Mechanisms for Kir channel inhibition by quinacrine: acute pore block of Kir2.x channels and interference in PIP<Subscript>2</Subscript> interaction with Kir2.x and Kir6.2 channels

Cardiac inward rectifier potassium currents determine the resting membrane potential and contribute repolarization capacity during phase 3 repolarization. Quinacrine is a cationic amphiphilic drug. In this work, the effects of quinacrine were studied on cardiac Kir channels expressed in HEK 293 cells and on the inward rectifier potassium currents, I_K1 and I_KATP, in cardiac myocytes. We found that quinacrine differentially inhibited Kir channels, Kir6.2 ∼ Kir2.3 > Kir2.1. In addition, we found in cardiac myocytes that quinacrine inhibited I_KATP > I_K1. We presented evidence that quinacrine displays a double action towards strong inward rectifier Kir2.x channels, i.e., direct pore block and interference in phosphatidylinositol 4,5-bisphosphate, PIP₂–Kir channel interaction. Pore block is evident in Kir2.1 and 2.3 channels as rapid block; channel block involves residues E224 and E299 facing the cytoplasmic pore of Kir2.1. The interference of the drug with the interaction of Kir2.x and Kir6.2/SUR2A channels and PIP₂ is suggested from four sources of evidence: (1) Slow onset of current block when quinacrine is applied from either the inside or the outside of the channel. (2) Mutation of Kir2.3(I213L) and mutation of Kir6.2(C166S) increase their affinity for PIP₂ and lowers its sensitivity for quinacrine. (3) Mutations of Kir2.1(L222I and K182Q) which decreased its affinity for PIP₂ increased its sensitivity for quinacrine. (4) Co-application of quinacrine with PIP₂ lowers quinacrine-mediated current inhibition. In conclusion, our data demonstrate how an old drug provides insight into a dual a blocking mechanism of Kir carried inward rectifier channels.     

Human Kir2.1 channel carries a transient outward potassium current with inward rectification

We have previously reported a depolarization-activated 4-aminopyridine-resistant transient outward K⁺ current with inward rectification (I _to.ir) in canine and guinea pig cardiac myocytes. However, molecular identity of this current is not clear. The present study was designed to investigate whether Kir2.1 channel carries this current in stably transfected human embryonic kidney (HEK) 293 cells using whole-cell patch-clamp technique. It was found that HEK 293 cells stably expressing human Kir2.1 gene had a transient outward current elicited by voltage steps positive to the membrane potential (around −70 mV). The current exhibited a current–voltage relationship with intermediate inward rectification and showed time-dependent inactivation and rapid recovery from inactivation. The half potential (V _0.5) of availability of the current was −49.4 ± 2.1 mV at 5 mM K⁺ in bath solution. Action potential waveform clamp revealed two components of outward currents; one was immediately elicited and then rapidly inactivated during depolarization, and another was slowly activated during repolarization of action potential. These properties were similar to those of I _to.ir observed previously in native cardiac myocytes. Interestingly, inactivation of the I _to.ir was strongly slowed by increasing intracellular free Mg²⁺ (Mg²⁺ _i , from 0.03 to 1.0, 4.0, and 8.0 mM). The component elicited by action potential depolarization increased with the elevation of Mg²⁺ _i . Inclusion of spermine (100 μM) in the pipette solution remarkably inhibited both the I _to.ir and steady-state current. These results demonstrate that the Mg²⁺ _i -dependent current carried by Kir2.1 likely is the molecular identity of I _to.ir observed previously in cardiac myocytes.     

