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Biomedical subjects

R Ferrari

Publications and source records attributed to R Ferrari.

At least 109 records · Page 6Linked to original sources
PubMed1997

The propionyl-L-carnitine hypothesis: an alternative approach to treating heart failure.

Propionyl-L-carnitine (PLC) is a naturally occurring compound that has been considered for the treatment of congestive heart failure (CHF). The rationale for its use in this pathology is related to its effects on cardiac and skeletal muscle. Chronic treatment with PLC improves the contraction of isolated and aerobic perfused rabbit hearts. The compound improves energy metabolism and myocardial contractility in different experimental models of heart failure, such as pressure-overloaded rats, infarct model of heart failure, and rabbit with streptozotocin-induced diabetes. In general, the effect of PLC is apparent in situations of high energy demand such as those induced by increased workload. It therefore seems likely that PLC is able to correct some metabolic steps of the process that leads to heart failure. In addition, PLC may be helpful in heart failure because of its specific action on peripheral skeletal muscle. Administration of PLC in patients with CHF improves skeletal muscle metabolism by increasing pyruvate flux into the Krebs cycle and by decreasing lactate production. These effects occur in the absence of major hemodynamic and neuroendocrinologic changes and may underlie the ability of PLC to increase exercise performance in patients with heart failure. In a randomized study of 50 patients with mild CHF, PLC increased the maximal exercise time, reduced lactate production, and improved left ventricular ejection fraction. There have been two large-scale trials on the effects of PLC on both cardiac and peripheral muscle function in CHF. One is ongoing; the other one, which just ended, failed to show an improvement in exercise capacity in the population studied. A benefit was evident only in a subgroup of patients with preserved ejection fraction and impaired baseline exercise duration.

Animals↗
PubMed1997

Reperfusion Injury: Does It Exist and Does It Have Clinical Relevance?

Although reperfusion is an absolute prerequisite for the survival of ischemic tissue, it is not necessarily without hazard. Many (but not all) cardiologists are of the opinion that some components of reperfusion may be detrimental and able to inflict injury over and above that attributable to the ischemia. In this article we define four sequelae of reperfusion that might be designated as "reperfusion injury." We identify possible underlying mechanisms and consider whether any of these forms of reperfusion injury are of clinical relevance.

Journal Article↗
PubMed1997

How European cardiologists perceive the role of calcium antagonists in the treatment of stable angina.

Some 100 European cardiologists discussed calcium antagonists' role in the management of stable angina. Sixty-two percent of those involved used calcium antagonists rather than beta-blockers as first line therapy; 46% were prepared to use calcium antagonists in patients who had had a myocardial infarction more than 6 months previously. Only one tenth would use calcium antagonists in angina patients with left ventricular dysfunction. There was a broad preference for the use of heart rate-moderating calcium antagonists in most forms of stable angina. The discussions also underlined the diagnostic importance of angiography, exercise testing and lipid profile analysis.

Adrenergic beta-Antagonists↗
PubMed1997

How european cardiologists perceive the role of calcium antagonists in the treatment of unstable angina.

Physicians in the United States have recently published a guide to the definition and management of unstable angina pectoris. The guideline divides this condition into three main groups: 'rest', 'new onset' and 'increasing' angina. For the great majority of patients, medication involves heparin, acetylsalicylic acid, nitrates and beta-blockers. In some patient groups, calcium antagonists are appropriate treatment. These recommendations seem to be broadly supported by European cardiologists. Study of individual cases, however, reveals a continuing diversity of opinion.

Angina, Unstable↗
PubMed1997

How European cardiologists perceive the role of calcium antagonists in follow-up after myocardial infarction.

About one hundred European cardiologists discussed the role of calcium antagonists in the follow-up management of myocardial infarction. beta-blockers are the treatment of choice. Where these are contra-indicated or otherwise unsuitable, many clinicians would use a non-dihydropyridine calcium antagonist alone or in combination with an ACE inhibitor. There is broad agreement that calcium antagonists should not be used in patients with concomitant left ventricular failure. Cholesterol estimation in post-infarction patients is essential.

Adrenergic beta-Antagonists↗
PubMed1997

Major differences among the three classes of calcium antagonists.

