Effects of detraining following short term resistance training on eccentric and concentric muscle strength

Healthy males were examined before and after 12 weeks of accommodated resistance training (three week^-1) and after 12 weeks of detraining. Training consisted of four to five sets of six coupled maximum voluntary bilateral concentric and eccentric (Grp ECCON; n= 10) or 12 concentric (Grp CON; n= 8) quadriceps muscle actions. Concentric and eccentric peak torque at various constant angular velocities and three repetition maximum half-squat and vertical jump height were measured. Grp ECCON showed greater (P < 0.05) overall increase in peak torque after training and detraining than Grp CON. Thus, concentric peak torque (0.52 rad s^-1) increased more (P < 0.05) over the experimental period in Grp ECCON and increases in eccentric peak torque were preserved in Grp ECCON only. Increases in peak torque in response to training were greater (P < 0.05) at 0.52 than at 2.62 rad s^-1. Alterations in the torque-velocity patterns induced by training remained after detraining in Grp ECCON but not in Grp CON. The retained increases (P < 0.05) in half-squat were 12 and 18% in Grps CON and ECCON, respectively. Neither group showed increased vertical jump height after detraining. This study showed greater preservation of concentric and eccentric peak torque after detraining following coupled concentric and eccentric than concentric resistance training. Only the former regime induced a change in the shape of torque-velocity curves that was manifest after detraining. These results suggest that the performance of eccentric muscle actions is critical to optimize increases in muscular strength in response to heavy resistance training, because it probably induce greater and more long-lived neural adaptations than the performance of concentric actions.     

Long‐term regeneration of fast and slow murine skeletal muscles after induced injury by ACL myotoxin isolated from Agkistrodon contortrix laticinctus (broad‐banded copperhead) venom

The aim of the present work was to analyze the regenerated muscle types I and II fibers of the soleus and gastrocnemius muscles of mice, 8 months after damage induced by ACL myotoxin (ACLMT). Animals received 5 mg/kg of ACLMT into the subcutaneous lateral region of the right hind limb, near the Achilles tendon; contralateral muscles received saline. Longitudinal and cross sections (10 μm) of frozen muscle tissue were evaluated. Eight months after ACLMT injection, both muscle types I and II fibers of soleus and gastrocnemius muscles still showed centralized nuclei and small regenerated fibers. Compared with the left muscle, the incidence of type I fibers increased in the right muscle (21% ± 03% versus 12% ± 06%, P = 0.009), whereas type II fibers decreased (78% ± 02% versus 88% ± 06%, P = 0.01). The incidence of type IIC fibers was normal. These results confirm that ACLMT induced muscle type fiber transformation from type II to type I, through type IIC. The area analysis of types I and II fibers of the gastrocnemius revealed that injured right muscles have a higher percentage of small fibers in both types I and II fibers (0–1,500 μm²) than left muscles, which have larger normal type I and II fibers (1,500–3,500 μm²). These results indicate that ACLMT can be used as an excellent model to study the rearrangement of motor units and the transformation of muscle fiber types during regeneration. Anat Rec 254:521–533, 1999. © 1999 Wiley‐Liss, Inc.     

Distribution of <Superscript>3</Superscript>H-Dopamine and <Superscript>3</Superscript>H-DAGO Binding Sites in the Central Part of Rat Sinoatrial Node

Distribution of ³H-dopamine and ³H-DAGO binding sites was studied by autoradiography on semithin sections of total preparations of rat sinoatrial node. The relative density of ³H-dopamine and ³H-DAGO binding sites in the functional nucleus of the sinoatrial node was minimum and increased in the cranial and caudal directions. The level of ³H-dopamine binding in the perinodal atrial myocardium was appreciably lower (22±6%), while binding of ³H-DAGO was similar (76±16%) to that in the periarterial zone of the sinoatrial node. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 210–214, August, 2005     

Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor‐deficient mice

Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of focal lesions caused by inflammation and fibrosis is challenging. We propose that quantitative susceptibility mapping (QSM) may be particularly sensitive for the identification of inflammation and fibrosis. In this study, we applied QSM in a mouse model deficient for angiotensin receptor type 1 (AT₁). This model is known for graded pathologies, including focal interstitial fibrosis, cortical inflammation, glomerulocysts and inner medullary hypoplasia. We acquired high‐resolution MRI on kidneys from AT₁‐deficient mice that were perfusion fixed with contrast agent. Two MR sequences were used (three‐dimensional spin echo and gradient echo) to produce three image contrasts: T₁, T₂* (magnitude) and QSM. T₁ and T₂* (magnitude) images were acquired to segment major renal structures and to provide landmarks for the focal lesions of inflammation and fibrosis in the three‐dimensional space. The volumes of major renal structures were measured to determine the relationship of the volumes to the degree of renal abnormalities and magnetic susceptibility values. Focal lesions were segmented from QSM images and were found to be closely associated with the major vessels. Susceptibilities were relatively more paramagnetic in wild‐type mice: 1.46 ± 0.36 in the cortex, 2.14 ± 0.94 in the outer medulla and 2.10 ± 2.80 in the inner medulla (10^–2 ppm). Susceptibilities were more diamagnetic in knockout mice: –7.68 ± 4.22 in the cortex, –11.46 ± 2.13 in the outer medulla and –7.57 ± 5.58 in the inner medulla (10^–2 ppm). This result was consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. QSM was very sensitive in detecting pathology caused by small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney. Copyright © 2013 John Wiley & Sons, Ltd.     

Low‐volume muscle endurance training prevents decrease in muscle oxidative and endurance function during 21‐day forearm immobilization

Aim: To examine the effects of low‐volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21‐day forearm immobilization (IMM‐21d). Methods: The non‐dominant arm (n = 15) was immobilized for 21 days with a cast and assigned to an immobilization‐only group (Imm‐group; n = 7) or an immobilization with training group (Imm+Tr‐group; n = 8). Training comprised dynamic handgrip exercise at 30% of pre‐intervention maximal voluntary contraction (MVC) at 1 Hz until exhaustion, twice a week during the immobilization period. The duration of each exercise session was 51.7 ± 3.4 s (mean ± SE). Muscle oxidative capacity was evaluated by the time constant for phosphocreatine recovery (τ_offPCr) after a submaximal handgrip exercise using ³¹phosphorus‐magnetic resonance spectroscopy. An endurance test was performed at 30% of pre‐intervention MVC, at 1 Hz, until exhaustion. Results: τ _offPCr was significantly prolonged in the Imm‐group after 21 days (42.0 ± 2.8 and 64.2 ± 5.1 s, pre‐ and post‐intervention respectively; P < 0.01) but did not change for the Imm+Tr‐group (50.3 ± 3.0 and 48.8 ± 5.0 s, ns). Endurance decreased significantly for the Imm‐group (55.1 ± 5.1 and 44.7 ± 4.6 s, P < 0.05) but did not change for the Imm+Tr‐group (47.9 ± 3.0 and 51.7 ± 4.0 s, ns). MVC decreased similarly in both groups (P < 0.01). Conclusions: Twice‐weekly muscle endurance training sessions, each lasting approx. 50 s, effectively prevented a decrease in muscle oxidative capacity and endurance; however, there was no effect on MVC decline with IMM‐21d.     

