ArticlePloS one2013
The positive inotropic effect of pyruvate involves an increase in myofilament calcium sensitivity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Preparation of Human Atrial Trabeculae for Ex Vivo Analysis of Human Myocardial Function.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Modeling the human heart ex vivo-current possibilities and strive for future applications.Journal of tissue engineering and regenerative medicine · 2022Review
- A Novel Therapeutic Approach With Sodium Pyruvate on Vital Signs, Acid-Base, and Metabolic Disturbances in Rats With a Combined Blast and Hemorrhagic Shock.Frontiers in neurology · 2022Article
- Cardiac Inotropic Effect of Long-Term Administration of Oral Thymoquinone.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Force-frequency relationship and early relaxation kinetics are preserved upon sarcoplasmic blockade in human myocardium.Physiological reports · 2018Article
- Pyruvate enhancement of cardiac performance: Cellular mechanisms and clinical application.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Can inorganic phosphate explain sag during unfused tetanic contractions of skeletal muscle?Physiological reports · 2016Article
- A technical review of optical mapping of intracellular calcium within myocardial tissue.American journal of physiology. Heart and circulatory physiology · 2016Review
- Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate.Pflugers Archiv : European journal of physiology · 2016Article
- Sarcolipin overexpression improves muscle energetics and reduces fatigue.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Article
- Article
- Automated analysis of contractile force and Ca2+ transients in engineered heart tissue.American journal of physiology. Heart and circulatory physiology · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pyruvate is a metabolic fuel that is a potent inotropic agent. Despite its unique inotropic and antioxidant properties, the molecular mechanism of its inotropic mechanism is still largely unknown. To examine the inotropic effect of pyruvate in parallel with intracellular calcium handling under near physiological conditions, we measured pH, myofilament calcium sensitivity, developed force, and calcium transients in ultra thin rabbit heart trabeculae at 37 °C loaded iontophoretically with the calcium indicator bis-fura-2. By contrasting conditions of control versus sarcoplasmic reticulum block (with either cyclopiazonic acid and ryanodine or with thapsigargin) we were able to characterize and isolate the effects of pyruvate on sarcoplasmic reticulum calcium handling and developed force. A potassium contracture technique was subsequently utilized to assess the force-calcium relationship and thus the myofilament calcium sensitivity. Pyruvate consistently increased developed force whether or not the sarcoplasmic reticulum was blocked (16.8±3.5 to 24.5±5.1 vs. 6.9±2.6 to 12.5±4.4 mN/mm(2), non-blocked vs. blocked sarcoplasmic reticulum respectively, p<0.001, n = 9). Furthermore, the sensitizing effect of pyruvate on the myofilaments was demonstrated by potassium contractures (EC50 at baseline versus 20 minutes of pyruvate infusion (peak force development) was 701±94 vs. 445±65 nM, p<0.01, n = 6). This study is the first to demonstrate that a leftward shift in myofilament calcium sensitivity is an important mediator of the inotropic effect of pyruvate. This finding can have important implications for future development of therapeutic strategies in the management of heart failure.
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