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Biomedical subjects

R Ferrari

Publications and source records attributed to R Ferrari.

At least 37 records · Page 2Linked to original sources
PubMed1998

Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced cardiac hypertrophy and failure. Relation to blood flow and degree of muscle atrophy.

BACKGROUND: In congestive heart failure (CHF) the skeletal muscle of the lower limbs develops a myopathy characterised by atrophy and shift from the slow to the fast type fibres. The mechanisms responsible for these changes are not clear yet. OBJECTIVES: We investigated the influence of blood flow and degree of muscle atrophy on the myosin heavy chains (MHC) composition of the soleus and extensor digitorum longus (EDL) of rats with right ventricle hypertrophy and failure. METHODS: CHF was induced in 16 rats by injecting 30 mg/kg monocrotaline. Eight animals had the same dose of monocrotaline but resulting in compensated right ventricle hypertrophy. Two age- and diet-matched groups of control animals (nine and five respectively) were also studied. The relative percentage of MHC1 (slow isoform), MHC2a (fast oxidative) and MHC2b (fast glycolytic) was determined by densitometric scan after electrophoretic separation. The relative weights of soleus and EDL (muscle weight/body weight) were taken as an index of muscle atrophy. Skeletal muscle blood flow was measured by injecting fluorescent micropheres. RESULTS: CHF and Control (Con) rats showed similar degree of atrophy both in soleus (0.40 +/- 0.06 vs. 0.44 +/- 0.06 p = NS), and EDL (0.47 +/- 0.04 vs. 0.45 +/- 0.02, p = 0.09). In CHF rats these two muscles showed a statistically significant MHCs redistribution toward the fast type isozymes. In fact in EDL of CHF rats MHC2a was 30.5 +/- 6.1% vs. 35.8 +/- 8.6% of the Con (p < 0.05). MHC2b was however higher (68.5 +/- 6.6% vs. 61.0 +/- 9.6%, p = 0.017). In the soleus of CHF rats MHC1 was decreased (87.6 +/- 3.4% vs. 91.9 +/- 5.2%, p = 0.02), while MHC2a was increased (12.04 +/- 3.5% vs. 7.9 +/- 5.2%; p = 0.028). Similar changes were not found in the muscles of the compensated hypertrophy animals. No correlation was found between MHC pattern and the relative muscle weight in the CHF animals. Soleus blood flow in CHF rats was significantly lower than that of Con (0.11 +/- 0.03 ml/min/g vs. 0.22 +/- 0.03 p < 0.05), while no differences were found in EDL (0.06 +/- 0.02 ml/min/g vs. 0.08 +/- 0.02, p = NS). CONCLUSIONS: In rats with CHF a skeletal muscle myopathy characterised by a shift of the MHCs toward the fast type isoforms occurs. The magnitude of the shift correlates neither with the degree of atrophy, nor with the skeletal muscle blood flow, suggesting that these two factors do not play a pivotal role in the pathogenesis of the myopathy.

Animals↗
PubMed1998

The emergence of the volume transmission concept.

Interneuronal communication in the central nervous system (CNS) have always been of basic importance for theories on the cerebral morphofunctional architecture. Our group has proposed that intercellular communication in the brain can be grouped into 2 broad classes based on some general features of the transmission: wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both morphological and functional evidence indicates that dopamine (DA) synapses in striatum are 'open' synapses, i.e., synapses which favor diffusion of the transmitter into the surrounding ECF and observations are compatible with the view that DA varicosities can synthesize, store and release DA for VT. The DAergic mesostriatal transmission has, therefore, been examined by several groups to give experimental support to VT. Moreover, due to its minor structural requirements, VT may become prevalent under some pathological conditions, e. g. Parkinson's disease. In animal models of DAergic pathway degeneration, it has been shown that a compensatory activation of surviving DA terminals may lead to a preferential potentiation of VT. WT and VT favor different and complementary types of computation. VT is markedly slower and less safe than WT, but has minor spatial constraints and allows the reach of a large number of targets. Models of neuronal systems integrating classical neuronal circuits and diffusible signals begin to show how WT and VT may interact in the neural tissue.

