Greater fatigue resistance of dorsiflexor muscles in people with prediabetes than type 2 diabetes

Although exercise can prevent progression to T2D among people with prediabetes, little is known about fatigue during exercise in people with prediabetes compared to T2D. The purpose of the study was to compare the magnitude and mechanisms of fatigability of the ankle dorsiflexor muscles between people with prediabetes and T2D. Ten people with prediabetes (6 females, 51.7 ± 6.9 years) and fourteen with T2D (6 females, 52.6 ± 6.2 years) who were matched for age, body mass index and physical activity performed an intermittent (6 s contraction: 4 s relaxation) fatiguing task at 75% maximal voluntary contraction (MVC) with the dorsiflexors. Electrical stimulation was used to assess contractile properties of the dorsiflexor muscles before and after the fatiguing task. People with prediabetes had a longer time-to-task failure, i.e. greater fatigue resistance (7.9 ± 5.1 vs. 4.9 ± 2.5 min, P = 0.04), and slower rate of decline of the (potentiated) twitch amplitude (6.5 ± 3.1 vs. 16.5 ± 11.7%·min⁻¹, P = 0.03) than people with T2D. Shorter time-to-task failure (i.e. greater fatigability) was associated with greater baseline MVC torque (r² = 0.21, P = 0.02) and faster rate of decline of twitch amplitude (r² = 0.39, P = 0.04). The ankle dorsiflexor muscles of males and females with prediabetes were more fatigue resistant than people with T2D, and fatigability was associated with contractile mechanisms.     

Effect of severe normocapnic hypoxia on renal function in growth-restricted newborn piglets

To examine the effects of intrauterine growth restriction and acute severe oxygen deprivation on renal blood flow (RBF), renovascular resistance (RVR), and renal excretory functions in newborns, studies were conducted on 1-day-old anesthetized piglets divided into groups of normal weight (NW, n = 14) and intrauterine growth-restricted (IUGR, n = 14) animals. Physiological parameters, RBF, RVR, and urinary flow, were similar in NW and IUGR piglets, but glomerular filtration rate (GFR) and filtration fraction were significantly less in IUGR animals (P < 0.05). An induced 1-h severe hypoxia (arterial PO(2) = 19 +/- 4 mmHg) resulted in, for both groups, a pronounced metabolic acidosis, strongly reduced RBF, and increased fractional sodium excretion (FSE; P < 0.05) with a less-pronounced increase of RVR and arterial catecolamines in IUGR piglets. Of significance was a smaller decrease in RBF for IUGR piglets (P < 0.05). Early recovery showed a transient period of diuresis with increased osmotic clearance and elevated FSE in both groups (P < 0.05). However, GFR and renal O(2) delivery remained reduced in NW piglets (P < 0.05). We conclude that, in newborn IUGR piglets, RBF is maintained, although GFR is compromised. Severe hypoxemia induces similar alterations of renal excretion in newborn piglets. However, the less-pronounced RBF reduction during hypoxemia indicates an improved adaptation of newborn IUGR piglets on periods of severely disturbed oxygenation. Furthermore, newborn piglets reestablish the ability for urine concentration and adequate sodium reabsorption early after reoxygenation so that a sustained acute renal failure was prevented.     

Prostaglandins and control of breathing in newborn piglets

To investigate the possible role of prostaglandins in regulation of postnatal breathing, phrenic neural activity (PMO) was recorded as an index of breathing in 42 anesthetized, paralyzed piglets less than 30 days of age (weight 2.4 +/- 0.2 kg, age 9.9 +/- 1.5 days) who were mechanically ventilated with 100% O2 at a fixed tidal volume (8-10 ml/kg). End-tidal CO2 was held constant by an electronic servocontroller which adjusted ventilator rate; ventilator rate was monitored as an index of CO2 production. Rectal temperature was maintained at 39.0 +/- 0.2 degrees C. The effects on PMO of intravenous and brain ventricular injections of NaCl and agents active in the prostaglandin cascade were compared. Intravenous (0.25-1.0 mg/kg, n = 9) and brain (5-33 micrograms/kg, n = 6) indomethacin, a cyclooxygenase inhibitor, doubled PMO within 30 min. Intravenous (1-10 micrograms/kg, n = 6) and brain (1-40 micrograms/kg, n = 6) prostaglandin E1 inhibited PMO by one-half at 10 and 30 min.     

