title: Cariporide enhances lactate clearance upon reperfusion but does not alter lactate accumulation during global ischaemia.
abstract: Cariporide (HOE 642) inhibits the Na+/H+ exchanger and would be expected to reduce lactate accumulation during ischaemia and stimulate lactate/H+ co-transporter upon reperfusion. The aim of this study was to determine the effect of cariporide on lactate production during global ischaemia and release during reperfusion. Guinea-pig hearts perfused in the Langendorff mode were exposed to 45 min global ischaemia and 30 min reperfusion with or without cariporide (5 or 10 micromol/l). Cardiac function was assessed by measurement of left ventricular developed pressure (LVDP). Lactate and pH were measured in coronary effluent before ischaemia and throughout reperfusion. Tissue metabolites (lactate, adenine nucleotides, guanine nucleotides and purine) were measured in ventricular biopsy samples collected at the beginning and end of ischaemia. Cariporide significantly improved recovery of LVDP (from 66% for control to 88% and 93% for 5 and 10 micromol/l cariporide, respectively). During ischaemia, only 10 micromol/l cariporide produced a small (10%) but significant preservation of ATP and GTP compared to control. This was associated with significant reduction (25%) in ischaemic contracture. Cariporide did not influence lactate accumulation during ischaemia but significantly increased lactate efflux (18%) during the first 60 s of reperfusion. In conclusion, cariporide does not alter lactate accumulation during ischaemia but enhances lactate efflux upon reperfusion, which may have implications for its cardioprotective action.
authors.affiliation: Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol, BS2 8HW, UK.
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: M-S
authors.initials: MS
authors.lastname: Suleiman
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D006146:Guanidines; D013450:Sulfones; D019344:Lactic Acid; C093373:cariporide