Fig. 1. Increased myocardial workload promotes local elevation of lactate:pyruvate ratio in the coronary arterial wall.

A Schematic showing protocol for induction of acute cardiac stress prior to collection of tissues for MALDI-MS imaging. To induce high cardiac work, anesthetized mice with stable heart rates of 400–450 bpm were treated with dobutamine (db; 10 mg/kg, i.p.). Heart rate was continuously monitored, and hearts were rapidly cryopreserved in the thoracic cavity and excised after 2–3 min of stabilized heart rate responses to either db or PBS (vehicle). B Symbol plot showing exemplary heart rates recorded every 30 s before (i.e., during induction and stabilization of anesthesia) and after administration of either db (10 mg/kg; i.p.) or PBS. C Images of left ventricular intramyocardial coronary arteries in H & E-stained heart sections and corresponding intensity-coded MALDI-MS images showing lactate (Lac) and pyruvate (Pyr) relative to background signals in hearts from low and high cardiac work mice. x–y resolution: ~20 μm. Insets show magnified region of interest at coronary arterial wall. Scale bars represent 200 μm. Experiment was repeated twice with similar results. D Box and whiskers plots (line: median, box: 25th to 75th percentile, whiskers: min and max) showing lactate:pyruvate ratios in perivascular myocardium (region of interest within ~250 μm from coronary wall; top) and coronary wall (bottom) in hearts of low and high cardiac work mice. (low cardiac work: n = 16 technical replicates, 4 mice, high cardiac work group: n = 8 technical replicates, 2 mice), perivascular, **p < 0.0001, coronary, **p = 0.0003 (unpaired two-sided t test). Source data are provided as a Source Data file.