Skeletal muscle fatigue in normal subjects and heart failure patients. Is there a common mechanism?

Skeletal muscle fatigue develops gradually during all forms of exercise, and develops more rapidly in heart failure patients. The fatigue mechanism is still not known, but is most likely localized to the muscle cells themselves. During high intensity exercise the perturbations of the Na⁺ and K⁺ balance in the exercising muscle favour depolarization, smaller action potentials and inexcitability. The Na⁺, K⁺ pump becomes strongly activated and limits, but does not prevent the rise in extracellular Na⁺, K⁺ pump concentration and intracellular Na⁺ concentration. However, by virtue of its electrogenic property the pump may contribute in maintaining excitability and contractility by keeping the cells more polarized than the ion gradients predict. With prolonged exercise perturbations of Na⁺ and K⁺ are smaller and fatigue may be associated with altered cellular handling of Ca²⁺ and Mg²⁺. Release of Ca²⁺ from the sarcoplasmic reticulum (SR) is reduced in the absence of changes of the cellular content of Ca²⁺ and Mg²⁺. In heart failure several clinical reports indicate severe electrolyte perturbations in skeletal muscle. However, in well controlled studies small or insignificant changes are found. We conclude that with high intensity exercise perturbations of Na⁺ and K⁺ in muscle cells may contribute to fatigue, whereas with endurance type of exercise and in heart failure patients the skeletal muscle fatigue is more likely to reside in the intracellular control of Ca²⁺ release and reuptake.     

Augmented peripheral chemoreflex in patients with heart failure and inspiratory muscle weakness

We hypothesized that heart failure patients with inspiratory muscle weakness (IMW) present greater peripheral chemoreflex responsiveness and augmented exercise ventilatory oscillation compared to patients with preserved inspiratory muscle strength. We studied 19 heart failure patients: 9 with IMW (maximal inspiratory pressure [PImax] < 70% of predicted) and 10 with preserved inspiratory muscle strength. Inspiratory muscle strength was measured via pressure transducer. Peripheral chemoreflex was evaluated by the single-breath CO₂ test. Exercise ventilatory oscillation was determined as the ratio between amplitude and mean of each oscillation during incremental exercise. Patients with IMW had greater peripheral chemoreflex response (0.11 ± 0.03 l min⁻¹ Torr⁻¹) than those with preserved inspiratory muscle strength (0.07 ± 0.03 l min⁻¹ Torr⁻¹, p = 0.02). Moreover, there was a significant and inverse correlation between PImax and peripheral chemoreflex response (r = −0.57, p = 0.01). Likewise, there was a significant and inverse correlation between PImax and ventilatory oscillations (r = −0.46, p = 0.04). Our findings indicate that IMW is linked to increased peripheral chemoreflex and augmented exercise ventilatory oscillation in patients with chronic heart failure.     

Na+/H+ countertransport and calcium exchange in peripheral blood cells of healthy subjects and patients with chronic heart failure

A comparative study is performed of Na⁺/H⁺ exchange and Ca²⁻ mobilization in erythrocytes and platelets of patients with stage I–II chronic heart failure caused by dilative cardiomyopathy and ischemic heart disease. A significant rise in the Na⁺/H⁺ exchange rate is found in the cells of chronic heart failure patients, which correlates with an elevated erythrocyte and platelet concentration of Ca²⁺ and an increased “calcium” response of platelets to inductors. The findings testify to a certain functional relationship between various cation-transporting cellular systems whose change in properties upon chronic heart failure can play an important pathogenic role. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 572–575, December, 1994     

Optimal timing in screening patients with congestive heart failure and healthy subjects during circadian observation

Congestive heart failure (CHF) is a major medical challenge in developed countries. In order to screen patients with CHF and healthy subjects during circadian observation, accurate judgment and fast response are imperative. In this study, optimal timing during circadian observation via the heart rate variability (HRV) was sought. We tested 29 CHF patients and 54 healthy subjects in the control group from the interbeat interval databases of PhysioBank. By invoking the α1 parameter in detrended fluctuation analysis of HRV, we found that it could be used as an indicator to screen the patients with CHF and subjects in normal sinus rhythm (NSR) under Kruskal–Wallis test. By invoking Fano factor, the optimal timing to screen CHF patients and healthy subjects was found to be from 7 PM to 9 PM during the circadian observation. In addition, this result is robust in a sense that the same result can be achieved by using different ECG recording lengths of 2, 5, 10, … , and 120 min, respectively. Furthermore, a support vector machine was employed to classify CHF and NSR with α1 parameter of a moving half-hour ECG recordings via leave-one-out cross validation. The results showed that the superlative screening performance was obtained in the 7 pm–9 pm period during circadian observation. It is believed that this result of optimal timing will be helpful in the non-invasive monitoring and screening of CHF patients and healthy subjects in the clinical practice.     

