Mechanical and electrophysiological effects of milrinone on the force-frequency relationship in mammalian myocardium

Isometric force, action potential and current-voltage relation were studied in guinea-pig and ferret papillary muscles. Milrinone (1 μu) increased peak twitch force by 40 + 4%, reduced time to peak tension (TPT) by 12.1 ± 3% (n= 6, P < 0.01) and reduced time to half relaxation by 17.3 ± 4.1 % (n= 6, P < 0.01). The effect of milrinone was potentiated by rolipram, a RI-PDE inhibitor which in itself had no inotropic effect. After the addition of rolipram peak isometric force was increased by 104 + 8% (n= 6, P < 0.001), TPT was further reduced whereas time to half relaxation was slightly increased after the addition of rolipram. Action potential duration at 75% repolarization was decreased by 11 + 5 ms (n= 6, P < 0.05). Milrinone also potentiated the second inward current (I_st) by 21 + 3.2% (n= 6, P < 0.01). Peak twitch force in response to a test stimulus after an interval, i.e. mechanical restitution was increased at all intervals. The onset of restitution was faster and time to full restitution also shortened. Maximum postextrasystolic potentiation was greater in the presence of milrinone, whereas relative potentiation was smaller in presence of milrinone (46 ± 7%) than in control (74 ± 7%). The recirculation fraction of activator calcium was enhanced by milrinone from 0.35 ± 0.04 to 0.48 ± 0.07. The results support the view that the positive inotropic effect of milrinone is due to a greater inflow of calcium during the action potential and a more efficient intracellular calcium handling. In addition, the effect on mechanical restitution would suggest a more direct action on sarcoplasmic reticulum calcium handling.     

The contractile and electrophysiological effects of rolipram in guinea-pig papillary muscles and isolated ventricular myocytes

Isometric force, action potentials and in voltage-clamp 1st (second inward current) and its current voltage relation were recorded in papillary muscles from guinea-pigs and from guinea-pig isolated ventricular myocytes (35–37 ^oC, 0.5-1 Hz). Rolipram (1–100 µM) had no significant effect on peak isometric twitch. The rate of rise of force and time to peak tension (TPT) was likewise unaffected. Time to half relaxation (THR) was increased in a dose-dependent manner and at 30 µM THR was prolonged by 25.3 ± 6% (n= 10, P < 0.001). The effect of 30µM rolipram on isometric force was frequency dependent. At 0.25 Hz peak force was increased by 6.3 ± 3.1% (n= 7, P < 0.05). At 2 Hz rolipram exhibited a negative inotropic effect of 9.8 ± 3.3% (n= 5, P < 0.02). Action potential duration at 90% repolarization was prolonged by 13 ± 6 ms (n= 7, P < 0.05), and there was usually no effect on resting potential or action potential amplitude. Sometimes, however, a depressed plateau was recorded. Rolipram was without effect on I¹_st and its current-voltage relations. Time to full mechanical restitution after a test interval was not changed but the shape of the restitution curve was altered. The restitution process was much slower in the presence of rolipram. Hence, peak force was lower at test intervals shorter than 800 ms. Likewise, the shape of the curve relating postextrasystolic potentiation to test interval was altered by rolipram. The interval required for maximum potentiation was increased by rolipram and did not significantly affect the recirculation fraction of activator calcium.     

Effects of isozyme-selective phosphodiesterase inhibitors on rat aorta and human platelets: smooth muscle tone,platelet aggregation and cAMP levels

