Coronary artery disease remains the leading cause of death worldwide. Reduction in infarct size may be a potential preventive strategy for cardiovascular complications. Increased left ventricular end-diastolic pressure (LVEDP) or Ischemic Peak Pressure (IPP) during ischemia, is associated with infarct size. Previously, we showed that naltrindole (NTI, selective delta opioid receptor antagonist), reduced LVEDP and infarct size in ex vivo rat hearts. This study examined the effects of NTI and analogues naltriben (NTB, delta opioid receptor antagonist) and guanidinonaltrindole (GNTI, kappa opioid receptor antagonist) (all 5 μM) compared to control hearts.

Isolated hearts from male Sprague-Dawley rats (~300g) were subjected to 30-min global ischemia (I)/45-min reperfusion (R) with treatments infused for 5 min before I and during the first 5 min of R. After R, 1% triphenyltetrazolium chloride staining assessed infarct size. Data were evaluated using ANOVA Student-Neuman-Keuls post-hoc analysis.

NTI (n=8) and NTB (n=6) elicited a transient decrease in the maximal rate in the rise of LV pressure (dP/dt max) to 1581±379 mmHg/s and 929±243 mmHg/s, respectively when given prior to I compared to control (2471±72 mmHg/s, n=12, p

These results suggest that NTI, NTB and GNTI are cardioprotective against myocardial I/R injury. The negative inotropic effects of NTI and NTB were associated with ~75% reduction and GNTI with ~50% reduction in infarct size compared to control. These results suggest that NTI and analogues exert tissue-salvaging effects. Future studies will examine the cardioprotective effects of NTI and analogues given at different ischemic times.