Effects and interaction, of cariporide and preconditioning on cardiac arrhythmias and infarction in rat in vivo

Although Na + ‐H + exchange (NHE) inhibitors are reported to protect the myocardium against ischaemic injury, NHE activation has also been proposed as a potential mechanism of ischaemic preconditioning‐induced protection. This study was performed to test any modifiable effect of cariporide, an NHE inhibitor, on cardioprotective effects of preconditioning. Anaesthetized rats were subjected to 30 min of coronary artery occlusion and 150 min of reperfusion. The preconditioning (PC) was induced by 3 min of ischaemia and 10 min of reperfusion (1PC) or three episodes of 3 min ischaemia and 5 min reperfusion (3PC). Cariporide (0.3 mg kg −1 ) an NHE inhibitor, was administered 30 min (cari(30)) or 45 min (cari(45)) before coronary ligation ( n =8–11 for each group). Ventricular arrhythmias during 30 min ischaemia and infarct size (measured by triphenyltetrazolium (TTC) and expressed as a per cent area at risk (%AAR)) were determined. Cari(30) reduced ventricular fibrillation (VF) incidence and infarct size (from 45 to 0% and 34±4 to 9±2%; each P <0.05), whereas cari(45) did not. Likewise, 3PC reduced these variables (to 0% and 10±2%; P <0.05 in each case) whereas 1PC did not. Moreover, subthreshold preconditioning (1PC) and cariporide (cari(45)), when combined, reduced VF incidence and infarct size (to 0% and 15 + 3%; each P <0.05). In conclusion, changes in NHE activity do not seem to be responsible for the cardioprotective action of ischaemic preconditioning. Protective effects of NHE inhibition and subthreshold preconditioning appear to act additively.British Journal of Pharmacology (1999) 127 , 1048–155; doi: 10.1038/sj.bjp.0702566