Fukushima J. Med. Sci.,Vol. 55, No. 2, 2009

[Original Article]

BILIRUBIN AND ITS OXIDATIVE METABOLITE BIOPYRRINS IN
PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

HIROYUKI KUNII¹⁾, KAZUNOBU ISHIKAWA^1,4), TOKIO YAMAGUCHI²⁾,
NOBUO KOMATSU³⁾, TOSHIKATSU ICHIHARA³⁾
and YUKIO MARUYAMA¹⁾

¹⁾First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan, ²⁾Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan, ³⁾Division of Cardiology, the Iwaki Kyoritsu General Hospital, Iwaki, Fukushima, Japan, ⁴⁾Center for Medical Education and Career Development, Fukushima Medical University

(Received December 2, 2008, accepted May 12, 2009)

Abstract: This study aimed to assess the involvement of bilirubin and its oxidative metabolite biopyrrin in patients with acute myocardial infarction (AMI) and to determine the responsible organs that overproduce these molecules. One hundred thirteen consecutive patients hospitalized for AMI were analyzed. Levels of serum bilirubin, plasma and urinary biopyrrins were measured on the day of admission, day 2, 3, 7 and 14. Expressions of biopyrrins and heme oxygenase-1 (HO-1), a stress-responsive bilirubin-producing enzyme, in heart, aorta, kidney, liver and lung were immunostained with autopsied specimens. Serum bilirubin, plasma and urinary biopyrrins were increased within 24 hr, formed a peak on day 3 and then decreased by day 14. These three parameters were well correlated to each other. The maximum biopyrrin elevation was higher in death cases and associated with impaired left ventricular function. Immunohistochemical analyses revealed biopyrrin accumulation and HO-1 expression in the infracted myocardium. Immunoreactive HO-1 and biopyrrins were also observed in renal tubular cells, aortic wall and lung. Serum bilirubin and its metabolite biopyrrins were elevated in patients with AMI. Plasma and urinary biopyrrin elevation were associated with mortality and morbidity. Induction of anti-oxidative enzyme HO-1 seemed to be involved in the activation of bilirubin/biopyrrin pathway.

Key words: biopyrrin, bilirubin, heme oxygenase, acute myocardial infarction, oxidative stress

国井浩之，石川和信，山口登喜夫，小松宣夫，市原利勝，丸山幸夫

Corresponding author: Kazunobu Ishikawa, MD, PhD, FAHA.
E-mail: kishikaw@fmu.ac.jp
Tokio Yamaguchi, PhD.
E-mail: toki.bgen@mri.tmd.ac.jp
http://fmu.ac.jp/home/lib/F-igaku/
http://www.sasappa.co.jp/online/