Abstract
The classic approach to treating coronary heart disease involves interventions aimed at either increasing the oxygen supply to the heart muscle or decreasing the oxygen demand of the muscle. A new approach to treating coronary heart disease involves improving the efficiency of oxygen utilization by the tissue. Inhibiting fatty acid oxidation and stimulating glucose oxidation can significantly improve cardiac efficiency (cardiac work/oxygen consumed). This metabolic approach is not only beneficial as monotherapy in the treatment of angina pectoris, but is also beneficial in angina patients when used in combination with conventional therapy. Trimetazidine is a widely used metabolic agent that directly optimizes energy metabolism in the heart without causing any direct negative hemodynamic, inotropic or chronotropic effects. Trimetazidine acts by directly inhibiting fatty acid oxidation, resulting in an increase in glucose oxidation in the heart. The actions of trimetazidine occur as a result of inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT), an important enzyme involved in mitochondrial fatty acid oxidation. Because of this action, trimetazidine has been classified as a 3-KAT inhibitor, and is the first metabolic agent used clinically for treating coronary heart disease. Inhibition of fatty acid oxidation and stimulation of glucose oxidation with trimetazidine result in a decrease in acidosis in the ischemic muscle, thereby decreasing the requirement of energy for non-contractile purposes (i. e. increasing cardiac efficiency). This increase in glucose oxidation and decreased production of acidosis in the myocardium probably account for the cardioprotective effects of trimetazidine, which have been observed in many experimental and clinical studies. Both during and after ischemia, trimetazidine causes a significant improvement in cardiac efficiency, allowing the heart to perform a greater amount of work at a given level of oxygen. This therapeutic approach not only lessens the severity and symptoms of an angina attack in patients with coronary artery disease, but also decreases the incidence of angina attacks. As a result, using trimetazidine to optimize energy substrate preference is a novel and effective approach to treating ischemic heart disease.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call