Localization of the ergtoxin-1 receptors on the voltage sensing domain of hERG K+ channel by AFM recognition imaging

The inhibition of the human ether-à-go-go-related (hERG) K⁺ channels is the major cause of long QT syndromes inducing fatal cardiac arrhythmias. Ergtoxin 1 (ErgTx1) belongs to scorpion-toxins, which are K⁺ channel-blockers, and binds to hERG channel with 1:1 stoichiometry and high affinity (K _d ∼ 10 nM). Nevertheless, patch-clamp recordings recently demonstrated that ErgTx1 does not establish complete blockade of hERG currents, even at high ErgTx1 concentrations. Such phenomenon is supposed to be consistent with highly dynamic conformational changes of the outer pore domain of hERG. In this study, simultaneous topography and recognition imaging (TREC) on hERG HEK 293 cells was used to visualize binding sites on the extracellular part of hERG channel (on S1–S2 region) for Anti-K_v11.1 (hERG-extracellular-antibody). The recognition maps of hERG channels contained recognition spots, haphazardly distributed and organized in clusters. Recognition images after the addition of ErgTx1 at high concentrations (∼1 μM) revealed subsequent partial disappearance of clusters, indicating that ErgTx1 was bound to the S1–S2 region. These results were supported by AFM force spectroscopy data, showing for the first time that voltage sensing domain (S1–S4) of hERG K⁺ channel might be one of the multiple binding sites of ErgTx1.     

Micropatterned surfaces for controlling cell adhesion and rolling under flow

Cell adhesion and rolling on the vascular wall is critical to both inflammation and thrombosis. In this study we demonstrate the feasibility of using microfluidic patterning for controlling cell adhesion and rolling under physiological flow conditions. By controlling the width of the lines (50–1000 μm) and the spacing between them (50–100 μm) we were able to fabricate surfaces with well-defined patterns of adhesion molecules. We demonstrate the versatility of this technique by patterning surfaces with 3 different adhesion molecules (P-selectin, E-selectin, and von Willebrand Factor) and controlling the adhesion and rolling of three different cell types (neutrophils, Chinese Hamster Ovary cells, and platelets). By varying the concentration of the incubating solution we could control the surface ligand density and hence the cell rolling velocity. Finally by patterning surfaces with both P-selectin and von Willebrand Factor we could control the rolling of both leukocytes and platelets simultaneously. The technique described in this paper provides and effective and inexpensive way to fabricate patterned surfaces for use in cell rolling assays under physiologic flow conditions.     

Release of cardiac troponin I from viable cardiomyocytes is mediated by integrin stimulation

Elevated cardiac troponin-I (cTnI) levels have been demonstrated in serum of patients without acute coronary syndromes, potentially via a stretch-related process. We hypothesize that this cTnI release from viable cardiomyocytes is mediated by stimulation of stretch-responsive integrins. Cultured cardiomyocytes were treated with (1) Gly–Arg–Gly–Asp–Ser (GRGDS, n = 22) to stimulate integrins, (2) Ser–Asp–Gly–Arg–Gly (SDGRG, n = 8) that does not stimulate integrins, or (3) phosphate-buffered saline (control, n = 38). Cells and media were analyzed for intact cTnI, cTnI degradation products, and matrix metalloproteinase (MMP)-2. Cell viability was examined by assay of lactate dehydrogenase (LDH) activity and by nuclear staining with propidium iodide. GRGDS-induced integrin stimulation caused increased release of intact cTnI (9.6 ± 3.0%) as compared to SDGRG-treated cardiomyocytes (4.5 ± 0.8%, p < 0.001) and control (3.0 ± 3.4%, p < 0.001). LDH release from GRGDS-treated cardiomyocytes (15.9 ± 3.8%) equalled that from controls (15.2 ± 2.3%, p = n.s.), indicating that the GRGDS-induced release of cTnI is not due to cell necrosis. This result was confirmed by nuclear staining with propidium iodide. Integrin stimulation increased the intracellular and extracellular MMP2 activity as compared to controls (both p < 0.05). However, despite the ability of active MMP2 to degrade cTnI in vitro, integrin stimulation in cardiomyocytes was not associated with cTnI degradation. The present study demonstrates that intact cTnI can be released from viable cardiomyocytes by stimulation of stretch-responsive integrins.     

