Trimethylamine-n-oxide acutely increases cardiac muscle contractility.

TRIMETHYLAMINE-N-OXIDE ACUTELY INCREASES CARDIAC MUSCLE CONTRACTILITY. Am J Physiol Heart Circ Physiol. 2020 Apr 03;: Authors: Oakley CI, Vallejo JA, Wang D, Gray MA, Tiede-Lewis LM, Shawgo T, Daon E, Zorn G, Stubbs JR, Wacker MJ Abstract Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-N-oxide (TMAO), a uremic metabolite that is elevated in the setting of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse cardiovascular outcomes, its direct effect on cardiac and smooth muscle function remains to be fully elucidated. We hypothesized that pathological concentrations of TMAO would acutely increase cardiac and smooth muscle contractility. These effects may ultimately contribute to cardiac dysfunction during CKD. High levels of TMAO significantly increased paced, ex vivo human cardiac muscle biopsy contractility (P<0.05). Similarly, TMAO augmented contractility in isolated mouse hearts (P<0.05). Reverse perfusion of TMAO through the coronary arteries via a Langendorff apparatus also enhanced cardiac contractility (P<0.05). In contrast, the precursor molecule, trimethylamine (TMA), did not alter contractility (P>0.05). Multi-photon microscopy, utilized to capture changes in intracellular calcium in paced, adult mouse hearts ex vivo, ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research