Synthetic Adenosine Receptor Agonists Minimize Markers Of Ischemic Damage

Prolonged ischemia results in progressive cardiac tissue loss, as evidenced by elevated serum lactate dehydrogenase (LDH) and creatinine (CRN). The primary mechanism involves oxygen deprivation and reactive oxygen species (ROS) accumulation during ischemia and reperfusion. Slowing cardiac function via adenosine receptor activation may reduce ROS generation, metabolic rate, and tissue damage. PURPOSE: Evaluate the effect of a synthetic adenosine receptor agonist on cardiac injury post-ischemia. METHODS: Under IACUC protocol #2277, 10-week-old male Sprague Dawley rats (n = 24) were divided into control, moderate dose, and low dose groups (n = 8/group). Cardiac tissue was isolated under anesthesia, perfused in a working heart apparatus with Krebs-Henseleit buffer (KH) for 15-min, then treated with the adenosine agonist or placebo for 15-min before a 20-min ischemic event. Post-ischemia, hearts were reperfused with KH for 30-min, and effluent samples were collected for LDH and CRN analysis via ELISA. Data was analyzed by two-way ANOVA with Tukey’s post hoc testing. RESULTS: LDH levels post-ischemia were significantly lower in the high-dose group (8.9 ± 5.2 mg/ml) compared to control (15.2 ± 5.6 mg/ml) and low-dose (10.6 ± 5.6 mg/ml) (P < 0.05). Creatinine post-ischemia levels were significantly lower in both low (243 ± 17 umol/ml) and high (245 ± 18 umol/ml) dose groups compared to control (248 ± 21 umol/ml) (P < 0.05). CONCLUSION: Pretreatment with a synthetic adenosine receptor agonist may reduce serum markers of ischemic injury, indicating potential cardioprotection. Supported by: GREAT PLAINS CTR - TEAM RESEARCH PILOT