Myocardial ferritin content is closely related to the degree of ischaemia
Ferritin acts as an iron scavanger and thereby may reduce iron catalysed oxygen radical production during reperfusion injury. We tested the hypothesis that the myocardial ferritin concentration is enhanced during ischaemia in proportion to the blood flow reduction. Methods:
In 10 anaesthetized, open chest Beagle dogs (six controls and four with 60 min coronary occlusion) regional myocardial blood flow (RMBF) was measured with the tracer microsphere technique and ferritin was determined in samples with an average mass of 125 mg (124–256 samples per heart). Results:
Under physiological conditions heart rate was 88 ± 12 bpm, mean aortic pressure 98 ± 8 mmHg, and RMBF 0.99 ± 0.33 mL min−1 g−1. Data did not differ between experimental groups, P > 0.05. In the control group regional myocardial ferritin concentration averaged 11.76 ± 3.54 ng mg−1 protein and exhibited a significant blood flow independent heterogeneity (CVbiol = 0.27). However, between low and high flow areas (relative flow <0.5 and >1.5 times the average RMBF, respectively) no significant difference in ferritin was found, P > 0.05. In four experiments, in which regional blood flow was reduced by 40% to 0.60 ± 0.23 mL min−1 g−1, regional ferritin content was significantly higher as compared with the control group 27.95 ± 6.16 vs. 11.76 ± 3.54 ng mg−1 protein, respectively. An inverse relationship was observed between ferritin and RMBF, r = −0.61, P < 0.001. Thus, a reduction of RMBF of >80% was associated with a 2.75-fold increase of the average ferritin content. Between subepicardium and subendocardium no significant difference in ferritin content was observed, neither in the control group nor in the group with induced ischaemia. Regions with control low and high flow responded similarly to the coronary constriction with regard to the local ferritin concentration: 27.88 ± 15.22 vs. 30.10 ± 14.91 ng mg−1, P > 0.05, respectively. A data analysis using Baye's theorem indicated that sensitivities were 0.28 and 0.94 for average flow reductions of 5 and 93%. In additional in vitro measurements (ischaemic incubation at 37 °C) myocardial ferritin content increased almost linearly within the first 60 min of incubation and thereafter remained unchanged. Conclusions:
(1) Local physiological ferritin content in myocardium is heterogeneous and unrelated to control myocardial blood flow. (2) Ischaemia results in an enhanced ferritin content in relation to the degree of ischaemia. (3) The increase of myocardial ferritin requires a severe degree of ischaemia.
Document Type: Research Article
Affiliations: 1: Institut für Hämostaseologie und Transfusionsmedizin, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany 2: Institut für Klinische Anästhesiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany 3: Institut für Physiologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Germany
Publication date: January 1, 2004