Metabolic manipulation in ischaemic heart disease, a novel approach to treatment

Abstract

Antianginal drugs that exert their anti-ischaemic effects primarily by altering myocardial metabolism have recently attracted attention. They have the potential to relieve symptoms in patients with refractory angina who are already on "optimal" medical therapy and have disease that is not amenable to revascularisation, making these drugs an attractive addition to therapy, particularly for the elderly population. In some cases, they may even be used as first-line treatment. These drugs increase glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Whilst they have been demonstrated to reduce ischaemia in several clinical trials, their use remains limited. This review aims to draw attention to these "metabolic" antianginal drugs while surveying the evidence supporting their use and mode of action. Four metabolic antianginal drugs are reviewed: perhexiline, trimetazidine, ranolazine, and etomoxir. We also discuss the metabolic actions of glucose-insulin-potassium and beta-blockers and describe myocardial metabolism during normal and ischaemic conditions. The potential of these metabolic agents may extend beyond the treatment of ischaemia secondary to coronary artery disease. They offer significant promise for the treatment of symptoms occurring due to inoperable aortic stenosis, hypertrophic cardiomyopathy, and chronic heart failure.

Scope of Nanotechnology in Drug Delivery

“…Nanoburrs technique has also been utilized by the researchers to combat cardiovascular diseases. These are the nanoparticles covered with an adhesive protein that makes them adhere to arterial walls while they gradually discharge medications [37].…”

“…Number of studies have been reported in past few years related to the efficacy and safety of various nanoparticles like cholesteroltethered platinum II-based supramolecular nanoparticle [37][38][39][40][41], polymeric-ceramic nanocarriers (NCs) in order to achieve oral delivery of the anticancer neutraceutical iron-saturated bovine lactoferrin (Fe-bLf) protein) [42,43], novel alginate-enclosed chitosan-calcium phosphate-loaded iron-saturated bovine lactoferrin nanocarriers for oral delivery in colon cancer therapy etc. [44][45][46][47][48][49][50].…”

Preventive cytoprotection in social diseases

“…Возни-кающее при этом уменьшение количества вырабатывае-мой митохондриями энергии не способствует образова-нию соединений, богатых макроэргическими связями, что приводит к истощению энергетических ресурсов кардиомиоцитов. Описанные функциональные наруше-ния проявляются структурными изменениями морфоло-гии митохондрий: отмечается их набухание и последую-щее сморщивание (при метаболическом ацидозе), уменьшение в размерах; изменяется проницаемость их мембран, приводящая к неминуемому разрушению орга-неллы; исчезают кристы, на которых проходит процесс окислительного фосфорилирования; появляются ка-пельные жировые включения [2]. Примерная схема по-следовательности метаболических нарушений при ише-мии миокарда представлена на рис.…”

Metabolic Modulators to Treat Cardiac Arrhythmias Induced by Ischemia and Reperfusion

“…Etomoxir {2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate} is an irreversible inhibitor of carnitine palmitoyl transferase I (CPT-I) that was initially introduced as a potential antidiabetic agent based on its hypoglycemic effects (Lee et al, 2004, Lopaschuk et al 2010). …”