Cardiopulmonary Protective Effects of Modified Remote Ischaemic Preconditioning in Mitral Valve Replacement Surgery

Myocardial Injury Clinical Trial

Official title:

Cardiopulmonary Protection of Modified Remote Ischaemic Preconditioning in Mitral Valve Replacement Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03010839
• Other study ID #: XYFY-2017-001
• Status: Completed
• Phase: N/A
• First received: December 31, 2016
• Last updated: March 15, 2018
• Start date: November 5, 2016
• Est. completion date: March 10, 2018

Study information

• Verified date: March 2018
• Source: Xuzhou Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

During cardiac surgery with cardiopulmonary bypass , injury occurs to the heart muscle and the lung.The heart and lung injury is a serious complication ,which increases both mortality and morbidity of cardiac surgery .Remote ischemic preconditioning(RIPC) with transient upper limb ischemia/reperfusion is a novel, simple, cost-free,non-pharmacological and non-invasive strategy.Recent some trials suggested that RIPC could provide myocardial protection by reducing serum cardiac biomarkers,however, more recent multicenter studies[9-11] had failed to show the protective effects of RIPC with respect to the troponin release and lung injury.

Remote ischemic preconditioning (RIPC) is reported to have the early-phase and delayed-phase organ protective effects, whether the modified RIPC protocol induced repeatedly has the cardiopulmonary protective effect is still uncertain.

Description:

modified RIPC was induced at 24 h, 12 h and 1 h before surgery to reinforce the protective effects of RIPC.The single RIPC protocol was induced by three cycles of upper-limb ischemia, a standard blood-pressure cuff was placed on the ringt upper arm, then inflated the cuff to 200 mm Hg for 5 minutes, followed by 5 min of cuff deflation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: March 10, 2018
• Est. primary completion date: January 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients undergoing heart surgery on cardiopulmonary bypass

2. Patients aged 18 years to 80 years

Exclusion Criteria:

1. Inability to give informed consent

2. Cardiogenic shock

3. Cardiac arrest on current admission

4. Left ventricular ejection fraction less than 30%

5. Current atrial fibrillation

6. Preoperative use of inotropics or mechanical assist device

7. Patients with significant hepatic dysfunction (Prothrombin>2.0 ratio)

8. Patients with known renal failure with a GFR<30 mL/min/1.73 m2

9. Patients with significant pulmonary disease (FEV1<40% predicted)

10. Recent myocardial infarction (within 7 days)

11. Recent systemic infection or sepsis (within 7 days)

12. Severe stroke (within 2 months)

13. Significant peripheral arterial disease affecting the upper limbs

14. Previous serious psychiatric disorders (e.g. schizophrenia, dementia)

15. Surgeries: cardiac transplantation, concomitant carotid endarterectomy , previous heart surgery,off-pump surgery, emergency surgery

Related Conditions & MeSH terms

• Ischemia
• Myocardial Injury
• Remote Ischemic Preconditioning

Intervention

Procedure:
• Modified Remote Ischemic Preconditioning
mRIPC will be induced at 24 h, 12 h and 1 h before surgery and once before induction of anesthesia by 3 cycles of 5-min upper limb ischemia and 5-min reperfusion using a blood-pressure cuff inflated to a pressure 200mmHg
• Control
Control group witnout remote ischemic preconditioning

Locations

Country	Name	City	State
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Xuzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (28)

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Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sørensen HT, Redington AN, Nielsen TT. Remote is — View Citation

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Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. — View Citation

Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing corona — View Citation

Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2. Review. — View Citation

Heusch G, Bøtker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031. Review. — View Citation

Hong DM, Lee EH, Kim HJ, Min JJ, Chin JH, Choi DK, Bahk JH, Sim JY, Choi IC, Jeon Y. Does remote ischaemic preconditioning with postconditioning improve clinical outcomes of patients undergoing cardiac surgery? Remote Ischaemic Preconditioning with Postco — View Citation

Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O'Sullivan M, Dutka DP. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulati — View Citation

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Johnsen J, Pryds K, Salman R, Løfgren B, Kristiansen SB, Bøtker HE. The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection. Basic Res Cardiol. 2016 Mar;111(2):10. doi: 10 — View Citation

Kerendi F, Kin H, Halkos ME, Jiang R, Zatta AJ, Zhao ZQ, Guyton RA, Vinten-Johansen J. Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of ad — View Citation

Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, Vogel M, Sorensen K, Redington AN, MacAllister R. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002 Dec 3;106(23):2881-3. — View Citation

Li G, Labruto F, Sirsjö A, Chen F, Vaage J, Valen G. Myocardial protection by remote preconditioning: the role of nuclear factor kappa-B p105 and inducible nitric oxide synthase. Eur J Cardiothorac Surg. 2004 Nov;26(5):968-73. — View Citation

Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, Zaugg M. Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surger — View Citation

Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Böning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, M — View Citation

Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124-36. — View Citation

Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B. Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol. 1997 Oct;273(4 Pt 2):H1707-12. — View Citation

Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. — View Citation

Remote Preconditioning Trialists' Group, Healy DA, Khan WA, Wong CS, Moloney MC, Grace PA, Coffey JC, Dunne C, Walsh SR, Sadat U, Gaunt ME, Chen S, Tehrani S, Hausenloy DJ, Yellon DM, Kramer RS, Zimmerman RF, Lomivorotov VV, Shmyrev VA, Ponomarev DN, Rahm — View Citation

Sivaraman V, Pickard JM, Hausenloy DJ. Remote ischaemic conditioning: cardiac protection from afar. Anaesthesia. 2015 Jun;70(6):732-48. doi: 10.1111/anae.12973. Epub 2015 Feb 26. Review. — View Citation

Sullivan PJ, Sweeney KJ, Hirpara KM, Malone CB, Curtin W, Kerin MJ. Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia-reperfusion injury. Br J Surg. 2009 Apr;96(4):381-90. doi: 10.1002/bjs.6554. — View Citation

Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H, Heusch G. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol. 2010 — View Citation

Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhäuser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass s — View Citation

Venugopal V, Hausenloy DJ, Ludman A, Di Salvo C, Kolvekar S, Yap J, Lawrence D, Bognolo J, Yellon DM. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled t — View Citation

Yamaguchi T, Izumi Y, Nakamura Y, Yamazaki T, Shiota M, Sano S, Tanaka M, Osada-Oka M, Shimada K, Miura K, Yoshiyama M, Iwao H. Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication o — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Troponin I serum release over 24 hours after surgery		24 hours post surgery
Secondary	PaO2/FiO2 ratio over 24 hours after surgery		24 hours post surgery
Secondary	salveolar-arterial oxygen gradient over 24 hours after surgery		24 hours post surgery
Secondary	Inotrope score		12 hours post surgery