Haemodynamic response following a 10% topload infusion of HemolinkTM in conscious, anaesthetized and treated spontaneously hypertensive rats.
HemolinkTM (HLK), a haemoglobin-based oxygen carrier (HBOC), is currently undergoing Phase II/III clinical trials in surgical patients. It causes some blood pressure rise in animal and human tests. This study was designed to investigate the systemic haemodynamic response to HemolinkTM in spontaneously hypertensive rats (SHR rats). Conscious or anaesthetized SHR rats and control Wistar Kyoto rats (WKY rats) received either HemolinkTM or homologous plasma as a 10% topload infusion. Some awake animals were pretreated with nifedipine and followed by HLK infusion. In the conscious animal study, HLK induced a greater pressure rise and less bradycardia in SHR rats than in WKY rats. In the anaesthetized animal experiment, HLK-induced pressure rise and bradycardia were similar in both strains and less pronounced than in the conscious animals. In the nifedipine pretreated SHR rats, HLK-induced pressure rise was significantly smaller than that observed in nontreated SHR rats and was not different from that of nontreated WKY rats. The HLK-induced bradycardia was significantly smaller in nifedipine-treated animals than in the nontreated SHR or WKY rats. This study suggests that the pressor effect of HemolinkTM can be attenuated in hypertensive animals with general anaesthesia or treatment with antihypertensive agents.
Ning
J
J
Hemosol Inc., Etobicoke, Ontario, Canada. jning@hemosol.com
Wong
L T
LT
Christoff
B
B
Carmichael
F J
FJ
Biro
G P
GP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000008:administration & dosage / Q000009:adverse effects*; D001803:Blood Transfusion; D006454:Hemoglobins / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007262:Infusions, Intravenous; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D011887:Raffinose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D001802:Blood Substitutes; D006454:Hemoglobins; C097124:O-raffinose cross-linked human hemoglobin; D014665:Vasodilator Agents; D009543:Nifedipine; D011887:Raffinose