[Effect of cariporide on immature rabbit heart].
OBJECTIVE
To investigate the protective effects of Cariporide on immature rabbit heart, and to search for the protective mechanism of the Na(+)/H(+) exchange inhibitor on immature rabbit hearts.


METHODS
New Zealand immature rabbits were randomly divided into two groups (n = 12 in each group). The isolated rabbit heart model was involved in this study. The hearts were submitted to 60 minutes of normothermic ischemia with cardioplegia per 20 minutes of reperfusion. Group I received St. Thomas No2 as cardioprotective solution. Group II received St. Thomas No2 with addition of cariporide (10 micro mol/L). The left ventricular function was recorded, including left ventricular systolic pressure (LVSP), left ventricular dystolic pressure (LVDP), coronary artery flow (CAF), mean aortic pressure (MAP), aortic flow (AF) and dp/dt max. The levels of creatine phosphokinase (CK), lactic dehydrogenase (LDH) of coronary sinus venous solution were measured. The ventricular cardiomyocytes isolated from other 6 immature rabbit hearts were subdivided into 3 groups of each heart, which were attained by means of collagenase-perfusion. All cells were incubated with calcium fluoresence indicator Fluo-3/AM, and then the intracellular free calcium was measured under the laser scanning con-focal microscopy. The baseline was measured after isolation without anoxic/re-oxygenation. The control group received anoxic conditions for 60 minutes and re-oxygenation for 30 minutes, then was measured. The experiment group received the same conditions as control group with addition of Cariporide (1 micromol/L).


RESULTS
After ischaemia/reperfusion, the percentage of recovery of myocardial function in group II was much better than group I; the LVDP, LVSP, MAP, AF, CAF and dp/dt max showed markedly better recovery in group II. The release of CK, LDH was significantly increased in Group I. After anoxic/re-oxygenation, the intracellular free calcium of isolated immature rabbit ventricular myocytes in control group increased significantly than baseline (P < 0.01); there were no significant difference of immature myocardial [Ca(2+)]i between experiment group and baseline (P > 0.05); and the experiment group myocardial [Ca(2+)]i reduced significantly than control (P < 0.01).


CONCLUSIONS
Cariporide demonstrates significant cardio-protective effects for immature myocardium ischemia/reperfusion, and the protective mechanism may be due to the inhibition of the intracellular free calcium overload.
Chen
Xiang
X
Department of Cardiac Surgery, 309th Hospital, The People's Liberation Army, Beijing 100091, China.
Yang
Jian-an
JA
Zhang
Xiang-hua
XH
Yu
Yi-fei
YF
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C069139:growth factor-activatable Na-H exchanger NHE-1; C093373:cariporide; D012964:Sodium; D002118:Calcium