The safety of calcium antagonists has recently become a controversial issue among cardiologists. Thus, the role of calcium antagonists in the treatment of myocardial infarction and in secondary cardiovascular prevention is under review. As a consequence, the concept that the words 'calcium antagonists' comprise various drug classes has re-emerged. These differ in basic pharmacological properties, tissue selectivity, pharmacokinetics, and final haemodynamic effect. Obviously, such differences alter their therapeutic effect. In this article, the major differences among the three classes of calcium antagonists, phenylalkylamines, dihydropyridines and benzothiazepines, are discussed and reviewed. A comparative analysis of available clinical trials focusing on the usefulness of each drug class is provided for the reader's interest. Some particularly relevant pathological conditions are considered: chronic stable angina pectoris, vasospastic angina, unstable angina pectoris with threatened myocardial infarction, myocardial infarction, and congestive heart failure.

Aniline Compounds↗
PubMed1997

Skeletal muscle function at low work level as a model for daily activities in patients with chronic heart failure.

AIM: Metabolic exercise abnormalities have been reported in chronic heart failure patients. This study sought to evaluate whether these abnormalities affected daily activity. METHODS AND RESULTS: In 16 patients with moderate-to-severe chronic heart failure and in eight controls we measured femoral flow (thermodilution) and metabolism (glucose, lactate, free fatty acids, blood gas values) at rest and during a constant load of 20 W, which may mimic a daily activity. At rest, chronic heart failure patients had a leg flow similar to controls, but showed a higher leg oxygen consumption (4.6 +/- 0.6 vs 2.6 +/- 0.4 ml.min-1; P < 0.05), a higher arteriovenous oxygen difference (7.2 +/- 0.5 vs 5.4 +/- 0.7 ml.dl-1; P < 0.05), and a lower femoral vein pH (7.37 +/- 5.03 vs 7.42 +/- 0.01; P = 0.01). At 20 W, chronic heart failure patients had a leg flow similar to controls, but showed increased lactate release (from resting 11.7 +/- 33 to 142 +/- 125 micrograms.min-1 P < 0.0001 vs controls, from resting 5.7 +/- 15.4 to 50 +/- 149 micrograms.min-1 ns), higher arterial concentration of free fatty acids (781 +/- 69 vs 481 +/- 85 mumol.l-1; P < 0.01), lower femoral vein HCO3 (24.1 +/- 2.6 vs 26.3 +/- 1.7 mmol.l-1; P < 0.05) and base excess (-2.3 +/- 2.3 vs -0.24 +/- 1.7 mmol.l-1; P = 0.01). CONCLUSION: In chronic heart failure patients, the important cellular metabolic alterations already present at rest partially affect daily activities, owing to a further decrease in the efficiency of muscle metabolic processes, and may preclude tolerance of heavier activities. Such alterations appear, at least in part, independent of peripheral haemodynamic responses to exercise.

Activities of Daily Living↗
PubMed1997

Short- and long-term changes in striatal neurons and astroglia after transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: The striatum is one of the regions most sensitive to transient forebrain ischemia. After 30-minute ischemia, areas of massive neuronal degeneration are clearly detectable a few hours after the insult and attain their maximal extension 24 hours after the insult. However, for most cellular and neurochemical parameters it is not known whether some recovery occurs at later times. We examined certain cell populations in the caudate putamen at different times after transient ischemia. METHODS: Adult male Sprague-Dawley rats were subjected to 30-minute forebrain ischemia (four-vessel occlusion model). Six experimental groups were considered: control animals and ischemic animals killed 4 hours, 1 day, 7 days, 40 days, and 8 months after reperfusion. Three striatal cell populations were examined by means of immunocytochemistry coupled to computer-assisted image analysis: vulnerable medium spiny neurons, resistant aspiny neurons, and reactive astrocytes, labeled for their content of dopamine- and cAMP-regulated phosphoprotein mr32 (DARPP-32), somatostatin and neuropeptide Y, and glial fibrillary acidic protein, respectively. RESULTS: (1) The area containing DARPP-32 immunoreactive neurons was markedly decreased (15% to 20% of control caudate putamen area) at 1 day after reperfusion and partially recovered at the following times (40% to 50% at 7 days and 50% to 60% at 40 days and 8 months after reperfusion). (2) The appearance of reactive astrocytes was precocious (4 hours to 1 day after ischemia) in the medial caudate putamen, the region in which DARPP-32 recovered within 40 days after ischemia, and late (7 to 40 days after ischemia) in the lateral caudate putamen, where no DARPP-32 recovery was detected. (3) Neuropeptide Y/somatostatin-containing neurons resisted the ischemic insult and could be detected in areas devoid of DARPP-32 immunoreactive neurons as long as 8 months after reperfusion. CONCLUSIONS: The present results show a marked recovery of DARPP-32-positive neurons within 40 days after 30-minute forebrain ischemia in the medial, but not the lateral, caudate putamen. Medial caudate putamen also contains a high density of reactive astrocytes on the first day after ischemia, suggesting that astrocytic support has an important role in the spontaneous recovery of ischemic neurons.

