Pulmonary hypertension in the newborn GTP cyclohydrolase I-deficient mouse

Tetrahydrobiopterin (BH4) is a regulator of endothelial nitric oxide synthase (eNOS) activity. Deficient levels result in eNOS uncoupling, with a shift from nitric oxide to superoxide generation. The hph-1 mutant mouse has deficient GTP cyclohydrolase I (GTPCH1) activity, resulting in low BH4 tissue content. The adult hph-1 mouse has pulmonary hypertension, but whether such condition is present from birth is not known. Thus, we evaluated newborn animals’ pulmonary arterial medial thickness, biopterin content (BH4 + BH2), H₂O₂ and eNOS, right ventricle-to-left ventricle + septum (RV/LV + septum) ratio, near-resistance pulmonary artery agonist-induced force, and endothelium-dependent and -independent relaxation. The lung biopterin content was inversely related to age for both types, but significantly lower in hph-1 mice, compared to wild-type animals. As judged by the RV/LV + septum ratio, newborn hph-1 mice have pulmonary hypertension and, after a 2-week 13% oxygen exposure, the ratios were similar in both types. The pulmonary arterial agonist-induced force was reduced (P < 0.01) in hph-1 animals and no type-dependent difference in endothelium-dependent or -independent vasorelaxation was observed. Compared to wild-type mice, the lung H₂O₂ content was increased, whereas the eNOS expression was decreased (P < 0.01) in hph-1 animals. The pulmonary arterial medial thickness, a surrogate marker of vascular remodeling, was increased (P < 0.01) in hph-1 compared to wild-type mice. In conclusion, our data suggest that pulmonary hypertension is present from birth in the GTPCH1-deficient mice, not as a result of impaired vasodilation, but secondary to vascular remodeling.     

Acid-base homeostasis of the newborn calf

Homeostasis of acid-base condition in newborn calves is ensured with metabolic, respiration--excretion and buffer systems, which allows for fast adaptation of animals to new living condition.     

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.     

Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency.

Insights into muscle energetics during exercise (e.g., muscular efficiency) are often inferred from measurements of pulmonary gas exchange. This procedure presupposes that changes of pulmonary O2 (VO2) associated with increases of external work reflect accurately the increased muscle VO2. The present investigation addressed this issue directly by making simultaneous determinations of pulmonary and leg VO2 over a range of work rates calculated to elicit 20-90% of maximum VO2 on the basis of prior incremental (25 or 30 W/min) cycle ergometry. VO2 for both legs was calculated as the product of twice one-leg blood flow (constant-infusion thermodilution) and arteriovenous O2 content difference across the leg. Measurements were made 3-5 min after each work rate imposition to avoid incorporation of the VO2 slow component above the lactate threshold. For all 17 subjects, the slope of pulmonary VO2 (9.9 +/- 0.2 ml O2.W-1.min-1) was not different (P greater than 0.05) from that for leg VO2 (9.2 +/- 0.6 ml O2.W-1.min-1). Estimation of "delta" efficiency (i.e., delta work accomplished divided by delta energy expended, calculated from slope of VO2 vs. work rate and a caloric equivalent for O2 of 4.985 cal/ml) using pulmonary VO2 measurements (29.1 +/- 0.6%) was likewise not significantly different (P greater than 0.05) from that made using leg VO2 measurements (33.7 +/- 2.4%). These data suggest that the net VO2 cost of metabolic "support" processes outside the exercising legs changes little over a relatively broad range of exercise intensities. Thus, under the conditions of this investigation, changes of VO2 measured from expired gas reflected closely those occurring within the exercising legs.     

Pulmonary hypertension associated with sarcoidosis

Pulmonary involvement is common in sarcoidosis, an immune-mediated inflammatory disorder that is characterized by non-caseating granulomas in tissue. Sarcoid patients with advanced pulmonary disease, especially end-stage pulmonary fibrosis, risk developing pulmonary hypertension (World Health Organization group III pulmonary hypertension secondary to hypoxic lung disease). Increased levels of endothelin (ET)-1 in plasma and bronchoalveolar lavage of some sarcoid patients suggest that ET-1 may be driving pulmonary fibrosis and sarcoidosis-associated pulmonary hypertension. Although a relationship between raised levels of ET-1 and clinical phenotype is yet to be identified, early evidence from studies of ET-1 blockade with drugs such as bosentan is encouraging. Such therapy possibly could be combined with standard anti-inflammatory agents to improve outcome.     

