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Mild metabolic acidosis impairs the β-adrenergic response in isolated human failing myocardium

Hanna Schotola1*, Karl Toischer2, Aron F Popov34, André Renner5, Jan D Schmitto6, Jan Gummert5, Michael Quintel1, Martin Bauer1, Lars S Maier2 and Samuel Sossalla2

Author Affiliations

1 Department of Anesthesiology, Emergency and Intensive Care Medicine, University Hospital Goettingen, Robert-Koch-Straße 40, Goettingen, 37075, Germany

2 Division of Cardiology and Pneumology, University Hospital Goettingen, Robert-Koch-Straße 40, Goettingen, 37075, Germany

3 Department of Thoracic and Cardiovascular Surgery, University Hospital Goettingen, Robert-Koch-Straße 40, Göttingen, 37075, Germany

4 Department of Cardiothoracic Transplantation and Mechanical Support, Royal Brompton and Harefield Hospital, Hill End Road, London, UB9 6JH, UK

5 Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center, North Rhine Westphalia, Bad Oeynhausen, Georgstraße 11, Bad Oeynhausen, 32545, Germany

6 Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover, 30625, Germany

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Critical Care 2012, 16:R153  doi:10.1186/cc11468

Published: 13 August 2012



Pronounced extracellular acidosis reduces both cardiac contractility and the β-adrenergic response. In the past, this was shown in some studies using animal models. However, few data exist regarding how the human end-stage failing myocardium, in which compensatory mechanisms are exhausted, reacts to acute mild metabolic acidosis. The aim of this study was to investigate the effect of mild metabolic acidosis on contractility and the β-adrenergic response of isolated trabeculae from human end-stage failing hearts.


Intact isometrically twitching trabeculae isolated from patients with end-stage heart failure were exposed to mild metabolic acidosis (pH 7.20). Trabeculae were stimulated at increasing frequencies and finally exposed to increasing concentrations of isoproterenol (0 to 1 × 10-6 M).


A mild metabolic acidosis caused a depression in twitch-force amplitude of 26% (12.1 ± 1.9 to 9.0 ± 1.5 mN/mm2; n = 12; P < 0.01) as compared with pH 7.40. Force-frequency relation measurements yielded no further significant differences of twitch force. At the maximal isoproterenol concentration, the force amplitude was comparable in each of the two groups (pH 7.40 versus pH 7.20). However, the half-maximal effective concentration (EC50) was significantly increased in the acidosis group, with an EC50 of 5.834 × 10-8 M (confidence interval (CI), 3.48 × 10-8 to 9.779 × 10-8; n = 9), compared with the control group, which had an EC50 of 1.056 × 10-8 M (CI, 2.626 × 10-9 to 4.243 × 10-8; n = 10; P < 0.05), indicating an impaired β-adrenergic force response.


Our data show that mild metabolic acidosis reduces cardiac contractility and significantly impairs the β-adrenergic force response in human failing myocardium. Thus, our results could contribute to the still-controversial discussion about the therapy regimen of acidosis in patients with critical heart failure.