Effector memory CD4+ T cells differentially express activation associated molecules depending on the duration of American cutaneous leishmaniasis lesions

A high number of Leishmania‐responder T cells is found in cutaneous leishmaniasis lesions, suggesting that important immunological events occur at the site of infection. Although activated, cytotoxic and regulatory T cells infiltrating into lesions may influence disease pathogenesis, the role of the T cell differentiation pattern of lymphocytes in lesions is unknown. Our aim was to investigate whether the phase of lesion development (early or late) is influenced by the functional status of cells present in inflammatory infiltrate. Activation, cytotoxity and T cell differentiation molecules were evaluated in lesion mononuclear cells by flow cytometry. The frequency of T cells was correlated with the lesion area (r = 0·68; P = 0·020). CD4⁺CD25⁺ T cells predominated over CD4⁺CD69⁺ T cells in early lesions (less than 30 days), whereas late lesions (more than 60 days) exhibited more CD4⁺CD69⁺ T cells than CD4⁺CD25⁺ T cells. The duration of illness was correlated positively with CD4⁺CD69⁺ (r = 0·68; P = 0·005) and negatively with CD4⁺CD25⁺ T cells (r = ?0·45; P = 0·046). Most CD8⁺ T cells expressed cytotoxic‐associated molecules (CD244⁺), and the percentages were correlated with the lesion area (r = 0·52; P = 0·04). Both CD4⁺ and CD8⁺ effector memory T cells (T_EM‐CD45RO⁺CCR7^–) predominated in CL lesions and were significantly higher than central memory (T_CM‐CD45RO⁺CCR7⁺) or naive T cells (CD45RO^–CCR7⁺). An enrichment of T_EM cells and contraction of naive T cells were observed in lesions in comparison to blood (P = 0·006) for both CD4⁺ and CD8⁺ T cells. Lesion chronicity is associated with a shift in activation phenotype. The enrichment of T_EM and activated cytotoxic cells can contribute to immune‐mediated tissue damage.     

Vastus lateralis surface and single motor unit electromyography during shortening,lengthening and isometric contractions corrected for mode‐dependent differences in force‐generating capacity

Aim: Knee extensor neuromuscular activity, rectified surface electromyography (rsEMG) and single motor unit EMG was investigated during isometric (60° knee angle), shortening and lengthening contractions (50–70°, 10° s^?1) corrected for force–velocity‐related differences in force‐generating capacity. However, during dynamic contractions additional factors such as shortening‐induced force losses and lengthening‐induced force gains may also affect force capacity and thereby neuromuscular activity. Therefore, even after correction for force–velocity‐related differences in force capacity we expected neuromuscular activity to be higher and lower during shortening and lengthening, respectively, compared to isometric contractions. Methods: rsEMG of the three superficial muscle heads was obtained in a first session [10 and 50% maximal voluntary contraction (MVC)] and additionally EMG of (46) vastus lateralis motor units was recorded during a second session (4–76% MVC). Using superimposed electrical stimulation, force‐generating capacity for shortening and lengthening contractions was found to be 0.96 and 1.16 times isometric (Iso) force capacity respectively. Therefore, neuromuscular activity during submaximal shortening and lengthening was compared with isometric contractions of respectively 1.04Iso (=1/0.96) and 0.86Iso (=1/1.16). rsEMG and discharge rates were normalized to isometric values. Results: rsEMG behaviour was similar (P > 0.05) during both sessions. Shortening rsEMG (1.30 ± 0.11) and discharge rate (1.22 ± 0.13) were higher (P < 0.05) than 1.04Iso values (1.05 ± 0.05 and 1.03 ± 0.04 respectively), but lengthening rsEMG (1.05 ± 0.12) and discharge rate (0.90 ± 0.08) were not lower (P > 0.05) than 0.86Iso values (0.76 ± 0.04 and 0.91 ± 0.07 respectively). Conclusion: When force–velocity‐related differences in force capacity were taken into account, neuromuscular activity was not lower during lengthening but was still higher during shortening compared with isometric contractions.     

Translational Mini‐Review Series on Immunology of Vascular Disease: Accelerated atherosclerosis in vasculitis

The cutaneous leucocyte‐associated antigen receptor (CLA) can direct Leishmania‐specific T lymphocytes towards inflamed skin lesions. Homing receptors [CLA, lymphocyte‐associated antigen 1 (LFA‐1) or CD62L] were analysed in lymphocytes from blood and cutaneous leishmaniasis (CL) lesions. CL patients with active lesions (A‐CL) presented lower levels of T lymphocytes expressing the CLA⁺ phenotype (T CD4⁺ = 10·4% ± 7·5% and T CD8⁺ = 5·8% ± 3·4%) than did healthy subjects (HS) (T CD4⁺ = 19·3% ± 13·1% and T CD8⁺ = 21·6% ± 8·8%), notably in T CD8⁺ (P < 0·001). In clinically cured patients these percentages returned to levels observed in HS. Leishmanial antigens up‐regulated CLA in T cells (CLA⁺ in T CD4⁺ = 33·3% ± 14·1%; CLA⁺ in T CD8⁺ = 22·4% ± 9·4%) from A‐CL but not from HS. An enrichment of CLA⁺ cells was observed in lesions (CLA⁺ in T CD4⁺ = 45·9% ± 22·5%; CLA⁺ in T CD8⁺ = 46·4% ± 16·1%) in comparison with blood (CLA⁺ in T CD4⁺ = 10·4% ± 7·5%; CLA⁺ in T CD8⁺ = 5·8% ± 3·4%). Conversely, LFA‐1 was highly expressed in CD8⁺ T cells and augmented in CD4⁺ T from peripheral blood of A‐CL patients. In contrast, CD62L was not affected. These results suggest that Leishmania antigens can modulate molecules responsible for migration to skin lesions, potentially influencing the cell composition of inflammatory infiltrate of leishmaniasis or even the severity of the disease.     

Demonstration of asymmetric muscle perfusion of the back after exercise in patients with adolescent idiopathic scoliosis using intravoxel incoherent motion (IVIM) MRI

The purpose of this work was to quantify muscular perfusion patterns of back muscles after exercise in patients with adolescent idiopathic scoliosis (AIS) using intravoxel incoherent motion (IVIM) MR perfusion imaging. The paraspinal muscles of eight patients with AIS (Cobb angle 35 ± 10°, range [25‐47°]) and nine healthy volunteers were scanned with a 1.5 T MRI, at rest and after performing a symmetric back muscle exercise on a Roman chair. An IVIM sequence with 16 b‐values from 0 to 900 s/mm² was acquired, and the IVIM bi‐exponential signal equation model was fitted in two steps. Perfusion asymmetries were evaluated using the blood flow related IVIM fD* parameter in regions of interest placed within the paraspinal muscles. Statistical significance was assessed using a Student t‐test. The observed perfusion pattern after performing a Roman chair muscle exercise differed consistently in patients with AIS compared with healthy normal volunteers, and consisted of an asymmetrical increase in IVIM fD* [10^?3 mm²/s] above the lumbar convexity from 6.5 ± 5.8 to 28.8 ± 26.8 (p < 0.005), with no increase in the concavity (decrease from 6.5 ± 10.0 to 3.2 ± 1.5 (p = 0.19)), compared with a bilateral symmetric increase in the healthy volunteers (right, increase from 3.3 ± 2.1 to 10.1 ± 4.6 (p < 0.05); left, 6.7 ± 10.7 to 13.3 ± 7.0 (p < 0.05)). In conclusion, patients with AIS exhibit significant asymmetric muscle perfusion over the convexity of the scoliotic curvature after Roman chair exercise.     

Effects of exercise‐induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used ³¹P‐magnetic resonance spectroscopy (³¹P‐MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min^‐1, CV_{inter‐subject} = 42%) as compared with PF (46 ± 20 mM min^‐1, CV_{inter‐subject} = 44%) and tended to be higher in FF (43 ± 35 mM min^‐1, CV_{inter‐subject} = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end‐exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end‐exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter‐ and intra‐individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright © 2013 John Wiley & Sons, Ltd.     

Stereological analysis of size and density of hepatocytes in the porcine liver

The porcine liver is frequently used as a large animal model for verification of surgical techniques, as well as experimental therapies. Often, a histological evaluation is required that include measurements of the size, nuclearity or density of hepatocytes. Our aims were to assess the mean number‐weighted volume of hepatocytes, the numerical density of hepatocytes, and the fraction of binuclear hepatocytes (BnHEP) in the porcine liver, and compare the distribution of these parameters among hepatic lobes and macroscopic regions of interest (ROIs) with different positions related to the liver vasculature. Using disector and nucleator as design‐based stereological methods, the morphometry of hepatocytes was quantified in seven healthy piglets. The samples were obtained from all six hepatic lobes and three ROIs (peripheral, paracaval and paraportal) within each lobe. Histological sections (thickness 16 μm) of formalin‐fixed paraffin‐embedded material were stained with the periodic acid‐Schiff reaction to indicate the cell outlines and were assessed in a series of 3‐μm‐thick optical sections. The mean number‐weighted volume of mononuclear hepatocytes (MnHEP) in all samples was 3670 ± 805 μm³ (mean ± SD). The mean number‐weighted volume of BnHEP was 7050 ± 2550 μm³. The fraction of BnHEP was 4 ± 2%. The numerical density of all hepatocytes was 146 997 ± 15 738 cells mm⁻³ of liver parenchyma. The porcine hepatic lobes contained hepatocytes of a comparable size, nuclearity and density. No significant differences were identified between the lobes. The peripheral ROIs of the hepatic lobes contained the largest MnHEP with the smallest numerical density. The distribution of a larger MnHEP was correlated with a larger volume of BnHEP and a smaller numerical density of all hepatocytes. Practical recommendations for designing studies that involve stereological evaluations of the size, nuclearity and density of hepatocytes in porcine liver are provided.     

In vivo 1H MRS for musculoskeletal lesion characterization: which factors affect diagnostic accuracy?

In vivo ¹H MRS is a noninvasive imaging technique for the identification of malignancy. Musculoskeletal lesions vary in their composition, causing field inhomogeneity and magnetic susceptibility effects which may be technical and diagnostic challenges for MRS. This study investigated the factors that affect diagnostic accuracy in the use of MRS for the characterization of musculoskeletal neoplasms. During a 7‐year period, 210 consecutive patients with musculoskeletal lesions larger than 1.5 cm in diameter were examined. MRS of a single‐voxel point‐resolved spectroscopy sequence with TE = 135 ms was undertaken using a 1.5‐T scanner. Lesions with a choline signal‐to‐noise ratio larger than 3.0 were considered to be malignant tumors. The diagnostic accuracy was calculated for all lesions and for subgroups on the basis of lesion type (bone and soft tissue), lesion composition (mixed and solid nonsclerotic), lesion size (≤4, >4–10 and >10 cm), MR scanner (MR scanner 1 and 2) and selected voxel size (≤3, >3–8 and >8 cm³). Multivariate logistic regressions were performed to estimate the associations between each factor and diagnostic accuracy. The diagnostic accuracy was 73.3% for all lesions. The accuracy was 54.4% for mixed lesions and 80.4% for solid nonsclerotic lesions (p < 0.001). The diagnostic accuracy was lower for larger lesions [86.8% for lesions of ≤4 cm, 71.6% for lesions of >4–10 cm (p = 0.04) and 63.6% for lesions of >10 cm (p = 0.007)]. There was no difference in diagnostic accuracy for bone versus soft‐tissue lesions or as a function of MR scanner or voxel size. By the use of multivariate logistic regression, a solid nonsclerotic lesion was 3.15 times (95% confidence interval, 1.59–6.27) more likely than a mixed lesion to have a diagnosis (p = 0.001). MRS can be used to characterize musculoskeletal lesions, particularly solid nonsclerotic lesions. Copyright © 2011 John Wiley & Sons, Ltd.     

Adenosine induces prolonged anti‐β‐adrenergic effects in guinea‐pig papillary muscle

A sustained anti‐β‐adrenergic effect of adenosine has been reported. This study was initiated to investigate this topic and especially elucidate the role of protein kinase C (PKC). Contractile force amplitude and action potential duration at 90% repolarization (APD₉₀) were measured in guinea‐pig papillary muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols contained 30 min exposure to the test agents adenosine 33 μm (ado), adenosine + PKC‐inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC‐activator 1,2‐dioctanoyl‐sn‐glycerol 10 μm (DOG) and α‐agonist phenylephrine 5 μm (phe). Isoproterenol was given at the end of test exposure and after 15 min washout. Results are mean ± SEM of percentage‐change, P ≤ 0.05 considered significant and labelled *. The first isoproterenol challenge significantly increased contractile force (27 ± 7%*) in the control group. Responses in the test groups were 2 ± 4 (ado), 1 ± 5 (ado + BIM), 14 ± 4* (DOG), 0 ± 2% (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3 ± 8 (ado), 23 ± 5* (ado + BIM), 13 ± 5* (DOG), 15 ± 7% (phe) increase in test groups compared with 22 ± 5%* increase in contractile force in the control group. After 45 min washout of adenosine the inotropic response was still significantly reduced compared with control (29 ± 4 vs. 79 ± 8%*). Isoproterenol stimulation shortened APD₉₀ in controls at both time points (5 ± 1%* and 4 ± 1%*), with no significant shortening in test groups. Adenosine induces sustained anti‐β‐adrenergic effects on contractile force as well as APD₉₀. A role for PKC in signal transduction is supported with respect to contractile force.     

Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

Aims: Adenosine causes vasoconstriction of afferent arterioles of the mouse kidney through activation of adenosine A₁ receptors and Gi‐mediated stimulation of phospholipase C. In the present study, we further explored the signalling pathways by which adenosine causes arteriolar vasoconstriction. Methods and results: Adenosine (10^?7 m ) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura‐2 fluorescence. Pre‐treatment with thapsigargin (2 μm ) blocked the vasoconstrictor action of adenosine (10^?7 m ) indicating that release of calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP₃, is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 μm ) blocked the adenosine‐induced constriction whereas the protein kinase C inhibitor calphostin C had no effect. The calcium‐activated chloride channel inhibitor IAA‐94 (30 μm ) inhibited the adenosine‐mediated constriction. Patch clamp experiments showed that adenosine treatment induced a depolarizing current in preglomerular smooth muscle cells which was abolished by IAA‐94. Furthermore, the vasoconstriction caused by adenosine was significantly inhibited by 5 μm nifedipine (control 8.3 ± 0.2 μm, ado 3.6 ± 0.6 μm, ado + nifedipine 6.8 ± 0.2 μm) suggesting involvement of voltage‐dependent calcium channels. Conclusion: We conclude that adenosine mediates vasoconstriction of afferent arterioles through an increase in intracellular calcium concentration resulting from release of calcium from the SR followed by activation of Ca²⁺‐activated chloride channels leading to depolarization and influx of calcium through voltage‐dependent calcium channels.     

Baroreflex control of sinus node during dynamic exercise in humans: effect of muscle mechanoreflex

Aim: This study evaluated the influence of muscle mechanical afferent stimulation on the integrated arterial baroreflex control of the sinus node during dynamic exercise. Methods: Systolic blood pressure (SBP) and pulse interval (PI) were measured continuously and non‐invasively in 15 subjects at rest and during passive cycling. The arterial baroreflex was evaluated with the cross‐correlation method (xBRS) for the computation of time‐domain baroreflex sensitivity on spontaneous blood pressure and PI variability. xBRS computes the greatest positive correlation between beat‐to‐beat SBP and PI, and when significant at P = 0.01, slope and delay are recorded as one xBRS value. Heart rate variability (HRV) was evaluated in the frequency domain. Results: Compared with rest, passive exercise resulted in a parallel increase in heart rate (67 ± 3.2 vs. 70 ± 3.6 beats min^?1; P < 0.05) and mean arterial pressure (87 ± 2 vs. 95 ± 2 mmHg; P < 0.05), and a significant decrease in xBRS (13.1 ± 1.8 vs. 10.5 ± 1.7 ms mmHg^?1; P < 0.01) with an apparent rightward shift in the regression line relating SBP to PI. Also low frequency power of HRV increased while high frequency power decreased (56.7 ± 3.5 vs. 62.7 ± 4.8 and 43.2 ± 3.4 vs. 36.9 ± 4.9 normalized units respectively; P < 0.05). Conclusion: These data suggest that the stimulation of mechanosensitive stretch receptors is capable of modifying the integrated baroreflex control of sinus node function by decreasing the cardiac vagal outflow during exercise.     

LABELLING PATTERN OBTAINED BY NON-ISOTOPIC IN SITU HYBRIDIZATION AS A PROGNOSTIC FACTOR IN HPV-ASSOCIATED LESIONS

In the study of infection of the lower female genital tract caused by human papillomavirus (HPV), one of the main concerns is the search for prognostic factors to predict the evolution of premalignant low- and high-grade squamous intraepithelial lesions. This study has evaluated the prognostic usefulness of the patterns of positive reaction obtained by non-isotopic in situ hybridization (NISH), referred to as diffuse, punctate, or mixed ‘labelling patterns’. The study examined 141 vulvar and uterine cervical biopsy specimens that were positive for HPV by a NISH screening technique and that had the following histological diagnoses: low-grade squamous intraepithelial lesion (LSIL; n =87); high-grade squamous intraepithelial lesion (HSIL, n =40); and squamous cell carcinoma (SCC n =14). Typing of all the specimens was carried out by NISH with DNA probes specific for HPV types 6/11 (low risk), 16/18 (high risk), and 31/33/51 (intermediate risk), and the labelling pattern observed in each specimen was recorded. Statistical analysis of the results showed that there was a significant difference in the distribution of labelling patterns, both by lesion diagnosis ( P ≤0·004) and by infecting viral type ( P ≤10⁻⁶). Lesions with a punctate or mixed pattern are considered more likely to undergo malignant evolution and consequently have a worse prognosis than lesions with a diffuse pattern.     

Effect of endurance training on muscle microvascular filtration capacity and vascular bed morphometry in the elderly

Aim: Exercise training is a strong stimulus for vascular remodelling and could restore age‐induced vascular alterations. The purpose of the study was to test the hypothesis that an increase in vascular bed filtration capacity would corroborate microvascular adaptation with training. Methods: We quantified (1) microvascularization from vastus lateralis muscle biopsy to measure the capillary to fibre interface (LC/PF) and (2) the microvascular filtration capacity (K_f) in lower limbs through a venous congestion plethysmography procedure. Twelve healthy older subjects (74 ± 4 years) were submitted to a 14‐week training programme during which lower‐limbs were trained for endurance exercise. Results: The training programme induced a significant increase in the aerobic exercise capacity of lower limbs (+11%Vo _2peak; P < 0.05; +28% Citrate Synthase Activity; P < 0.01). K_f was largely increased (4.3 ± 0.9 10^?3 mL min^?1 mmHg^?1 100 mL^?1 post‐training vs. 2.4 ± 0.8 pre‐training, mean ± SD; P < 0.05) and microvascularization developed as shown by the rise in LC/PF (0.29 ± 0.06 post‐ vs. 0.23 ± 0.06 pre‐training; P < 0.05). Furthermore, K_f and LC/PF were correlated (r = 0.65, P < 0.05). Conclusion: These results demonstrated the microvascular adaptation to endurance training in the elderly. The increase in K_f with endurance training was probably related to a greater surface of exchange with an increased microvessel/fibre interface area. We conclude that measurement of the microvascular filtration rate reflects the change in the muscle exchange area and is influenced by exercise training.     

