Takotsubo or stress cardiomyopathy.

Many case reports have been published of reversible left ventricular dysfunction precipitated by sudden emotional stress. We have evaluated 10 women hospitalized for acute chest pain and dyspnea, mimicking an acute coronary syndrome, after a severe emotional trigger. Those patients, postmenopausal women, presented ST segment alterations on the EKG, minor elevations of cardiac enzymes, and biomarkers levels. At the coronarography there was not coronary thrombosis or severe stenosis, but the ventriculography showed wall motion abnormalities involving the left ventricular apex and midventricle, in the absence of significant obstructive coronary disease. The course was benign without complication, with a full recovery of left ventricular function in some weeks. These observations, like other reports, demonstrate the impact of emotional stress on left ventricular function and the risk of cardiovascular disease. The cause of this cardiomyopathy is still unknown, and several mechanisms have been proposed: catecholamine myocardial damage, microvascular spasm, or neural mediated myocardial stunning.

[Influence of sex on the prognosis of high risk acute coronary syndromes treated by early angioplasty]. / Influence du sexe sur le pronostic des syndromes coronaires aigus à haut risque traités par angioplastie précoce.

The aim of this study was to evaluate the influence of sex on the prognosis of high risk acute coronary syndromes treated early with angioplasty. Over a period of two years, 694 consecutive patients (151 female, 543 male) underwent revascularisation within the first 24 hours of an acute coronary syndrome without permanent ST elevation (ST depression (52.5%) or relapse of angina despite medical treatment (47.5%). The females were older than the males (67.9 vs 62.3 years; p < 0.0001), smoked less (7.3 vs. 32.8%; p < 0.001) and had a higher prevalence of hypertension (53 vs. 42.1%; p = 0.017). The angiographic characteristics were equivalent in both sexes, except for a lower frequency of thrombus in the females (6.9 vs. 15.2%; p < 0.0001). All lesions were treated with endoprosthesis implantation. The angiographic success rate was comparable (94 vs. 93.7%) as was the rate of major cardiac events while in hospital (3.8 versus 4%). With an average survival of 2 years, the incidence of major cardiac events remained identical in both sexes (15.4 vs 15.7%: p = 0.43): cardiac mortality (3.2 vs 2%; p = 0.18), myocardial infarction (7.3 vs 6.7%; p = 0.37), further revascularisation (8.3 vs 7.2%; p = 0.47). The survival without major cardiac event was comparable at 1 year (87 +/- 0.1 vs 88 +/- 0.3%) and at 2 years (78 +/- 0.2 vs 83 +/- 0.3%; p = 0.58). In conclusion, the progression both in hospital and at two years with a strategy of early revascularisation for high risk acute coronary syndromes was comparable in males and females.

[Prognosis scores to help revascularization for ischemic heart failure]. / Scores pronostiques pour la revascularisation des myocardiopathies ischémiques.

AIMS: Patients suffering from coronary heart disease with ventricular systolic dysfunction present a bad prognosis and should be potentially revascularized. Up to now, surgery appeared to be the most feasible revascularization technique for such patients. Aims of this study were to assess the influence of different treatments (surgery, angioplasty or exclusively medical treatment) on clinical outcome and to establish a prognostic score practitioners to select the most appropriate therapy adapted to their patient profiles. METHOD: From 1995 to 2000, 492 patients were included in this cohort: 365 in the angioplasty group, 96 in the surgical group and 31 in the medical group. Kaplan Meier curves were made with a multivariate analysis to determine the significant predictive factors of mortality and major adverse cardiac events. RESULTS: After a mean follow-up of 32 +/- 19 months, there was no statistical difference in mortality rate between the groups. However, the survival rate without MACE is higher in the surgical group, intermediate in the angioplasty group and lower in the medical group. Using the significant predictive factors of MACE in multivariate analysis, a prognostic score has been established in order to discriminate three categories of severity. For each category, angioplasty was compared with surgery in terms of the event-free-survival rate. For the two extreme categories (severe and non-severe), both treatments were equal. For the intermediate category, surgery obtained greater results. CONCLUSION: This prognostic score could help physicians in choosing the appropriate revascularization technique to treat patients with severe ischemic heart failure.

