[Sleep apnea syndrome and heart failure]. / Syndrome d'apnées du sommeil et insuffisance cardiaque.

More than half of all patients with stable heart failure are affected by sleep apnea syndrome. The mechanism of apnea may be either obstructive, by collapse of the upper airways, or central with nocturnal Cheyne-Stokes respiration. Changes in intrathoracic pressure, awakening and hypoxemia all lead to an increase in left ventricular afterload and to sympathetic activation, which can aggravate heart failure and prognosis. Treatment with positive pressure ventilation improves symptoms as well as cardiac function and prognosis. Sleep respiratory disorders are underdiagnosed and undertreated in patients with stable heart failure. To improve management of sleep apnea, patients with stable heart failure should be screened with small outpatient oximeters.

Different effects of ambulatory blood pressure monitoring on subjective and objective sleep quality.

OBJECTIVE: To determine whether ambulatory blood pressure monitoring affects objective and subjective sleep quality in patients tested at home. METHODS: Seventy consecutive patients (40 women and 30 men, aged 53+/-15 years), having ambulatory blood pressure monitoring to monitor the efficacy of antihypertensive treatment or to distinguish between hypertension or white-coat hypertension had an evaluation of their sleep quality on a first night with ambulatory blood pressure monitoring and the three following nights without ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring was performed with an auscultatory device with a measure every 15 min during 24 h. Sleep evaluation criteria were both subjective (sleep quality score and sleep questionnaire) and objective (wrist actigraphy monitoring). Sleep parameters during night 1 with ambulatory blood pressure monitoring were compared with those during night 4 without ambulatory blood pressure monitoring. Usual quality of sleep of the patients was assessed by the mean sleep quality score over 7 consecutive days. RESULTS: The sleep quality score was significantly higher for night 4 than for night 1 (7.3+/-2.1 vs. 5.3+/-2.3; P<0.0001). In contrast, actigraphy parameters (actual sleep time, mean activity score, and fragmentation index) were similar on night 1 and night 4 (6.7+/-1.2 vs. 6.9+/-1.2, 13.2+/-9.8 vs. 12.1+/-8.4, and 31.0+/-14.5 vs. 29.9+/-14.3, respectively). Subjective sleep quality was significantly altered by ambulatory blood pressure monitoring in good sleepers (mean sleep quality score > or =7, 73% of patients) but not in poor sleepers. The effect of ambulatory blood pressure monitoring on subjective sleep quality did not differ between dippers and nondippers. CONCLUSIONS: Objective sleep quality as assessed by wrist actigraphy is not significantly altered by ambulatory blood pressure monitoring, whereas subjective sleep quality is adversely affected in good sleepers.

N-acetylcysteine treatment normalizes serum tumor necrosis factor-alpha level and hinders the progression of cardiac injury in hypertensive rats.

BACKGROUND: Studies in isolated cardiomyocytes showed that replenishment in cellular glutathione, achieved with the glutathione precursor N-acetylcysteine (NAC), abrogated deleterious effects of tumor necrosis factor-alpha (TNF-alpha). METHODS AND RESULTS: We examined the ability of NAC to limit the progression of cardiac injury in the rat model of hypertension, induced by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg per day SC) and high-salt diet (HS) (8% NaCl). Four-week HS/L-NAME administration induced hypertension (193+/-8 versus 122+/-4 mm Hg for low-salt diet [LS] group) and left ventricular (LV) dysfunction, revealed by echocardiography and characterized by decreased LV shortening fraction (38+/-2% versus 49+/-4% for LS group; P<0.05) and decreased LV posterior wall thickening (49+/-3% versus 70+/-4% for LS group; P<0.05). LV dysfunction worsened further after 6-week HS/L-NAME administration. Importantly, increase in serum TNF-alpha level was strongly correlated with shortening fraction decrease and cardiac glutathione depletion. NAC (75 mg/d) was given as a therapeutic treatment in a subgroup of HS/L-NAME animals during weeks 5 and 6 of HS/L-NAME administration. NAC treatment, which replenished cardiac glutathione, had no effect on hypertension but reduced LV remodeling and dysfunction, normalized serum TNF-alpha level, and limited activation of matrix metalloproteinases -2 and -9 and collagen deposition in LV tissues. CONCLUSIONS: These findings suggest that glutathione status determines the adverse effects of TNF-alpha in cardiac failure and that TNF-alpha antagonism may be achieved by glutathione supplementation.

Chronic infusion of bradykinin delays the progression of heart failure and preserves vascular endothelium-mediated vasodilation in conscious dogs.