Enhanced beta-adrenergic response in rat papillary muscle by inhibition of inducible nitric oxide synthase after myocardial infarction

Aim: Myocardial infarction (MI) induces a progressive ventricular remodelling leading to a contractility depression. During the acute phase of MI inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production increases in the heart. The aim of this study was to investigate the role of iNOS in the left ventricular contractility at 3 days after MI. Methods: Wistar rats were divided into: sham operated (SHAM, n = 23), infarction (INF, n = 18); sham operated plus the iNOS inhibitor, S‐methylisothiourea (SMT) 5 mg kg^?1 day^?1, i.p. treatment (SHAM‐SMT, n = 26) and infarction plus SMT (INF‐SMT, n = 22). Concentration–response curves for isoprenaline, Ca²⁺ and frequency–force curve were studied in isolated papillary muscle from left ventricle. Results: After 3 days infarct area was similar between groups. SMT treatment reduced the time to peak tension during frequency–force curve in the infarct group (SHAM = 63 ± 3; SHAM‐SMT = 71 ± 3; INF = 90 ± 4; INF‐SMT = 79 ± 4 ms, P < 0.05) and increased the maximal response to isoprenaline (SHAM = 0.93 ± 0.11; SHAM‐SMT = 1.13 ± 0.1; INF =0.84 ± 0.16; INF‐SMT = 1.49 ± 0.15 g mm^?2, P < 0.05). The response to Ca²⁺ was equally reduced in the INF and INF‐SMT groups. SMT treatment did not change the reduced post‐rest potentiation performed by INF group, but attenuated the plasma nitrite and nitrate (NOx) levels in the INF group without any haemodynamic effect. Conclusion: These finding suggest that at 3 days after MI the iNOS modulates the isolated papillary muscle response to isoprenaline and its inhibition improves the β‐adrenergic inotropic responses.     

Human skeletal muscle myosin function at physiological and non-physiological temperatures

Aim: The aim of the study was to assess the function of human skeletal muscle myosin across a wide range of temperatures, including physiological. Methods: We used a single fibre in vitro motility assay. The in vitro motility speed of actin filaments propelled by myosin extracted from fibres expressing type I myosin heavy chain (MyHC; n = 9), IIa MyHC (n = 6), IIax MyHC (n = 4) and I/IIa MyHC (n = 1) was measured at 15, 20, 25, 30 and 35 °C. Results: The motility speed between groups of fibres expressing different MyHC differed significantly (P ? 0.001). The increase in motility speed with an increase in temperature was statistically significant (P ? 0.001) between all temperatures. The relative difference in motility speed between the slow type I and the fast IIax MyHC fibres decreased with increasing temperature, i.e. a 7.5‐fold difference at 15 °C was reduced to twofold at 35 °C. Furthermore, the twofold difference in motility speed between type IIa and IIax MyHC at 15 °C disappeared completely at 35 °C. The activation energy, E_A, and temperature coefficient, Q₁₀, over the 15–35 °C temperature range was higher for type I MyHC, 54.47 ± 4.37 kJ mol^?1 and 2.09 ± 0.12, respectively, than for type IIa MyHC, 45.41 ± 3.12 kJ mol^?1 (P < 0.001) and 1.85 ± 0.08 (P < 0.001), or IIax MyHC, 34.71 ± 1.75 kJ mol^?1 (P ? 0.001) and 1.60 ± 0.04 (P ? 0.001). Conclusion: The present results suggest a significantly reduced difference in shortening velocity between different human muscle fibre types at physiological temperature than previously reported at lower temperatures (12 or 15 °C) with implications for human in vivo muscle function.