Animals↗
PubMed1998

Quantification of apolipoprotein AI-containing lipoprotein particles in non-insulin-dependent diabetes mellitus.

Quantification of LpAI (lipoprotein particles containing apolipoprotein AI not associated with apolipoprotein AII) was performed through an electroimmunoassay on serum from 49 non-insulin-dependent diabetic patients (mean age 60 +/- 9 years) and 53 age-matched control subjects of both sexes not affected by coronary heart disease. Serum lipid and lipoprotein levels were not significantly different between the two groups. Serum levels of LpAI determined for diabetic patients did not differ from those of control subjects, while concentrations of LpAI in men were significantly lower than in women, both among diabetics (P < 0.05) and controls (P < 0.005). Serum levels of apolipoprotein AI and high density lipoprotein cholesterol were significantly correlated with those of LpAI (P < 0.005, for both variables). On the contrary, levels of LpAI/AII (lipoprotein particles containing both apolipoprotein AI and AII) were significantly increased in diabetic patients (P < 0.005).

Apolipoprotein A-I↗
PubMed1998

Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure.

Carnitine is an important cofactor in the intermediary metabolism of the heart, and carnitine deficiency is associated with congestive heart failure. We therefore studied the effects of acute (IV bolus, 30 mg/kg body weight) and chronic administration (1.5 mg/d for 1 month) of propionyl-L-carnitine on hemodynamics, hormone levels, ventricular function, exercise capacity, and peak oxygen consumption in 30 patients with chronic congestive heart failure (NYHA II-III, mean EF 29.5 +/- 7%) in a phase II, parallel, single-blind, randomized, and placebo-controlled study. Acute administration of propionyl-L-carnitine caused a significant reduction in pulmonary artery and pulmonary wedge pressures at both day 1 (P < 0.001) and day 30 (P < 0.05) of the study but no other hemodynamics changes. Hormone levels did not change following acute administration of the drug. Chronic administration of propionyl-L-carnitine increased peak oxygen consumption by 45% (from 16.0 +/- 3 to 23.5 +/- 2 mL/kg/min, P +/- 0.001), exercise time by 21% (from 8.1 +/- 0.5 to 9.8 +/- 0.4 minutes, P < 0.01), and peak exercise heart rate by 12% (P < 0.01). These changes were concomitant with a reduction of pulmonary artery pressure. In the treated group, there was a slight, but significant (P < 0.01), reduction in left ventricular dimensions. Hemodynamics and hormones measured after 1 month of oral therapy remained unchanged, except for a fall in pulmonary artery pressures, with a nonsignificant trend towards a fall in filling pressures and plasma norepinephrine. The chronic changes in the propionyl-L-carnitine group were seen at 15 days of treatment, and no further changes in these parameters were seen at 1 month. We conclude that propionyl-L-carnitine increases exercise capacity and reduces ventricular size in patients with congestive heart failure. The drug has no significant effects on hemodynamics or neurohormone levels. The use of a single-blind design reduces the impact of the positive finding on exercise capacity.

Adult↗
PubMed1998

Whiplash and temporomandibular disorders: a critical review.

Some authors have hypothesized a relationship between rear-impact motor vehicle collisions and subsequent symptoms of neck pain and temporomandibular disorders, or TMD, despite no facial impact. This article examines the TMD aspect in terms of the physiological basis and cultural factors influencing the reporting of such symptoms.

Accidents, Traffic↗
PubMed1998

Oxidative stress during myocardial ischaemia and heart failure.

Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. The heart needs oxygen but it is also susceptible to oxidative stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals. At the same time, production of oxygen free radicals increases. In man, there is evidence of oxidative stress during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. At present, there are few data on oxidative stress in the failing heart. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Importantly, tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but also occurs at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. The immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis. A better understanding of these mechanisms may lead to novel therapeutic strategies.

