Experimental investigation of direct myocardial protective effect of atrial natriuretic peptide in cardiac surgery

Wakui, Shinji; Sezai, Akira; Tenderich, Gero; Hata, Mitsumasa; Osaka, Syunji; Taniguchi, Yoshiki; Koerfer, Reiner; Minami, Kazutomo

doi:10.1016/j.jtcvs.2009.08.030

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 139, Issue 4 , Pages 918-925, April 2010

Experimental investigation of direct myocardial protective effect of atrial natriuretic peptide in cardiac surgery

Shinji Wakui, MD
- Advanced Research Institute for the Sciences and Humanity (ARISH), Nihon University, Tokyo, Japan
- Department of Cardiovascular Surgery, Nihon University, Tokyo, Japan
- Department of Thoracic and Cardiovascular Surgery, Heart Center North-Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany
- Address for reprints: Shinji Wakui, MD, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Georgstraße 11, 32545 Bad Oeynhausen, Germany.
Akira Sezai, MD, PhD
- Department of Cardiovascular Surgery, Nihon University, Tokyo, Japan
Gero Tenderich, MD, PhD
- Department of Thoracic and Cardiovascular Surgery, Heart Center North-Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany
Mitsumasa Hata, MD, PhD
- Department of Cardiovascular Surgery, Nihon University, Tokyo, Japan
Syunji Osaka
- Department of Cardiovascular Surgery, Nihon University, Tokyo, Japan
Yoshiki Taniguchi
- Department of Collaboration, Nihon University, Tokyo, Japan
Reiner Koerfer, MD, PhD
- Department of Thoracic and Cardiovascular Surgery, Heart Center North-Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany
Kazutomo Minami, MD, PhD
- Advanced Research Institute for the Sciences and Humanity (ARISH), Nihon University, Tokyo, Japan
- Department of Cardiovascular Surgery, Nihon University, Tokyo, Japan
- Department of Thoracic and Cardiovascular Surgery, Heart Center North-Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany

Received 23 November 2008; received in revised form 26 July 2009; accepted 9 August 2009. published online 12 November 2009.

Objective

Human atrial natriuretic peptide has recently become known not only as a heart failure drug but also for myocardial protection. We investigated its direct myocardial protective effect on ischemia–reperfusion injury in cardiac surgery.

Methods

Male pigs (35–45 kg) undergoing surgery with cardiopulmonary bypass, with 60-minute reperfusion after 30-minute cardioplegia, were grouped by timing of atrial natriuretic peptide administration: group C (n = 8), no atrial natriuretic peptide (cardioplegia only); group H1 (n = 8); 100-μg atrial natriuretic peptide administration after aortic crossclamping; group H2 (n = 8), administration before aortic declamping; and group H1 + H2 (n = 8), administration both after crossclamping and before declamping. Blood and myocardial cyclic guanosine monophosphate, calcium, and residual adenosine triphosphate levels were determined. Histologic investigation was conducted by electron and optical microscopy.

Results

Atrial natriuretic peptide increased blood and myocardial cyclic guanosine monophosphate levels (P < .0001, P < .0001, P < .007 H1 + H2 vs C; P < .0014, P < .0007, P < .003 H1 vs C), decreased myocardial calcium (P < .0038 H1 + H2 vs C), and increased myocardial residual adenosine triphosphate. Electron microscopy revealed ischemic changes in mitochondria and nuclei in group C but not in treatment groups.

Conclusions

Ischemia–reperfusion injury was inhibited with equal effectiveness by atrial natriuretic peptide both during ischemia and immediately before reperfusion, acting directly on myocardium through cyclic guanosine monophosphate. Atrial natriuretic peptide may be useful as a supportive measure for patients with long aortic crossclamping time or difficulties in weaning from cardiopulmonary bypass.

CTSNet classification: 31

Abbreviations and Acronyms: ANP, atrial natriuretic peptide, ATP, adenosine triphosphate, cGMP, cyclic guanosine monophosphate, CPB, cardiopulmonary bypass, hANP, human atrial natriuretic peptide