The inhibitors of the cGMP-inhibited, low-K_m cAMP phosphodiesterase—milrinone and OPC 3911-and an inhibitor of a non-cGMP-inhibited low-K_m cAMP phosphodiesterase—rolipram—were used to evaluate the functional importance of the two cAMP phosphodiesterase activities in vascular smooth muscle and in platelets. Vinpocetine, an inhibitor of a calcium-calmodulin-dependent phosphodiesterase was also studied. OPC 3911 and milrinone relaxed the contracted rat aorta, inhibited ADP-induced platelet aggregation and also enhanced isoprenaline-induced relaxation as well as the antiaggregatory effects of adenosine. In platelets, OPC 3911 and milrinone increased cAMP levels, but in the rat aorta the increase was significant only for milrinone (OPC 3911 P= 0.062). In both tissues OPC 3911 and milrinone enhanced the increase in cAMP caused by activators of adenylate cyclase (isoprenaline/adenosine). Rolipram had no effects on aggregation or cAMP levels in platelets and no overadditive effects in combination with adenosine. Rolipram had little effect on relaxation and cAMP levels, did not alter isoprenaline-induced relaxation of guanfacin-contracted rat aorta, but showed synergistic effects with isoprenaline in raising cAMP levels. In PGF_2α-contracted aorta rolipram enhanced relaxation caused by isoprenaline. Vinpocetine had a relaxant effect without affecting cAMP levels, but had no effect on platelets. These results support the concept that the cGMP-inhibited phosphodiesterase is an important modulator of vascular smooth muscle tone and platelet function. The role of the non-cGMP-inhibited phosphodiesterase in these tissues is less obvious.     

Cardiovascular and endocrine responses to haemorrhage in the pig

Heart rate (HR), mean arterial pressure (MAP), indices of sympathetic and parasympathetic activity (plasma concentrations of adrenaline, noradrenaline and pancreatic polypeptide, PP), vasopressin (VP) and aldosterone (ALDO) were measured in six pigs during continuous bleeding resulting in hypovolaemic shock, from which five survived. Three stages of haemorrhage could be defined. Stage I. Resting MAP was 85 ± 6 mmHg and increased to 96 ± 5 mmHg with a blood loss of 275 (range 250–300) (10 (9–12)% of the estimated blood volume) concomitant with an increase in HR from 105 ± 5 to 113 ± 6 beats min^-1 (P < 0.05). Stage II. After a blood loss of 375 (300–500) ml (15 (13–16)%) MAP fell to 62 ± 9 mmHg and HR to 95 ± 5 beats min^-1 (P < 0.05). Stage III. A blood loss of 1113 (825–1450) ml (44 (30–52)%) resulted in a MAP of 50 ± 4 mmHg and an increase in HR to 206 ± 3 beats min^-1 (P < 0.05). Adrenaline increased from 0.3 ± 0.1 to 0.8 ± 0.3 (stage II) and 3.6 ± 1.1 nmol l^-1 (stage III) (P < 0.05); noradrenaline from 0.4 ± 0.1 to 1.5 ± 0.4 (stage II) and 5.9 ± 1.7 nmol l^-1 (stage III) (P < 0.05); PP from 6.2 ± 1.6 to 13.3 ± 2.3 (stage II) and 20.9 ± 7.8 pmol l^-1 (stage III) (P < 0.05). VP changed only marginally, but ALDO increased from 496 ± 54 to 623 ± 76 pmol l^-1 (stage III) (P < 0.05). The results suggest that a high HR and intense sympathetic activity is seen during severe haemorrhage in the pig while vagal slowing of the heart and moderate hypotension are prominent when bleeding amounts to approximately 15% of the estimated blood volume.     

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.     

The novel non-peptide selective endothelin A receptor antagonist LU 135 252 protects against myocardial ischaemic and reperfusion injury in the pig

