Effects of prophylactic or therapeutic application of bovine haemoglobin HBOC-200 on ischaemia-reperfusion injury following acute coronary ligature in rats.
BACKGROUND
Haemoglobin-based oxygen carriers (HBOCs) are assessed as blood substitutes in patients with perioperative anaemia including patients at risk for perioperative cardiac ischaemia. There is controversy as to whether HBOCs are beneficial or deleterious during ischaemia-reperfusion (I-R). Therefore the effects of HBOC-200 on I-R injury were evaluated in a randomized placebo-controlled animal trial.


METHODS
Animals were randomized to receive either placebo i.v. without I-R (sham group, n=9), placebo i.v. with I-R (control group, n=10), HBOC-200 0.4 g kg(-1) i.v. prior to I-R (prophylaxis group, n=12) or HBOC-200 0.4 g kg(-1) i.v. during I-R (therapy group, n=15). I-R consisted of 25 min of acute ligature of the left coronary artery followed by 120 min of reperfusion. Measurements included assessment of the area at risk and infarct size using triphenyl tetrazolium chloride (TTC) stain, DNA single-strand breaks (in situ nick translation with autoradiography/densitometry) and cardiac arrhythmias.


RESULTS
Infarct size within the area at risk was 62 (sd 15)% (control), 46 (10)% (prophylaxis, P<0.025 vs control) and 61 (9)% (therapy, P<0.85 vs control). The frequency of DNA single-strand breaks was reduced vs control in the sham (P<0.01) and prophylaxis (P<0.04) groups and was almost the same in the therapy group (P<0.75). The severity of cardiac arrhythmias during ischaemia was lower compared with control in the sham (P<0.001) and prophylaxis (P<0.039) groups, but there was no difference in the therapy group.


CONCLUSIONS
This study demonstrates that neither prophylactic nor therapeutic application of the cell-free haemoglobin solution HBOC-200 aggravates cardiac I-R injury. Furthermore, the prophylactic approach may offer a new opportunity for pretreatment of patients at risk for perioperative ischaemic cardiac events.
Burmeister
M A
MA
Department of Anaesthesia, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. burmeister@uke.uni-hamburg.de
Rempf
C
C
Standl
T G
TG
Rehberg
S
S
Bartsch-Zwemke
S
S
Krause
T
T
Tuszynski
S
S
Gottschalk
A
A
Schulte am Esch
J
J
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000517:prevention & control; D001831:Body Temperature / Q000187:drug effects; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D004334:Drug Administration Schedule; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control*
D004277:DNA, Single-Stranded; D006454:Hemoglobins; C402601:hemoglobin glutamer-200