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.     

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.     

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.     

Training effect and fatigue in polypyrrole-based artificial muscles

Artificial muscles based on an electrochemomechanical strain (ECMS) in conducting polymers, namely polypyrrole (PPy) film, have been studied from viewpoints of training, fatigue and aging by repeat cycles under tensile loads. ECMS was approximately 2% in a saline solution, resulting from both insertion and exclusion of Na(+) with solvated water molecules as well in the film. Transient responses of ECMS and current induced by voltage stimuli were measured under tensile stresses up to 5 MPa to see the training effect, fatigue and aging of the film. At higher stresses the film showed larger creeping, which resulted from realignment or conformation change, slipping and breaking of polymer chains. After the experience of large stresses, the training effect in ECMS was appreciably observed as an increase of the strain. Without stress the conductivity of the film was stable (no fatigue) upon an electrochemical cycle; however, under high tensile stresses the conductivity decreased remarkably (fatigue and aging). It is to be noted that straightened polymer chains can be easily oxidized and degraded due to lower pi-electron energy. The conversion efficiency from electrical to mechanical energy in this system was found to be less than 0.03%.     

Mechanisms of intracellular trigger signal transmission in muscles: Strategy of rearrangements in evolution of the contractile function

The paper describes our concept about the existence of a certain strategy of rearrangements of ionic mechanisms of he intracellular trigger signal transmission in muscles during their contractile function evolution. It is shown that the rearrangements of muscles to accelerate the single (discrete) contraction cycle is accompanied by a change of mechanisms of external stimulus transduction into an intracellular trigger signal: direct activation of intracellular effectors by extracellular Ca²⁺ is replaced by indirect mechanisms of Ca²⁺-, then Ca²⁺- and Na⁺-induced, and in skeletal muscle fibers of vertebrates (SMFV) of Na⁺-induced Ca²⁺ release from the intracellular depot, sarcoplasmic reticulum. These rearrangements promoted an intensification of the Ca²⁺ intracellular mobilization to provide for the most complete pulse control of SMFV phasic contractions by the CNS and their protection from undesirable peripheral influences.     

A comparison of contractile properties in human arm and leg muscles

Isometric twitch properties have been compared in two pairs of opposing human limb muscles; these were the brachial biceps and triceps, and the anterior tibial and plantarflexor muscles. All four muscles were examined in each of 24 healthy subjects (16 men and 8 women). The brachial triceps had the shortest contraction and half-relaxation times and the greatest twitch potentiation, while the plantarflexors had the most prolonged twitches and least potentiation; the anterior tibial and brachial biceps muscles had similar characteristics. Susceptibility to fatigue was less in the plantarflexors than in the other three muscles. When muscles were assessed without reference to their anatomical sites, a significant relationship was noted between contraction time and potentiation, but not between either of these features and fatiguability. There was no evidence that muscles were uniformly 'faster' or 'slower' in some subjects than in others.     

Effects of post-resuscitation treatment with N-acetylcysteine on cardiac recovery in hypoxic newborn piglets

Aims

Although N-acetylcysteine (NAC) can decrease reactive oxygen species and improve myocardial recovery after ischemia/hypoxia in various acute animal models, little is known regarding its long-term effect in neonatal subjects. We investigated whether NAC provides prolonged protective effect on hemodynamics and oxidative stress using a surviving swine model of neonatal asphyxia.

Methods and Results

Newborn piglets were anesthetized and acutely instrumented for measurement of systemic hemodynamics and oxygen transport. Animals were block-randomized into a sham-operated group (without hypoxia-reoxygenation [H–R, n = 6]) and two H-R groups (2 h normocapnic alveolar hypoxia followed by 48 h reoxygenation, n = 8/group). All piglets were acidotic and in cardiogenic shock after hypoxia. At 5 min after reoxygenation, piglets were given either saline or NAC (intravenous 150 mg/kg bolus + 20 mg/kg/h infusion) via for 24 h in a blinded, randomized fashion. Both cardiac index and stroke volume of H-R controls remained lower than the pre-hypoxic values throughout recovery. Treating the piglets with NAC significantly improved cardiac index, stroke volume and systemic oxygen delivery to levels not different from those of sham-operated piglets. Accompanied with the hemodynamic improvement, NAC-treated piglets had significantly lower plasma cardiac troponin-I, myocardial lipid hydroperoxides, activated caspase-3 and lactate levels (vs. H-R controls). The change in cardiac index after H-R correlated with myocardial lipid hydroperoxides, caspase-3 and lactate levels (all p<0.05).

