[Cardiac dysfunction and the obstructive sleep apnoea syndrome]. / Dysfonction cardiaque et syndrome d'apnée du sommeil.

INTRODUCTION: Cardiac insufficiency affects nearly 2% of the population with increased morbidity/mortality despite advances in therapeutic management. The sleep apnoea syndrome (SAS) is a risk factor for, and cause of aggravation of, myocardial dysfunction. BACKGROUND: SAS is found in 70% of patients with chronic cardiac failure, 65% of patients with refractory hypertension, 60% of patients with cerebro-vascular accidents and 50% of patients with atrial fibrillation. The associated cardiovascular mortality is multiplied by a factor of 2 to 3. The pathophysiological mechanisms are intermittent nocturnal hypoxia, variations in CO2 levels, variations in intrathoracic pressure and repeated arrousals from sleep, concurrent with sympathetic hyperactivity, endothelial dysfunction and systemic inflammation. CONCLUSIONS: SAS and cardiological management in patients presenting with myocardial dysfunction should be combined. It is necessary to pursue the scientific investigations with the aim of determining a precise care pathway and the respective places of each of the cardiological and pulmonary measures.

Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation.

To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of intracellular energetic units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum and sarcolemma ion-pump ATPases. The role of ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to adjust to intracellular energy needs through the dynamic system of compartmentalized phosphoryl transfer networks. One of the key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (MOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and microcompartmentalization. Based on the experimental and theoretical (mathematical modelling) arguments, we describe regulation of mitochondrial ATP synthesis within ICEUs allowing heart workload to be linearly correlated with oxygen consumption ensuring conditions of metabolic stability, signal communication and synchronization. Particular attention was paid to the structure-function relationship in the development of ICEU, and the role of mitochondria interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM permeability in response to energy metabolic signals providing regulation of mitochondrial respiration. Emphasis was given to the importance of creatine metabolism for the cardiac energy homoeostasis.

Effects of training at mild exercise intensities on quadriceps muscle energy metabolism in patients with chronic obstructive pulmonary disease.

AIM: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects. METHODS: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities. RESULTS: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects. This work corresponds to a mechanical power set at 65.2 ± 7.5% of the maximum power for patients with COPD and 52 ± 3.3% of the maximum power in control group. Despite this low level of exercise intensities, we observed an improvement in mitochondrial oxidative phosphorylation through the creatine kinase system revealed by the increased apparent K(m) for ADP (from 105.5 ± 16.1 to 176.9 ± 26.5 µm, P < 0.05 in the COPD group and from 126.9 ± 16.8 to 177.7 ± 17.0, P > 0.05 in the control group). Meanwhile, maximal mechanical and metabolic power increased significantly from 83.1 ± 7.1 to 91.3 ± 7.4 Watts (P < 0.05) and from 16 ± 0.8 to 18.7 ± 0.98 mL O(2) kg(-1) min(-1) (P < 0.05) only in the COPD group. CONCLUSION: This study shows that physical training at mild intensity is able to induce comparable changes in skeletal muscles oxidative energy metabolism in patients with COPD and sedentary healthy subjects, but different changes of maximal mechanical and metabolic power.

Systems bioenergetics of creatine kinase networks: physiological roles of creatine and phosphocreatine in regulation of cardiac cell function.

Physiological role of creatine (Cr) became first evident in the experiments of Belitzer and Tsybakova in 1939, who showed that oxygen consumption in a well-washed skeletal muscle homogenate increases strongly in the presence of creatine and with this results in phosphocreatine (PCr) production with PCr/O(2) ratio of about 5-6. This was the beginning of quantitative analysis in bioenergetics. It was also observed in many physiological experiments that the contractile force changes in parallel with the alteration in the PCr content. On the other hand, it was shown that when heart function is governed by Frank-Starling law, work performance and oxygen consumption rate increase in parallel without any changes in PCr and ATP tissue contents (metabolic homeostasis). Studies of cellular mechanisms of all these important phenomena helped in shaping new approach to bioenergetics, Molecular System Bioenergetics, a part of Systems Biology. This approach takes into consideration intracellular interactions that lead to novel mechanisms of regulation of energy fluxes. In particular, interactions between mitochondria and cytoskeleton resulting in selective restriction of permeability of outer mitochondrial membrane anion channel (VDAC) for adenine nucleotides and thus their recycling in mitochondria coupled to effective synthesis of PCr by mitochondrial creatine kinase, MtCK. Therefore, Cr concentration and the PCr/Cr ratio became important kinetic parameters in the regulation of respiration and energy fluxes in muscle cells. Decrease in the intracellular contents of Cr and PCr results in a hypodynamic state of muscle and muscle pathology. Many experimental studies have revealed that PCr may play two important roles in the regulation of muscle energetics: first by maintaining local ATP pools via compartmentalized creatine kinase reactions, and secondly by stabilizing cellular membranes due to electrostatic interactions with phospholipids. The second mechanism decreases the production of lysophosphoglycerides in hypoxic heart, protects the cardiac cells sarcolemma against ischemic damage, decreases the frequency of arrhythmias and increases the post-ischemic recovery of contractile function. PCr is used as a pharmacological product Neoton in cardiac surgery as one of the components of cardioplegic solutions for protection of the heart against intraoperational injury and injected intravenously in acute myocardial ischemic conditions for improving the hemodynamic response and clinical conditions of patients with heart failure.

[Efficiency of perstarium in the treatment of patients with chronic obstructive bronchitis and pulmonary hypertension]. / Effektivnost' prestariuma v lechenii bol'nykh khronicheskim obstruktivnym bronkhitom s legochnoi gipertenziei.

Thirty-two patients with chronic obstructive bronchitis (COB) aged 38 to 52 years (mean 40.5 +/- 3.8 years) who had clinical and functional parameters of NYHA functional class (FC) IV (WHO, 1998) pulmonary hypertension (PH). Hemodynamic parameters were recorded by M- and B-mode and Doppler echocardiography. The gaseous composition of blood was studied by the Astrup micromethod; the rheological properties of venous blood were explored by an AKP-2 rotational viscometer. According to their therapy, the examinees were divided into 2 groups. Group 1 included 18 patients given prestarium (Servier, France) in a dose of 2-4 mg/day. Group 2 (a control group) comprised 14 patients receiving the basal therapy provided by the medical and economical standards of therapy for COB. The studies have indicated that the inclusion of prestarium into the combined treatment of COB patients with FC IV PH promotes a significant improvement of the clinical status of patients, causes a reduction in the size of the right atrium (by 16.2%; p < 0.05) and the right ventricle (by 12.4%; p < 0.001), a 12.0%-fold increase in left ventricular ejection fraction. The drug produced no negative effect on ERF and blood gaseous composition and rheological properties. Therefore, a course and long-term use of prestarium in the combined therapy of COB patients with FC IV PH leads to clinical improvement, to correction of basic cardiohemodynamic parameters, and exerts a remodeling effect on the right and left ventricles, and improves life quality in patients.