Differences in forearm strength, endurance, and hemodynamic kinetics between male boulderers and lead rock climbers.

This study examined differences in the oxygenation kinetics and strength and endurance characteristics of boulderers and lead sport climbers. Using near infrared spectroscopy, 13-boulderers, 10-lead climbers, and 10-controls completed assessments of oxidative capacity index and muscle oxygen consumption (m⩒O2) in the flexor digitorum profundus (FDP), and extensor digitorum communis (EDC). Additionally, forearm strength (maximal volitional contraction MVC), endurance (force-time integral FTI at 40% MVC), and forearm volume (FAV and ΔFAV) was assessed. MVC was significantly greater in boulderers compared to lead climbers (mean difference = 9.6, 95% CI 5.2-14 kg). FDP and EDC oxidative capacity indexes were significantly greater (p = .041 and .013, respectively) in lead climbers and boulderers compared to controls (mean difference = -1.166, 95% CI (-3.264 to 0.931 s) and mean difference = -1.120, 95% CI (-3.316 to 1.075 s), respectively) with no differences between climbing disciplines. Climbers had a significantly greater FTI compared to controls (mean difference = 2205, 95% CI= 1114-3296 and mean difference = 1716, 95% CI = 553-2880, respectively) but not between disciplines. There were no significant group differences in ΔFAV or m⩒O2. The greater MVC in boulderers may be due to neural adaptation and not hypertrophy. A greater oxidative capacity index in both climbing groups suggests that irrespective of climbing discipline, trainers, coaches, and practitioners should consider forearm specific aerobic training to aid performance.

Impact-induced muscle damage and urinary pterins in professional rugby: 7,8-dihydroneopterin oxidation by myoglobin.

Muscle damage caused through impacts in rugby union is known to increase oxidative stress and inflammation. Pterins have been used clinically as markers of oxidative stress, inflammation, and neurotransmitter synthesis. This study investigates the release of myoglobin from muscle tissue due to force-related impacts and how it is related to the subsequent oxidation of 7,8-dihydroneopterin to specific pterins. Effects of iron and myoglobin on 7,8-dihydroneopterin oxidation were examined in vitro via strong cation-exchange high-performance liquid chromatography (SCX-HPLC) analysis of neopterin, xanthopterin, and 7,8-dihydroxanthopterin. Urine samples were collected from 25 professional rugby players pre and post four games and analyzed for myoglobin by enzyme-linked immunosorbent assay, and 7,8-dihydroneopterin oxidation products by HPLC. Iron and myoglobin oxidized 7,8-dihydroneopterin to neopterin, xanthopterin, and 7,8-dihydroxanthopterin at concentrations at or above 10 µM and 50 µg/mL, respectively. All four games showed significant increases in myoglobin, neopterin, total neopterin, biopterin, and total biopterin, which correlated between each variable (P < 0.05). Myoglobin and iron facilitate 7,8-dihydroneopterin oxidation to neopterin and xanthopterin. In vivo delocalization of myoglobin due to muscle damage may contribute to oxidative stress and inflammation after rugby. Increased concentrations of biopterin and total biopterin may indicate production of nitric oxide and monoamine neurotransmitters in response to the physical stress.

Assessing the Effectiveness of Selected Biomarkers in the Acute and Cumulative Physiological Stress Response in Professional Rugby Union through Non-invasive Assessment.

Rugby union is a sport involving high force and frequency impacts making the likelihood of injury a significant risk. The aim of this study was to measure and report the individual and group acute and cumulative physiological stress response during 3 professional rugby games through non-invasive sampling. 24 professional rugby players volunteered for the study. Urine and saliva samples were collected pre and post 3 matches. Myoglobin, salivary immunoglobulin A, cortisol, neopterin and total neopterin (neopterin+7,8-dihydroneopterin) were analysed by high performance liquid chromatography or enzyme linked immunosorbent assay. Significant increases in cortisol, myoglobin, neopterin and total neopterin when urine volume was corrected with specific gravity were observed (p<0.05). Significant decreases in salivary immunoglobulin A concentration were observed for games 1 and 2 while secretion rate decreased after games 2 and 3. Significant decreases were seen with the percent of 7,8-dihydroneopterin being converted to neopterin following games 2 and 3. The intensity of 3 professional rugby games was sufficient to elicit significant changes in the physiological markers selected for our study. Furthermore, results suggest the selected markers not only provide a means for analysing the stress encountered during a single game of rugby but also highlight the unique pattern of response for each individual player.

