[Chronic heart failure as a crisis event of the family].

The family greatly influences any of its members and significantly contributes to the patient rehabilitation. A limited and superficial interest from the family as well as an overprotective and anxiogenic behavior may lead to chronicization, relapse or even to progression of the disease. The close relationship between the patient and the physician is an illusion, since family members deeply affect this interaction.

Effects of endotoxic shock on neuronal NOS and calcium transients in rat cardiac myocytes.

Objective: The effects of endotoxic shock on transcriptional and translational pattern of nitric oxide synthase isoforms (NOSs) and cytoplasmic calcium were investigated.

Methods: Male SD rats injected with lipopolysaccharides or saline were sacrificed after 6 and 20 h. Cardiac myocytes were enzimatically isolated from the excised hearts and evaluated for: (1) expression of constitutive (e and n) and inducible (i) NOSs by RT-PCR; (2) NOSs protein levels by Western blot, enzymatic activities by a radioimmunometric assay and nitric oxide metabolites by spectrophotometry; (3) calcium transients by Indo-1 fluorescence.

[Anxiety, depression, and stressed life in patients awaiting heart transplantation: are these factors to be considered?].

Rationale: Heart transplantation is a therapeutic procedure in which biological, psychological, social and ethical aspects play an important role, none of them has to be underestimated. It is known that the waiting period up to heart transplantation is extremely stressful for patients and their families, causing psychopathological and disadaptive reactions. Aim of the present study was to investigate psychological tract characteristics, stress reactions and quality of life in a group of patients registered for heart transplantation.

TNFalpha in patients with congestive heart failure.

It is now generally accepted that chronically extensive stimulation of the cytokine system-and of TNFalpha in particular-is detrimental to the heart and to peripheral tissue and that such stimulation may contribute to the pathogenesis of congestive heart failure of various causes. During the past decade, basic and clinical research has provided growing evidence for the role of systemic and local inflammatory responses that, however, have so far failed to translate into new treatments for patients. The present paper represents an attempt to critically review the general concepts that lie behind the dichotomy existing between an impressive bulk of biologic research showing the role of TNFalpha as a pathogen in congestive heart failure and the difficulties in translating this evidence into patients' treatment.

Oxidative stress in cardiovascular disease: myth or fact?

Oxidative stress is a mechanism with a central role in the pathogenesis of atherosclerosis, cancer, and other chronic diseases. It also plays a major role in the aging process. Ischemic heart disease is perhaps the human condition in which the role of oxidative stress has been investigated in more detail: reactive oxygen species and consequent expression of oxidative damage have been demonstrated during post-ischemic reperfusion in humans and the protective role of antioxidants has been validated in several experimental studies addressing the pathophysiology of acute ischemia.

Skeletal muscle abnormalities in rats with experimentally induced heart hypertrophy and failure.

Background: In congestive heart failure (CHF), function and metabolism of skeletal muscles are abnormal.

Aim: To evaluate whether the reduced oxidative capacity of skeletal muscles in CHF is due to impaired O(2) utilisation.

Methods: CHF was induced in rats by injecting 50 mg/Kg monocrotaline.

Future strategies of reverse remodeling prevention of hibernation.

A complex interrelationship exists among chronic ischemic left ventricular dysfunction, persistence of myocardial viability and possibility to limit progression of chronic heart failure. Cardiac remodeling is influenced by several factors still under investigation. Hibernation is basically an adaptive mechanism to chronically abnormal coronary blood flow, characterized by metabolic and structural alterations of the cardiac tissue, that are fully recovered upon revascularization.

Beta-adrenergic receptors and intracellular signalling pathway in stunned and non-ischemic regions of pig myocardium.

The beta-adrenergic pathway may have a role in the pathophysiology of ischemic syndromes characterised by reversible left ventricular dysfunction, such as myocardial stunning and other clinical conditions of unstable angina or coronary spasms, or chronic reversible left ventricular dysfunction, which might be a consequence of repeated events of short-term ischemia ("repetitive stunning"). A partial-to-total occlusion of the left anterior descending coronary artery in pigs was used to induce short periods of ischemia (total ischemic time 12 +/- 2 min). Hypokinesis and dyskinesis of the myocardium were considered signs of myocardial dysfunction.

