Histidine as a protective agent in cardiac surgery and myocardial ischemic syndromes
AssigneeCytos Pharmaceuticals LLC
InventorsRakesh C. Kukreja, Michael L. Hess
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AssigneeCytos Pharmaceuticals LLC
InventorsRakesh C. Kukreja, Michael L. Hess
Estimating the term…
Histidine has been found to be efficacious in preventing ischemic/reperfusion induced myocardial injury both functionally and ultrastructurally. Isolated perfused rat hearts (n=8/group) were subjected to 30 minutes of global ischemia and 20 minutes of reperfusion. Histidine concentrations ranging from 10 to 50 mM were given throughout the experiment. During ischemia and reperfusion without histidine the contractile function and coronary flow were 59.+-.10% and 78.+-.6% of control, respectively. Perfusion with histidine (25 mM and above) resulted in significant increases in contractility (94.+-.4%) and coronary flow (92.+-.4) levels. The incidence of arrhythmias (ventricular tachycardia and ventricular fibrillation) during reperfusion was 100 percent (8/8) in the ischemic/reperfused group with an average duration of 13.23.+-.4.48 min. The addition of 25 mM histidine to the perfusion medium reduced the incidence and duration of arrhythmias significantly (mean.+-.SEM 2.25.+-.0.98 min) (P<0.01). The protective effects of histidine (25 mM and 50 mM) were significantly better than SOD/catalase/mannitol. Histidine has also been found to significantly reduce the infarct size and the occurrence of arrhythmias in vivo.
A method for protecting a patient from arrhythmia, comprising the steps of:
A method of controlling at least one of arrhythmia, ultrastructural damage, and infarction of coronary or cardiac tissue of a patient at risk for arrhythmia, ultrastructural damage, or infarction, comprising the steps of:
A method for enhancing expression of heat shock proteins in cardiac cells of a patient, comprising the step of administering to said patient a composition consisting essentially of a therapeutic dose of histidine effective to enhance expression of heat shock proteins in said cardiac cells.
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