The aim of the study was to investigate the efficacy of the novel non-peptide selective endothelin A (ET_A) receptor antagonist LU 135 252 to limit the extent of myocardial ischaemic and reperfusion injury. Administration of LU 135 252 (1 and 5 mg kg^–1 i.v.) to anaesthetised pigs reduced mean arterial pressure (MAP) from 91 ± 4 to 79 ± 3 mmHg (P < 0.05) and 96 ± 3–82 ± 3 mmHg (P < 0.01), respectively. Heart rate, coronary blood flow and coronary vascular resistance were not affected by LU 135 252. The infarct size induced by 45-min ligation of the left anterior descending coronary artery (LAD) followed by 4-h reperfusion in pigs was 81 ± 5% of the area at risk in control animals given vehicle (n = 8). In pigs receiving 1 mg kg^–1 (n = 6) or 5 mg kg^–1 (n = 8) of LU 135 252 i.v. 20 min before ischaemia the infarct size was reduced to 64 ± 3% (P < 0.05) and 35 ± 4% (P < 0.001), respectively, of the area at risk. During the reperfusion period there was a non-significant trend towards a higher coronary blood flow and a lower coronary vascular resistance in the groups given LU 135 252 compared to controls. Myocardial overflow of ET-like immunoreactivity was increased during the reperfusion period but it was not affected by administration of LU 135 252. It is concluded that administration of the selective ET_A receptor antagonist LU 135 252 effectively protects the myocardium from ischaemia/reperfusion injury, indicating that the ET_A receptor subtype is involved in the development of ischaemia/reperfusion injury.     

Post-tetanic potentiation increases energy cost to a higher extent than work in rat fast skeletal muscle

We studied the effects of (post-tetanic) potentiation on myosin light chain (MLC-2) phosphorylation, work and energy cost in skeletal muscle. Experiments were performed using in situ medial gastrocnemius muscles of male Wistar rats, which were electrically stimulated through the severed sciatic nerve. One group of muscles was first potentiated with an isometric tetanus before a series of 10 concentric contractions (PRC). A second group performed the same series of contractions without previous potentiation (RC). Following the last contraction the muscles were rapidly frozen and excised after which the high-energy phosphate content, lactate concentration and the level of MLC-2 phosphorylation were measured. The results indicate that PRC muscles had a higher (P < 0.05) total work output 144.5 ± 17.0 (SD) (n = 6) vs. 121.6 ± 11.4 (SD) (n = 6) mJ and level of MLC-2 phosphorylation (49.2 ± 7.3 vs. 40.8 ± 3.6%) than RC muscles. The energy cost of the series of concentric contractions in the PRC muscles (9.8 ± 1.9 μmol∼P/muscle) was significantly higher (P < 0.05) than the energy cost in the RC muscles (6.2 ± 0.97 μmol∼P/muscle). It was shown that the relative increase in energy cost of PRC muscles was higher (P < 0.05) than in total work output. It is proposed that the relative high increase in energy cost is the direct result of the increase in muscle performance rather than a property of potentiation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Specificity of training velocity and training load on gains in isokinetic knee joint strength

The present study investigated the effects of three different strength training regimes on the isokinetic strength profile of the knee extensors (quadriceps, Q) and flexors (hamstrings, H) and if increases in isokinetic strength were accompanied by an enhanced performance during a more complex leg movement, the soccer kick. Twenty-two elite soccer players performed 12 weeks of strength training (three times per week) at either high resistance (HR group: 4 sets, 8 reps, 8RM loading), low resistance (LR group: 4 sets, 24 reps, 24RM loading), loaded kicking movements (LK group: 4 sets, 16 reps, 16RM loading) while one group served as controls (CO group). Isokinetic concentric and eccentric moment of force was obtained (KinCom) as peak moment (M_peak) and moment at 50° knee flexion (M₅₀) at angular velocities of 30, 120, 240° s^-1. Isokinetic knee joint strength was unchanged in groups LR, LK, CO. However, after the HR strength training, concentric M_peak (±SD) increased (P<0.01) at 30° s^-1 (Q, 258±37 to 297±57 Nm; H, 122±22 to 140±21 Nm). Furthermore, eccentric M_peak increased at 30, 120 and 240° s^-1 (Q, 274±60 to 345±57 Nm (P<0.01), 291±56 to 309±49 Nm and 275±43 to 293±36 Nm (P<0.05), respectively; H, 143±32 to 158±25 Nm, 152±39 to 169±31 Nm and 148±27 to 163±19 Nm (P<0.05)). Corresponding increases (P<0.05) were observed for M₅₀. The H/Q ratio calculated as eccentric hamstring strength divided by concentric quadriceps strength (H_ecc/Q_con, representative for knee extension) at 240° s^-1 increased (P<0.05) from 107 to 118% (based on M_peak) and from 90 to 105% (M₅₀). Kicking performance estimated by maximal ball flight velocity was unaffected by any of the strength training regimes investigated. In conclusion, only heavy-resistance strength training induced increases in isokinetic muscle strength in the absence of learning effects. Concentric strength gains were observed at the actual velocity of training, while eccentric strength gains were found over the entire range of velocities examined. The capacity of the hamstring muscles for providing stability to the knee joint during fast extension was augmented as a result of the heavy-resistance strength training. Strength training should be integrated with other types of training involving the actual movement pattern in order to increase the performance within more complex movement patterns.     

Role of adenosine in exercise‐induced human skeletal muscle vasodilatation

The role of adenosine in exercise‐induced human skeletal muscle vasodilatation remains unknown. We therefore evaluated the effect of theophylline‐induced adenosine receptor blockade in six subjects and the vasodilator potency of adenosine infused in the femoral artery of seven subjects. During one‐legged, knee‐extensor exercise at ～48% of peak power output, intravenous (i.v.) theophylline decreased (P < 0.003) femoral artery blood flow (F_aBF) by ～20%, i.e. from 3.6 ± 0.5 to 2.9 ± 0.5 L min^?1, and leg vascular conductance (VC) from 33.4 ± 9.1 to 27.7 ± 8.5 mL min^?1 mmHg^?1, whereas heart rate (HR), mean arterial pressure (MAP), leg oxygen uptake and lactate release remained unaltered (P = n.s.). Bolus injections of adenosine (2.5 mg) at rest rapidly increased (P < 0.05) F_aBF from 0.3 ± 0.03 L min^?1 to a 15‐fold peak elevation (P < 0.05) at 4.1 ± 0.5 L min^?1. Continuous infusion of adenosine at rest and during one‐legged exercise at ～62% of peak power output increased (P < 0.05) F_aBF dose‐dependently to level off (P = ns) at 8.3 ± 1.0 and 8.2 ± 1.4 L min^?1, respectively. One‐legged exercise alone increased (P < 0.05) F_aBF to 4.7 ± 1.7 L min^?1. Leg oxygen uptake was unaltered (P = n.s.) with adenosine infusion during both rest and exercise. The present findings demonstrate that endogenous adenosine controls at least ～20% of the hyperaemic response to submaximal exercise in skeletal muscle of humans. The results also clearly show that arterial infusion of exogenous adenosine has the potential to evoke a vasodilator response that mimics the increase in blood flow observed in response to exercise.     

Restoration of blood pH between repeated bouts of high-intensity exercise: effects of various active-recovery protocols

To determine which active-recovery protocol would reduce faster the high blood H⁺ and lactate concentrations produced by repeated bouts of high-intensity exercise (HIE). On three occasions, 11 moderately trained males performed 4 bouts (1.5 min) at 163% of their respiratory compensation threshold (RCT) interspersed with active-recovery: (1) 4.5 min pedalling at 24% RCT (S_HORT); (2) 6 min at 18% RCT (M_EDIUM); (3) 9 min at 12% RCT (L_ONG). The total work completed during recovery was the same in all three trials. Respiratory gases and arterialized-blood samples were obtained during exercise. At the end of exercise, L_ONG in comparison to S_HORT and M_EDIUM increased plasma pH (7.32 ± 0.02 vs. ~7.22 ± 0.03; P < 0.05), while reduced lactate concentration (8.5 ± 0.9 vs. ~10.9 ± 0.8 mM; P < 0.05). Ventilatory equivalent for CO₂ was higher in L_ONG than S_HORT and M_EDIUM (31.4 ± 0.5 vs. ~29.6 ± 0.5; P < 0.05). Low-intensity prolonged recovery between repeated bouts of HIE maximized H⁺ and lactate removal likely by enhancing CO₂ unloading.     