Body fluid distribution in elderly subjects with congestive heart failure

The aims of this study were to investigate body fluid changes in elderly patients suffering from congestive heart failure (CHF) and to identify the fluid measurement that best characterizes fluid overload states in CHF patients by comparison with normal hydration in the elderly. In a case-controlled experimental design, 72 elderly subjects (65-98 yr), 38 healthy and 34 with CHF, were studied. Total body water (TBW) and extracellular water (ECW) were determined by dilution methods; fat-free mass (FFM) and fat mass (FM) were determined by dual-energy X-ray absorptiometry (DEXA). In healthy subjects, the FFM hydration expressed as TBW% FFM (males 72.0 +/- 4.3 vs females 72.4 +/- 5.0%) and ECW% TBW (males 47.3 +/- 3.4 vs females 47.8 +/- 5.1) were similar in both genders. ECW in liters for FFM and for TBW (ECW% TBW), corrected for body weight, was greater in the group with CHF than in the control group, in both sexes. Among the relative fluid measures, only ECW% TBW [odds ratio (OR) 1.5] independently predicted fluid retention. Having an ECW% TBW greater than 50% corresponded to an OR of about 10. In conclusion, elderly patients suffering from CHF have a characteristic increase in body fluid levels, mainly affecting the extracellular compartment, and ECW% TBW is a useful indicator of fluid retention.     

Uridine transport in human erythrocytes: data from normal subjects and from patients with renal failure

Erythrocyte uridine transport has been studied in eight normal individuals and eight patients on haemodialysis for chronic renal failure. The initial rate of zero-trans uridine influx at 37 degrees C has been measured as a function of extracellular uridine concentration using [14C]-labelled uridine. The results are consistent with Michaelis-Menten kinetics. In normal humans the mean Vmax for uridine influx was 32.8 +/- 6.4 mumol (1 cells)-1 s-1 (mean +/- S.D.) and the mean Km was 190 +/- 12.3 microM. The measurements made in renal failure patients were not significantly different (mean Vmax 30.1 +/- 7.1 mumol (1 cells)-1 s-1, mean Km, 185 +/- 13.2 microM). These results are discussed with reference to the reported data on uridine transport in human erythrocytes at temperatures between 4 and 35 degrees C; it is suggested that zero-trans uridine influx shows a decrease in temperature dependence above 25 degrees C. The Vmax for zero-trans uridine influx at 37 degrees C in normal erythrocytes represents a turnover number for the nucleoside transporter of 180 uridine molecules per second.     

A comparison of stent-induced stenosis in coronary and peripheral arteries

BACKGROUND AND OBJECTIVES: Restenosis is a complication of interventional procedures such as angioplasty and stenting, often limiting the success of these procedures. Knowledge regarding the relative behaviour of different arteries after these procedures is limited, despite the extensive use of different vascular models. Although the results from studies using different vessels are analysed to predict the behaviour of coronary arteries and other vasculature, direct controlled comparisons between different arteries are necessary for a better understanding of the differential response to restenosis. METHODS: This study examines the response to stenting in coronary and internal iliac arteries as characterised by intimal hyperplasia and restenosis. In a swine model of in-stent stenosis, coronary arteries exhibited higher levels of intimal hyperplasia and per cent stenosis than internal iliac arteries. RESULTS: After normalisation for injury score, coronary arteries were found to undergo 47% more intimal hyperplasia (p<0.05), whereas per cent stenosis normalised for injury score tended to be higher (p = 0.01). Other measurements reflecting post-stenting intimal hyperplasia (maximal intimal thickness, medial area) did not exhibit significant differences between the artery groups. CONCLUSIONS: These results show that coronary vessels are more prone to develop significant intimal hyperplasia and subsequent restenosis than internal iliac vessels. A better insight into how different arteries and arterial components behave is important in understanding and developing newer and better therapeutic measures for restenosis.     