Maternal influence on defecation and urination in the newborn calf

Defecation and urination were observed in newborn calves which were kept either with their dam or separately in individual boxes. Of 39 mother-reared calves, 8 defecated and 9 urinated within 4 h after birth. All these excretions occurred while the dam licked the ano-genital region of the calf. Four of the 8 defecations and 5 urinations were not preceeded by any colostrum intake. None of the 28 observed isolated calves defecated or urinated within the first 4 h, although they all drank colostrum in this period.In a group of 25 mother-reared calves observed for 24 h, the mean time of first defecation was 6.6 h and the mean time of first urination was 7.4 h post-partum. In a comparable group of 15 isolated calves, the corresponding figures were 11.3 and 15.5 h, respectively. In the mother-reared calves, time of first defecation and time of first urination were significantly correlated with total time previously licked by the mother (r_s = +0.75 and r_s = +0.52, respectively). Fifteen out of 23 first defecations and 11 out of 18 urinations took place during maternal licking of the ano-genital area. Female mother-reared calves urinated earlier for the first time than the male calves, but in the isolated-calves there was no difference between the sexes. As regards time of first defecation, the sexes did not differ in eit     

新生牛血清促牛肾细胞生长试验测定方法的建立

为了建立一种测定新生牛血清促牛肾细胞生长试验的方法,采用测定新生牛血清对原代牛肾细胞培养增殖的克隆率来评价新生牛血清的质量。结果显示,用克隆率大于25%的新生牛血清培养原代牛肾细胞至7～8d时均能形成良好单层,而克隆率小于25%的新生牛血清培养原代牛肾细胞时形成良好单层的时间将延长。由此可得出:对原代牛肾细胞培养增殖的克隆率大于25%的新生牛血清符合口服轮状病毒活疫苗生产的需要,依此结果可进行新生牛血清的筛选。     

Differential cardiorespiratory response to combined exercise with different combinations of forearm and calf exercise

The purpose of this study was to examine whether cardiorespiratory responses to combined rhythmic exercise (60 contractions · min^–1) was affected by different combinations of upper and lower limb exercise in seven healthy women. Six different rhythmic exercises were compared: 6-min rhythmic handgrip at 10% of isometric maximal voluntary contraction (MVC) (H10); 6-min rhythmic plantar flexion at 10% MVC (P10); exhausting rhythmic handgrip at 50% MVC (H50); exhausting rhythmic plantar flexion at 50% MVC (P50); H50 was added to P10 (P1OH50); and P50 was added to H10 (H10P50). Exercise duration, after handgrip was combined with plantar flexion (P10H50), was shorter than that of H50, although the exercise duration of HIOP50 was not significantly different from P50. No significant difference was found between the difference from rest in oxygen uptake ( O₂) during H10P50 and the sum of O₂ during H10 and P50. Also, the differences from rest in forearm blood flow ( FBF) and calf blood flow ( CBF) during H10P50 were not significantly different from FBF in H10 and from CBF in P50. In contrast, O₂ in P10H50 was lower than the sum of O₂ in P10 and H50 (P < 0.05), and J FBF in P10H50 was lower than that in H50 (P < 0.05) , while CBF was not significantly different between P1OH50 and P10. The changes in heart rate from rest (d HR) during the combined exercises were lower than the sums of HR in the corresponding single exercises (P < 0.05). These results demonstrated an inhibitory summation of several cardiorespiratory responses to combined exercise resulting in a reduction in exercise performance which would seem to occur easily when upperlimb exercise is added to lower limb exercise.     

Muscle acidosis during static exercise is associated with calf vasoconstriction

In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, and pH with 31P-nuclear magnetic resonance (31P-NMR) in the human forearm during static work at 30% of maximal voluntary contraction (MVC) for 2 min followed immediately by 3 min of circulatory arrest (forearm arterial occlusion). Static exercise, with its central volitional and skeletal muscle metabolic and mechanical afferent components, caused a rise in heart rate (HR, 32%), blood pressure (BP, 29%), and calf vascular resistance (calf R, 30%). During forearm occlusion after static exercise, HR returned to base line, the increase in BP was attenuated by 30%, and calf R remained elevated and unchanged. The percent change in calf R was correlated with forearm cellular pH (R = 0.56, P less than 0.001) but only weakly associated with PCr/Pi (R = 0.33, P less than 0.042). 30% MVC for 1 min followed by arterial occlusion (3 min) reduced PCr/Pi by 65% and pH by 0.16 U (P less than 0.05). Calf R was unchanged. Circulatory arrest alone (20 min) caused no change in either pH or calf R but large changes in PCr/Pi (50% reduction). We conclude that 1) there is an association between forearm cellular acidosis and calf vasconstriction during static forearm exercise and 2) large changes in PCr/Pi without concomitant changes in pH are not associated with changes in calf R.     

Pulmonary control systems in exercise

We reviewed the response and regulation of alveolar ventilation, chest wall mechanics, and alveolar-to-arterial gas exchange to the demands imposed by increases in tissue metabolic rate. The primary mediator of iso-capnic exercise hyperpnea remains a dilemma--with conflicting evidence presented on both sides of a "CO2 flow" humoral hypothesis versus a "neurogenic" non-humoral hypothesis. The increased expiratory flows and tidal volumes at any given level of hyperpnea are achieved at a "minimum" of increased mechanical work exerted on the lung and chest wall, owing to a control system that has multiple levels of nervous integration (from cortex to spinal motor neuron) readily accessible to a wide variety of sensory information concerning the mechanical status of the lung and respiratory muscles. The maintenance of arterial PO2 in the face of a falling CVO2 during exercise was attributed to a precise regulation over factors that limit diffusion equilibrium and intra- and interregional ventilation: perfusion distributions in the lung. Finally, we noted that the near-optimal nature of these responses and their control during exercise had many exceptions in the real world of physical exercise outside of the laboratory.