[Effects of bradykinin in the cardiovascular effects of angiotensin-converting enzyme inhibitors]. / Effets de la bradykinine dans les effets cardiovasculaires des inhibiteurs de l'enzyme de conversion.

The role of bradykinin in the cardiovascular effects of angiotensin converting enzyme inhibitors remains difficult to establish. On their haemodynamic effects, bradykinin acts during their acute administration, participating in their vasodilatation action, while during their chronic administration they act slightly or not at all. On their trophic effects, the action of the tissue kallikrein-kinin system, suggested by the results of animal experimentation, is yet to be demonstrated in man. For their effects on cardiovascular morbidity and mortality the role of bradykinin remains under discussion. Nevertheless, besides ACE inhibitors, the other therapeutic agents which increase the levels of bradykinin, such as neutral endopeptidase inhibitors, have a significant field of development in the course of cardiovascular pathologies.

[Registry of heart failure patients hospitalized in 2000. Data from the National College of Cardiology and General Hospital]. / Registre des insufisants cardiaques hospitalisés en 2000. Données du Collége national des cardiologues des hôpitaux généraux (CNCHG).

The French epidemiological data on cardiac insufficiency in the hospital environment are scarce. A register collecting 1772 patients was produced by the services of the National College of General Hospital Cardiologists (C.N.C.H.G.) during two periods: autumn 1999 (November) and spring 2000 (June). It involved completing a form for each of the first 20 patients with cardiac failure hospitalized over a month. 1011 and 761 observations from 59 and 47 centres (that is 17 and 16 observations per centre) were collected during the autumn and spring periods respectively. In France, in the general hospital centres (CHG) cardiology services during the year 2000, the characteristics and the medical treatment of hospitalized patients with cardiac failure are very similar to those presented in 1998 by A. Cohen-Solal in the name of the working group "Cardiomyopathy and Cardiac Insuficiency of the French Society of Cardiology". The hospitalized patient with cardiac failure is very old, usually male, has an ischaemic cardiopathy in one in two cases, and is at stage II and III on the New York Heart Association (NYHA) scale in 83% of cases. There is practically always an electrocardiographic anomaly. Loop diuretics are prescribed nine times out of ten, digitalis one in three, anagiotensin converting enzyme inhibitors are underused being prescribed two out of three times, but an increase in the prescription of anti-aldosterone and betablockers is found. The majority of patients improve during their stay, 7.8% dying and this mortality is influenced by age, ejection fraction (FE), functional NYHA class, causal cardiopathy, and the existence of severe renal failure. The data collected by the cardiology services of the C.N.C.H.G. are representative of the profile of the population affected and are important to know in order to improve the management of these patients.

Rehabilitation of patients with congestive heart failure with or without beta-blockade therapy.

BACKGROUND: Management of heart failure includes beta-blockade (betaB) therapy and cardiac rehabilitation. The aim of this study was to compare the exercise training response of patients with congestive heart failure (CHF) receiving betaB therapy with that of patients not receiving treatment. METHODS AND RESULTS: Thirty-four consecutive patients with CHF were included in a 4-week training program at their ventilatory threshold (VT); 6 patients received betaB treatment and 18 did not. The patients underwent a cardiopulmonary exercise test before and after training. Oxygen uptake (VO(2)) at peak exercise and at VT increased in both groups (P < or =.0001) without any significant differences between the groups. The same results were found after adjustment to ejection fraction and VO(2) at the start of the training program. There was no difference in VT improvement, measured as a percentage of utilization of maximal oxygen uptake, between the groups. After training, heart rate and ventilation decreased (P < or =.0001) at submaximal levels in both groups without significant differences between the groups. CONCLUSIONS: betaB therapy does not impair functional improvement induced by a rehabilitation program in patients with CHF. betaB therapy does not interfere with exercise training prescription if patient exercise evaluations are made at the time of therapeutic intake.

