Influence of Medication-Induced Preconditioning or Remote Ischemic Preconditioning on the Intrinsic Vascular Extracellular RNA/Ribonuclease System in Cardioprotection

Konstantin J. Tolkmitt; Sakine Simsekyilmaz; Julia Schipke; Christian Mühlfeld; Klaus T. Preissner; Andreas Böning

doi:10.1055/s-0038-1675398

The Thoracic and Cardiovascular Surgeon, Table of Contents

Thorac Cardiovasc Surg 2019; 67(06): 494-501
DOI: 10.1055/s-0038-1675398

Original Basic Science

Georg Thieme Verlag KG Stuttgart · New York

Influence of Medication-Induced Preconditioning or Remote Ischemic Preconditioning on the Intrinsic Vascular Extracellular RNA/Ribonuclease System in Cardioprotection

Konstantin J. Tolkmitt

¹Department of Cardiovascular Surgery, Medical School, Justus-Liebig-University, Giessen, Germany

,

Sakine Simsekyilmaz

²Institute of Pharmacology and Clinical Pharmacology, Universitatsklinikum Dusseldorf, Dusseldorf, Germany

,

Julia Schipke

³Medizinische Hochschule Hannover, Institute of Functional and Applied Anatomy, Hannover, Germany

⁴Cluster of Excellence REBIRTH (Regenerative Biology to Reconstructive Therapy), Hannover, Germany

,

Christian Mühlfeld

³Medizinische Hochschule Hannover, Institute of Functional and Applied Anatomy, Hannover, Germany

⁴Cluster of Excellence REBIRTH (Regenerative Biology to Reconstructive Therapy), Hannover, Germany

,

Klaus T. Preissner

⁵Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany

,

Andreas Böning

⁶Department of Cardiovascular Surgery, University Hospital Giessen, Giessen, Germany

› Author Affiliations

Abstract

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Abstract

Background It has been demonstrated that remote ischemic preconditioning (RIPC) increases ribonuclease (RNase) levels and protects the heart by reducing extracellular ribonucleic acid (eRNA). As medication-induced preconditioning (MIPC) is also a powerful tool for cardioprotection, we examined the influence of both types of preconditioning on the eRNA/RNase system.

Methods In 17 male rats, RIPC (3 × 5 minute hind-leg ischemia) or MIPC (isoflurane and buprenorphine anesthesia) was performed. Five rats served as control and did not undergo preconditioning (non-MIPC). After preconditioning, eRNA levels and RNase activity were determined in plasma, and the hearts were mounted on a blood-perfused Langendorff ischemia/reperfusion apparatus. Hemodynamic, metabolic, and electron microscopic parameters were determined. Furthermore, MIPC with one anesthetic drug only (isoflurane, buprenorphine, or etomidate) was induced in another five rats. After 30 minutes, eRNA levels and RNase activity were determined and compared with an RIPC group (n = 5).

Results The plasma of RIPC-treated rats had higher RNase activity and lower eRNA levels than that of MIPC-treated rats. In addition, RIPC increased RNase activity more than MIPC with one drug alone. The RNase activity and eRNA levels in these MIPC groups differed considerably. Hemodynamic parameters of RIPC- and MIPC-treated hearts were better preserved after 90-minute ischemia than those of non-MIPC hearts. No obvious differences were noted between MIPC and RIPC regarding hemodynamics, metabolism, or structural parameters.

Conclusions Our results suggest that RIPC does not have any additional cardioprotective benefit in this experimental system. However, the influence of RIPC on the eRNA/RNase system was greater than that of MIPC.

