Peirano, Felipe

Ischemia/reperfusion (I/R) injury occurs during acute myocardial infarction and is a frequent cause of contractile failure, morbidity and mortality. There is evidence that reduced cardiac contractility following I/R injury is associated with disruption of excitation‐contraction (E‐C) coupling. We hypothesized that I/R injury alters E‐C coupling in cardiomyocytes by reducing the Ca 2+ sensitivity of contraction. Cardiomyocytes were isolated from adult rat (Sprague Dawley) hearts using a modified Langendorff system. Cardiomyocytes were then loaded with fura‐2 AM (Ca 2+ fluorescent indicator; 1 μM) and electrically stimulated every 2 s (0.5 Hz). Cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) and sarcomere length shortening responses to stimulation were simultaneously measured using an IonOptix System equipped with a hypoxia‐regulated incubator system (Live Cell Instrument). To model I/R, cardiomyocytes were initially exposed to normoxia (21% O 2 ) for 30 min followed by 30 min exposure to 2.5% O 2 and finally 30 min exposure to normoxia. Throughout the I/R protocol, Ca 2+ sensitivity of cardiomyocytes was assessed using a phase loop plot of concurrently measured [Ca 2+ ] cyt and sarcomere length shortening. I/R reduced the extent of sarcomere length shortening, but it had no effect on the amplitude of evoked [Ca 2+ ] cyt transients. Furthermore, I/R reduced Ca 2+ sensitivity reflected by a rightward shift in the phase loop plots. These results support the hypothesis that I/R alters E‐C coupling in cardiomyocytes by reducing the Ca 2+ sensitivity of contraction. Support or Funding Information Supported by Mayo Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .