Administration of bovine polymerized haemoglobin before and during coronary occlusion reduces infarct size in rabbits.
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.
Rempf
C
C
Department of Anaesthesiology, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany.
Standl
T
T
Schenke
K
K
Chammas
K
K
Gottschalk
A
A
Burmeister
M-A
MA
Gottschalk
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000627:therapeutic use*; D002245:Carbon Dioxide / Q000097:blood; D002417:Cattle; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011817:Rabbits
D001802:Blood Substitutes; D006454:Hemoglobins; C402601:hemoglobin glutamer-200; D002245:Carbon Dioxide; D010100:Oxygen