Cultured ruminal epithelial cells express a large-conductance channel permeable to chloride, bicarbonate, and acetate

The absorption of short-chain fatty acids (SCFA) from the rumen requires efficient mechanisms for both apical uptake and basolateral extrusion. Previous studies suggest that the rumen expresses a basolateral chloride conductance that might be permeable to SCFA. In order to characterize this conductance in more detail, isolated cultured ruminal epithelial cells were studied with the patch-clamp technique, revealing a whole-cell conductance with p(Cl⁻) ≈ p(NO₃ ⁻) > p(HCO₃ ⁻) > p(acetate⁻) > p(gluconate⁻). Currents could be blocked by diisothiocyanato-stilbene-2,2′-disulfonic acid (1 mmol l⁻¹ > 100 μmol l⁻¹), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (50 μmol l⁻¹), niflumic acid (100 μmol l⁻¹), and p-chloromercuribenzoate (1 mmol l⁻¹). Single-channel conductance was 350 ± 7 pS for chloride and 142 ± 7 pS for acetate. Open probability could be fitted with a three-state gating model. We propose a role for this channel in mediating the permeation of chloride, bicarbonate, and acetate across the basolateral membrane of the ruminal epithelium.     

The effects in humans of rapid loss of body mass on a boxing-related task

The physiological effects of strategies for a rapid loss of body mass immediately before weighing-in for competition in weight-governed sports are unclear. This study examined the effects of a 3%–4% loss in body mass on a boxing-related task. Seven novice amateur boxers completed three 3 min rounds of simulated boxing on a prototype boxing ergometer in an euhydrated state (E-trial) and after exercise-induced thermal dehydration (D-trial). All subjects lost body mass following dehydration–mean body mass fell 3.8 (SD ± 0.3)% [77.3 (SD ± 11.3) to 74.4 (SD ± 10.7) kg, P < 0.001] – but changes in plasma volume (PV) were inconsistent. Four subjects suffered reductions in PV between 15% and 30%, one subject maintained his E-trial value and two recorded an increase. The D-trial mean PV value was 8.0 (SD ± 17.2)% lower but this fall was not statistically significant (P > 0.05). Analysis of D-trial boxing performance showed one subject maintained his performance over the two trials and a second improved 17.8%. A two-way ANOVA (condition × time) with repeated measures on both factors showed no significant main effect differences for condition (F _1,6=3.93 P > 0.05), time (F _1.83,48=1.12, P > 0.05) or interaction between them (F _1.93,48, P > 0.05). Furthermore, neither heart rate nor blood lactate responses in the boxing task differed between trials. These data were affected by the small sample. Power and effect size analysis using η² procedure and removing the outlier data produced a mean fall in boxing performance of 26.8%. However, some subjects appeared able to resist the deleterious effects of a rapid loss of body mass prior to competition and further research is needed to explain the mechanisms under-pinning this ability. Accepted: 12 May 2000     

Estimating Interfacial Tension from the Shape Histories of Cells in Compressed Aggregates: A Computational Study

A 3D cell-based finite element (FE) model is used to show that the tensions postulated to act along cell–cell interfaces can be determined from tests in which an aggregate of cells is compressed between parallel plates. The aspect ratios κ of individual cells are found to depend on whether they are in contact with the plates, on the surface of the aggregate or in the interior of the mass, a result confirmed experimentally. When the platen spacing is then held constant, interior cells anneal at a rate that depends only on the cell–cell interfacial tension γ_cc, whereas the annealing rate of plate and surface cells depends on γ_cc, the cell–plate interfacial tension γ_cp and the surface tension γ_cm acting along the cell-medium boundary. The model shows that the ratio of the interfacial tension γ_cc to the cytoplasmic viscosity μ can be determined from the shape history of the interior cells. Cell shape anisotropies make the relationship between cross-sectional shapes and 3D shapes nontrivial. Experiments by others are then used to determine, for the first time, and without compression force data, the interfacial tensions that act in aggregated cells. This property has implications for theories about the forces that drive tissue self-organization.     