Urinary excretion of prostaglandin F2α and 6-keto-prostaglandin F1α during volume expansion in man

Renal function and the urinary excretion of immunoreactive prostaglandin F_2α (PGF_2α) and 6-keto-prostaglandin F_1α (6-keto-PGF_1α) were investigated during volume expansion (VE) in 9 healthy young adults. The studies were started after at least 17 h of food and fluid deprivation. Volume expansion (3% of body weight) was achieved by a continuous infusion of Ringer's solution (0.22 ml/kg/min). This increased the urinary excretion of sodium from 195±25 to 714±55 μmol/min/1.73 m²(mean ± S.E.) and decreased the excretion of potassium by 24% and plasma renin activity by 60% (P<0.01). The clearance of inulin increased slightly (from 102.4±3.7 to 114.5±6.2 ml/min/1.73 m², P<0.025), whüe clearance of PAH did not change. The excretion of immunoreactive PGF_2α decreased in 8 out of 9 individuals during VE, from 1.58±0.15 to 0.97±0.10 ng/min/1.73 m²(P<0.01). In contrast, excretion of immunoreactive 6-keto-PGF_1α increased in 8 out of 9 subjects, from 2.32±0.20 to 3.47±0.48 ng/min/1.73 m²(P<0.05). Urinary excretion of PGF_2α and 6-keto-PGF_1α may reflect renal synthesis of prostaglandins (PGs) and prostacyclin (PGI₂), respectively. The results indicate that synthesis of PGs is decreased and that of PGI₂ is increased during VE in man. However, no simple relationship could be found between the prostaglandins and the renal functional parameters.     

Sensitivity of somatic mutations in human umbilical cord blood to maternal environments

To assess the potential effect of maternal environments on human embryonic/fetal somatic mutation, we measured the frequencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (M_f), and glycophorin A (GPA) variant erythrocytes (V_f) of both allele-loss (ø/N) and allele-loss-and-duplication (N/N) phenotypes in umbilical cord blood. The mean hprt M_f (1.40 ± 1.11 × 10^?6, N = 66) and GPA V_f (ø/N 4.0 ± 2.2 × 10^?6, N = 114; N/N 2.7 ± 2.0 × 10^?6, N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt M_f was significantly higher than that of a published study of newborn cord blood samples from a geographically distant population (0.64 ± 0.41 × 10^?6, N = 45, P < 0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt M_f (0.70 ± 0.49 × 10^?6) of this selected population was consistent with the published report and significantly lower than that of our initial population (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These results indicate that there is an environmental effect related to maternal socioeconomic status on the frequency of embryonic/fetal somatic mutations. Molecular analyses of hprt mutants from this cohort with elevated M_f revealed a significant decrease in the relative contribution of gross structural mutations to the overall M_f (25 of 38, 66% vs. 34 of 41, 83%, P = 0.024, x² test), suggesting that the higher M_f resulted from an elevated level of “point” mutations. No individual maternal demographic or environmental factor was identified as contributing more significantly than other any factor to the observed variability in hprt M_f or GPA V_f. © 1995 Wiley-Liss, Inc.     

Individual differences in the responses to endurance and resistance training

Large individual differences in the responsiveness of cardiorespiratory fitness (VO_2peak) to endurance training have been observed in healthy subjects. We tested the hypothesis that subjects with a poor responsiveness to endurance training might benefit from resistance training in terms of aerobic fitness. The study population consisted of sedentary healthy male and female subjects (n=91, 42±5 year) assigned to either a training (n=73) or a control group (n=18). The randomized cross-over study design included a 2-week laboratory-controlled endurance or resistance training period with a 2-month detraining period between the interventions. Large individual differences were observed in the changes of VO_2peak (ΔVO_2peak) after both the endurance (average 8±6 %, P<0.001, range −5 to +22%) and resistance training (average 4±5%, P<0.001, range −8 to +16%). The average increase in ΔVO_2peak between genders was similar after both the endurance (8±6% for both genders, P=ns) and resistance training (3±5% for males and 5±6% for females, P=ns). There was no linear relationship between the changes in VO_2peak after each training intervention (r=−.09, P=ns). On the contrary, when the study group was divided into quartiles according to the endurance training response (1±3, 6±1, 9±1, and 16±3% increase in VO_2peak), the group with the lowest response to endurance training increased VO_2peak after the resistance training intervention (ΔVO_2peak 7±5%, P<0.001). The individual responsiveness of VO_2peak to exercise training is related to the mode of training. The healthy males and females whose training response is low after endurance training seem to result in a marked improvement in their cardiorespiratory fitness by resistance training.     

