Long-term maternal hypoxia: the role of extracellular Ca2+ entry during serotonin-mediated contractility in fetal ovine pulmonary arteries

Antenatal maternal long-term hypoxia (LTH) can alter serotonin (5-HT) and calcium (Ca(2+)) signaling in fetal pulmonary arteries (PAs) and is associated with persistent pulmonary hypertension of the newborn (PPHN). In humans, the antenatal maternal hypoxia can be secondary to smoking, anemia, and chronic obstructive pulmonary disorders. However, the mechanisms of antenatal maternal hypoxia-related PPHN are unresolved. Because both LTH and 5-HT are associated with PPHN, we tested the hypothesis that antenatal maternal LTH can increase 5-HT-mediated PA contraction and associated extracellular Ca(2+) influx through L-type Ca(2+) channels (Ca(L)), nonselective cation channels (NSCCs), and reverse-mode sodium-calcium exchanger (NCX) in the near-term fetus. We performed wire myography and confocal-Ca(2+) imaging approaches on fetal lamb PA (～ 140 days of gestation) from normoxic ewes or those acclimatized to high-altitude LTH (3801 m) for ～110 days. Long-term hypoxia reduced the potency but not the efficacy of 5-HT-induced PA contraction. Ketanserin (100 nmol/L), a 5-HT(2A) antagonist, shifted 5-HT potency irrespective of LTH, while GR-55562 (1 μmol/L), a 5-HT(1B/D) inhibitor, antagonized 5-HT-induced contraction in normoxic fetuses only. Various inhibitors for Ca(L), NSCC, and reverse-mode NCX were used in contraction studies. Contraction was reliant on extracellular Ca(2+) regardless of maternal hypoxia, NSCC was more important to contraction than Ca(L), and reverse-mode NCX had little or no role in contraction. Long-term hypoxia also attenuated the effects of 2-APB and flufenamic acid and reduced Ca(2+) responses observed by imaging studies. Overall, LTH reduced 5HT(1B/D) function and increased NSCC-related Ca(2+)-dependent contraction in ovine fetuses, which may compromise pulmonary vascular function in the newborn.     

Does eccentric exercise reduce pain and improve strength in physically active adults with symptomatic lower extremity tendinosis? A systematic review

OBJECTIVE: To critically review evidence for the effectiveness of eccentric exercise to treat lower extremity tendinoses. DATA SOURCES: Databases used to locate randomized controlled trials (RCTs) included PubMed (1980-2006), CINAHL (1982-2006), Web of Science (1995-2006), SPORT Discus (1980-2006), Physiotherapy Evidence Database (PEDro), and the Cochrane Collaboration Database. Key words included tendon, tendonitis, tendinosis, tendinopathy, exercise, eccentric, rehabilitation, and therapy. STUDY SELECTION: The criteria for trial selection were (1) the literature was written in English, (2) the research design was an RCT, (3) the study participants were adults with a clinical diagnosis of tendinosis, (4) the outcome measures included pain or strength, and (5) eccentric exercise was used to treat lower extremity tendinosis. DATA EXTRACTION: Specific data were abstracted from the RCTs, including eccentric exercise protocol, adjunctive treatments, concurrent physical activity, and treatment outcome. DATA SYNTHESIS: The calculated post hoc statistical power of the selected studies (n = 11) was low, and the average methodologic score was 5.3/10 based on PEDro criteria. Eccentric exercise was compared with no treatment (n = 1), concentric exercise (n = 5), an alternative eccentric exercise protocol (n = 1), stretching (n = 2), night splinting (n = 1), and physical agents (n = 1). In most trials, tendinosis-related pain was reduced with eccentric exercise over time, but only in 3 studies did eccentric exercise decrease pain relative to the control treatment. Similarly, the RCTs demonstrated that strength-related measures improved over time, but none revealed significant differences relative to the control treatment. Based on the best evidence available, it appears that eccentric exercise may reduce pain and improve strength in lower extremity tendinoses, but whether eccentric exercise is more effective than other forms of therapeutic exercise for the resolution of tendinosis symptoms remains questionable.