TIME-DEPENDENT PROTECTION BY NA+ H+ EXCHANGE INHIBITION IN A REGIONALLY ISCHEMIC, REPERFUSED PORCINE HEART PREPARATION WITH LOW RESIDUAL BLOOD-FLOW/

Inhibition of Na+/H+ exchange has been shown to protect the ischemic r eperfused myocardium. This study investigated the time-dependent benef icial effect of the Na+/H+ exchange inhibitor HOE642 (4-isopropyl-3-me thylsulphonylbenzoyl-guanedine methanesulphonite, cariporide). The lef t anterior descending coronary artery was ligated in 21 pigs (seven co ntrol animals) for 60 min and then reperfused for 24 h. An extracorpor eal bypass system was used to achieve a constant residual blood flow o f 3 ml/min within the ischemic myocardium. Cariporide (1 mg/kg) was in jected intravenously in seven pigs after 15 min of ischemia (group A), and in another seven animals after 45 min of ischemia (group B), Hist ochemical (tetrazolium stain) and histologic infarct sizes were determ ined at the end of the experiments, Regional systolic shortening was d etermined by sonomicrometry. Mean calculated residual blood flows (ml/ min/g of ischemic myocardium) amounted to 0.106 (group A), 0.093 (grou p B), and 0.117 (control group). Histochemical (32.9 +/- 21%) and hist ologic infarct sizes (36.7 +/- 17.7%) were significantly reduced in gr oup A compared to both the control group (histochemical infarct size, 62.5 +/- 16.1%, P<0.01; histologic infarct size, 67.8 +/- 16.3%, P = 0 .013) and group B (histochemical infarct size 64.8 +/- 12.2%, P<0.01; histologic infarct size 67.1 +/- 15.6%, P<0.01). Infarct sizes of grou p B did not differ from control values. Recovery of regional systolic shortening after 24 h of reperfusion was insignificantly improved in g roup A compared to both other groups. In conclusion, inhibition of Na/H+ exchange during early ischemia reduced cell death in an ischemic r eperfused preparation with low residual blood flow. (C) 1998 Academic Press Limited.