title: S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts.
abstract: Cell-free hemoglobin (Hb) derivatives that have been developed as Hb-based artificial oxygen carrier cause both coronary vasoconstriction and platelet aggregation due to the scavenging actions of nitric oxide (NO). Recently, native Hb is found to undergo S-nitrosylation, which regulates blood flow, whereas artificial oxygen carriers are lacking of S-nitrosylation. Therefore, S-nitrosylated and pegylated hemoglobin (SNO-PEG-Hb) was prepared to overcome the above defects, where pegylation was included to avoid extravasation and to prolong the circulatory half-live. Since SNO-PEG-Hb possesses SNO property, we tested whether SNO-PEG-Hb increases coronary blood flow (CBF) and improves the severity of myocardial ischemia. In 19 open chest dogs, the left anterior descending coronary artery was perfused with blood from the carotid artery via the bypass tube, and then CBF and coronary perfusion pressure (CPP) were measured. After hemodynamic stabilization, CPP was reduced so that CBF decreased to 33% of the baseline and thereafter CPP was maintained constant. Ten minutes after the onset of coronary hypoperfusion, we infused 10% SNO-PEG-Hb into the coronary artery (2.5 ml/min). SNO-PEG-Hb increased CBF (28.1+/-3.3 to 43.3+/-3.9 ml/100 g/min, p<0.05), fractional shortening (4.6+/-1.2 to 16.6+/-2.4%, p<0.01) and lactate extraction ratio (-38.5+/-8.6 to 25.5+/-1.3%, p<0.01). Thus, we conclude that SNO-PEG-Hb increases coronary blood flow and improves the contractile and metabolic dysfunction of the ischemic myocardium. SNO-PEG-Hb, a newly developed artificial oxygen carrier, may mediate a cardioprotection in ischemic heart diseases in addition to blood supplementation.
authors.affiliation: Cardiovascular Division, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka Pref. 565-8565, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujita
authors.forename: Akio
authors.initials: A
authors.lastname: Hirata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Wakeno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahama
authors.forename: Jiyoong
authors.initials: J
authors.lastname: Kim
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003326:Coronary Circulation; D004285:Dogs; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001802:Blood Substitutes; D002316:Cardiotonic Agents; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols