The 110-kD spindle pole body component of Saccharomyces cerevisiae is a phosphoprotein that is modified in a cell cycle-dependent manner.

Spc110p (Nuf1p) is an essential component of the yeast microtubule organizing center, or spindle pole body (SPB). Asynchronous wild-type cultures contain two electrophoretically distinct isoforms of Spc110p as detected by Western blot analysis, suggesting that Spc110p is modified in vivo. Both isoforms incorporate 32Pi in vivo, suggesting that Spc110p is post-translationally modified by phosphorylation. The slower-migrating 120-kD Spc110p isoform after incubation is converted to the faster-migrating 112-kD isoform after incubation with protein phosphatase PP2A, and specific PP2A inhibitors block this conversion. Thus, additional phosphorylation of Spc110p at serine and/or threonine residues gives rise to the slower-migrating 120-kD isoform. The 120-kD isoform predominates in cells arrested in mitosis by the addition of nocodazole. However, the 120-kD isoform is not detectable in cells grown to stationary phase (G0) or in cells arrested in G1 by the addition of alpha-factor. Temperature-sensitive cell division cycle (cdc) mutations demonstrate that the presence of the 120-kD isoform correlates with mitotic spindle formation but not with SPB duplication. In a synchronous wild-type population, the additional serine/threonine phosphorylation that gives rise to the 120-kD isoform appears as cells are forming the mitotic spindle and diminishes as cells enter anaphase. None of several sequences similar to the consensus for phosphorylation by the Cdc28p (cdc2p34) kinase is important for these mitosis-specific phosphorylations or for function. Carboxy-terminal Spc110p truncations lacking the calmodulin binding site can support growth and are also phosphorylated in a cell cycle-specific manner. Further truncation of the Spc110p carboxy terminus results in mutant proteins that are unable to support growth and now migrate as single species. Collectively, these results provide the first evidence of a structural component of the SPB that is phosphorylated during spindle formation and dephosphorylated as cells enter anaphase.

DNA-binding activities of Hop1 protein, a synaptonemal complex component from Saccharomyces cerevisiae.

The meiosis-specific HOP1 gene is important both for crossing over between homologs and for production of viable spores. hop1 diploids fail to assemble synaptonemal complex (SC), which normally provides the framework for meiotic synapsis. Immunochemical methods have shown that the 70-kDa HOP1 product is a component of the SC. To assess its molecular function, we have purified Hop1 protein to homogeneity and shown that it forms dimers and higher oligomers in solution. Consistent with the zinc-finger motif in its sequence, the purified protein contained about 1 mol equivalent of zinc whereas mutant protein lacking a conserved cysteine within this motif did not. Electrophoretic gel mobility shift assays with different forms of M13 DNA showed that Hop1 binds more readily to linear duplex DNA and negatively superhelical DNA than to nicked circular duplex DNA and even more weakly to single-stranded DNA. Linear duplex DNA binding was enhanced by the addition of Zn2+, was stronger for longer DNA fragments, and was saturable to about 55 bp/protein monomer. Competitive inhibition of this binding by added oligonucleotides suggests preferential affinity for G-rich sequences and weaker binding to poly(dA-dT). Nuclear extracts of meiotic cells caused exonucleolytic degradation of linear duplex DNA if the extracts were prepared from hop1 mutants; addition of purified Hop1 conferred protection against this degradation. These findings suggest that Hop1 acts in meiotic synapsis by binding to sites of double-strand break formation and helping to mediate their processing in the pathway to meiotic recombination.

A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.

age-1(hx546) is a recessive mutant allele in Caenorhabditis elegans that results in an increase in mean life span averaging 40% and in maximal life span averaging 60% at 20 degrees; at 25 degrees age-1(hx546) averages a 65% increase in mean life span (25.3 days vs. 15.0 days) and a 110% increase in maximum life span (46.2 days vs. 22.0 days for wild-type hermaphrodites). Mutant males also show extended life spans. age-1(hx546) is associated with a 75% decrease in hermaphrodite self-fertility as compared to the age-1+ allele at 20 degrees. Using two novel strategies for following the segregation of age-1, we present evidence that longer life results from a mutation in a single gene that increases the probability of survival at all chronological ages. The long-life and reduced-fertility phenotypes cosegregate and are tightly linked to fer-15, a locus on linkage group II. age-1(hx546) does not affect the timing of larval molts, the length of embryogenesis, food uptake, movement, or behavior in any way tested. Although age-1(hx546) lowers hermaphrodite self-fertility, it does not markedly affect the length of the reproductive period with all the increase in life expectancy due to an increase in the length of postreproductive life. In so far as we are aware, this mutant in age-1 is the only instance of a well-characterized genetic locus in which the mutant form results in lengthened fife. It is likely that the action of age-1 in lengthening life results not from eliminating a programmed aging function but rather from reduced hermaphrodite self-fertility or from some other unknown metabolic or physiologic alteration.

Insertional mutations in the yeast HOP1 gene: evidence for multimeric assembly in meiosis.

The HOP1 gene of Saccharomyces cerevisiae has been shown to play an important role in meiotic synapsis. In this study we analyzed the mechanism of this function by phenotypic characterization of novel in-frame linker-insertion mutations located at various sites throughout the HOP1 coding sequence. Among 12 mutations found to cause defects in meiotic recombination and spore viability, three were temperature-sensitive for the spore viability defect. Although substantial meiotic recombination was found for these conditional alleles at the restrictive temperature, the level of exchange measured in spo13 meiosis was reduced in some of the monitored intervals, indicating that nondisjunction resulting from a deficit in crossing over could account for SPO13 spore inviability. Intragenic complementation between linker-insertion alleles was assessed by testing the viability of spores generated from heteroallelic diploids after SPO13 meiosis. Complex patterns of complementation and enhancement of the spore-inviability phenotype indicate that HOP1 functions in a multimeric complex. In addition, the ability of alleles which map near the carboxyl terminus to complement several other alleles provides evidence for a functional domain in this region of the protein. Two previously identified multicopy suppressors of the conditional hop1-628ts allele were tested for their effects in cells bearing the linker-insertion hop1 alleles. Overexpression of REC104 from a 2 mu plasmid was shown to enhance the spore viability of every allele tested, including a hop1 disruption allele. On the other hand, suppression by overexpression of RED1 from a 2 mu plasmid was found only for allele hop1-628ts. Surprisingly, similar overexpression of RED1 in strains bearing several other conditional hop1 linker-insertion alleles caused enhanced spore lethality. This finding, in conjunction with the evidence for a carboxy-terminal domain, provides new insight into the nature of interactions between the HOP1 and RED1 products in meiosis.

Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta 2 adrenoceptors in the sinoatrial node.

To test the hypothesis that beta 2 adrenergic receptors mediate the chronotropic more than the inotropic response to endogenous catecholamines the effects on the haemodynamic responses to exercise in dogs of the beta 1 specific antagonist atenolol were compared with those of the non-selective beta antagonist propranolol. Heart rate, left ventricular dP/dt at 40 mmHg developed pressure (dP/dt40), and oxygen consumption (VO2) were determined at seven to eight exercise levels in 16 chronically instrumented adult mongrel dogs with and without beta blockade. In doses that produced equivalent suppression of resting heart rate, propranolol and atenolol affected dP/dt40 similarly at all exercise levels. In contrast to atenolol, which affected heart rate equally at all workloads, propranolol inhibited heart rate more as the workload increased, resulting in a 1.55-fold greater percentage inhibition of chronotropy at a VO2 of 60 ml.Kg-1.min-1 a than at a VO2 of 30 ml.kg-1.min-1. These results are compatible with the hypothesis that, although beta 2 receptors appear to have little influence over cardiac inotropy during exercise, sinoatrial beta 2 receptors may be stimulated by circulating catecholamines and contribute greatly to sympathetic modulation of heart rate during heavy exercise in dogs.

Identification of a phosphotyrosyl-protein phosphatase in mouse epidermis.