BACKGROUND: This study examined the effects of chronic bradykinin infusion on hemodynamics and myocardial and endothelial functions during the development of heart failure. METHODS AND RESULTS: Sixteen instrumented dogs were randomized to receive through the left atria either vehicle or bradykinin (1 microg/min) during ventricular pacing (250 bpm, 5 weeks). Hemodynamic and left ventricular (LV) parameters and the vasodilator responses to intravenous acetylcholine (0.3 to 3 microg/kg) and nitroglycerin (1 to 10 microg/kg) were examined in the control and after 3 and 5 weeks of pacing. The expression of endothelial NOS in femoral, carotid, and renal arteries was determined by Western blot analysis. After 3 weeks of pacing, changes in LV diastolic and systolic parameters were significantly lower in bradykinin-treated than vehicle-treated dogs (LV end-diastolic pressure, +10+/-3 versus +19+/-2 mm Hg; time constant of LV isovolumic relaxation, +11+/-2 versus +17+/-1 ms; LV wall thickening, -33+/-18% versus -75+/-9%; and cardiac output, -16+/-6% versus -32+/-6%; all P<0.05). Compared with vehicle-treated dogs, bradykinin-treated dogs had a reduced rightward shift of the diastolic LV pressure-diameter relation and a reduced diastolic LV wall stress. Similar trends were observed after 5 weeks. The vasodilator response to nitroglycerin was preserved in both groups. The response to acetylcholine was blunted in vehicle-treated but preserved in bradykinin-treated dogs. Vascular endothelial NOS expression decreased in vehicle-treated but was preserved in bradykinin-treated dogs. CONCLUSIONS: In conscious dogs, chronic bradykinin infusion delays the heart failure progression by preserving LV diastolic and systolic functions and by preserving vascular endothelial function.

Does angiotensin-converting enzyme inhibition improve the energetic status of cardiac and skeletal muscles in heart failure induced by aortic stenosis in rats?

Recently, we have demonstrated that heart failure in rats is associated with a myopathy altering energy metabolism in different muscles, but the origin of this myopathy is still unknown. Here, we studied the possible involvement of increased angiotensin II (Ang II) by treatment with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). The beneficial effects of ACE inhibition could result either from vasodilatation-induced cardiac unloading or from inhibition of the direct angiotensin action on the muscle cells. The model of aortic banding with persisting left ventricular (LV) overload where the cardiac unloading does not occur allows to distinguish between the two effects of ACE inhibition. Four months after aortic clipping (just before the treatment), echocardiographic study showed an impairment of the systolic function (decrease of the LV shortening by 30% and ejection fraction by 21%). Ten-week treatment with perindopril dramatically decreased Ang II plasma level but did not reduce LV hypertrophy though a significant decrease in right ventricular (RV) hypertrophy occurred. Perindopril did not improve alterations in activities of energy metabolism enzymes (creatine kinase, citrate synthase, cytochrome c oxidase, lactate dehydrogenase) either in ventricular or in skeletal (gastrocnemius) muscle. Similarly, ACE inhibition did not improve the main parameters of mitochondrial respiration in permeabilized muscle fibers. These data suggest that the generalized metabolic myopathy induced by the hemodynamic abnormalities conditioned by the continuous LV overload (aorta clipping) does not result from the increase in Ang II level per se. Correction of hemodynamic parameters and LV unloading seem to be the prerequisite for the improvement of muscle energy metabolism abnormalities.

Role of creatine kinase in cardiac excitation-contraction coupling: studies in creatine kinase-deficient mice.

To understand the role of creatine kinase (CK) in cardiac excitation-contraction coupling, CK-deficient mice (CK-/-) were studied in vitro and in vivo. In skinned fibers, the kinetics of caffeine-induced release of Ca2+ was markedly slowed in CK-/- mice with a partial restoration when glycolytic substrates were added. These abnormalities were almost compensated for at the cellular level: the responses of Ca2+ transient and cell shortening to an increased pacing rate from 1 Hz to 4 Hz were normal with a normal post-rest potentiation of shortening. However, the post-rest potentiation of the Ca2+ transient was absent and the cellular contractile response to isoprenaline was decreased in CK-/- mice. In vivo, echocardiographically determined cardiac function was normal at rest but the response to isoprenaline was blunted in CK-/- mice. Previously described compensatory pathways (glycolytic pathway and closer sarcoplasmic reticulum-mitochondria interactions) allow a quasi-normal SR function in isolated cells and a normal basal in vivo ventricular function, but are not sufficient to cope with a large and rapid increase in energy demand produced by beta-adrenergic stimulation. This shows the specific role of CK in excitation-contraction coupling in cardiac muscle that cannot be compensated for by other pathways.