Conclusions

Post-resuscitation administration of NAC reduces myocardial oxidative stress and caused a prolonged improvement in cardiac function and in newborn piglets with H-R insults.     

Plasma catecholamine concentrations of newborn piglets in thermoneutral and cold environments

Plasma epinephrine and norepinephrine concentrations were measured in seventeen unanaesthetized 3 to 4 days-old piglets while in a thermoneutral environment (31.3 degrees C) and 30, 45 and 60 min after induction of environmental cold stress (19.9-23.1 degrees C). Plasma epinephrine and norepinephrine concentrations in a warm environment were 142 +/- 26 pg/ml, and 456 +/- 44 pg/ml respectively. Environmental cold stress evoked significant increases in norepinephrine values after 30 (624 +/- 58 pg/ml), 45 (626 +/- 60 pg/ml) and 60 (626 +/- 54 pg/ml) min of cold stress. Plasma epinephrine concentrations did not significantly change during environmental cold stress. Post-hoc stratification of piglets into normothermic (deep rectal temperature 38.6 degrees C-38.8 degrees C, n = 9) and hypothermic (deep rectal temperature 37.1 degrees C-37.7 degrees C, n = 7) subgroups revealed significant increases in plasma norepinephrine concentrations only in the hypothermic subgroup. We conclude that plasma norepinephrine, but not epinephrine, is increased in newborn piglets during environmental cold stress and that the changes in norepinephrine concentrations are related to body core hypothermia. We speculate that hypothermia-mediated reductions in peripheral norepinephrine breakdown and re-uptake contribute to the rise in circulating levels.     

Effects of carotid and aortic chemoreceptor denervation in newborn piglets.

The objective of the present study was to test the hypothesis that in neonatal piglets there would be no hypoventilation after sham denervation or aortic denervation (AOD) alone, but there would be transient hypoventilation after carotid body denervation (CBD) and the hypoventilation would be greatest after combined carotid and aortic denervation (CBD+AOD). There was a significant (P < 0.05) hypoventilation in CBD and CBD+AOD piglets denervated at 5, 15, and 25 days of age. The hypoventilation in CBD+AOD piglets denervated at 5 days of age was greater (P < 0.05) than that of all other groups. Conversely, sham-denervated and AOD piglets did not hypoventilate after denervation. Injections of sodium cyanide showed that aortic chemoreceptors were a site of recovery of peripheral chemosensitivity after CBD. This aortic sodium cyanide response was abolished by prior injection of a serotonin 5a receptor blocker. Residual peripheral chemosensitivity after CBD+AOD was localized to the left ventricle. We conclude that 1) aortic chemoreceptors contribute to eupneic breathing in piglets that were carotid denervated at 5 days of age and 2) there are multiple sites of residual peripheral chemosensitivity after CBD.     

Mode of delivery is associated with different hematological profiles in the newborn calf