Relationship between the blood thyroid hormones and lipid profile in Moghani sheep; influence of age and sex

The aim of this study was to determine the correlation between thyroid hormones and lipid profile in blood of Iranian Moghani sheep in different ages and sexes. Blood samples were taken from the jugular vein of 260 clinically healthy and nonpregnant animals in eight age groups (1–14 days, 1–2, 2–3, 3–6, 6–12, 12–24, 24–48, and  > 48 months) in autumn. The plasma was analyzed to determine thyroxine (T₄), triiodothyronine (T₃), free thyroxine (fT₄), free triiodothyronine (fT₃), cholesterol, triglyceride, high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol) and very low-density lipoprotein (VLDL-cholesterol) concentrations. According to our data from Moghani sheep, an increase in age results in significant decreases in the plasma concentrations of T₄, T₃, fT₄, fT₃, cholesterol, and HDL-cholesterol (P < 0.05) but no gender-dependent significant differences in the studied parameters were found.     

Volume-sensitive chloride current activated by hyposmotic swelling in antral gastric myocytes of the guinea-pig

 The characteristics of volume-sensitive chloride current (I _Cl) induced by osmotic cell swelling were studied using the whole-cell patch-clamp technique and cell diameters of antral circular guinea-pig myocytes were simultaneously measured under isosmotic and hyposmotic conditions by using a video image analysis system. At –60 mV, osmotic cell swelling (200 mosmol/l) activated a sustained inward current. Instantaneous current/voltage (I-V) relations obtained by step voltage pulses showed an outward rectification. At potentials above +40 mV, the current exhibited time-dependent decay. The outward current amplitude was decreased and the reversal potential was shifted to more positive potentials by replacement of external Cl^– with gluconate^–, while the current amplitude and the I/V relation were not affected by replacing extracellular Na⁺ with N-methyl-D-glucamine. The anion permeability sequence of the swelling-induced current was I^– (1.80) > Br^– (1.31) > Cl^– (1) > F^– (0.85) > gluconate^– (0.18). The I _Cl was effectively inhibited by the Cl^– channel blockers, 4,4′-diisothiocyanatostilbene-2,2’-disulphonic acid (DIDS, 100 μM), and niflumic acid (10 μM). DIDS suppressed outward current more effectively than inward current. Also, the I _Cl was dose-dependently inhibited by arachidonic acid, an unsaturated fatty acid and also inhibited by other unsaturated fatty acids (linoleic acid and oleic acid) but not by stearic acid, a saturated fatty acid. The inhibitory effect of arachidonic acid on I _Cl was not prevented by indomethacin, a cyclo-oxygenase inhibitor and chelerythrine, a protein kinase C inhibitor. Under whole-cell patch-clamp conditions, the cell diameter was continuously measured using video image analysis, which reflects the change in cell volume. A hyposmotic-stimulation-induced increase of cell diameter was followed by I _Cl activation. In intact single gastric myocytes, relatively severe hyposmotic (176 mosmol/l) superfusing solution increased the cell diameter and the pretreatment with DIDS or with niflumic acid significantly potentiated the above effect of hyposmotic superfusion. These results suggest that volume-sensitive outwardly rectifying chloride current (I _Cl) is present in guinea-pig gastric myocyte and the I _Cl may play a role in smooth muscle cell volume regulation. Received: 6 June 1997 / Received after revision and accepted: 24 July 1997     