Cerebral oxygenation is reduced during hyperthermic exercise in humans

Aim: Cerebral mitochondrial oxygen tension (P_mitoO₂) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO₂) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods: This study evaluated the effect of heat stress during exercise on P_mitoO₂ calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO_2max) 63 ± 6 mL kg⁻¹ min⁻¹]. Results: The CBF, CMRO₂ and P_mitoO₂ remained stable during 1 h of moderate cycling (170 ± 11 W, ∼50% of VO_2max, RPE 9–12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), P_mitoO₂ declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO₂ increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19–20; P < 0.05); the RPE correlated inversely with P_mitoO₂ (r² = 0.42, P < 0.05). Conclusion: These data indicate that strenuous exercise in the heat lowers cerebral P_mitoO₂, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation.     

Functional maximal strength training induces neural transfer to single-joint tasks

The purpose of this study was to investigate whether neural adaptations following functional multiple-joint leg press training can induce neural adaptations to the plantar flexor muscles in a single-joint contraction task. Subjects were randomised to a maximal strength training (MST) (n = 10) or a control group (n = 9). MST consisted of 24 sessions (8 weeks) of 4 × 4 repetitions of horizontal leg press using maximal intended velocity in the concentric phase with the movement ending in a plantar flexion. Neural adaptations in the soleus and gastrocnemius medialis (GM) were assessed by surface electromyographic activity and V-waves during maximum voluntary isometric contraction (MVIC), and also by H-reflexes in the soleus during rest and 20% MVIC. One repetition maximum leg press increased by 44 ± 14% (mean ± SD; P < 0.01). Plantar flexion MVIC increased by 20 ± 14% (P < 0.01), accompanied by 13 ± 19% (P < 0.05) increase in soleus, but not GM surface electromyography. Soleus V/M_SUP increased by 53 ± 66% and in GM by 59 ± 64% (P < 0.05). Normalised soleus H-reflexes remained unchanged by training. No changes occurred in the control group. These results suggest that leg press MST can induce neural adaptations in a single-joint plantar flexion MVIC task.     

Serial effects of high-resistance and prolonged endurance training on Na+–K+ pump concentration and enzymatic activities in human vastus lateralis

The purpose of this study was to compare two contrasting training models, namely high-resistance training and prolonged submaximal training on the expression of Na⁺–K+ ATPase and changes in the potential of pathways involved in energy production in human vastus lateralis. The high-resistance training group (VO _2peak = 45.3 ± 1.9 mL kg^?1 min^?1, mean ± SE, n = 9) performed three sets of six to eight repetitions maximal, each of squats, leg presses and leg extensions, three times per week for 12 weeks, while the prolonged submaximal training group (VO _2peak = 44.4 ± 6.6 mL kg^?1 min^?1, n = 7) cycled 5–6 times per week for 2 h day^?1 at 68% VO _2peak for 11 weeks. In the HRT group, Na⁺–K⁺ ATPase (pmol g^?1 wet wt), measured with the ³H-ouabain binding technique, showed no change from 0 (289 ± 22) to 4 weeks (283 ± 15), increased (P < 0.05) by 16% at 7 weeks and remained stable until 12 weeks (319 ± 19). For prolonged submaximal training, a 22% increase (P < 0.05) was observed from 0 (278 ± 31) until 3 weeks (339 ± 29) with no further changes observed at either 9 weeks (345 ± 25) or 11 weeks (359 ± 34). In contrast to high-resistance training, where a 15% increase (P < 0.05) was observed, only in the maximal activity of phosphorylase, prolonged submaximal training resulted in increases in malate dehydrogenase, β-hydroxyl-CoA dehydrogenase, hexokinase and phosphofructokinase. In contrast to high-resistance training which failed to result in an increase in VO _2peak, prolonged submaximal training increased VO _2peak by ≈15%. Only for prolonged exercise training was a relationship observed for VO _2peak and Na⁺–K⁺-ATPase (r = 0.59; P < 0.05). Correlations between VO _2peak and mitochondrial enzyme activities were not significant (P > 0.05) for either training programme. It is concluded that although both training programmes stimulate an up-regulation in Na⁺–K⁺ ATPase concentration, only the prolonged submaximal training programme enhances the potential for β-oxidation, oxidative phosphorylation and glucose phosphorylation.     