Intravenous nanosomes of quercetin improve brain function and hemodynamic instability after severe hypoxia in newborn piglets

Perinatal asphyxia is a major cause of death and neurological morbidity in newborns and oxidative stress is one of the critical mechanisms leading to permanent brain lesions in this pathology. In this context we have chosen quercetin, a natural antioxidant, known also by its brain protective effects to study its potential as a therapy for brain pathology provoked by severe hypoxia in the brain. To overcame the difficulties of quercetin to access the brain, we have developed lecithin/cholesterol/cyclodextrin nanosomes as a safe and protective vehicle.We have applied the nanosomal preparation intravenously to newborn piglets submitted to a severe hypoxic or ischemic/hypoxic episode and followed them for 8 or 72 h, respectively. Either towards the end of 8 h after hypoxia or up to 72 h after, electroencephalographic amplitude records in animals that received the nanosomes improved significantly. Animals receiving quercetin also stabilized blood pressure and recovered spontaneous breathing. In this experimental group mechanical ventilation assistance was withdrawn in the first 24 h while the hypoxic and vehicle groups required more than 24 h of mechanical ventilation. Three days after the hypoxia the suckling and walking capacity in the group that received quercetin recovered significantly compared with the hypoxic groups. Pathological studies did not show significant differences in the brain of newborn piglets treated with nanosomes compared with hypoxic groups. The beneficial effects of quercetin nanosomal preparation after experimental perinatal asphyxia show it as a promising putative treatment for the damaged brain in development.     

Alterations in cardiac contractile performance and sarcoplasmic reticulum function in sucrose-fed rats is associated with insulin resistance

Diabetes mellitus (DM) causes the development of a specific cardiomyopathy that results from the metabolic derangements present in DM and manifests as cardiac contractile dysfunction. Although myocardial dysfunction in Type 1 DM has been associated with defects in the function and regulation of the sarcoplasmic reticulum (SR), very little is known about SR function in Type 2 DM. Accordingly, this study examined whether abnormalities in cardiac contractile performance and SR function occur in the prestage of Type 2 DM (i.e., during insulin resistance). Sucrose feeding was used to induce whole body insulin resistance, whereas cardiac contractile performance was assessed by echocardiography and SR function was measured by SR calcium (Ca²⁺) uptake. Sucrose-fed rats exhibited hyperinsulinemia, hyperglycemia, and hyperlipidemia relative to control rats. Serial echocardiographic assessments in the sucrose-fed rats revealed early abnormalities in diastolic function followed by late systolic dysfunction and concurrent alterations in myocardial structure. The hearts of the 10-wk sucrose-fed rats showed depressed SR function demonstrated by a significant reduction in SR Ca²⁺ uptake. The decline in SR Ca²⁺ uptake was associated with a significant decrease in the cAMP-dependent protein kinase and Ca²⁺/calmodulin-dependent protein kinase II-mediated phosphorylation of phospholamban. The results show that abnormalities in cardiac contractile performance and SR function occur at an insulin-resistant stage before the manifestation of overt Type 2 DM. cardiomyopathy; diabetes mellitus; echocardiography     

Influence of adaptation to stressor effects on bioelectrical activity, contractile function and resistance of the papillary muscles to the excess of intracellular calcium

In experiments on papillary muscles of rats it was established that adaptation to stressor effects increases resistance of the myocardium to contracture effects and restricts depression of electrophysiological parameters caused by the excess of calcium. Such adaptation decreased contracture by 6.5 times. On the next stage it was established that adaptation restricts depression of electrophysiological parameters of cardiomyocytes with the action of large concentrations of calcium. Possible mechanism of cardiac protector effect of adaptation to stressor effects is being discussed.     