Several studies on babies have shown that the type of delivery can influence the hematological and immune status of the newborn. In bovine medicine, some authors reported the hematological pattern of the newborn calf, but never related it with the calving process or other perinatal factors. The purpose of the present study was to evaluate the hematological profile in newborn calves in relation to the type of delivery. A total of 41 healthy calves were enrolled; 16 Friesian calves which were born by vaginal delivery without assistance (VD), and 25 Belgian Blue calves that were born by elective Caesarean section (CS). As soon as the calves were born, a complete clinical examination was performed to verify viability and maturity. At 10 min after birth, 2 mL venous blood was collected to perform the blood gas and acid-base evaluation. Blood samples were subsequently collected from the jugular vein within 30 min after birth, and at 1, 2, 3, 7, and 14 days of age. An automatic analyzer was used to determine hemoglobin concentration (Hb), hematocrit (Ht), and red and white blood cell counts, while differential leukocyte count was performed microscopically. Statistical analysis was applied to assess differences between the groups and within the group for all parameters between each sampling time (P ≤ 0.05). All the calves were born alive, viable, and mature. There were no acidotic calves, but statistical analysis revealed many differences, as higher pH, base excess (BE) (P ≤ 0.05), PO₂ (P < 0.001), and sO₂ (P < 0.0001) in the VD group. Levels of hemoglobin concentration, hematocrit, and red blood cell number were constantly higher in CS calves (P < 0.001). In comparison with the VD calves, white blood cell and neutrophil absolute number were higher at birth and at 14 days of age in the CS group (P < 0.001 and P ≤ 0.05). The mode of delivery, therefore, seems to have an influence on the oxygenation levels and on the hematological and nonspecific immunity profile of the newborn calf.     

Changes in cardiac contractile function and myocardial

Cutaneous burn trauma causes cardiac contraction and relaxation defects, but the mechanism is unclear. Previous studies suggest that burn-related changes in myocyte handling of calcium may play an important role in postburn cardiac dysfunction. With the use of a high dissociation constant (K(d)) calcium indicator 1,2-bis(2-amino-5,6-difluorophenoxy)-ethane-N,N,N',N'-tetraacetic acid (TF-BAPTA) and (19)F NMR spectroscopy, this study examined the correlation between the changes in cytosolic free calcium concentration ([Ca(2+)](i)) and cardiac function after burn trauma. Sprague-Dawley rats were given scald burn (over 40% of the total body surface area) or sham burn. Twenty-four hours later, the hearts were excised and perfused by the Langendorff method with a modified phosphate-free Krebs-Henseleit bicarbonate buffer. Left ventricular (LV) developed pressure (LVDP), calculated from peak systolic LV pressure and LV end-diastolic pressure, was assessed through a catheter attached to an intraventricular balloon. At the same time, (31)P and (19)F NMR spectroscopy was performed before and after TF-BAPTA loading. LVDP measured in hearts from burned rats was <40% than that measured in hearts from sham burn rats (65 +/- 6 vs. 110 +/- 12 mmHg, P < 0.01); [Ca(2+)](i) was increased fourfold in hearts from the burned group compared with that measured in the sham burn group (0.807 +/- 0.192 vs. 3.891 +/- 0.929 microM). Loading TF-BAPTA in hearts transiently decreased LVDP by 15%. Phosphocreatine-to-P(i) ratio decreased, but ATP and intracellular pH remained unchanged by either TF-BAPTA loading or burn trauma. In conclusion, burn trauma impaired cardiac contractility, and this functional defect was paralleled by a significant rise in [Ca(2+)](i) in the heart.     

Proteomic analysis of cardiac metabolic enzymes in asphyxiated newborn piglets

Hypoxia/reoxygenation (H/R) creates an energetic deficiency in the heart, which may contribute to myocardial dysfunction. We hypothesized that H/R-induced impairment of cardioenergetic enzymes occurs in asphyxiated newborn animals. After hypoxia for 2 h (10-15% oxygen), newborn piglets were resuscitated with 100% oxygen for 1 h, followed by 21% oxygen for 3 h. Sham-operated control piglets had no H/R. Hemodynamic parameters in the piglets were continuously measured. At the end of experiment, hearts were isolated for proteomic analysis. In asphyxiated hearts, the level of isocitrate dehydrogenase and malate dehydrogenase was reduced compared to controls. Inverse correlations between the level of myocardial malate dehydrogenase and cardiac function were observed in the control, but not the H/R hearts. We conclude that reoxygenation of asphyxiated newborn piglets reduces the level of myocardial isocitrate dehydrogenase and malate dehydrogenase. While the cause is not clear, it may be related to the impaired tricarboxylic acid cycle pathway and energy production in the heart.