (0.86–1.30; P = 0.586). CONCLUSIONS Remote ischaemic preconditioning with 3 cycles of 5-min ischaemia/reperfusion of the upper limb before cardiac surgery does not make human myocardium more resistant to ischaemia/reperfusion injury. Clinical trial registration number NCT01994707.</abstract><cop>Germany</cop><pub>Oxford University Press</pub><pmid>30649238</pmid><doi>10.1093/ejcts/ezy441</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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title Can human myocardium be remotely preconditioned? The results of a randomized controlled trial
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