Binding of epidermal growth factor (EGF) stimulates tyrosyl protein kinase activity of its receptor in the epidermis. This tyrosine residue phosphorylation is thought to be one mechanism by which EGF mediates its effects such as growth stimulation. To modulate a cellular response to EGF, an enzyme which dephosphorylates phosphotyrosyl residues should be present to oppose the effect of the tyrosyl kinase activity of the EGF receptor. We have identified an enzyme in the neonatal mouse epidermis which has the ability to dephosphorylate tyrosyl residues in vitro on EGF receptors. This phosphatase is a soluble protein with a molecular weight greater than 10,000 daltons and shows optimum activity at neutral pH. This epidermal tyrosyl protein phosphatase is not inhibited by tartrate, ATP, and micromolar levels of zinc, but is inhibited by millimolar levels of zinc, magnesium, manganese, and fluoride. Unlike other well-known phosphotyrosyl phosphatases, alkaline phosphatase, and calcineurin, this enzyme is not inhibited by EDTA. Thus, we have identified and partially characterized a possibly unique phosphotyrosyl phosphatase from the epidermis.

Compliance and efficacy of cardiac rehabilitation and risk factor modification in the medically indigent.

To compare the compliance and efficacy of cardiac rehabilitation in medically indigent patients with more affluent patients, we evaluated the first 65 patients referred to a new cardiac rehabilitation program of whom 36 were medically indigent (i.e., dependent on Medicaid for health care reimbursement) and 29 were funded by private medical insurance. Attendance during 12 weeks of monitored, supervised, phase II cardiac rehabilitation was examined retrospectively. In addition, training history, cardiovascular response to submaximal exercise, dietary fat intake, and smoking incidence were studied at baseline and repeated prospectively between 6 months and 1 year (8.2 +/- 1.1 months) after program completion. Both the indigent and private patients attended >90% of scheduled sessions and achieved a significant improvement in submaximal work capacity which was well maintained at the time of follow-up. Also, both groups continued to eat a diet low in saturated and total fat. The indigent patients smoked more before the program but were equally successful at quitting cigarette smoking as the private patients. We conclude that in the appropriate setting, indigent patients can successfully complete and maintain excellent compliance with a program of coronary risk factor modification including exercise training, dietary modification, and cessation of cigarette smoking, to a degree equivalent to more affluent and educated patients. Compliance may be enhanced by employing a small program emphasizing extensive personal contact with rehabilitation staff.

Relation of thrombus in the left atrial appendage by transesophageal echocardiography to clinical risk factors for thrombus formation.

Transesophageal echocardiography provides excellent visualization of the left atrial appendage (LAA). This study was conducted to determine whether specific clinical risk factors could predict the presence of LAA thrombus as demonstrated by transesophageal echocardiography. The most recent 860 transesophageal echocardiographic studies performed at our institution were retrospectively reviewed. The LAA was adequately visualized in 778 patients (90%). For each study, the presence or absence of 5 specific clinical risk factors (mitral stenosis, severe left ventricular dysfunction, left atrial dilatation, atrial fibrillation, or a prosthetic mitral valve) and the presence or absence of LAA thrombi were assessed. One or more clinical risk factors were present in 149 patients, whereas no defined risk factors were noted in 629. Left atrial appendage thrombi were found in 20 of 149 patients with versus 6 of 629 patients without a clinical risk factor (13% vs 1%, p = 0.0001). By logistic regression analysis, mitral stenosis, severe left ventricular dysfunction, and left atrial dilatation were independent risk factors for LAA thrombus formation. Neither atrial fibrillation nor the presence of a mitral prosthetic valve achieved statistical significance as independent risk factors for LAA thrombus. Thus, LAA thrombi occur most often in patients with risk factors for thrombus formation that can be determined by clinical evaluation and transthoracic echocardiography. Transesophageal echocardiography rarely identifies LAA thrombi in patients without such clinical risk factors.

Cardiovascular responses to voluntary and nonvoluntary static exercise in humans.