[Atrial flutter: a possible early sign of acute rejection in heart transplantation. A case report]. / Le flutter atrial: un témoin précoce possible du rejet aigu chez le transplanté cardiaque. A propos d'une observation.

The authors report the case of a cardiac transplant patient with a recurrence of atrial flutter two months after electrical cardioversion and despite long-term preventive treatment with amiodarone. Early investigation for signs of rejection with 4 endomyocardial biopsies was negative. Aggravation of the haemodynamic status due to flutter with a rapid ventricular response led to an attempted radio-frequency ablation. Endocavitary mapping confirmed persistence of sinus activity in the native atrium and the presence of a circuit of type I isthmic flutter (anticlockwise circuit) in the donor atrium. Ablation by radio-frequency in the same procedure was successful. A fifth myocardial biopsy the same day finally confirmed stage 3A acute rejection. No signs of recurrent rejection or arrhythmia have been observed after 24 months' follow-up in this patient. This preliminary experience confirms the need to look for graft rejection by repeated myocardial biopsies in cardiac transplant, patients with atrial flutter and the efficacy of radio-frequency ablation in cases of resistance to conventional therapy.

Prognostic value of heart rate variability in time domain analysis in congestive heart failure.

AIMS: Analysis of heart rate variability is a noninvasive tool that allows to study autonomic control of the heart. Several studies have shown disturbed heart rate variability in patients with chronic heart failure (CHF). We sought to assess the prognostic value of time domain measures of heart rate variability in CHF. METHODS AND RESULTS: We prospectively enrolled 190 patients with CHF in sinus rhythm, mean age 61+/-12 years, 109 (57.4 %) in NYHA class II and 81 (42.6 %) in class III or IV, mean cardiothoracic ratio 57.6+/-6.4 % and mean left ventricular ejection fraction 28.2+/-8.8 %, 85 (45 %) with ischemic and 105 (55 %) with idiopathic dilated cardiomyopathy. Time domain measures of heart rate variability were obtained from 24 h Holter ECG recordings. During follow-up (22+/-18 months), 55 patients died. In multivariate analysis, independent predictors for all-cause mortality were: ischemic heart disease, cardiothoracic ratio > or =60 % and standard deviation of all normal RR intervals <67 ms (RR=2.5, 95 % CI 1.5--4.2). CONCLUSIONS: Depressed heart rate variability has independent prognostic value in patients with CHF.

[Prophylactic value of automatic implantable defibrillators: a case report of a patient with asymptomatic Brugada syndrome]. / Intérêt prophylactique du défibrillateur automatique implantable: à propos d'une observation de patient ayant un syndrome de Brugada asymptomatique.

The authors report the case of an asymptomatic 32 year old man with no family history of sudden death but with ECG changes suggesting Brugada's syndrome. He underwent implantation of an automatic defibrillator after inducible syncope ventricular fibrillation had been demonstrated during electrophysiological investigation. The later occurrence of three episodes of ventricular fibrillation treated by the defibrillator confirmed a posteriori the logic of this therapeutic approach.

[Anticoagulant treatment and cardiac insufficiency]. / Traitements anticoagulants et insuffisance cardiaque.

In cardiac failure, should conventional therapy be associated systematically with anticoagulant or antiplatelet therapy? Embolic complications are uncommon (1 to 2.5% per year) and the benefit/risk ratio seems to be marginal. The absence of prospective randomised controlled trials makes it impossible to give a definitive reply to this question. The indications of oral anticoagulants are based on experience, good sense, the recognition of known embolic risk factors: severe cardiac failure, atrial fibrillation, EF < 0.30 and low VO2 max, mitral valve disease or prosthetic valve, detection of intracavitary thrombus or spontaneous contrast on transoesophageal echocardiography. Aspirin does not seem to be mandatory even if it reduces the thromboembolic risk non-significantly. In this elderly population with a high co-morbidity, the risks of haemorrhage cannot be ignored, and, if oral anticoagulants are prescribed, biological surveillance must be intensive.

Depressed low frequency power of heart rate variability as an independent predictor of sudden death in chronic heart failure.