Gender differences in sweat lactate

Sweat rate may affect sweat lactate concentration. The current study examined potential gender differences in sweat lactate concentrations because of varying sweat rates. Males (n=6) and females (n=6) of similar age, percentage body fat, and maximal oxygen consumption (VO_2max) completed constant load (CON) cycling (30 min – approximately 40% VO_2max) and interval cycling (INT) (15 1-min intervals each separated by 1 min of rest) trials at 32 (1) °C wet bulb globe temperature (WBGT). Trials were preceded by 15 min of warm-up (0.5 kp, 60 rpms) and followed by 15 min of rest. Blood and sweat samples were collected at 15, 25, 35, 45, and 60 min during each trial. Total body water loss was used to calculate sweat rate. Blood lactate concentrations (CON ≅ 2 mmol · l⁻¹, INT ≅ 6 mmol · l⁻¹) and sweat lactate concentrations (CON and INT ≅ 12 mmol · l⁻¹) were not significantly different (P > 0.05) at any time between genders for CON or INT. Overall sweat rates (ml · h⁻¹) were not significantly different (P > 0.05) between trials but were significantly greater (P ≤ 0.05) for males than for females for CON [779.7 (292.6) versus 450.3 (84.6) ml · h⁻¹] and INT [798.0 (268.3) versus 503.0 (41.4) ml · h⁻¹]. However, correcting for surface area diminished the difference [CON: 390.7 (134.4) versus 277.7 (44.4) ml · h⁻¹, INT: 401.5 (124.1) versus 310.6 (23.4) ml · h⁻¹ (P ≤ 0.07)]. Estimated total lactate secretion was significantly greater (P ≤ 0.05) in males for CON and INT. Results suggest that sweat rate differences do not affect sweat lactate concentrations between genders. Accepted: 7 February 2000     

Functional assembly and purinergic activation of bestrophins

Proteins of the bestrophin family produce Ca²⁺-activated Cl⁻ currents and regulate voltage-gated Ca²⁺ channels. Bestrophin 1 was first identified in the retinal pigment epithelium. Four human paralogs (hBest1–hBest4) exist, and for some bestrophins, dimeric and heterotetrameric structures have been proposed. Here, we demonstrate that hBest1–hBest4 induce Cl⁻ conductances of different amplitudes when expressed in HEK293 cells and when activated through purinergic stimulation. hBest1 mutants that are known to cause autosomal dominant macular dystrophy (Best disease) did not produce a Cl⁻ current. Bestrophins were colocalized and showed molecular and functional interaction in HEK293 cells, overexpressing hBest1 and hBest2 or hBest4. Interaction was confirmed in airway epithelial cells coexpressing endogenous bestrophins. A fraction of hBest2 and hBest4 was expressed in the membrane, while most of hBest1 was found in the endoplasmic reticulum. Nevertheless, hBest1 has a clear role for the adenosine triphosphate (ATP; or uridine triphosphate)-induced Cl⁻ current in both HEK293 and Calu-3 cells. Since native epithelial tissues typically express several bestrophin paralogs, these proteins may exist as heterooligomeric structures. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Pannexin 1 forms an anion-selective channel

Pannexin 1 (Panx1) is expressed in various mammalian tissues including the brain and immune cells. Here, we present evidence that Panx1 when expressed in mammalian cells, forms anion-selective channels, with a rank order of permeabilities: NO₃⁻ > I⁻ > Br⁻ > Cl⁻ > F⁻ ≫ aspartate⁻ ≈ glutamate⁻ ≈ gluconate⁻. Single-channel Panx1-mediated currents have a unitary conductance around 68 pS. Our results show that Panx1 assembles into a membrane anion channel with a relatively low single-channel conductance.     

Design and validation of an endothelial progenitor cell capture chip and its application in patients with pulmonary arterial hypertension

The number of circulating endothelial progenitor cells (EPCs) inversely correlates with cardiovascular risk and clinical outcome, and thus has been proposed as a valuable biomarker for risk assessment, disease progression, and response to therapy. However, current strategies for isolation of these rare cells are limited to complex, laborious approaches. The goal of this study was the design and validation of a disposable microfluidic platform capable of selectively capturing and enumerating EPCs directly from human whole blood in healthy and diseased subjects, eliminating sample preprocessing. We then applied the “EPC capture chip” clinically and determined EPC numbers in blood from patients with pulmonary arterial hypertension (PAH). Blood was collected in tubes and injected into polymeric microfluidic chips containing microcolumns pre-coated with anti-CD34 antibody. Captured cells were immunofluorescently stained for the expression of stem and endothelial antigens, identified and counted. The EPC capture chip was validated with conventional flow cytometry counts (r = 0.83). The inter- and intra-day reliability of the microfluidic devices was confirmed at different time points in triplicates over 1–5 months. In a cohort of 43 patients with three forms of PAH (idiopathic/heritable, drug-induced, and connective tissue disease), EPC numbers are ≈50% lower in PAH subjects vs. matched controls and inversely related to two potential disease modifiers: body mass index and postmenopausal status. The EPC capture chip (5 × 30 × 0.05 mm³) requires only 200 μL of human blood and has the strong potential to serve as a rapid bedside test for the screening and monitoring of patients with PAH and other proliferative cardiovascular, pulmonary, malignant, and neurodegenerative diseases.     

The modulation of attachment,growth and morphology of cancerous prostate cells by polyelectrolyte nanofilms

The behaviour of cancerous epithelial prostatic cells (PC3) growing on polyelectrolytes (PE) coatings was compared to the behaviour of immortalized normal prostatic cells (PNT-2). The cell behaviour was evaluated and quantified in terms of initial cell attachment, growth, metabolic activity, morphometry, adhesion, apoptosis and stress related gene expression. Both the anionic PSS (poly(sodium 4-styrenesulphonate))-terminated surface and cationic PAH (poly(allylamine hydrochloride))-terminated surfaces were not cytotoxic. The initial attachment of cells was better on the PAH-terminated surface compared to fibronectin. However, the proliferation rate of PC3 cells was reduced on the PAH-terminated surface and slightly increased on the PSS coatings. Only PAH prevented the clustering phenotype of PC3 and reduced the number of focal adhesion points as compared to fibronectin or PSS coatings. In contrast, none of the PE surfaces significantly affected the biological responses of PNT-2 cells. PAH-terminating films provide a tool to preferentially modulate the growth of some cancerous phenotypes, in this case as a micro-environment that reduces the growth of metastatic PC3 cells.     

Transient oxygen uptake response to exercise characterizes functional capacity of the cardiocirculatory system in patients with chronic heart failure: a random stimulus approach

The transient response of oxygen uptake (V˙O₂) to submaximal exercise, known to be abnormal in patients with cardiovascular disorders, can be useful in assessing the functional status of the cardiocirculatory system, however, a method for evaluating it accurately has not yet been established. As an alternative approach to the conventional test at constant exercise intensity, we applied a random stimulus technique that has been shown to provide relatively noise immune responses of system being investigated. In 27 patients with heart failure and 24 age-matched control subjects, we imposed cycle exercise at 50 W intermittently according to a pseudo-random binary (exercise-rest) sequence, while measuring breath-by-breath V˙O₂. After determining the transfer function relating exercise intensity (W˙) to V˙O₂ and attenuating the high frequency ranges (>6 exercise-rest cycles · min⁻¹), we computed the high resolution band-limited (0–6 cycles · min⁻¹) V˙O₂ response (0–120 s) to a hypothetical step exercise. The V˙O₂ response showed a longer time constant in the patients than in the control subjects [47 (SD 37) and 31 (SD 8) s, respectively, P < 0.05]. Furthermore, the amplitude of the V˙O₂ response after the initial response was shown to be significantly smaller in the patients than in the control subjects [176 (SD 50) and 267 (SD 54) ml · min⁻¹ at 120 s]. The average amplitude over 120 s correlated well with peak V˙O₂ (r = 0.73) and ΔV˙O₂/ΔW˙ (r = 0.70), both of which are well-established indexes of exercise tolerance. The data indicated that our band-limited V˙O₂ step response using random exercise was more markedly attenuated and delayed in the patients with heart failure than in the normal controls and that it could be useful in quantifying the overall functional status of the cardiocirculatory system. Accepted: 6 January 1998     

Towards microfabricated biohybrid artificial lung modules for chronic respiratory support