Haemodynamic kinetics and intermittent finger flexor performance in rock climbers.

Currently it is unclear whether blood flow (BF) or muscle oxidative capacity best governs performance during intermittent contractions to failure. The aim of this study was to determine oxygenation kinetics and BF responses during intermittent (10 s contraction: 3 s release) contractions at 40% of MVC in rock climbers of different ability (N=38). Total forearm BF, as well as de-oxygenation and re-oxygenation of the flexor digitorum profundus (FDP) and the flexor carpi radialis (FCR) were assessed. Compared to the control, intermediate and advanced groups, the elite climbers had a significantly (p<0.05) greater force time integral (FTI), MVC and MVC/kg. Furthermore, the elite climbers de-oxygenated the FDP significantly more during the first (7.8, 11.9, 12.4 vs. 15.7 O2%) and middle (7.3, 8.8, 10.4 vs.15.3 O2%) phases of contractions as well as for the FCR during the first phase only (8.3, 7, 11.7 vs. 13.3 O2%). They also had a significantly higher BF upon release of the contractions (656, 701, 764 vs. 971 mL ∙ min(-1)). The higher FTI seen in elite climbers may be attributable to a greater blood delivery, and an enhanced O2 recovery during the 3 s release periods, as well as a superior muscle oxidative capacity associated with the greater de-oxygenation during the 10 s contractions.

A psychophysiological comparison of on-sight lead and top rope ascents in advanced rock climbers.

Research suggests that lead climbing is both physiologically and psychologically more stressful than top rope climbing for intermediate performers. This observation may not be true for advanced climbers, who train regularly on lead routes and are accustomed to leader falls. The aim of this study was to compare the psychophysiological stresses of lead and top rope on-sight ascents in advanced rock climbers. Twenty-one climbers (18 men and three women) ascended routes near or at the best of their ability (22 Ewbank). Psychological stress was measured preclimb using the Revised Comparative State Anxiety Inventory (CSAI-2R). Plasma cortisol was sampled at six intervals. The volume of oxygen (VO2 ) and heart rate (Hr) were measured throughout the climbs. No significant differences were found in self-confidence, somatic, or cognitive anxiety between the conditions lead and top rope. No significant differences in plasma cortisol concentration were found between any time points. No significant relationships were found between cortisol and any CSAI-2R measures. No significant differences were found between conditions for VO2 or blood lactate concentration. During the lead climb, Hr was significantly elevated during the last part of the route. Findings suggest that advanced rock climbers do not find lead climbing to be more stressful than top rope climbing during an on-sight ascent.

Comparison of plasma cortisol sampling sites for rock climbing.

AIM: Blood samples for the determination of plasma cortisol concentration are generally obtained via venipuncture or capillary sampling at the fingertip. During rock climbing the upper body, forearms and fingertips are subject to continual loading and gripping making sampling at these sites problematic. The purpose of this study was to examine differences in plasma cortisol concentrations from capillary samples taken at the fingertip and first (big) toe in a rock climbing context. METHODS: Nine (8 males, 1 female) climbers completed a succession of climbing bouts at three different angles (91°,100° and 110°). Capillary blood samples were taken simultaneously from the fingertip and first toe pre and post climb at each angle. Plasma samples were collected via centrifugation and subsequently analysed for cortisol using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. All standards and samples were analysed in duplicate. Intra assay coeffiecients of variation (CV%) were 5.91% and 7.94% for finger and toe respectively. RESULTS: A limits of agreement plot revealed all data points to be well within upper and lower bounds of the 95% population confidence interval. Paired samples t-tests (for finger and toe) indicated there were no significant differences between sample sites. Subsequent regression analysis revealed a strong relationship (R2=0.78, y=1.031x - 2.079) between fingertip and first toe capillary plasma cortisol concentrations. CONCLUSION: Findings suggest that the first toe offers a valid alternative sampling site for plasma cortisol concentration in a rock climbing context.

Capillary cortisol sampling during high-intensity exercise.