New insights on myocardial pyridine nucleotides and thiol redox state in ischemia and reperfusion damage.

Objective: to investigate the changes of pyridine nucleotides and thiol redox state in cardiac tissue following ischemia and reperfusion. NADH/NAD and NADPH/NADP redox couples were specifically studied and the influence of NADPH availability on cellular thiol redox was also investigated.

Methods: isolated rabbit hearts were Langendorff perfused and subjected to a protocol of ischemia and reperfusion.

Reduction of oxidative stress by carvedilol: role in maintenance of ischaemic myocardium viability.

Objectives: To differentiate the impact of the beta-blocking and the anti-oxidant activity of carvedilol in maintaining myocardium viability.

Methods: Isolated rabbit hearts, subjected to aerobic perfusion, or low-flow ischaemia followed by reperfusion, were treated with two doses of carvedilol, one dose (2.0 microM) with marked negative inotropic effect due to beta-blockage and the other (0.

Role of A2A receptor in the modulation of myocardial reperfusion damage.

Adenosine protects myocardium from ischemia and reperfusion damage; however, the mechanism of action is still under discussion. We investigated whether (a) adenosine protects isolated crystalloid-perfused rabbit heart from ischemia/ reperfusion injury; (b) this action is receptor mediated and what receptor subtypes are involved, and (c) this action is dependent on an enhanced nitric oxide production. Our results showed a cardioprotective effect of adenosine (10(-4) M), of nonselective adenosine-receptor agonist 5'-N-ethyl-carboxamidoadenosine (NECA; 5 x 10(-6) M), and of A2A agonists CGS 21680 (10(-8) and 10(-6) M), 2-hexynylNECA (10(-7) M).

Changes in oxidative stress and cellular redox potential during myocardial storage for transplantation: experimental studies.

Background: Cardioplegic solutions assure only a sub-optimal myocardial protection during prolonged storage for transplantation. The ultimate cause of myocardial damage during storage is unknown, but oxygen free radicals might be involved. We evaluated the occurrence of oxidative stress and changes in cellular redox potential after different periods of hypothermic storage.

Modification of the gating of the cardiac sarcoplasmic reticulum Ca(2+)-release channel by H2O2 and dithiothreitol.

The effect of hydrogen peroxide (H2O2) on the sheep cardiac sarcoplasmic reticulum (SR) Ca(2+)-release channel has been investigated under voltage-clamp conditions after incorporation of native membrane vesicles into planar phospholipid bilayers. In the presence of micromolar activating calcium concentrations on the cytosolic side of the membrane, H2O2 (3-5 mM) increased open probability of the channels. H2O2 did not affect the conductance of the channel or the response to activating compounds, such as ATP and caffeine.

How do calcium antagonists differ in clinical practice?

The majority of calcium antagonists used clinically belong to three distinct chemical classes: the phenylalkylamines, the dihydropyridines, and the benzothiazepines. In recent years their mode of action has been unravelled, their limitations recognized, and their efficacy and use in the management of patients with a broad spectrum of cardiovascular and other disorders defined. It is clear, however, that these drugs are not all alike, providing an explanation for their differing effects.

Effect of angiotensin converting enzyme inhibition with quinaprilat on the ischaemic and reperfused myocardium.

We assessed whether the local inhibition of myocardial converting enzyme by quinaprilat and captopril reduces the functional and metabolic damage caused by ischaemia and reperfusion. Quinaprilat and captopril were either subcutaneously injected (0.3 mg/kg once daily for 5-6 days) in the rabbit before isolation of the heart or delivered to the isolated hearts in the perfusate (10(-6) M) 60 min before ischaemia.

[Congestive heart failure: from cardiac muscle to skeletal muscle].

It is well established that in patients with chronic heart failure, exercise capacity and clinical symptoms such as fatigue or dyspnea correlate poorly with the extent of left ventricular dysfunction. The increase in cardiac output caused by vasodilators, cannot be translated immediately into increased exercise capacity and peak oxygen consumption in patients with chronic heart failure. These observations have prompted the hypothesis that in chronic heart failure intrinsic abnormalities of skeletal muscle emerge that prevent acute improvement in peak VO2 and blood lactate accumulation.

Effect of lacidipine on ischaemic and reperfused isolated rabbit hearts.

Lacidipine is a new developed dihydropyridine calcium-antagonist, showing a slow onset and long lasting-selective activity. To assess whether the administration of lacidipine protects the myocardium in a dose-dependent manner against ischaemia and reperfusion, isolated rabbit heart were infused with three different concentrations of lacidipine: 10(-10); 10(-9); 10(-8) M. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for CPK activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity, ATP production and calcium content and tissue concentration of ATP, creatine phosphate (CP) and calcium were determined.

The effects of L-arginine mono(2-mercaptoethanesulfonate) on the ischemic and reperfused heart.

We evaluated the effectiveness of L-arginine mono(2-mercaptoethanesulfonate) (argimesna) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Argimesna is a sulfhydryl group containing molecule which has no effect on glutathione status or on the total thiol pool. The effects of 10(-6) M argimesna were compared with those of 10(-6) M L-arginine and of 10(-6) M sodium salt of 2-mercaptoethanesulfonate (mesna).

Role of timing of administration in the cardioprotective effect of fructose-1,6-bisphosphate.

We administered fructose-1,6-bisphosphate (FDP), 1 mM, to isolated and perfused rabbit hearts submitted, after 90 minutes of equilibration, to an ischemic period (60 minutes at a coronary flow of 0.17 ml/min/g), followed by a period of reperfusion (30 minutes at a coronary flow of 3.6 ml/min/g).

Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action.

We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state.

Role of timing of administration in the cardioprotective effect of iloprost, a stable prostacyclin mimetic.

We administered iloprost, a stable prostacyclin mimetic, 27 nM, to isolated and perfused rabbit hearts submitted, after 60 min of equilibration, to an ischaemic period (60 min at a coronary flow of 1 ml/min) followed by a period of reperfusion (30 min at a coronary flow of 25 ml/min). Iloprost was delivered at different times during the experimental protocol: 60 min before ischaemia, at the onset and after 30 min of ischaemia and only during reperfusion. The iloprost cardioprotective effect was evaluated in terms of recovery of left ventricular pressure developed during reperfusion, creatine phosphokinase (CPK) and noradrenaline release, mitochondrial function (expressed as yield, RCI (respiratory control index), QO2, ADP/O), ATP and creatine phosphate (CP) tissue contents, calcium homeostasis and by measuring several parameters of oxidative stress: reduced and oxidized glutathione release and tissue contents, Mn and Cu-Zn superoxide dismutase activities; glutathione reductase and peroxidase activities.

Effect of propionyl-L-carnitine on mechanical function of isolated rabbit heart.

We studied the acute and chronic effects of propionyl-L-carnitine (PLC) on mechanical function of isolated rabbit heart. Propionyl-L-carnitine was either directly delivered in the perfusate (10(-9) to 10(-3) M) or intraperitoneally injected (250 mg/kg) for 10 days to the animals. When added acutely, propionyl-L-carnitine had no effect on inotropism, heart rate, or coronary perfusion pressure.

Effects of anipamil on myocardial sarcolemmal and mitochondrial calcium transport, comparison with verapamil and nifedipine.

The calcium antagonists anipamil, verapamil and nifedipine inhibited, dose dependently, passive and ATP-driven 45Ca2(+)-uptake in purified rabbit ventricular sarcolemmal vesicles exposed to a wide range of free calcium concentration (from 0 to 200 microM). The IC50 values for passive binding were virtually identical for all calcium antagonists and the inhibition was relatively independent of the amount of free calcium employed. On the contrary, the order of potency for inhibition of the ATP-driven calcium uptake was: anipamil greater than verapamil greater than nifedipine.

Effect of D-600 on ischemic and reperfused rabbit myocardium: relation with timing and modality of administration.

In this study we have investigated the possibility that D-600, a phenylalkylamine calcium antagonist, protects the isolated rabbit heart against ischemia and reperfusion-induced damage. D-600 was either subcutaneously injected (2mg/kg, twice daily for 5 to 6 days) in the rabbit before isolation of the heart, or delivered to the isolated hearts in the perfusate (10(-7) M), either at the onset of ischemia and during reperfusion, or only during post-ischemic reperfusion. Ischemia (90 min) was induced by reducing coronary flow from 25 to 1 ml/min, followed by 30 min of reperfusion.