[Anxiety, depression, and stressed life in patients awaiting heart transplantation: are these factors to be considered?]. / Ansia, depressione e vita stressante nel paziente in attesa di trapianto cardiaco: dimensioni da considerare?

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. METHODS: Sixty two patients (47 M, 15 F), with mean age of 53 +/- 9.9 years in NYHA class (16 class II, and 43 class III/IV) and ejection fraction 29 +/- 10 have filled in the following two questionnaires: the Cognitive Behavioural Assessment form H (CBA-H), to measure psychological functioning and/or behaviours at risk for heart disease, and the Short Form 36 (SF-36), to evaluate physical and functional health status. RESULTS: In patients awaiting heart transplantation, the presence of anxiety contributes to reduce physical activity, vitality and mental health. Depressed mood disorders negatively influence physical and mental health and vitality. Perception of stressed life limits role and physical activity, vitality, and emotional status and augments intensity of physical pain. CONCLUSIONS: Symptoms of anxiety, depression and stress influence negatively mental health and daily physical activity. These aspects may vary of intensity with progression of the disease and lengthening of waiting. The importance of an early and continuous psychological support to the patient becomes fundamental to individuate and treat these disorders to favour optimal post-transplant outcomes.

[Chronic heart failure as a crisis event of the family]. / La malattia cardiaca cronica come evento critico familiare.

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. They may first influence the cardiologist's choice and later, through comments or actions, treatment expectations, diagnosis and therapy by sustaining or, on the contrary, minimizing the patient-physician interaction. A therapeutic triangle, which includes the family, the patient and the physician, develops from the beginning; thus the physician needs to be aware of it to use these interactions in the best interest of the patient himself. In this context clinical psychologists play a pivotal role first in identifying dysfunctional relations within the family and then in supporting the family to overcome crisis events.

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. RESULTS: Increase in iNOS mRNA, and decrease in e and nNOS mRNAs were observed in cardiac myocytes isolated 6h after LPS injection with recovery to basal levels at 20 h. Significant down-regulation of e and nNOS protein levels (p < 0.01) and calcium-dependent activity (p < 0.05) were detected at 20 h. Serum TNF-alpha increased after 6 and 20 h (p < 0.05), whereas NO metabolites rose only after 20 h (p < 0.0001). The diastolic calcium increased 6 h from LPS injection (p < 0.0001) and remained significantly higher after 20 h. Calcium transients amplitude was not affected by LPS injection. CONCLUSIONS: Endotoxic shock stimulates iNOS and down-regulates expression of nNOS in purified cardiac myocytes, but endogenous NO production does not likely affect calcium transients.

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. The estimate of the prevalence of myocardial viability in patients with chronic ischemic left ventricular dysfunction is crucial and different figures can be obtained by applying different diagnostic techniques and analyzing different cohorts of patients. In patients with chronic heart failure and substantial areas of myocardial ischemia and viability, revascularization is likely to prolong survival. The amount of viable myocardium needed to be clinically relevant remains to be established: only randomized prospective studies, focusing on both functional improvement and prognosis, will give an evidence-based conclusion. An aggressive and thoughtful surgical approach to patients with ischemic heart failure can yield satisfying long-term results, with survival rates superior to medical management alone, and can constitute a true and valid alternative to heart transplantation.

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. Although an impressive bulk of experimental studies substantiate the role of oxidative stress in the progression of the damage induced by acute ischemia, not a single pathophysiologic achievement has had a significant impact on the treatment of patients and randomized, controlled clinical trials, both in primary and secondary prevention, have failed to prove the efficacy of antioxidants in the treatment of ischemic cardiovascular disease. This dichotomy, between the experimental data and the lack of impact in the clinical setting, needs to be deeply investigated: certainly, the pathophysiologic grounds of oxidative stress do maintain their validity but the concepts of the determinants of oxidative damage should be critically revised. In this regard, the role of intermediate metabolism during myocardial ischemia together with the cellular redox state might represent a promising interpretative key.

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.

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. Several animals received the same dose of monocrotaline but only compensated right ventricular hypertrophy and no sign of congestion resulted. Two age- and diet-matched groups of control animals were also studied. In soleus and extensor digitorum longus (EDL) muscles, we studied skeletal muscle blood flow, oxidative capacity and respiratory function of skinned muscle fibres. RESULTS: In CHF, we observed a decrease of muscle blood flow (statistically significant in the soleus, p < 0.05 vs. controls). In compensated rats, a similar trend in blood flow was observed. In both soleus and EDL, a significant reduction of high energy phosphate and a shift of the redox potential towards accumulation of reducing equivalents were observed. The reduction of energy charge was not correlated to the decrease of blood flow. In skinned myofibres, the ratio of O(2) utilised in the presence and in absence of ADP (an index of phoshorilating efficiency) was reduced from 8.9 +/- 1.9 to 2.7 +/- 0.2 (p < 0.001) and from 5.7 +/- 1.0 to 2.0 +/- 0.3 (p < 0.01) in soleus and EDL, respectively. Activity of the different complexes of respiratory chain was investigated by means of specific inhibitors, showing major abnormalities at the level of complex I. In fact, inhibition of VO(2) by rotenone was decreased from 83.5 +/- 3.2 to 36.4 +/- 9.6 % (p < 0.005) and from 81.8 +/- 6.1 to 38.2 +/- 7.4 % (p < 0.005) in soleus and EDL, respectively. CONCLUSIONS: In rats with CHF, abnormalities of oxidative phosphorylation of muscles occur and complex I of the respiratory chain seem to be primarily affected. The metabolic alterations of skeletal muscles in CHF may be explained, at least in part, by an impaired O(2) utilisation.