Animals↗
PubMed1998

Catecholamines: the cardiovascular and neuroendocrine system.

The development of profound autonomic dysfunction and of neuroendocrine activation characterizes and possibly contributes to the progression of heart disease to congestive heart failure. Sympathetic activation is a generalized process and the proposed mechanisms for neurohumoral activation include decreased input from excitatory afferences and increased input from excitatory chemoceptors and metabaroceptor. These phenomena vary to a great extent in different subjects: in the more impaired patients, renal and cardiac overflow of catecholamines can increase three- and ten-fold, respectively, accounting for about 60% of the increase of noradrenaline in congestive heart failure. Efficient methods to quantify sympathetic cardiovascular influences and neuroendocrine indices have been developed and it has been recognized that sympathoneural activation independently predicts the survival of patients. The pathophysiological role and the clinical relevance of neuroadrenergic abnormalities also constitute the grounds for the understanding of the therapeutic benefit obtained with interventions aimed at mitigating the harmful consequences of adrenergic hyperactivity.

Cardiovascular System↗
PubMed1998

The neuroendocrine and sympathetic nervous system in congestive heart failure.

A review of recent randomized clinical trials has shown that neurohormonal activation starts early in the natural history of left ventricular dysfunction and levels of the circulating hormones increase in proportion to the severity of heart failure. Most studies suggest that high levels of neurohormones predict a poor prognosis. Among the several neurohormones, the sympathetic system is the one which is activated earlier, it increases in proportion to the severity of the disease and has a negative prognostic implication. These concepts have been also proven in untreated patients. Augmented sympathetic activity in the syndrome of heart failure is initially beneficial, appears to be adaptive and helps support blood pressure and cardiac output. Prolonged and excessive sympathetic activation has deleterious effects with adverse consequences at both cardiac and vascular levels which aggravates the clinical status of the syndrome and negatively affects its prognosis. Evidence is accumulating that, contrary to popular belief, beta-blockers may be beneficial in heart failure by inhibiting sympathetic activation. In addition to neuroendocrine activation, another class of biologically active molecules, termed cytokines, are excessively secreted by cells in heart failure. Important among these cytokines are tumour necrosis factor-alpha and interleukin-6. They appear to exert deleterious effects on the heart and circulation which may be also involved in the progression of heart failure.

Adrenergic beta-Antagonists↗
PubMed1998

Endothelial function and dysfunction in heart failure.

The endothelium controls vascular smooth muscle tone by secreting substances that cause relaxation and contraction. Under physiological, basal conditions the endothelium constantly releases nitric oxide, a process closely regulated by the effect of shear stress on endothelial cells. Recent data raise the possibility that, among many other substances, bradykinin also plays an important role in the regulation of vascular tone. Bradykinin is a vasodilator that increases the activity of constitutive nitric oxide. Congestive heart failure (CHF) is a complex clinical syndrome in which abnormal vascular endothelial function has been shown to occur at both the experimental and clinical level. The reduced nitric oxide-mediated vasodilation in CHF is multifactorial. Constitutive nitric oxide synthase is downregulated as shear stress is reduced. Vascular angiotensin-converting enzyme (ACE), which produces angiotensin II and inactivates bradykinin, is up-regulated. Angiotensin II is a powerful vasoconstrictor, and the reduced availability of bradykinin will further down-regulate constitutive nitric oxide synthase. The CHF-induced activation of tumour necrosis factor also leads to a down-regulation of constitutive nitric oxide synthase and to an increased rate of endothelial-cell apoptosis. These observations suggest that abnormalities of endothelial function in CHF may contribute to increased peripheral vasomotor tone both at rest and during exercise, and raise the possibility that the beneficial effects of ACE inhibition in CHF may be due in part to improved endothelial function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Reversible left ventricular dysfunction: does it affect clinical practice and does it matter?

