S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts.
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.
Asanuma
Hiroshi
H
Cardiovascular Division, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka Pref. 565-8565, Japan.
Nakai
Kunihiko
K
Sanada
Shoji
S
Minamino
Tetsuo
T
Takashima
Seiji
S
Ogita
Hisakazu
H
Fujita
Masashi
M
Hirata
Akio
A
Wakeno
Masakatsu
M
Takahama
Hiroyuki
H
Kim
Jiyoong
J
Asakura
Masanori
M
Sakuma
Ichiro
I
Kitabatake
Akira
A
Hori
Masatsugu
M
Komamura
Kazuo
K
Kitakaze
Masafumi
M
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
D001802:Blood Substitutes; D002316:Cardiotonic Agents; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols