Mitochondria may be a principle source of oxidative stress causing MI/R injury. Coenzyme Q10 (CoQ10) is essential for electron transport in normal mitochondria, has antioxidant properties but its bioavailability is likely reduced due to oxidative stress during MI/R. Coenzyme Q1 (CoQ1) is a derivative of CoQ10, but is a more potent antioxidant than CoQ10 due to a shorter isoprene chain. We hypothesize that CoQ1 will exhibit better cardioprotective effects during MI/R. CoQ1 (MW=250 g/mol; 20 μM, n=4) and CoQ10 (MW=863 g/mol; 20 μM, n=5) were given at reperfusion in isolated rat hearts subjected to I (30 min)/R (45 min). We found that MI/R hearts (n=7) and MI/R+DMSO hearts (n=4) (1% DMSO was used to solubilize CoQ1 and CoQ10) exhibited significantly compromised cardiac contractile/diastolic pressures and coronary flow during reperfusion compared to those of sham hearts (n=5). By contrast, the final left ventricular developed pressure was significantly improved by CoQ1 treatment (53.5±5.5 mmHg), but not CoQ10 treatment (38.4±8.6 mmHg), when compared to that in MI/R hearts (33.6±6.2 mmHg) and MI/R+DMSO hearts (36.4±9.7 mmHg) (p<0.05). Similarly, the final peak of the first derivative of left ventricular pressure was significantly higher in CoQ1 treatment (1180.2±103.0 mmHg/s), but not CoQ10 treatment (770.6±120.1 mmHg/s), when compared to that in MI/R hearts (700.6±134.7 mmHg/s) and MI/R+DMSO hearts (and 741.5±168.6 mmHg/s) (p<0.05). CoQ1 and CoQ10 treated hearts showed no improvement on diastolic pressure and coronary flow compared to the controls. Moreover, infarct size was reduced by CoQ1 treatment (25±3%) and CoQ10 treatment (29±4%) compared to that in untreated MI/R (44±6%) and MI/R+DMSO (32±4%). In summary, our preliminary results indicate that CoQ1 was more effective than CoQ10 in restoring post‐reperfused cardiac contractile function, but not infarct size during MI/R.Support or Funding InformationThis study was supported by Division of Research, the Center for Chronic Disorders of Aging, and Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.