There is substantial evidence that many patients with impaired left ventricular function secondary to coronary artery disease may have hibernating or stunned myocardium. The identification of these patients is important, as revascularisation is associated with an improvement in function, and there is some evidence that revascularisation of these patients will actually improve prognosis. The most useful investigations for the identification of reversible left ventricular dysfunction are dobutamine echocardiography, thallium scanning and, although not available in many centres, PET scanning.

Coronary Disease↗
PubMed1998

Hibernating myocardium: its pathophysiology and clinical role.

Myocardial hibernation, as first defined by Rahimtoola, is a state of chronic contractile dysfunction in patients with coronary artery disease which is fully reversible upon reperfusion. Clinical conditions consistent with the existence of myocardial hibernation include unstable and stable angina, myocardial infarction heart failure, and anomalous origin of coronary arteries. The mechanisms of hibernation are not known. Morphological alterations have been described in the hibernating area of patients, but these information are strongly affected by the diagnostic criteria utilized to screen patients. It has been postulated that hibernation is an adaptive phenomenon occurring during ischemia. In this context, downregulation of contraction is not regarded as a consequence of energetic deficit, but as a regulatory event aimed at reducing energy expenditure, thereby maintaining integrity and viability. Thus, hibernation might bear a relationship to the phenomenon of low-flow perfusion-contraction matching, or repetitive stunning or preconditioning. Clear-cut evidence for the mechanism of hibernation in the clinical setting seems likely to remain elusive, because of the nature of the studies needed to document it. Current experimental evidence supports the view that hibernation, stunning, preconditioning, or their coexistence can be responsible for regional myocardial contractile dysfunction which is reversible upon reperfusion. These are all adaptive and protective phenomena independent of their terminology and strict definitions and do not always apply to the extremely complex situation of myocardial ischemia in man.

Adaptation, Physiological↗
PubMed1998

Effect of ACE inhibition on myocardial ischaemia.

During ischaemia, both the circulating renin-angiotensin system and the local angiontensin converting enzyme are activated. The circulating renin-angiotensin system has a short-term role in the regulation of the cardiovascular system. Its aim is to restore blood pressure and cardiac homeostasis. Activation of the local system causes long-term regulation of cardiovascular homeostasis via sustained activation of local angiotensin and the gradation of bradykinin. This results in the secondary permanent structural changes that underline many aspects of coronary artery disease. Recently it has been shown that ACE inhibition is useful in the early and late phase of myocardial infarction. ACE inhibitors have been shown to reduce in vitro vascular hypertrophy and attenuate arteriolosclerosis and to maintain endothelial function. Interestingly, unexpected data from trials on heart failure have shown that patients receiving ACE inhibitors have a reduced incidence of infarction, hospitalization for cardiovascular disease and the need for coronary artery bypass surgery or angioplasty. As a consequence, several trials have been designed to assess the effect of ACE inhibition on the progression of coronary artery disease, as well as on its morbidity and mortality. The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) is one of these. This article summarised a number of independent and complementary mechanisms and points to the role played by ACE and ACE inhibition in coronary artery disease. In particular it considers the possibility that ACE inhibition improves endothelial function, exerts anti-atherogenic and anti-proliferation activity and modulates sympathetic activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

The European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA).

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have an accepted place in the treatment of hypertension and heart failure. However, at present they have no specific role in the prevention or treatment of coronary artery disease: evidence from animal experiments and some of the large ACE inhibitor cardiac studies makes this effect well worth testing. OBJECTIVE: The objective of EUROPA is to assess the effects of perindopril (an ACE inhibitor) on outcome in patients with stable coronary artery disease, but no clinical heart failure. METHODS: This is a double-blind, placebo-controlled, multicentre study with a duration of 3.5 years. It is proposed to recruit 10500 patients from 24 countries in Europe. The primary end-point is a combined one: total mortality, non-fatal acute myocardial infarction, unstable angina pectoris and cardiac arrest with successful resuscitation are included; the outcome is studied in patients with proven coronary artery disease and no clinical heart failure. Secondary end-points consist of these events individually calculated. The first patient was recruited in October 1997, and it is planned to finish recruitment by the end of 1998.

Adolescent↗