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 assessedas blood substitutes in patients with perioperative anaemiaincluding patients at risk for perioperative cardiac ischaemia.There is controversy as to whether HBOCs are beneficial or deleteriousduring ischaemia–reperfusion (I–R). Therefore theeffects of HBOC-200 on I–R injury were evaluated in arandomized 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. priorto I–R (prophylaxis group, n=12) or HBOC-200 0.4 g kg^–1i.v. during I–R (therapy group, n=15). I–R consistedof 25 min of acute ligature of the left coronary artery followedby 120 min of reperfusion. Measurements included assessmentof the area at risk and infarct size using triphenyl tetrazoliumchloride (TTC) stain, DNA single-strand breaks (in situ nicktranslation 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) and61 (9)% (therapy, P<0.85 vs control). The frequency of DNAsingle-strand breaks was reduced vs control in the sham (P<0.01)and prophylaxis (P<0.04) groups and was almost the same inthe therapy group (P<0.75). The severity of cardiac arrhythmiasduring ischaemia was lower compared with control in the sham(P<0.001) and prophylaxis (P<0.039) groups, but therewas no difference in the therapy group. Conclusion. This study demonstrates that neither prophylacticnor therapeutic application of the cell-free haemoglobin solutionHBOC-200 aggravates cardiac I–R injury. Furthermore, theprophylactic approach may offer a new opportunity for pretreatmentof patients at risk for perioperative ischaemic cardiac events. The results were presented in part at the Congress of the EuropeanSociety of Anaesthesia, Glasgow, UK, June 2003 (‘BestAbstract Award’), and at the Annual Meeting of the AmericanSociety of Anesthesiologists, San Francisco, CA, USA, October2003. Declaration of interest. T. G. Standl has received lecture honorariaand travel fees from Biopure Corporation, Boston, MA, the manufacturerof HBOC. The Department of Anaesthesiology, University Hospital,Hamburg-Eppendorf, received restricted grants from Biopure Corporation,Boston, MA, between 1994 and 1998 for animal and clinical phaseII and III trials. M.A. Burmeister is Vice President Researchand Development, Hospital Care Division, B. Braun MelsungenAG, Melsungen, Germany. B. Braun, a global health care supplier,cooperated with Biopure Corporation, Boston, MA, on HBOC developmentuntil 1996. The work presented in this paper was done independentlyof and without any support from B. Braun.