Venepuncture is the established "gold standard" for sampling cortisol, but it is expensive, highly invasive and impractical for many experimental and clinical settings. Salivary free cortisol is a non-invasive and practical alternative; however, when cortisol concentrations exceed 500 nmol · L there is a lack of agreement between salivary (free) and venous (bound) cortisol. No known research has assessed whether capillary cortisol accurately reflects venous blood cortisol across a range of concentrations. The objective of the current study was to determine the agreement between capillary and venous blood samples of total plasma cortisol across a range of concentrations. 11 healthy male subjects (26.1 ± 5.3 years) were recruited. Capillary and venous blood samples were collected pre and post (immediately post and post 5, 10, 15 and 20 min) a treadmill VO2max test. Regression analysis revealed a strong relationship (R2=0.96, y=1.0028x + 1.2964 (P<0.05)) between capillary and venous cortisol concentrations. A Bland-Altman plot showed all data was within the upper and lower bounds of the 95% confidence interval, and no systematic bias was evident. In conclusion, capillary sampling is a valid technique for measuring bound cortisol across a range of concentrations.

Plasma cortisol concentrations and perceived anxiety in response to on-sight rock climbing.

Previous research suggested plasma cortisol concentrations in response to rock climbing have a cubic relationship with state anxiety and self-confidence. This research, however, was conducted in a situation where the climbers had previously climbed the route. The purpose of our study was to examine this relationship in response to on-sight climbing. Nineteen (13 male, 6 female) intermediate climbers volunteered to attend anthropometric and baseline testing sessions, prior to an on-sight ascent (lead climb or top-rope) of the test climb (grade 19 Ewbank/6a sport/5.10b YDS). Data recorded included state anxiety, self-confidence and cortisol concentrations prior to completing the climb. Results indicated that there were no significant differences in state anxiety, self-confidence and plasma cortisol concentration regardless of the style of ascent (lead climb or top-rope) in an on-sight sport climbing context. Regression analysis indicated there was a significant linear relationship between plasma cortisol concentrations and self-confidence (r= - 0.52, R2=0.267, p=0.024), cognitive (r=0.5, R2=0.253, p=0.028), and somatic anxieties (r=0.46, R2=0.210, p=0.049). In an on-sight condition the relationships between plasma cortisol concentrations with anxiety (cognitive and somatic) and self-confidence were linear.

Sport-specific power assessment for rock climbing.

AIM: The popularity of rock climbing has resulted in a growing research base for the sport. However, at present there is a lack of sport-specific measures of performance in the field. The aim of this study was to examine the use of the powerslap test as a sport specific power measure. METHODS: The participants in this study were categorised into four different ability groups (novice, intermediate, advanced and elite) based on self reported lead grade. Two separate experiments were conducted to determine validity and reliability. The powerslap test was conducted on a revolution board with two variations - wide and narrow grip, for both sides of the body. The test started with the climber hanging at full extension from two holds from which a pull up movement was made releasing one hand to slap a scaled score board above. RESULTS: There was a significant relationship between powerslap scores and climbing ability (Left Wide: r=0.7, P<0.0005; right wide: r=0.69, P<0.0005; left narrow: r=0.73, P<0.0005; right narrow: r =0.72, P<0.0005). Further to this, scores on the powerslap narrow test were significantly differentiated by climber ability (LEFT: F(3,37)=15.74, P<0.0005; right: F(3,37)=12.16, P<0.0005). Limits of agreement and intra-class correlation indicated that the powerslap test is a reliable performance measure. CONCLUSION: According to the present findings the narrow grip variation of the powerslap test is a useful sport-specific power test that is related to climbing performance.

Comparison of lactate sampling sites for rock climbing.

Comparisons of capillary blood lactate concentrations pre and post climb have featured in the protocols of many rock climbing studies, with most researchers obtaining samples from the fingertip. The nature of rock climbing, however, places a comparatively high physiological loading on the foreaand fingertips. Indeed, the fingertips are continually required for gripping and this makes pre-climb sampling at this site problematic. The purpose of our study was to examine differences in capillary blood lactate concentrations from samples taken at the fingertip and first (big) toe in a rock climbing context. 10 participants (9 males and 1 female) completed climbing bouts at 3 different angles (91°, 100° and 110°). Capillary blood samples were taken simultaneously from the fingertip and first toe pre and post climb. A limit of agreement plot revealed all data points to be well within the upper and lower bounds of the 95% population confidence interval. Subsequent regression analysis revealed a strong relationship (R (2)=0.94, y=0.940x + 0.208) between fingertip and first toe capillary blood lactate concentrations. Findings from our study suggest that the toe offers a valid alternative site for capillary blood lactate concentration analysis in a rock climbing context.

