Conclusions
These results provide additional evidence in a large animal model of disease that PKCα/β inhibition (with ruboxistaurin) represents a tenable and novel therapeutic approach for treating human heart failure.
Objective
Large and small mammals differ in several key indexes of heart function and biochemistry, lending uncertainty as to how PKCα/β inhibition might affect or protect a large animal model of heart failure.
Results
We demonstrate that ruboxistaurin administration to a pig model of myocardial infarction-induced heart failure was protective. Twenty-kilogram pigs underwent left anterior descending artery occlusion resulting in myocardial infarctions and were then divided into vehicle or ruboxistaurin feed groups, after which they were monitored monthly for the next 3 months. Ruboxistaurin administered pigs showed significantly better recovery of myocardial contractility 3 months after infarction injury, greater ejection fraction, and greater cardiac output compared with vehicle-treated pigs. Conclusions: These results provide additional evidence in a large animal model of disease that PKCα/β inhibition (with ruboxistaurin) represents a tenable and novel therapeutic approach for treating human heart failure.