We have utilized soft lithography techniques to create three-dimensional arrays of blood microchannels and gas pathways in poly(dimethylsiloxane) (PDMS) that approach the microvascular scale of the natural lung. The blood microchannels were lined with endothelial cells in an effort to provide a non-thrombogenic surface that might ultimately reduce the need for systemic anticoagulation. A novel design and fabrication method were developed to create prototype modules for gas permeance and cell culture testing. The gas permeance modules contained 6 layers, four gas and two blood, while the modules for cell culture testing contained two layers of blood channels. The gas permeance of the modules was examined and maximum values of 9.16 × 10⁻⁶ and 3.55 × 10⁻⁵ mL/s/cm²/cmHg, for O₂ and CO₂ respectively, were obtained. Finally, endothelial cells were seeded and dynamically cultured in prototype cell culture modules. Confluent and viable cell monolayers were achieved after 10 days of perfusion.     

Cardiac dimensions, physical activity, and submaximal working capacity in youth of the Québec Family Study

The relationships between cardiac dimensions and physical activity and submaximal working capacity were examined in 198 boys and 154 girls, aged 9–18 years, who were participants in the first phase of the Québec Family Study. The sample was divided into three age groups, 9–12 years, 13–15 years, and 16–18 years. Indicators of physical activity included estimated daily energy expenditure (EE) and time spent in moderate-to-vigorous physical activity (median metabolic equivalents of energy expenditure above resting metabolic rate ≥4.8). Submaximal physical working capacity (PWC₁₅₀) was determined using a submaximal exercise test on a Monark cycle ergometer. Echocardiographically determined dimensions included posterior wall thickness, septal wall thickness, and left ventricular mass (LVM). The analyses were based on partial correlation and analysis of covariance, controlling for age and body surface area. Relationships between EE/physical activity variables and cardiac dimensions were low and, at best, moderate (r < 0.45). With subjects grouped into tertiles by indicators of physical activity, LVM was significantly different only among 16- to 18-year-old girls (157 g vs 134 g in the highest and lowest quartiles, respectively; P < 0.05). Correlations between cardiac dimensions and PWC₁₅₀ were also low (r < 0.30), with few significant relationships. In general, cardiac dimensions were not related to habitual physical activity and PWC₁₅₀ in young subjects aged 9–18 years. However, significant correlations were positive, as expected. LVM may be related to submaximal power output in boys since it accounts for 3% of the variance, after adjusting for age and BSA. Received: 4 January 1999 / Accepted: 8 June 1999     

Force recovery after eccentric exercise in males and females

In this study we investigated force loss and recovery after eccentric exercise, and further characterized profound losses in muscle function (n=192 subjects – 98 males, 94 females; population A). Maximal voluntary contractile force (MVC) was assessed before, immediately after, and at 36 and 132 h after eccentric exercise. Two groups were then established (A₁ and A₂). Group A₁ demonstrated a >70% reduction in MVC immediately after exercise, but were recovering at 132 h after exercise. These subjects performed a follow-up MVC 26 days later (n=32). Group A₂ demonstrated a >70% reduction in MVC immediately post-exercise, but still exhibited a >65% reduction in force at 132 h post-exercise; these subjects also performed a follow-up MVC every 7 days until full recovery was established (n=9). In population A, there was a 57% reduction in MVC immediately post-exercise and a 67% recovery by 132 h post-exercise (P < 0.01), with no significant gender differences (P > 0.05). In group A₁, although more females (two-thirds) showed large force losses after exercise, these females demonstrated greater %MVC recovery at 132 h post-exercise (59% vs 44%) and at 26 days post-exercise (93% vs 81%) compared to the males. In group A₂, MVC recovery occurred between 33 and 47 days post-exercise. In conclusion, 21% of all subjects showed a delayed recovery in MVC after high-force eccentric exercise. Although there were no significant gender differences in force loss, a disproportionately larger number of females demonstrated force reductions of >70%. However, their recovery of force was more rapid than that observed for the males who also demonstrated a >70% force loss. Accepted: 2 October 2000