Perceived anxiety and plasma cortisol concentrations following rock climbing with differing safety rope protocols.

OBJECTIVES: To examine how different safety rope protocols impact on subjective anxiety and self-confidence levels and plasma cortisol concentrations and the relationship between subjective states and cortisol during rock climbing. METHODS: Participants (n = 12) were tested in three climbing conditions that were designed to invoke low, moderate and high physical and mental stress. Plasma cortisol concentrations were collected before and after climbing and participants reported subjective anxiety and self-confidence states for each climb. RESULTS: Repeated measures analysis of variance showed significant differences between conditions for somatic anxiety (F(2, 22) = 7.74, p = 0.009), self-confidence (F(2, 22) = 9.52, p = 0.001) and change in plasma cortisol concentration (F(2, 22) = 3.71, p = 0.041). Preplanned polynomial comparisons showed that these were linear effects; somatic anxiety was higher in the higher stress conditions whilst self-confidence was lower. Plasma cortisol concentration change was also linear. Regression analyses showed cubic relationships between plasma cortisol concentration and cognitive anxiety (R(2) = 0.452), self-confidence (R(2) = 0.281) and somatic anxiety (R(2) = 0.268). CONCLUSIONS: There is a relationship between plasma cortisol concentration and subjective anxiety and self-confidence states during rock climbing. Changes in the way the safety rope is organised can impact on anxiety, cortisol concentration and self-confidence during rock climbing.

Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.

RATIONALE: Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Therefore, creatine supplementation should lessen the negative effects of sleep deprivation. OBJECTIVES: The objective of this study was to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. METHOD: Subjects were divided into a creatine group (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a time a day for 7 days, immediately prior to the experiment. The study was double blind. Subjects undertook tests of random movement generation (RMG), verbal and spatial recall, choice reaction time, static balance and mood state pre-test (0 h), after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 h. RESULTS: At 24 h, the creatine group demonstrated significantly less change in performance from 0 h (delta) in RMG, choice reaction time, balance and mood state. There were no significant differences between groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 h than 0 h, but cortisol were lower. CONCLUSIONS: Following 24-h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex.

Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population.

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a crucial role in converting hormonally active cortisol to inactive cortisone, thereby conferring specificity upon the mineralocorticoid receptor (MR). Mutations in the gene encoding 11beta-HSD2 (HSD11B2) account for an inherited form of hypertension, the syndrome of "Apparent Mineralocorticoid Excess" (AME) where cortisol induces hypertension and hypokalaemia. We report five different mutations in the HSD11B2 gene in four families from Oman with a total of 9 affected children suffering from AME. Sequence data demonstrate the previously described L114Delta6nt mutation in exon 2 and new mutations in exon 3 (A221V), exon 5 (V322ins9nt) and for the first time in exon 1 (R74G and P75Delta1nt) of the HSD11B2 gene. These additional mutations provide further insight into AME and the function of the 11beta-HSD2 enzyme. The prevalence of monogenic forms of hypertension such as AME remains uncertain. However, our data suggests AME may be a relevant cause of hypertension in certain ethnic groups, such as the Oman population.

Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism.

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an oxo-reductase (E to F) expressed in several glucocorticoid target tissues, including liver and adipose tissue, where it facilitates glucocorticoid-induced gluconeogenesis and adipocyte differentiation, respectively. We have isolated a full-length HSD11B1 genomic clone; the gene is more than 30 kb in length, not 9 kb in length as previously reported, principally due to a large intron 4. Two polymorphic (CA)(n) repeats have been characterized within intron 4: a CA(19) repeat 2.7 kb 3' of exon 4 and a CA(15) repeat 3 kb 5' of exon 5. The microsatellites, CA(19) and CA(15), were PCR amplified using fluorescent primers and were genotyped on an ABI 377 DNA sequencer from DNA of 413 normal individuals enrolled in the MONICA study of cardiovascular risk factors and 557 Danish men (ADIGEN study), of whom 234 were obese [body mass index (BMI), >/=31 kg/m(2) ] at draft board examination and 323 were randomly selected controls from the draftee population with BMI below 31 kg/m(2) (mean +/- SE, 21.7 +/- 0.41). Genotypic data from the normal MONICA cohort was compared with gender, 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio, and waist to hip (W:H) ratio. When analyzed by allele length (0, 1, or 2 short alleles) for the CA(19) marker, there was a trend toward a higher 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio (P = 0.058) and an increased W:H ratio (2 vs. 0.1 short; P(c) = 0.10) with overrepresentation of short alleles. The opposite was true for the CA(15) locus, with longer alleles at this locus predicting increased 11beta-HSD1 activity, particularly in females. Genotypic data from the ADIGEN case-control population was compared with clinical markers of obesity such as BMI and W:H ratio. There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.

Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms.

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) inactivates cortisol to cortisone. In the placenta 11beta-HSD2 activity is thought to protect the fetus from the deleterious effects of maternal glucocorticoids. Patients with apparent mineralocorticoid excess owing to mutations in the 11beta-HSD2 gene invariably have reduced birth weight, and we have recently shown reduced placental 11beta-HSD2 activity in pregnancies complicated by intrauterine growth restriction. This is reflected in the literature by evidence of hypercortisolemia in the fetal circulation of small babies. In this study we have determined the levels of placental 11beta-HSD2 mRNA expression across normal gestation (n = 86 placentae) and in pregnancies complicated by intrauterine growth restriction (n = 19) and evaluated the underlying mechanism for any aberrant 11beta-HSD2 mRNA expression in intrauterine growth restriction. 11beta-HSD2 mRNA expression increased more than 50-fold across gestation, peaking at term. Placental 11beta-HSD2 mRNA levels were significantly decreased in intrauterine growth restriction pregnancies when compared with gestationally matched, appropriately grown placentae [e.g. at term DeltaCt (11beta-hydroxysteroid dehydrogenase type 2/18S) 12.8 +/- 0.8 (mean +/- SE) vs. 10.2 +/- 0.2, respectively, P < 0.001]. These differences were not attributable to changes in trophoblast mass in intrauterine growth restriction placentae, as assessed by parallel analyses of cytokeratin-8 mRNA expression. No mutations were found in the 11beta-HSD2 gene in the intrauterine growth restriction cohort, and imprinting analysis revealed that the 11beta-HSD2 gene was not imprinted. Although the underlying cause is unknown, 11beta-HSD2 gene expression is reduced in intrauterine growth restriction pregnancies. These data highlight the important role of 11beta-HSD2 in regulating fetal growth, a known factor in determining fetal morbidity but also the subsequent development of cardiovascular disease in adulthood.

Ca2+-independent inhibition of myocardial contraction by coronary effluent of hypoxic rat hearts.

Endothelial cells release agents that influence cardiac contraction. We recently reported that cultured hypoxic endothelial cells release an unidentified factor(s) that inhibits myocardial contraction. In this study, we investigated the effects of coronary effluent of isolated hypoxic rat hearts on isolated rat ventricular myocyte contraction. Coronary effluent collected during brief moderate hypoxia significantly depressed myocyte twitch shortening and decreased diastolic length, with only minor reduction in intracellular Ca2+ transients. These effects were similar to those of hypoxic rat coronary microvascular endothelial cell superfusates and were reversed by reoxygenation of hearts. "Hypoxic" coronary effluent exerted essentially Ca2+-independent effects on myofilament interaction in intact myocytes, as assessed by 1) peak Ca2+-shortening relations, 2) phase-plane analysis of instantaneous Ca2+-cell length relations, and 3) "steady-state" myofilament responses in tetanized, sarcoplasmic reticulum-disabled cells. Thus an unidentified substance(s) that inhibits myocyte shortening predominantly via effects on the myofilaments is reversibly released during acute moderate hypoxia of isolated hearts, presumably from coronary endothelial cells. Release of such an agent may be relevant to the cardiac contractile response to hypoxia.

Expression of functional neutrophil-type NADPH oxidase in cultured rat coronary microvascular endothelial cells.

