CARDIOPROTECTION WITH ACE INHIBITORS: NON-ANGIOTENSIN II-RELATED MECHANISMS

Review, no abstract availabl

Aspetti Metabolici del Miocardio in Condizioni Fisiologiche

Descrizione dettagliata del metabolismo cardiaco in condizioni fisiologich

Endothelial dysfunction in acute and chronic coronary syndromes: evidence for a pathogenetic role of oxidative stress

The past two decades have highlighted the pivotal role of the endothelium in preserving vascular homeostasis. Among others, nitric oxide (NO) is currently believed to be the main component responsible for endothelium dependent vasorelaxation and therefore for endothelial function integrity. Reduced NO bioavailability causes the so-called "endothelial dysfunction," which seems to be the common molecular disorder comprising stable atherosclerotic narrowing lesions or acute plaque rupture causing unstable angina or myocardial infarction. Compelling evidence is accumulating, stressing the role of oxidative stress in causing reduced NO bioavailability and subsequently endothelial dysfunction (ED). More recently, the role of endothelial cell (EC) apoptosis as a possible final stage of ED and plaque activation has been suggested. In vitro and in vivo evidence suggests a role of oxidative stress also as a putative mechanism finally leading to plaque denudation and activation through increased EC apoptosis. Thus, oxidative stress, irrespective of atherosclerotic disease stages, seems to represent a key phenomenon in vascular disease progression and possible prevention

IL METABOLISMO DEL MIOCARDIO ISCHEMICO IBERNATO E STORDITO: DIFFERENZA TRA NECROSI E APOPTOSI

Descrizione del metabolismo cardiaco in condidioni di adattamento o maladattamento in varie condizioni patologiche. Differenziazione dei meccanismi della morte cellulare per necrosi e per apoptos

Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review.

Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long-chain acyl-CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long-chain acyl-CoA; and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac functio

Angiotensin II overproduction: enemy of the vessel wall

Unfortunately, the vessel wall has several enemies and, regrettably, overproduction of angiotensin II seems to be one of the most aggressive, often causing several principal diseases such as arteriosclerosis, hypertension, coronary artery disease and heart failure. Obviously, it is unrealistic to consider angiotensin II as the only player but, certainly, it is one of the most important, as the reduction of its overproduction by drugs such as ACE inhibitors or angiotensin II receptor blockers is able to counteract the above mentioned pathological conditions. This review mainly deals with the importance of overproduction of angiotensin II in causing endothelial dysfunction and the mechanisms which are involved, such as the activation of angiotensin I and II which have opposite effects. It is clear that a precise picture of the molecular changes induced by angiotensin II at tissue level cannot yet be described although progress is continuously made at the additive role of oxidative stress and activation of the nuclear factor kB is addressed. The mechanism of action of ACE inhibitors and the angiotensin II receptor blockers is also highlighted in the attitude which is considering the biological effect of these drugs and rather than their pharmacological effects