Experimental investigation of direct myocardial protective effect of atrial natriuretic peptide in cardiac surgery.
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-mug 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.
Wakui
Shinji
S
Advanced Research Institute for the Sciences and Humanity, Nihon University, Tokyo, Japan. wakui.shinji@googlemail.com)
Sezai
Akira
A
Tenderich
Gero
G
Hata
Mitsumasa
M
Osaka
Syunji
S
Taniguchi
Yoshiki
Y
Koerfer
Reiner
R
Minami
Kazutomo
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013552:Swine
D002317:Cardiovascular Agents; D020011:Protective Agents; D009320:Atrial Natriuretic Factor