Yoshimasa Oyama 1 , Justin Blaskowsky 1 , Tobias Eckle 1 Show Affiliations »
Abstract
BACKGROUND: Animal studies on cardiac arrest found that a combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction. Based on these findings, we hypothesized that esmololepinephrine combination therapy would be superior to a reported cardioprotective esmolol therapy alone in a mouse model of myocardial ischemia and reperfusion (IR) injury. METHODS: C57BL/6J mice were subjected to 60 min of myocardial ischemia and 120 min of reperfusion. Mice received either saline, esmolol (0.4 mg/kg/h), epinephrine (0.05 mg/kg/h), or esmolol combined with epinephrine (esmolol: 0.4 mg/kg/h or 0.8 mg/kg/h and epinephrine: 0.05 mg/kg/h) during reperfusion. After reperfusion, infarct sizes in the area-at-risk and serum cardiac troponin-I levels were determined. Hemodynamic effects of drugs infused were determined by measurements of heart rate (HR) and mean arterial blood pressure (MAP) via a carotid artery catheter. RESULTS: Esmolol during reperfusion resulted in robust cardioprotection (esmolol vs. saline: 24.3±8% vs. 40.6±3% infarct size), which was abolished by epinephrine co-administration (38.1±15% infarct size). Increasing the esmolol dose, however, was able to restore esmolol-cardioprotection in the epinephrine-esmolol (18.6±8% infarct size) co-treatment group with improved hemodynamics compared to the esmolol group (epinephrine-esmolol vs. esmolol: MAP 80 vs. 75 mmHg, HR 452 vs. 402 beats/min). CONCLUSION: These results confirm earlier studies on esmolol-cardioprotection from myocardial IR-injury and demonstrate that a dose optimized epinephrine-esmolol co-treatment maintains esmolol-cardioprotection with improved hemodynamics compared to esmolol treatment alone. These findings might have implications for current clinical practice in hemodynamically unstable patients suffering from myocardial ischemia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
BACKGROUND: Animal studies on cardiac arrest found that a combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction . Based on these findings, we hypothesized that esmololepinephrine combination therapy would be superior to a reported cardioprotective esmolol therapy alone in a mouse model of myocardial ischemia and reperfusion (IR) injury. METHODS: C57BL/6J mice were subjected to 60 min of myocardial ischemia and 120 min of reperfusion. Mice received either saline , esmolol (0.4 mg/kg/h), epinephrine (0.05 mg/kg/h), or esmolol combined with epinephrine (esmolol : 0.4 mg/kg/h or 0.8 mg/kg/h and epinephrine : 0.05 mg/kg/h) during reperfusion. After reperfusion, infarct sizes in the area-at-risk and serum cardiac troponin-I levels were determined. Hemodynamic effects of drugs infused were determined by measurements of heart rate (HR) and mean arterial blood pressure (MAP) via a carotid artery catheter. RESULTS: Esmolol during reperfusion resulted in robust cardioprotection (esmolol vs. saline : 24.3±8% vs. 40.6±3% infarct size), which was abolished by epinephrine co -administration (38.1±15% infarct size). Increasing the esmolol dose, however, was able to restore esmolol -cardioprotection in the epinephrine-esmolol (18.6±8% infarct size) co -treatment group with improved hemodynamics compared to the esmolol group (epinephrine-esmolol vs. esmolol : MAP 80 vs. 75 mmHg, HR 452 vs. 402 beats/min). CONCLUSION: These results confirm earlier studies on esmolol -cardioprotection from myocardial IR-injury and demonstrate that a dose optimized epinephrine-esmolol co -treatment maintains esmolol -cardioprotection with improved hemodynamics compared to esmolol treatment alone. These findings might have implications for current clinical practice in hemodynamically unstable patients suffering from myocardial ischemia . Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Disease
Gene
Species
Keywords:
Epinephrine; TTC; blood pressure; esmolol; heart rate; myocardial ischemia and reperfusion injury; troponin.
Year: 2019
PMID： 31258066 PMCID： PMC6764887 DOI： 10.2174/1381612825666190618124829
Source DB: PubMed Journal: Curr Pharm Des ISSN： 1381-6128 Impact factor: 3.116