AIMS: Identification of patients with chronic heart failure at risk for sudden death remains difficult. We sought to assess the prognostic value for all-cause and sudden death of time and frequency domain measures of heart rate variability in chronic heart failure. METHODS AND RESULTS: We prospectively enrolled 190 patients with chronic heart failure in sinus rhythm, mean age 61+/-12 years, 109 (57.4%) in NYHA class II and 81 (42.6%) in classes III or IV, mean cardiothoracic ratio 57.6+/-6.4% and mean left ventricular ejection fraction 28.2+/-8.8%, 85 (45%) with ischaemic and 105 (55%) with idiopathic dilated cardiomyopathy. Time and frequency domain measures of heart rate variability were obtained from 24 h Holter ECG recordings, spectral measures were averaged for calculation of daytime (1000h-1900h) and night-time (2300h-0600h) values. During follow-up (22+/-18 months), 55 patients died, 21 of them suddenly and two presented with a syncopal spontaneous sustained ventricular tachycardia. In multivariate analysis, independent predictors for all-cause mortality were: ischaemic heart disease, cardiothoracic ratio > or =60% and standard deviation of all normal RR intervals <67 ms (RR = 2.5, 95% CI 1.5-4.2). Independent predictors of sudden death were: ischaemic heart disease and daytime low frequency power <3.3 ln (ms(2)) (RR = 2.8, 95% CI 1.2-8.6). CONCLUSION: Depressed heart rate variability has independent prognostic value in patients with chronic heart failure; spectral analysis identifies an increased risk for sudden death in these patients.

[Utilization of heart rate at the ventilatory threshold for the prescription of intensity of exercise training in cardiac failure]. / Utilisation de la fréquence cardiaque au seuil ventilatoire dans la prescription des intensités d'entraînement à l'effort chez l'insuffisant cardiaque.

Physical exercise is a treatment for cardiac failure but a large range of intensities of exercise is proposed. The aims of this study were to determine the range of intensities of effort used and to individualize the intensities used. Thirty patients with stable cardiac failure (NYHA Classes II-III, age: 53 +/- 2.1 years, ejection fraction: 31 +/- 1.4%) underwent a cardiorespiratory exercise stress test before and after individualized training at the ventilatory threshold. However, before and after the training period, standard methods of calculation of the intensities at the ventilatory threshold showed individual differences greater than +/- 2 standard deviations, indicating different metabolic stimulations. After the individualized training programme, peak oxygen consumption on exercise (1679 +/- 100 vs 1487 +/- 89 ml.min-1, p = 0.0001) and at ventilatory threshold increased (1365 +/- 85 vs 1133 +/- 65 ml.min-1, p = 0.0001), the ventilatory threshold/peak exercise ratio increased (81.2 +/- 1.3 vs 76.7 +/- 1.4%, p = 0.0008), and there was a decrease in heart and ventilatory rates at submaximal metabolic levels (p = 0.0001). The authors conclude that protocols using intensity of effort at the ventilatory threshold give similar results with respect to improvement of aerobic capacity as other methods of indirect calculation, based on maximal heart rate of oxygen consumption. The value of this particular method lies in the adequation between aerobic capacity of the patient and the intensity of training. The results obtained attain the physiopathological aims of rehabilitation.

[Hyperinsulinism, heart rate variability and circadian variation of arterial pressure in obese hypertensive patients]. / Hyperinsulinisme, variabilité de la fréquence cardiaque et variation circadienne de la pression artérielle chez les sujets obèses hypertendus.

