Administration of bovine polymerized haemoglobin before and during coronary occlusion reduces infarct size in rabbits

Abstract

Background. Haemoglobin-based oxygen carriers (HBOC) seem to increase the risk of mortality and myocardial infarction in clinical trials. Therefore, we designed this randomized placebo-controlled animal study to evaluate the effects of prophylactic and therapeutic administration of HBOC in a myocardial ischaemia-reperfusion model with respect to infarct size and areas of impaired perfusion (no reflow, NR). Methods. Thirty-two anaesthetized, mechanically ventilated rabbits were randomized to one of the four groups. Group G1 received 0.4 g kg-1 i.v. HBOC-200 25 min before coronary artery occlusion, G2 received the same dose i.v. 10 min after occlusion, and G3 and 4 received i.v. saline. G1, 2, and 3 were subjected to 30 min occlusion of left coronary artery followed by 240 min of reperfusion. G4 was treated without ischaemia- reperfusion. Measurement included assessment of the area at risk and infarct size using triphenyltetrazolium chloride stain and areas of NR using thioflavin stain. Ischaemia-reperfusion was confirmed by microspheres technique. Results. Infarct size as a percentage of the area at risk was significantly reduced in G1 [25 (sd 13)%, P=0.026] and G2 [22 (20)%, P=0.009] compared with G3 [48 (17)%]. The areas of NR in percentage of the area at risk [G1, 26 (15)%; G2, 34 (22)%; G3, 36 (12)%; G4, 5 (3)%] did not differ between the groups of animals undergoing coronary occlusion and reperfusion. Conclusions. Prophylactic and therapeutic administration of HBOC-200 reduces infarct size in myocardial ischaemia and reperfusion in rabbits. This reduction of infarct size is not accompanied by an improvement of areas of NR.