We have measured the cardiovascular responses during voluntary and nonvoluntary (electrically induced) one-leg static exercise in humans. Eight normal subjects were studied at rest and during 5 min of static leg extension at 20% of maximal voluntary contraction performed voluntarily and nonvoluntarily in random order. Heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were determined, and peripheral vascular resistance (PVR) and stroke volume (SV) were calculated. HR increased from approximately 65 +/- 3 beats/min at rest to 80 +/- 4 and 78 +/- 6 beats/min (P < 0.05), and MAP increased from 83 +/- 6 to 103 +/- 6 and 105 +/- 6 mmHg (P < 0.05) during voluntary and nonvoluntary contractions, respectively. CO increased from 5.1 +/- 0.7 to 6.0 +/- 0.8 and 6.2 +/- 0.8 l/min (P < 0.05) during voluntary and nonvoluntary contractions, respectively. PVR and SV did not change significantly during voluntary or nonvoluntary contractions. Thus the cardiovascular responses were not different between voluntary and electrically induced contractions. These results suggest that the increases in CO, HR, SV, MAP, and PVR during 5 min of static contractions can be elicited without any contribution from a central neural mechanism (central command). However, central command could still have an important role during voluntary static exercise.

Effect of axillary blockade on regional cerebral blood flow during static handgrip.

Regional cerebral blood flow (rCBF) was determined at rest and during static handgrip before and after regional blockade with lidocaine. A fast rotating single photon emission computer tomograph system with 133Xe inhalation was used at orbitomeatal plane (OM) +2.5 and +6.5 cm in eight subjects. Median handgrip force during the control study was 41 (range 24-68) N, which represented 10% of the initial maximal voluntary contraction (MVC) and was 24 (18-36) N after axillary blockade (P less than 0.05), which represented 21% of the new MVC. During static handgrip, the rating of perceived exertion was 14 (10-16) exertion units before and 18 (15-20) after blockade (P less than 0.05). Hemispheric mean CBF did not change during handgrip. However, premotor rCBF increased from 55 (44-63) to 60 (50-69) ml.100 g-1.min-1 (P less than 0.05) and motor sensory rCBF from 57 (46-65) to 63 (55-71) ml.100 g-1.min-1 (P less than 0.05) to both the ipsilateral and contralateral sides during handgrip before, but not after, axillary blockade. There was no change in rCBF to other regions of the brain. Regional anesthesia with lidocaine did not alter resting rCBF. However, despite a greater sense of effort during static handgrip, there was no increase in rCBF after partial sensory and motor blockade. Thus bilateral activation occurs in the premotor and motor sensory cortex during static handgrip, and this activation requires neural feedback from the contracting muscles.

Exercise-induced functional desensitization of canine cardiac beta-adrenergic receptors.

To test the hypothesis that the high levels of endogenous catecholamines associated with strenuous exercise produce functional desensitization of cardiac beta-adrenergic receptors, we measured the bolus chronotropic dose of isoproterenol necessary to produce a 25-beats/min increase in heart rate (CD25) in the resting state and after the return of heart rate to resting levels after 60 min of treadmill running in 13 normal dogs. Immediately after exercise, 12 of 13 dogs were less sensitive to the chronotropic effects of beta-adrenergic receptor stimulation: mean CD25 increased from 1.16 +/- 0.17 to 3.50 +/- 0.98 micrograms (P less than 0.02). A similar reduction in isoproterenol sensitivity was evident regardless of whether testing was performed in the presence or absence of vagal blockade with atropine. By 3 h after exercise, CD25 had returned to the preexercise level, with no further change noted 24 h after exercise. There was no change in the CD25 when measured serially in three unexercised dogs. We conclude that a single bout of dynamic exercise is sufficient to produce a significantly decreased chronotropic responsiveness to isoproterenol. This phenomenon may represent an acute but transient desensitization of cardiac beta-adrenergic receptors.

Neural control of the forearm cutaneous vasoconstrictor response to dynamic exercise.