OBJECTIVES: The production of reactive oxygen species (e.g., superoxide) by endothelial cells is relevant to tissue injury during ischemia-reperfusion, and may also play a role in intracellular signaling pathways. However, the molecular identities of the enzymes responsible for endothelial superoxide production are poorly defined, although xanthine oxidase, NADH/NADPH oxidoreductases and nitric oxide synthase are among proteins suggested to contribute. Recent studies suggest that an NADH/NADPH oxidase similar to that found in neutrophils is an important source of superoxide in vascular smooth muscle. METHODS: We investigated whether a phagocyte-type NADH/NADPH oxidase complex is present in rat cultured coronary microvascular endothelial cells. The expression of NADPH oxidase components was studied by RT-PCR and Western blot analyses, while functional activity was assessed by measurement of superoxide production by lucigenin-enhanced chemiluminescence. RESULTS: The major component of the phagocyte-type NADH/NADPH oxidase complex, a cytochrome b558 heterodimer, was shown to be present both at mRNA and protein levels, using oligonucleotide primers designed from published neutrophil and vascular smooth muscle sequences and anti-neutrophil antibodies respectively. Functional activity of the enzyme was also confirmed by NADPH-evoked superoxide production in cell homogenates, which was inhibited either by the superoxide chelator Tiron or by diphenyleneiodonium, an inhibitor of the oxidase. CONCLUSIONS: A functional phagocyte-type NADPH oxidase is expressed in coronary microvascular endothelial cells, where it may contribute to the physiological and/or pathophysiological effects of reactive oxygen species. These data, together with reports of the presence of a similar oxidase in other non-phagocytic cell types, suggest that this enzyme complex is widely expressed in many tissues where it may subserve signaling and other functions.

Beneficial effects of a nitric oxide donor on recovery of contractile function following brief hypoxia in isolated rat heart.

Brief myocardial hypoxia causes both systolic and diastolic dysfunction, the latter often persisting during re-oxygenation. The underlying mechanisms may involve cytosolic Ca2+ overload as well as altered myofilament properties. Recent studies show that nitric oxide enhances myocardial relaxation via a cGMP-induced reduction in myofilament response to Ca2+. We studied the effects of pretreatment with a nitric oxide donor, sodium nitroprusside (0.1-1 microM) on the response to 5 min hypoxia in isovolumic rat hearts perfused at constant coronary flow. Left ventricular relaxation was assessed by an exponential time constant of pressure fall. Sodium nitroprusside reduced the depression of peak left ventricular pressure and peak dP/dt during hypoxia, and improved left ventricular relaxation both during hypoxia and re-oxygenation. Similar results were observed with a Ca2+ antagonist, nicardipine (10 nM). However, adenosine (400 nM), which reduced coronary perfusion pressure to a similar extent as the other two drugs, failed to improve left ventricular function. Addition of sodium nitroprusside or nicardipine at re-oxygenation did not improve relaxation, but instead impaired recovery of peak left ventricular pressure. These results suggest that exogenous nitric oxide improves LV contractile function, in particular relaxation, during brief hypoxia-re-oxygenation independent of changes in coronary flow or coronary perfusion pressure. Its failure to be protective if administered only during re-oxygenation suggests that its action does not involve an anti-oxidant effect.

Determining compliance with a dietary fiber supplement.

The purpose of this pilot study was to evaluate possible ways to determine compliance with a dietary fiber supplement. A wheat bran supplement (30 g daily) significantly increased mean daily wet and dry stool weights (SW) in 7 adults, when compared to SW during an ad libitum low-fiber diet (paired t-test, P less than .01). Because unpaired data would be used during a clinical trial, distribution of the 7 ad libitum low-fiber mean SW observations was used to establish a reference distribution and an upper confidence limit against which the bran supplement SW could be compared. Only one of the seven bran supplement mean SW was above the confidence limit of the low-fiber period, independent of the number of days of collection (2-10) used to calculate the individual mean daily SW. Total fecal output over varying periods of time (2-10 days) suffered the same intersubject and intrasubject variability. Most (5-6) of the bran mean daily SW were above the group mean SW of the low-fiber period. However, this dose of bran was large enough to significantly decrease calcium absorption, and differences in SW produced by lower doses of wheat bran would probably not be as great. The bulk (greater than or equal to 80%) of a single dose of a fecal marker, chromium sesquioxide, which could be incorporated into a specific day's fiber supplement, was recovered in 5 days of excretion during the control period and in 4 days during the bran period. However, the blue color of the chromium before ingestion is clearly a negative feature. Another marker, polyethylene glycol, could not be recovered in excreta when transient time was 4 days or more. In a separate study, demonstration of very little overlap in the concentration of fecal neutral detergent fiber between the control and bran periods suggests that fecal fiber may be a marker of compliance with a fiber supplement.