Opioid Preconditioning in Human Left Ventricular Trabeculae

Opioids have been shown in many animal models to be involved in cardiac ischemic preconditioning. Currently, there is a limited amount of data available describing the role of opioid receptor activation in humans. Clinically, pharmacological preconditioning with opioid agonists could be used on patients at high risk for an ischemic event such as bypass or stenting procedures. The objective of this study is to determine whether mu- or delta-opioid receptor stimulation in human hearts improves contractile function upon reperfusion following a 90-minute period of hypoxia (simulated ischemia). For this study, left ventricular trabeculae from recipients undergoing a heart transplant are isolated and perfused with a modified Krebs solution. The trabeculae are incubated for 30 minutes with either Krebs buffer (controls) or specific opioid agonists. We are currently studying the effects of morphine (mu-opioid agonist), DPDPE (delta-opioid agonist), and hibernation induction trigger (HIT) found in the serum of hibernating bears and woodchucks. HIT is thought to be a delta-opioid agonist. Following incubation, the trabeculae are subjected to 90 minutes of hypoxia followed by 120 minutes of reperfusion. The percent recovery of pre-hypoxic force generation at different timepoints during reperfusion is determined to assess whether treatment with these specific opioid agonists has a cardioprotective effect. Future studies will focus on using specific opioid antagonists and KATP channel blockers to understand the mechanisms involved in preconditioning with these agents.