Periodic respiration in patients with heart failure

Summary Patients with heart failure are known to demonstrate periodic respiration (PR) during sleep. The factors causing PR are not well known. We therefore studied 20 patients (aged 18–66 years) with idiopathic dilated cardiomyopathy. Full-night polysomnography and evaluation of respiration and transcutaneous oxygen saturation were performed. Hypercapnic ventilatory response (HCVR) was evaluated during daytime. The patients showed PR for 25 ± 26% (mean ± standard deviation) of total sleep time. During PR, oxygen desaturated 7.1±4.6%. Sleep was impaired. HCVR was normal. Oxygen desaturation during PR was predicted by HCVR (r=0.47, P<0.05) and left atrial diameter (r=0.60, P<0.05). The time period of PR expressed as a fraction of total sleep time was correlated with HCVR (r=0.45, P<0.05) and left atrial diameter (r=0.51, P<0.05). In conclusion, PR with oxygen desaturation, arousals, and impaired sleep was observed in stable heart failure. HCVR and left heart dimensions were related to PR. These findings confirm the concept of a feedback loop describing respiratory control in PR.Abbreviations PR periodic respiration - HCVR hypercapnic ventilatory response - LA left atrial diameter - LVED left ventricular end-diastolic diameter - REM rapid eye movement     

Noninvasive assessment of mechanical properties of peripheral arteries

An ultrasound examination was used to noninvasively determine the changes in mechanical properties associated with age for the common carotid, brachial, popliteal, femoral, and tibial arteries. Forty-two normal male subjects, ranging in age from 8 to 60 years of age, were examined. The subjects were placed in one of three age groups: <29 years of age, 29 to 38, and >38. Mechanical properties including percentage variation in diameter, pressure-strain, and circumferential elastic modulus were determined from changes in wall thickness and pulse pressure. Percentage variation in diameter (PVD) was seen to decrease with age for all arteries except the brachial, which remained relatively constant. Pressure-strain (Ep) and circumferential elastic moduli (Eo) were seen to increase with age in all arteries except the brachial, which remained relatively constant. Values of Ep and Eo were normalized into a stiffness index by dividing by the value found for the brachial artery. Stiffness indexes for the common carotid and femoral arteries were observed to increase more rapidly with age than the indexes obtained for the popliteal and tibial arteries. It is proposed that the stiffness index and changes in this parameter that occur with age may be useful in noninvasively assessing the progression of atherosclerosis.     

Familial recurrence of heart defects in subjects with congenitally corrected transposition of the great arteries

Familial recurrence of congenitally corrected transposition of the great arteries (CCTGA) is considered uncommon. Most of the previous familial studies involved a small number of patients and referred to all situs and looping anomalies including single ventricle, heterotaxia, and other cardiac defects different from CCTGA. We performed a large, consecutive clinical case series study in order to detect the recurrence of congenital heart defects in families of children with the classic form of CCTGA. From January 1997 through December 2004, 102 consecutive patients with CCTGA were evaluated in four institutions. There were 59 male (57.8%) and 43 female (42.2%). Mean age was 8.6 +/- 7.8 years. Eighty-eight patients (86.3%) had situs solitus of the atria, 14 (13.7%) situs inversus. The cardiac and extracardiac anomalies among relatives and the patterns of familial recurrence were investigated. Relatives with congenital heart defects were found in 16/102 families (15.7%). Transposition of the great arteries (TGA) was the most common recurrent defect (6/102 families). Consanguinity was identified in the parents of three probands. Six probands had an unaffected twin-sib. Recurrence risks for congenital heart defects were calculated at 5.2% (6/116) for siblings. In conclusion, CCTGA is not always sporadic in families. The pattern of inheritance, the presence of consanguinity among parents and the recurrence of situs inversus could suggest, in some families, an autosomal recessive mechanism with similarities with that occurring in some pedigrees with heterotaxia. The recurrence of TGA and CCTGA in the same family suggests a pathogenetic link between these two anatomically different malformations.