Cariporide attenuates myocardial ischaemia, reperfusion injury and apoptosis in isolated rat hearts.
OBJECTIVE
Inhibition of Na+/H+ exchanger (NHE) may protect the ischaemic reperfused myocardium by attenuating sodium overload. This study investigated the time-dependent beneficial effect of the NHEI inhibitor cariporide and the effect on early apoptosis in a rat model of ischaemia and reperfusion.


RESULTS
The hearts of rats were perfused in a Langendorff apparatus. In the first part of the experiment, rats were divided into four groups: I/R (cariporide was not given), HOE-Pr+I/R (cariporide was given 15 min before ischaemia), HOE-Is+I/R (cariporide was given shortly before ischaemia), HOE-Re+I/R (cariporide was given during reperfusion). The left ventricular systolic pressure (LVSP), the left ventricular end-diastolic pressure (LVEDP), arrhythmia, coronary flow and myocardial enzymes were measured. In the second part of the experiment, hearts were bathed in the presence or absence of cariporide before ischaemia. Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assays were used to quantify apoptotic cells. Improvement of recovery from ischaemia, defined as increased LVSP, decreased LVEDP, improvement in arrhythmia score, CK-MB and LDH was more significant in the HOE-Pr+I/R group than in the I/R group. Furthermore, cariporide given during ischaemia caused intermediate improvement of ischaemic recovery, while there was no difference between HOE-Re+I/R and I/R hearts. The number of apoptotic cells after ischaemia and reperfusion was 51.8 +/- 15.2 per 1000 cardiomyocytes compared to 11.5 +/- 5.7 (p < 0.05) in hearts pretreated before ischaemia with cariporide.


CONCLUSIONS
In conclusion, cariporide decreases the degree of impaired cardiac recovery and early apoptosis after ischaemia/reperfusion injury. The cardioprotective effects of cariporide are more pronounced when the drug is given before ischaemia.
Zhang
Yun
Y
Division of Cardiovascular Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. zhangyun93@163.com
Chen
Junzhu
J
Zhang
Furong
F
Xia
Qiang
Q
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
D006146:Guanidines; D013450:Sulfones; C093373:cariporide; D052279:Creatine Kinase, MB Form; D004253:DNA Nucleotidylexotransferase