Abstract 212: Pharmacologic Late Preconditioning With Opioid δ1-agonist Confers Cardio- And Neuroprotetive Benefits During Cardiac Arrest
Cardiac arrest affects thousands of patients every year and the outcome continues to be dismal. Administration of opioid delta1-receptor agonists induces pharmacologic late preconditioning against myocardial infarction. We hypothesized that administration of TAN 670, a selective opioid d1-agonist, 24 h prior to a resuscitated cardiac arrest would confer cardio- and neuroprotection in an analogous fashion. C57BL/6 mice received TAN 670 (60 mg/kg i.p.) or vehicle (n = 9/group) and 24 h later were subjected to cardiac arrest (pulseless electrical activity) by exsanguination via withdrawal of blood from LV cavity. Mice were resuscitated by reinfusion of normothermic blood and gentle chest compression. Sham controls underwent the same procedure without blood withdrawal (n = 9). Cardiac and neurologic function was assessed prior to and at serial time-points after cardiac arrest. Apoptosis was quantitated by immunostaining. Preconditioning with TAN 670 attenuated cardiac arrest-induced apoptosis in cardiomyocytes (Fig 1A⇓) and neurons in the CA2 region of the hippocampus (Fig 1B⇓) and improved neurologic function, evidenced by preservation of learning and memory assessed by modified Barnes maze (Fig 1C⇓). Activity testing showed improvement in the margin time in TAN 670-treated mice. We conclude that pretreatment with an opioid d1-receptor agonist 24 h prior to a resuscitated cardiac arrest induces delayed protection against apoptosis in both the heart and brain. These findings reveal the existence of late preconditioning against cardiac arrest-induced cellular damage, a novel strategy that has therapeutic implications for organ protection during cardiac arrest in humans.