A thermostable mutant of a bacterial cocaine esterase reverses acute cocaine toxicity in the rabbit isolated heart

Abstract

Cocaine use is reported to be the most common cause for drug‐related hospital emergency department visits. Currently, there are no effective therapeutic agents available to directly treat cocaine‐associated toxicity. Cardiovascular events associated with cocaine use include angina pectoris, myocardial infarction, arrhythmias and aortic dissection. The goal of this study was to test the ability of a thermostable mutant of a bacterial cocaine esterase (CocE) to reverse the cardiotoxicty associated with acute cocaine use. The effects of cocaine and CocE treatment on cardiovascular functional parameters and markers of injury were examined in the Langendorff perfused rabbit isolated heart. Cocaine, when added to the perfusion buffer, caused a significant decrease in heart rate, an increase in left ventricular end‐diastolic pressure (LVEDP), an increase in coronary perfusion pressure and a decrease in left ventricular developed pressure. CocE infusion was able to completely reverse the effects on heart rate, LVEDP and developed pressure. CocE was also able to reduce the degree of propidium iodide staining for irreversibly damaged cells in isolated heart sections. In conclusion, this thermostable mutant of CocE is effective in reversing acute cocaine cardiotoxicity. Funding for this project is provided by the University of Michigan Cardiovascular Research Fund.