AIMS: During insulin resistance, sympathetic nerve activity is increased. However insulin resistance is a common feature of obesity and essential hypertension, it is unclear if chronic hyperinsulinemia per se contributes to sympathetic overactivation. The purpose of our study was to explore++ the relationships between chronic hyperinsulinemia and heart rate variability (HRV), a non-intensive tool to assess autonomic function, in obese and hypertensive subjects. METHODS: 24 hours Holter ECG for HRV time and frequency domain analysis was performed in 77 patients, mean age 53 +/- 10 years, 52 men and 25 women, free of diabetes, without beta-blockers, divided in four groups according to three parameters, body mass index (BMI > 27 kg/m2 in man and > 25 kg/m2 in woman defined obesity), arterial pressure and insulinemia (fasting insulinemia > 25 mUI/L defined hyperinsulinemia): 27 patients obese, hypertensive, with hyperinsulinemia; 28 patients obese, hypertensive, without hyperinsulinemia; 12 patients non obese, hypertensive, without hyperinsulinemia; 10 patients obese, normotensive, without hyperinsulinemia. RESULTS: In comparison with the three other groups, patients with hyperinsulinemia showed a significant decrease (p < 0.05) of SDNN and the power of total spectrum (0.01-1 Hz) band, which are indexes of global HRV, and a significant decrease (p < 0.005) of SD and the normalized power of the low frequency (0.04-0.15 Hz) band, both indexes reflecting sympathetic modulation of HRV. In contrast, no significant difference was observed between the four groups for indexes of HRV reflecting parasympathetic tone. These relations were independent of mean RR. Fasting insulinemia was significantly (p < 0.0001) related with HRV in time domain (SDNN; r = -0.43; SD: r = -0.49) and spectral domain (total spectrum: r = -0.49; low frequency: r = -0.52). CONCLUSION: Chronic hyperinsulinemia appears to be an important determinant of HRV, particularly for the indexes reflecting sympathetic influence, independent of obesity and hypertension.

[Treatment of cardiac insufficiency: does treatment depend on whether its cause is ischemic or idiopathic?]. / Le traitement de l'insuffisance cardiaque est-il différent selon sa cause, ischémique ou idiopathique?

Angiotensin converting enzyme (ACE) inhibitors are associated with a greater reduction in mortality in non-ischaemic cardiomyopathy than in ischaemic cardiomyopathy after the results of the V-HeFT-II and SOLVD trials in symptomatic patients. However, a recent analysis of the global, symptomatic and therapeutic, results of the SOLVD trials, demonstrated a similar reduction in mortality with ACE inhibitors in ischaemic and non-ischaemic cardiomyopathies. Moreover, after myocardial infarction, the beneficial effects of ACE inhibitors have been well established in patients with left ventricular dysfunction. Betablockers, especially bisoprolol in the CIBIS-I trial, also seem to be more effective in non-ischaemic cardiomyopathy. However, CIBIS-II and the US Carvedilol Heart Failure Trial Program clearly showed that the benefits of betablockade were identical whether ischaemic or not. The beneficial effects of betablockers in the post-infarction period are more marked when left ventricular dysfunction is severe. The PROVED and RADIANCE trials suggest that digitalis is more effective in non-ischaemic cardiomyopathy. These results were not confirmed by the DIG trial which showed a significant reduction in the combined criterion, mortality and hospital admission for aggravation of cardiac failure, both in ischaemic and in non-ischaemic cardiomyopathy. However, the use of digitalis should be prudent during ischaemic cardiomyopathy, the neutral effect on global mortality in the DIG trial masking divergent results with a tendency to reducing mortality due to aggravation of cardiac failure and a significant increase of other causes of cardiac death, especially from myocardial infarction and arrhythmias. Amiodarone could also be useful in non-ischaemic cardiomyopathy. The reduction in risk of death in the GESICA study, which comprised 60% of patients with non-ischaemic cardiomyopathy, contrasting with the absence of an effect with this molecule in the STAT-CHF trial which only comprised 29% of patients with non-ischaemic cardiomyopathy. The new generation of calcium antagonists could also be more effective in non-ischaemic cardiomyopathy. Although amlodipine significantly reduced mortality in the PRAISE trial in non-ischaemic cardiomyopathy, there was no favourable effect with felodipine in the V-HeFT-III tria. Finally, if in the earlier studies oral anticoagulants were more effective in non-ischaemic cardiomyopathy, the recent results of the SOLVD trial showed that warfarin decreased the mortality in both ischaemic and non-ischaemic cardiomyopathy. The value of anti-aggregant therapy is not questioned in coronary artery disease, but its role in dilated cardiomyopathy has not yet been established. In conclusion, apart from the use of digitalis which must be prudent in post-infarction cardiomyopathy or in patients with ventricular arrhythmias, the treatment of cardiac failure differs little with respect to its ischaemic or non-ischaemic aetiology, and should be based on the NYHA (New York Heart Association) classification.

