Experimental study of pegylated liposomal hemoglobin on norepinephrine release and reperfusion arrhythmias in isolated guinea pig hearts.
OBJECTIVE
Under myocardial reperfusion conditions, hemoglobin (Hb)-based artificial blood showed effectiveness for post-ischemic dysfunction. However, there are no studies about the effects of this product on reperfusion arrhythmias (ventricular fibrillation, VF) associated with norepinephrine (NE) release. This study was to evaluate the effects of the timing of the administration of pegylated liposomal Hb (LHb, P(50)=40-45 mmHg, 1 mg/mL) on NE release and VF.


METHODS
Isolated guinea pig hearts (n=6 in each group) were randomly divided into four groups in Krebs-Henseleit solution being supplemented or not with LHb as follows: pre-ischemia (PRE), reperfusion (REP), or PRE+REP groups. The hearts were perfused for 30 min (preischemic period) and then subjected to 30 min of global ischemia, followed by 30 min of reperfusion with a normothermic Langendorff apparatus at 30 mm Hg aortic pressure in a constant pressure model.


RESULTS
No differences were documented among the four groups in heart rate, left ventricular-developed pressure, or coronary flow rate. However, the REP group significantly decreased the duration of VF and NE release, but it did not inhibit the incidence of VF.


CONCLUSIONS
These results suggest that the administration of LHb, especially with the timing of reperfusion, might prevent reperfusion arrhythmias linked to the inhibition of NE release.
Isaka
Mitsuhiro
M
Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Imamura
Michiaki
M
Sakuma
Ichiro
I
Shiiya
Norihiko
N
Ishizuka
Takanobu
T
Ogata
Yoshitaka
Y
Yasuda
Keishu
K
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000502:physiology; D006168:Guinea Pigs; D006454:Hemoglobins / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D009638:Norepinephrine / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D001802:Blood Substitutes; D006454:Hemoglobins; D008081:Liposomes; D009638:Norepinephrine