Keywords

myocardial protection/cardioplegia - ischemia/reperfusion - organ preservation - anesthesia

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References

References
1 Hausenloy DJ, Candilio L, Evans R. , et al; ERICCA Trial Investigators. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 2015; 373 (15) 1408-1417
2 Meybohm P, Bein B, Brosteanu O. , et al; RIPHeart Study Collaborators. A multicenter trial of remote ischemic preconditioning for heart surgery. N Engl J Med 2015; 373 (15) 1397-1407
3 Thielmann M, Kottenberg E, Kleinbongard P. , et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013; 382 (9892): 597-604
4 Zangrillo A, Musu M, Greco T. , et al. Additive effect on survival of anaesthetic cardiac protection and remote ischemic preconditioning in cardiac surgery: a Bayesian network meta-analysis of randomized trials. PLoS One 2015; 10 (07) e0134264
5 Heusch G, Rassaf T. Time to give up on cardioprotection? A critical appraisal of clinical studies on ischemic pre-, post-, and remote conditioning. Circ Res 2016; 119 (05) 676-695
6 Kottenberg E, Thielmann M, Bergmann L. , et al. Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol - a clinical trial. Acta Anaesthesiol Scand 2012; 56 (01) 30-38
7 Cabrera-Fuentes HA, Niemann B, Grieshaber P. , et al. RNase1 as a potential mediator of remote ischaemic preconditioning for cardioprotection. Eur J Cardiothorac Surg 2015; 48 (05) 732-737 , discussion 737
8 Cabrera-Fuentes HA, Ruiz-Meana M, Simsekyilmaz S. , et al. RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-α in cardiac ischaemia/reperfusion injury. Thromb Haemost 2014; 112 (06) 1110-1119
9 Stieger P, Daniel JM, Thölen C. , et al. Targeting of extracellular RNA reduces edema formation and infarct size and improves survival after myocardial infarction in mice. J Am Heart Assoc 2017; 6 (06) e004541
10 Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S. , et al. Role of extracellular RNA in atherosclerotic plaque formation in mice. Circulation 2014; 129 (05) 598-606
11 Fischer S, Gerriets T, Wessels C. , et al. Extracellular RNA mediates endothelial-cell permeability via vascular endothelial growth factor. Blood 2007; 110 (07) 2457-2465
12 Kannemeier C, Shibamiya A, Nakazawa F. , et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci U S A 2007; 104 (15) 6388-6393
13 Zernecke A, Preissner KT. Extracellular ribonucleic acids (RNA) enter the stage in cardiovascular disease. Circ Res 2016; 118 (03) 469-479
14 Böning A, Hagmüller S, Heep M, Rohrbach S, Niemann B, Mühlfeld C. Is warm or cold Calafiore blood cardioplegia better? Hemodynamic, metabolic, and electron microscopic differences. Thorac Cardiovasc Surg 2014; 62 (08) 683-689
15 Böning A, Rohrbach S, Kohlhepp L. , et al. Differences in ischemic damage between young and old hearts--Effects of blood cardioplegia. Exp Gerontol 2015; 67: 3-8
16 DiBona DR, Powell Jr WJ. Quantitative correlation between cell swelling and necrosis in myocardial ischemia in dogs. Circ Res 1980; 47 (05) 653-665
17 Mühlfeld C, Richter J. High-pressure freezing and freeze substitution of rat myocardium for immunogold labeling of connexin 43. Anat Rec A Discov Mol Cell Evol Biol 2006; 288 (10) 1059-1067
18 Schmiedl A, Schnabel PA, Mall G. , et al. The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia. Virchows Arch A Pathol Anat Histopathol 1990; 416 (04) 305-315
19 Fischer S, Nishio M, Dadkhahi S. , et al. Expression and localisation of vascular ribonucleases in endothelial cells. Thromb Haemost 2011; 105 (02) 345-355
20 Zimmerman SB, Sandeen G. A sensitive assay for pancreatic ribonuclease. Anal Biochem 1965; 10: 444-449
21 Swyers T, Redford D, Larson DF. Volatile anesthetic-induced preconditioning. Perfusion 2014; 29 (01) 10-15
22 Headrick JP, See Hoe LE, Du Toit EF, Peart JN. Opioid receptors and cardioprotection - ‘opioidergic conditioning’ of the heart. Br J Pharmacol 2015; 172 (08) 2026-2050
23 Lucchinetti E, Bestmann L, Feng J. , et al. Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection?. Anesthesiology 2012; 116 (02) 296-310