[The CAPITOL study (Captopril Post Infarction Tolerance). A trial of progressive titration of captopril after myocardial infarct with left ventricular dysfunction]. / L'étude CAPITOL. Essai de titration progressive du captopril après infarctus du myocarde avec altération de la fonction ventriculaire gauche.

The objective of CAPITOL (Captopril Post Infarction Tolerance) multicentre open trial was to study the tolerance of a protocol of titration of Captopril in patients with recent myocardial infarction complicated by left ventricular dysfunction. Five hundred and four patients, with a mean age of 62 +/- 12 years, were included during the hospital period in the 74 participating intensive care units, 9 +/- 6 days after myocardial infarction (ejection fraction 34 +/- 6%). After a 6.25 mg test dose of Captopril, the dosage was progressively increased to the target dose of 150 mg at the end of the first month. Of the 504 patients included, 343 finished the trial and 161 stopped the trial prematurely. At the end of the hospital period, 73% received 75 mg/day: at the first follow-up visit (27 +/- 16 days after inclusion), 59% had attained 150 mg/day, this proportion increasing to 71% at the end of the trial (79 +/- 33 days after inclusion). There was no significant change in blood pressure for the whole study population. However, the systolic blood pressure of the patients receiving 150 mg/day of Captopril at the end of the trial was slightly higher than that observed at the end of the hospital period (126 +/- 17 mmHg and 116 +/- 17 mmHg respectively, p = 0.006). Severe Intercurrent events were observed in 89 patients: 24 deaths, 7 recurrent infarctions, 58 hospital admissions (21 for cardiac failure, 15 for recurrence of angina, 11 aorto-coronary bypass operations, 7 coronary angioplasties, 2 cerebro-vascular accidents, 2 systemic emboli). Of the benign complications, hypotension was observed in 25% of patients, nearly half of which occurred during the hospital admission. The drugs prescribed in association with Captopril were Aspirin (78%), betablockers (57%), nitrate derivatives (42%) and diuretics (27%). Multivariate analysis showed 3 factors associated with good tolerance of the 150 mg dosage of Captopril: Killip Class I or II on admission, an ejection fraction > 30% and an initial systolic blood pressure > 100 mmHg. In conclusion, in this trial of dose titration, 3 out of 4 patients with myocardial infarction and left ventricular dysfunction, tolerated the 150 mg/day dosage of Captopril. Patients in the trial could also be treated with drugs recommended after myocardial infarction, in particular the betablockers. Arch Mal Coeur 1999: 92: 395-403.

[Congestive cardiomyopathies originating from arrhythmia]. / Cardiomyopathies congestives d'origine arythmique.

Arrhythmia-induced cardiomyopathy is partially or totally reversible left ventricular dysfunction after normalisation of the tachycardia or arrhythmia. On the one hand, there are pure forms in which the arrhythmia occurs in apparently normal hearts and, on the other hand, the more common form in which there is minimal underlying cardiac disease associated with the arrhythmia. Total or partial recovery after reduction of the arrhythmia or "ablation" of its substrate remains a key feature of the diagnosis. Many experimental studies of the functional and structural myocardial and neurohormonal effects of prolonged tachycardias or tachyarrhythmias have provided insight into the modes of occurrence and the characteristics of this type of "reversible" left ventricular dysfunction. But, in fact, there is a lack of anatomical, clinical and follow-up data of this syndrome, the diagnosis of which is always difficult and essentially retrospective after recovery of left ventricular function.

[Evaluation of arrhythmic risk in coronary insufficiency]. / Evaluation du risque rythmique chez l'insuffisant cardiaque.