Increased fatigue resistance of respiratory muscles during exercise after respiratory muscle endurance training

Respiratory muscle fatigue develops during exhaustive exercise and can limit exercise performance. Respiratory muscle training, in turn, can increase exercise performance. We investigated whether respiratory muscle endurance training (RMT) reduces exercise-induced inspiratory and expiratory muscle fatigue. Twenty-one healthy, male volunteers performed twenty 30-min sessions of either normocapnic hyperpnoea (n = 13) or sham training (CON, n = 8) over 4-5 wk. Before and after training, subjects performed a constant-load cycling test at 85% maximal power output to exhaustion (PRE(EXH), POST(EXH)). A further posttraining test was stopped at the pretraining duration (POST(ISO)) i.e., isotime. Before and after cycling, transdiaphragmatic pressure was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Overall, RMT did not reduce respiratory muscle fatigue. However, in subjects who developed >10% of diaphragm or abdominal muscle fatigue in PRE(EXH), fatigue was significantly reduced after RMT in POST(ISO) (inspiratory: -17 +/- 6% vs. -9 +/- 10%, P = 0.038, n = 9; abdominal: -19 +/- 10% vs. -11 +/- 11%, P = 0.038, n = 9), while sham training had no significant effect. Similarly, cycling endurance in POST(EXH) did not improve after RMT (P = 0.071), while a significant improvement was seen in the subgroup with >10% of diaphragm fatigue after PRE(EXH) (P = 0.017), but not in the sham training group (P = 0.674). However, changes in cycling endurance did not correlate with changes in respiratory muscle fatigue. In conclusion, RMT decreased the development of respiratory muscle fatigue during intensive exercise, but this change did not seem to improve cycling endurance.     

Depressed contractile performance and reduced fatigue resistance in single skinned fibers of soleus muscle after long-term disuse in rats

Long-term disuse results in atrophy in skeletal muscle, which is characterized by reduced functional capability, impaired locomotor condition, and reduced resistance to fatigue. Here we show how long-term disuse affects contractility and fatigue resistance in single fibers of soleus muscle taken from the hindlimb immobilization model of the rat. We found that long-term disuse results in depression of caffeine-induced transient contractions in saponin-treated single fibers. However, when normalized to maximal Ca(2+)-activated force, the magnitude of the transient contractions became similar to that in control fibers. Control experiments indicated that the active force depression in disused muscle is not coupled with isoform switching of myosin heavy chain or troponin, or with disruptions of sarcomere structure or excessive internal sarcomere shortening during contraction. In contrast, our electronmicroscopic observation supported our earlier observation that interfilament lattice spacing is expanded after disuse. Then, to investigate the molecular mechanism of the reduced fatigue resistance in disused muscle, we compared the inhibitory effects of inorganic phosphate (Pi) on maximal Ca(2+)-activated force in control vs. disused fibers. The effect of Pi was more pronounced in disused fibers, and it approached that observed in control fibers after osmotic compression. These results suggest that contractile depression in disuse results from the lowering of myofibrillar force-generating capacity, rather than from defective Ca(2+) mobilization, and the reduced resistance to fatigue is from an enhanced inhibitory effect of Pi coupled with a decrease in the number of attached cross bridges, presumably due to lattice spacing expansion.     

Metabolic and contractile differentiation of rabbit muscles during growth

• 1.1. A study was carried out of post-natal evolution of the oxidative, glycolytic and contractile capacities in various types of rabbit muscle.
• 2.2. At birth, muscles are non-differentiated and present very limited metabolic and contractile activity, metabolism is mainly oxidative in all muscles.
• 3.3. Although muscular discrimination is manifest from the sixth week after birth, the glycolytic metabolism reaches its maximum capacity only after six to eight weeks.
• 4.4. Subsequently, oxidative metabolic capacity steadily decreases until adulthood.