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Trimethylamine-N-oxide (TMAO) is an end-product of gut microbiome metabolism linked to cardiovascular disease (CVD). However, precise cardiovascular influences of the TMAO concentrations reported in early or severe disease remain to be detailed. We investigated acute effects of TMAO on cardiac contractile, coronary and mitochondrial function. Male C57Bl/6 mouse hearts were Langendorff perfused to assess concentration-dependent effects of TMAO (1-300 µM) on left ventricular (LV) function, coronary flow and select protein expression. Effects of 10 µM and 100 µM TMAO on LV mitochondrial function were examined via respirometry. TMAO at 10-300 μM concentration-dependently depressed LV contractile function, with coronary flow paralleling changes in isovolumic pressure development. Direct coronary effects were evident at >30 µM TMAO in hearts performing minimal isovolumic work …