Anaemia is associated with severe RBC dysfunction and a reduced circulating NO pool: vascular and cardiac eNOS are crucial for the adaptation to anaemia

Anaemia is frequently present in patients with acute myocardial infarction (AMI) and contributes to an adverse prognosis. We hypothesised that, besides reduced oxygen carrying capacity, anaemia is associated with (1) red blood cell (RBC) dysfunction and a reduced circulating nitric oxide (NO) pool,...

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Published in:Basic research in cardiology 2020-07, Vol.115 (4), p.43-43, Article 43
Main Authors: Wischmann, Patricia, Kuhn, Viktoria, Suvorava, Tatsiana, Muessig, Johanna M., Fischer, Jens W., Isakson, Brant E., Haberkorn, Sebastian M., Flögel, Ulrich, Schrader, Jürgen, Jung, Christian, Cortese-Krott, Miriam M., Heusch, Gerd, Kelm, Malte
Format: Article
Language:English
Subjects:
Adaptation
Anemia
Animal models
Blood
Blood circulation
Cardiology
Carrying capacity
Erythrocytes
Heart
Ischemia
Medical prognosis
Medicine
Medicine & Public Health
Muscle contraction
Myocardial infarction
Nitric oxide
Nitric-oxide synthase
Original Contribution
Redox properties
Reperfusion
Ventricle
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Summary:Anaemia is frequently present in patients with acute myocardial infarction (AMI) and contributes to an adverse prognosis. We hypothesised that, besides reduced oxygen carrying capacity, anaemia is associated with (1) red blood cell (RBC) dysfunction and a reduced circulating nitric oxide (NO) pool, (2) compensatory enhancement of vascular and cardiac endothelial nitric oxide synthase (eNOS) activity, and (3) contribution of both, RBC dysfunction and reduced circulatory NO pool to left ventricular (LV) dysfunction and fatal outcome in AMI. In mouse models of subacute and chronic anaemia from repeated mild blood loss the circulating NO pool, RBC, cardiac and vascular function were analysed at baseline and in reperfused AMI. In anaemia, RBC function resulted in profound changes in membrane properties, enhanced turnover, haemolysis, dysregulation of intra-erythrocytotic redox state, and RBC-eNOS. RBC from anaemic mice and from anaemic patients with acute coronary syndrome impaired the recovery of contractile function of isolated mouse hearts following ischaemia/reperfusion. In anaemia, the circulating NO pool was reduced. The cardiac and vascular adaptation to anaemia was characterised by increased arterial eNOS expression and activity and an eNOS-dependent increase of end-diastolic left ventricular volume. Endothelial dysfunction induced through genetic or pharmacologic reduction of eNOS-activity abrogated the anaemia-induced cardio-circulatory compensation. Superimposed AMI was associated with decreased survival. In summary, moderate blood loss anaemia is associated with severe RBC dysfunction and reduced circulating NO pool. Vascular and cardiac eNOS are crucial for the cardio-circulatory adaptation to anaemia. RBC dysfunction together with eNOS dysfunction may contribute to adverse outcomes in AMI.
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-020-0799-x