The action of 2,3-butanedionemonoxime on the inotropic state in guinea-pig myocardium

Isolated papillary muscles from guinea-pig right ventricles were used (temperature 33 °C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2, 3-butanedionemonoxime (BDM) (2 mm) the peak twitch force was reduced from 4.17 ± 0.4 mN/mm² to 1.68 ± 0.3 mN/mm² (n = 9, P < 0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 ± 3% (n = 9, P < 0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise offorce was reduced by 35 ± 3.2 mN/mm²s i.e. 46 ± 3 %. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3-butanedionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 ± 0.4 mN/mm² in 2 mm 2,3-butanedionemonoxime and 7.6 ± 0.7 mN/mm² in control (n= 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3-butanedionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 ± 0.04 in control and 0.30 ± 0.02 in 2_J-butane dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell. As previously suggested the negative inotropic action of BDM can be explained by an action on cross-bridge kinetics, however the effects on the mechanical restitution curve suggests an additional action on the calcium handling by the sarcoplasmic reticulum.     

Rate‐dependent electrical,contractile and restitution properties of isolated left ventricular myocytes in guinea‐pig hypertrophy

Left ventricular hypertrophy predisposes to sudden cardiac death (SCD) and studies of human SCD suggest that the antecedent heart rate (HR) is usually <100 beats min^–1. This is surprising in view of the known association between adrenergic receptor stimulation and SCD which by itself would suggest that it is more likely to occur from high rather than low HR. We therefore hypothesized that there may be electrical or mechanical abnormalities present in myocytes isolated from animals with left ventricular hypertrophy that predispose to SCD at low stimulation frequencies but which may not be present at high HR. Mild left ventricular hypertrophy was induced in guinea‐pigs by infra‐renal aortic banding. Electrical and mechanical properties of isolated myocytes were studied at different stimulation frequencies between 0.1 and 3 Hz. Action potential duration (APD) is prolonged in hypertrophy at stimulation frequencies <1 Hz but not at faster rates. Contraction size, time‐to‐peak contraction (TTPC) and half‐relaxation time are greatly enhanced in hypertrophy at all frequencies between 0.1 and 3 Hz. Electrical (50.3 ± 5.2 ms in hypertrophy and 78.4 ± 12.1 ms in control, P < 0.03) and mechanical (205 ± 16 ms for hypertrophy and 266 ± 24 ms for control cells, P < 0.03) restitution time constants are quicker in hypertrophy. The finding of APD prolongation at low but not at high frequencies is consistent with the finding that SCD arises from low and not high HR. This data supports the role of abnormal repolarization in SCD.     

