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Biomedical subjects

R Ferrari

Publications and source records attributed to R Ferrari.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1998

Metabolic disarrangement in ischemic heart disease and its therapeutic control.

The term myocardial ischaemia describes a condition which exists when fractional uptake of oxygen in the heart is not sufficient to maintain the rate of cellular oxidation. This leads to extremely complex situations which have been extensively studied in recent years. A large amount of experimental research has been directed to establish the precise sequence of biochemical events leading to myocyte necrosis as such knowledge could lead to rational treatments designed to delay myocardial cell death. At the present time there is no simple answer to the question of what determines cell death and no recovery on reperfusion. Problems arise because: (1) ischaemic damage is not homogeneous and many factors may combine to cause cell death; (2) severity of biochemical changes and development of necrosis are usually associated (both processes being dependent on the duration of the ischaemia) and it is impossible to establish a causal relationship; (3) the inevitability of necrosis can only be assessed by reperfusion of the ischaemic myocardium. Restoration of flow, however, might result in numerous further negative consequences, thus directly influencing the degree of recovery. From the clinical point of view, I have recently learned that there are several potential manifestations and outcomes associated with myocardial ischaemia and reperfusion. Without doubt ventricular dysfunction (either systolic or diastolic) of the ischaemic zone is the most reliable clinical sign of ischaemia, since ECG changes and symptoms are often absent. The ischaemia-induced ventricular dysfunction, at least initially, is reversible, as early reperfusion of the myocardium results in restoration of normal metabolism and contraction. In the ischaemic zone, recovery of contraction might occur instantaneously or, more frequently, with a considerable delay, thus yielding the condition recently recognized as the stunned myocardium. On the other hand, when ischaemia is severe and prolonged, cell death might occur. Reperfusion at this stage is associated with the release of intracellular enzymes, disruption of cell membranes, influx of calcium, persistent reduction of contractility, and eventual necrosis of at least a portion of the tissue. This entity has been called reperfusion damage by those who believe that much of the injury is the consequence of events occurring at the moment of reperfusion rather than as result of changes occurring during the period of ischaemia. The existence of reperfusion damage, however, has been questioned, and it has been argued that, with the exception of the induction of arrhythmias, it is difficult to be certain that reperfusion causes further injury. The existence of such an entity has clinical relevance, as it would imply the possibility of improving recovery with specific interventions applied at the time of reperfusion. In 1985 Rahimtoola described another possible out-come of myocardial ischaemia. He demonstrated that late reperfusion (after months or even years) of an ischaemic area showing ventricular wall-motion abnormalities might restore normal metabolism and function. He was the first to introduce the term hibernating myocardium, referring to ischaemic myocardium in which the myocytes remain viable but in which contraction is chronically depressed. Our data on metabolic changes occurring during ischaemia followed by reperfusion obtained either in the isolated and perfused rabbit hearts or in CAD patients undergoing intracoronary thrombolysis or aortocoronary by-pass grafting will be reviewed.

Animals↗
PubMed1998

Recognized molecular mechanisms of heart failure: approaches to treatment.

Abnormalities of cytosolic calcium handling and myocyte energetics appear to play an important role in mediating contractile dysfunction in heart failure. Systolic and diastolic dysfunction in the failing heart are related to abnormalities of the excitation-contraction mechanism as well as myofilament calcium sensitivity. These abnormalities can be viewed as a compensatory mechanism as the myocytes by down regulating its function and metabolic activity preserve energy consumption and allow better maintenance of basal cellular homeostasis. The end point of myocyte dysfunction, however, is a reduced contraction, which, in turn, might cause a reduced cardiac output and a threatening of arterial pressure. This causes a second level of adaptation, which implies a neuroendocrine response of the whole organism. Consequently, the syndrome of congestive heart failure is characterized not only by impaired ventricular function, but also by an increase in some endogenous substances leading to vasoconstriction and water and salt retention. Although activation of the systems that release these substances is presumed to be compensatory, the sympathetic nervous system and renin-angiotensin-aldosterone system as well as the endothelins may contribute to the pathogenesis of the syndrome. Opposite to the effects of these systems are those evoked by the release of atrial natriuretic peptides. The peptides exert a potent direct vasodilatation and natriuresis. In addition, atrial natriuretic peptides inhibit the release of norepinephrine from nerve terminals and suppress the formation of renin. However, the natriuretic and vasodilator effects of these peptides in patients with congestive heart failure are outweighed by the sodium retention and vasoconstriction caused by sympathetic stimulation and activation of the renin-angiotensin-aldosterone system. The reasons for this are not entirely known. The atrial stretch receptors that are responsible for the release of the atrial peptides become impaired, and it has been suggested that patient with heart failure may adapt to the physiologic effects of atrial natriuretic peptides. The possibility that congestive heart failure is in part a humoral disease is reviewed here and consequently pharmacologic treatment aimed at reducing the effects of the neuroendocrine response as to be advantageous for patients with heart failure.

Animals↗
PubMed1998

Protective effects of delapril, indapamide and their combination on stroke occurrence and lifespan in salt-loaded stroke-prone spontaneously hypertensive rats.

The effects of long-term oral administration of delapril (CAS 83435-67-0), indapamide (CAS 26807-65-8) and their combination on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp) for 31 weeks of treatment (8th-39th week of age) and up to 8 weeks thereafter. Body weight and saline consumption were investigated at regular intervals and cerebrovascular lesions, renal and heart weight were assessed after sacrifice. Untreated SHRsp served as controls. About 50% of control animals died within 6 weeks of saline administration and in 56% of surviving animals cerebral lesions were present at sacrifice, while no death and no cerebral lesions were observed in animals drinking saline, to which delapril, indapamide and their combination had been added, up to the end of treatment. This protective effect was maintained even in the withdrawal period. All treatments induced a highly significant (p < 0.001) reduction of heart weight/body weight and kidney weight/body weight ratios.

Angiotensin-Converting Enzyme Inhibitors↗