Half of all deaths occurring in patients with heart failure are sudden deaths probably related to a malignant ventricular arrhythmia. The pathophysiological mechanisms of these arrhythmias are unclear, but left ventricular function, hypokalaemia accentuated by diuretics and treatments altering inotropism play a definite role. Because of the diversity of aetiologies generating heart failure, the multiplicity of fatal arrhythmias and the multifactorial origin of these arrhythmias, there is no formal marker for the risk of sudden death in patients with heart failure, at the present time. In addition to the NYHA classification and detection of episodes of syncope, assessment of these patients must be as complete as possible, at least including repeated evaluation of the ejection fraction, Holter ECG monitoring and detection of delayed ventricular potentials.

[Is the treatment of left ventricular systolic dysfunction different according to the etiology?]. / Le traitement de l'insuffisance cardiaque avec altération de la fonction systolique est-il différent selon l'étiologie?

Cardiac failure is the terminal stage of evolution, the finality of many valvular, vascular, myocardial, general, congenital or acquired conditions. The therapeutic decisions should be based on the search for a curable cause of a predisposing factor and the evaluation of the severity of the cardiac failure. At advanced stages of ventricular dysfunction when the myocardial lesions are constituted, when cardiac and vascular remodelling has occurred, the aetiological treatment, which is the constant objective, is unfortunately too late. The treatment is the same, whatever the aetiology, in order to improve functional problems. At early stages, and, if possible, preventively, surgery, revascularisation techniques, the correction of an arrhythmia, the suppression of a cardiotoxic factor, are essential. The different therapeutic classes used could have different efficacies depending on the aetiology, but, finally, this point is negligible: the medications are based on the results of large scale, controlled, therapeutic trials.

[Functional decoupling of left ventricular beta-adrenoceptor in a canine model of obesity-hypertension]. / Découplage fonctionnel des récepteurs beta-adrénergiques ventriculaires gauches dans un modèle canin d'obésité-hypertension.

OBJECTIVE: To assess cardiac beta-adrenoceptors (beta-AR) in an obesity-hypertension model. METHODS: Six male beagle dogs (aged 35 +/- 5 months) receiving during 30 weeks a high-fat diet with 60% uncooked beef fat were compared to 6 normal beagle dogs. With right auricular and left ventricular samples we analysed cardiac beta-AR density through binding study using [125I]-cyanopindolol. beta 1 and beta 2 densities were obtained by competition with CGP 20712A. Affinity state of beta-AR was assessed by competition with isoproterenol. Noradrenaline plasma level was assayed by HPLC. Left ventricular mass (LV mass) was measured by echocardiography. Results are expressed as mean +/- SE. All comparisons were performed using a variance analysis (*: p < 0.05). RESULTS: Systolic blood pressure was significantly higher in obesses (245 +/- 8 vs 197 +/- 10 mmHg in controls). Diastolic blood pressure did not differed between both groups (93 +/- 3 vs 84 +/- 3 mmHg in controls). Noradrenaline plasma levels were similar in both groups (276 +/- 30 vs 235 +/- 50 pg/mL in controls). Obesses were characterized by higher LV mass (80 +/- 24 vs 67 +/- 15 g in controls*). Right auricular and left ventricular beta-AR densities were not different in obesses (57 +/- 6 and 67 +/- 4 fmoles/mg protein) and in controls (68 +/- 7 and 63 +/- 9 fmoles/mg protein). The beta 1-AR proportion was the same in obesses and controls in right auricule (63 +/- 4 vs 64 +/- 3% in controls) and left ventricule (59 +/- 3 vs 60 +/- 4% in controls). The proportion of beta-AR receptors in a high affinity state was similar in right auricular samples (69 +/- 4 vs 67 +/- 3%) in controls) but was significantly different in left ventricule (28 +/- 6 vs 74 +/- 6%) in controls). CONCLUSION: Left ventricular beta-adrenoceptors came under a specific desensibilisation independent of plasma noradrenaline levels. This functional decoupling of beta-adrenoceptors may account for the progressive systolic dysfunction of hypertensive cardiomyopathy.