S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts

Hiroshi Asanuma, Kunihiko Nakai, Shoji Sanada, Tetsuo Minamino, Seiji Takashima, Hisakazu Ogita, Masashi Fujita, Akio Hirata, Masakatsu Wakeno, Hiroyuki Takahama, Jiyoong Kim, Masanori Asakura, Ichiro Sakuma, Akira Kitabatake, Masatsugu Hori, Kazuo Komamura, Masafumi Kitakaze

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)924-930
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume42
Issue number5
DOIs
Publication statusPublished - 2007 May

Keywords

  • Artificial oxygen carrier
  • Ischemic heart disease
  • S-nitrosylated and pegylated hemoglobin
  • S-nitrosylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Asanuma, H., Nakai, K., Sanada, S., Minamino, T., Takashima, S., Ogita, H., Fujita, M., Hirata, A., Wakeno, M., Takahama, H., Kim, J., Asakura, M., Sakuma, I., Kitabatake, A., Hori, M., Komamura, K., & Kitakaze, M. (2007). S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts. Journal of Molecular and Cellular Cardiology, 42(5), 924-930. https://doi.org/10.1016/j.yjmcc.2006.12.001