13. New approaches to myocardial ischaemia Rho kinase inhibition (Fasudil) Metabolic modulation ( Trimetazidine ) Preconditioning ( Nicorandil ) Sinus node inhibition ( Ivabradine ) Late Na+ current inhibition (Ranolazine)
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17. Basis of pFOX 1. Myocardial ischemia is associated with sudden increase in fatty acid levels resulting in enhanced oxidation of long chain fatty acids 2. Oxidation of fatty acids needs more ATPs and also an increased oxygen demand for their breakdown than oxidation of carbohydrates 3. Moreover this may lead to accumulation of free fatty acids and lactic acid increasing the acidosis and affecting heart performance. 4. These mechanisms have harmful effects on the contractility and efficiency of the heart. 5. Treatment must aim to shift myocardial substrate utilisation to glucose metabolism as this will then provide benefits to ischemic patients. 6. This is achieved by drugs which suppress fatty acid oxidation. Trimetazidine Ranolazine
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22. Ranolazine - summary Ischaemia ↑ Late I Na Na + Overload Diastolic relaxation failure (Increased diastolic tension) Extravascular compression Ca ++ Overload Ranolazine: Inhibits the late inward Na current Ranolazine prevents the diastolic stiffness and thereby preserves myocardial blood flow Intramural small vessel compression ( ↓ O2 supply) and ↑ O2 demand
27. Ranolazine – the studies MARISA = Monotherapy Assessment of Ranolazine In Stable Angina CARISA = Combination Assessment of Ranolazine In Stable Angina ERICA = Evaluation of Ranolazine in Chronic Angina MERLIN-TIMI = Metabolic Efficiency with Ranolazine for Less Ischemia in Non ST elevation acute coronary syndromes
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