Myocardial dysfunction, hypotension, and increased pulmonary artery pressure are induced by asphyxia in neonates. We sought to define left ventricular (LV) systolic function by measuring longitudinal and radial contraction by strain Doppler echocardiography (SDE) in hypoxemic newborn pigs. Hypoxemia was induced in 11 anesthetized and instrumented newborn pigs by ventilation with 8% O2 in nitrogen. When mean arterial blood pressure (BP) decreased to 15 mm Hg or arterial base excess reached -20 mmol/L or less, the pigs were reoxygenated and ventilated for 150 min. Echocardiography was performed at baseline and during hypoxemia and reoxygenation. Baseline measurements of myocardial peak systolic strain demonstrated normal longitudinal shortening and radial thickening. During hypoxemia, systolic longitudinal shortening in the mid-posterior and septal segments changed to systolic stretching. Peak strain in the mid-lateral and anterior segments decreased but without signs of paradox wall motion. Short-axis peak strain remained positive during hypoxemia, although the amplitude was reduced and delayed with respect to timing. In the newborn pig heart, we found a complex and heterogeneous systolic pattern with distinct regional differences during global hypoxemia. Rapid changes in LV function during hypoxemia and reoxygenation are assessable by SDE, and the results indicate that longitudinal systolic contraction is more vulnerable to hypoxemic changes than radial contraction. To explore the full picture of a global hypoxemic injury, both long- and short-axis functions have to be considered.