Changes in electromyographic activity,muscle fibre and force production characteristics during heavy resistance/power strength training in middle‐aged and older men and women

The effects of a 6‐month resistance training (2 day/week) designed to develop both strength and power on neural activation by electromyographic activity (EMG) of the agonist and antagonist knee extensors, muscle fibre proportion and areas of type I, IIa, and IIb of the vastus lateralis (VL) as well as maximal concentric one repetition maximum (1 RM) strength and maximal and explosive isometric strength of the knee extensors were examined. A total of 10 middle‐aged men (M40; 42 ± 2), 11 middle‐aged women (W40; 39 ± 3), 11 elderly men (M70; 72 ± 3) and 10 elderly women (W70; 67 ± 3) served as subjects. Maximal and explosive strength values remained unaltered during a 1‐month control period. After the 6‐month training maximal isometric and 1RM strength values increased in M40 by 28 ± 14 and 27 ± 7% (P < 0.001), in M70 by 27 ± 17 and 21 ± 9% (P < 0.001), in W40 by 27 ± 19 and 35 ± 14% (P < 0.001) and in W70 by 26 ± 14 and 31 ± 14% (P < 0.001), respectively. Explosive strength improved in M40 by 21 ± 41% (P < 0.05), in M70 by 21 ± 24% (P < 0.05), in W40 by 32 ± 45% (NS) and in W70 by 22 ± 28% (P < 0.05). The iEMGs of the VL and vastus medialis (VM) muscles increased during the training in M40 (P < 0.001 and 0.05), in M70 (P < 0.001 and 0.05), in W40 (P < 0.001 and 0.05) and in W70 (P < 0.001 and 0.05). The antagonist biceps femoris (BF) activity during the isometric knee extension remained unaltered in M40, in W40, and in M70 but decreased in W70 (from 42 ± 34 to 32 ± 26%; P < 0.05) during the first 2 months of training. Significant increases occurred during the training in the mean fibre areas of type I in W70 (P < 0.05) and of overall type II along with a specific increase in IIa in both W40 (P < 0.05) and in W70 (P < 0.05), while the changes in the male groups were not statistically significant. The individual percentage values for type II fibres at pretraining correlated with the individual values for 1 RM strength in both W70 (r=0.80; P < 0.05) and M70 (r=0.61; P < 0.05) and also at post‐training for maximal isometric torque in W70 (r=0.77, P < 0.05). The findings support the concept of the important role of neural adaptations in strength and power development in middle‐aged and older men and women. The muscle fibre distribution (percentage type II fibres) seems to be an important contributor on muscle strength in older people, especially older women. Women of both age groups appear to be hypertrophically responsive to the total body strength training protocol performed two times a week including heavier and lower (for fast movements) loads designed for both maximal strength and power development, while such a programme has limited effects on muscle hypertrophy in men.     

Changes in muscle function in response to 10 days of lower limb unloading in humans

Force-generating capacity and electromyographic (EMG) activity of the knee extensor muscles were studied before and after short-term (10 d) unilateral lower limb unloading and during 4 days of recovery. Ten healthy males used crutches to prevent one of their lower limbs from weight-bearing while maintaining joint mobility as well as daily ambulatory activities. Knee extensor torque and quadriceps rectified EMG during maximal voluntary isometric contraction (MVC) was measured repeatedly before and after the intervention. Also, EMG at a fixed submaximal level (100 Nm; 30–45% MVC) and maximal angular velocity (AV_max), during unresisted knee extension, were assessed. Maximum torque decreased (P<0.05) by 13±8% in response to unloading while maximum EMG activity did not change after unloading or during recovery (P=0.35). Submaximum EMG increased (P<0.05) by 25±16% after unloading. Maximum and submaximum torque/EMG ratios decreased (P<0.05) after unloading. AV_max decreased (P<0.05) by 9±8% after unloading. The post value, however, was not different from that of the weight-bearing limb. Torque, EMG and AV_max were recovered (P>0.05) after 4 days of resumed weight-bearing. The pronounced decrease and the rapid recovery in maximum torque appears not to be attributed to a change in muscle mass alone. Because the findings of unchanged maximum EMG and increased EMG at a submaximal force level suggest no change in neural drive, we propose that unspecific tissue factors in part impair muscle function in response to short-term loss of weight-bearing activity. Results also indicate that recovery in muscle function after short-term unloading seems to be completed in a time span shorter than the period of preceding inactivity.