Animals↗
PubMed1997

Angiotensin converting enzyme inhibitor-calcium antagonist combination: an alliance for cardioprotection?

MECHANISMS OF ACTION IN SMOOTH MUSCLE: Calcium antagonists and angiotensin converting enzyme (ACE) inhibitors act synergistically in reducing blood pressure. Calcium antagonists counter an excess of calcium entry through the voltage-operated channels of the vascular smooth muscle. ACE inhibitors reduce the vasoconstrictive properties of local and circulating angiotensin II. In addition, they improve endothelium-dependent vasodilation by increasing the expression of endothelial inositol by a bradykinin-related mechanism. Thus, at the smooth muscle level, calcium antagonists cause dilation by reducing external calcium entry and ACE inhibitors cause dilation by reducing internal calcium cycling and improving nitric oxide production. EFFECTS AT MOLECULAR LEVEL: The two agents have synergistic antagonists exert a potent cardioprotective action; this effect requires prophylactic administration and relies on the ATP-sparing capacity of these drugs. Moreover, prophylactic administration of verapamil but not to other calcium antagonists in patients who have suffered an acute myocardial infarction reduces overall mortality, provided no overt heart failure is present. The molecular effect of ACE inhibitors on the ischaemic heart is less well known but seems to be related to a reduction in noradrenaline release or to an improvement in bradykinin; the effect is thus complementary to that of calcium antagonists. OTHER ACTIONS OF ACE INHIBITORS: There is evidence that ACE inhibitors may have additional cardioprotective properties in being able to improve coronary flow, prevent arrhythmias, reduce the toxicity of oxygen free radicals, improve myocardial energy metabolism and prevent remodelling of the heart. ACE inhibitors can also protect the ischaemic heart by inhibiting bradykinin breakdown and by interfering with the central and peripheral nervous and hormone systems such as the kallikrein-kinin, prostaglandin and sympathetic nervous systems. The administration of ACE inhibitors to patients with acute myocardial infarction failed to reduce mortality. However, prophylactic administration to patients with myocardial infarction and heart failure resulted in a significant reduction in mortality and in hospitalization for cardiac disease. CONCLUSIONS: The combination of verapamil with an ACE inhibitor is promising not only for the treatment of hypertension, but also for ischaemic heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Metabolic adaptation during a sequence of no-flow and low-flow ischemia. A possible trigger for hibernation.

BACKGROUND: Myocardial hibernation is an adaptive phenomenon occurring in patients with a history of acute ischemia followed by prolonged hypoperfusion. METHODS AND RESULTS: We investigated, in isolated rabbit heart, whether a brief episode of global ischemia followed by hypoperfusion maintains viability. Four groups were studied; group 1,300 minutes of aerobia; group 2,240 minutes of total ischemia and 60 minutes of reperfusion; group 3, 10 minutes of total ischemia, 230 minutes of hypoperfusion (90% coronary flow reduction), and 60 minutes of reperfusion; and group 4, 240 minutes of hypoperfusion followed by reperfusion. In group 3, viability was maintained. Ten minutes of ischemia caused quiescence, a fall in interstitial pH (from 7.2 +/- 0.01 to 6.1 +/- 0.8), creatine phosphate (CP), and ATP (from 54.5 +/- 5.0 and 25.0 +/- 1.9 to 5.0 +/- 1.1 and 15.3 +/- 2.5 mumol/g dry wt, P < .01). Subsequent hypoperfusion failed to restore contraction and pH but improved CP (from 5.0 +/- 1.1 to 20.1 +/- 3.4, P < .01). Reperfusion restored pH, developed pressure (to 92.3%), and NAD/NADH and caused a washout of lactate and creatine phosphokinase with no alterations of mitochondrial function or oxidative stress. In group 4, hypoperfusion resulted in progressive damage. pH fell to 6.2 +/- 0.7, diastolic pressure increased to 34 +/- 5.6 mm Hg, CP and ATP became depressed, and oxidative stress occurred. Reperfusion partially restored cardiac metabolism and function (47%). CONCLUSIONS: A brief episode of total ischemia without intermittent reperfusion maintains viability despite prolonged hypoperfusion. This could be mediated by metabolic adaptation, preconditioning, or both.

Adaptation, Physiological↗