This study was designed to evaluate the relative importance of intended effort ("central command") and of the absolute intensity of dynamic exercise to the cutaneous vasoconstrictor response to the onset of exercise in humans. Skin blood flow (laser-Doppler flowmetry) was measured from the forearm in six healthy individuals during 3-min periods of high- and low-intensity exercise with and without partial neuromuscular blockade. Cutaneous vascular conductance (CVC) was calculated from the ratio of skin blood flow to mean arterial pressure and expressed as a percent change from rest. A rating of perceived exertion (RPE) was expressed as a subjective measure of intended effort. Under control conditions, CVC decreased by 22% (median; range 7-42%, P less than 0.05) during high-intensity exercise [218 (186-268) W; RPE 16 (14-19) exertion units]. In contrast, during control low-intensity exercise [106 (88-128) W; RPE 10 (9-14) exertion units], during low-level exercise with curare [77 (54-98) W; RPE 13 (11-16) exertion units], and during maximal exercise with curare [106 (88-124) W; RPE 19 (18-20) exertion units], CVC did not change significantly. These results suggest that factors related to the activity of the exercising muscle and its metabolism rather than intended effort determine the cutaneous vasoconstrictor response to the initiation of intense dynamic exercise in humans.

Effects of axillary blockade on regional cerebral blood flow during dynamic hand contractions.

Regional cerebral blood flow (rCBF) was measured at orbitomeatal (OM) plane +5.0 and +9.0 cm in 10 subjects at rest and during dynamic hand contractions before and after axillary blockade. Handgrip strength was significantly reduced, and rating of perceived exertion increased after blockade. During hand contractions before blockade, contralateral hemispheric cerebral blood flow (CBF) at OM +9.0 increased from a resting value of 58 (49-75) to 63 (52-82) ml.100 g-1.min-1; contralateral motor sensory rCBF at OM +9 from 58 (50-77) to 71 (64-84); motor sensory rCBF at OM +5 from 67 (54-76) to 77 (64-87) and 70 (62-84) contralaterally and ipsilaterally, respectively; and supplementary motor area (SM) rCBF from 64 (53-69) to 75 (67-88) ml.100 g-1.min-1. During dynamic hand contractions after axillary blockade, CBF did not increase at OM +5 or in the SM. Furthermore, contralateral motor sensory rCBF at OM +9 increased much less. Axillary blockade had no effect on resting CBF, rCBF, or increases in the two during hand contractions of the opposite hand. Thus neural feedback from the contracting muscle is necessary for the increases in SM bilateral OM +5 motor sensory rCBF and the maximal increase in contralateral OM +9 motor sensory rCBF during dynamic hand contractions.

Cardiovascular responses at the onset of static exercise in patients with dual-chamber pacemakers.

Cardiac output (CO) responses to exercise can be altered by ventricular pacing in pacemaker-dependent patients. The relative contributions of CO and peripheral vascular resistance (PVR) toward the initial increase in blood pressure with the initiation of static exercise were investigated in eight otherwise healthy pacemaker-dependent subjects [age 24 +/- 2 yr (range 17-37 yr)]. Beat-by-beat measures of heart rate (HR; electrocardiography), mean arterial pressure (MAP), and CO derived from stroke volume (SV) (CO = HR.SV; 2-D echocardiography) were determined during the first 20 s of a one-legged static knee extension performed at 20% maximal voluntary effort by using three pacing modalities: dual pacing and sensing mode (DDD, i.e., normal physiological HR response), fixed at resting HR (DOO-R), and fixed at peak exercise HR (DOO-E), as previously achieved during 5 min of sustained contraction in the DDD mode. There were no differences in MAP, CO, or PVR (PVR = MAP/CO) between modes at rest (P > 0.05). With DOO-E pacing, SV was lower at rest compared with the other modes and increased with exercise (P < 0.05). Although there were no significant increase in MAP or CO during DOO-R pacing, both variables were elevated by leg contraction during DDD and DOO-E pacing (P < 0.05), with no significant change in PVR. Additionally, the CO and MAP increases were significantly greater with DOO-E pacing (P < 0.05). Thus the magnitude of the initial increase in arterial pressure at the onset of mild one-legged static exercise was dictated by the changes in CO as PVR remained unchanged.

Mechanisms regulating regional cerebral activation during dynamic handgrip in humans.

Dynamic hand movement increases regional cerebral blood flow (rCBF) of the contralateral motor sensory cortex (MS1). This increase is eliminated by regional anesthesia of the working arm, indicating the importance of afferent neural input. The purpose of this study was to determine the specific type of afferent input required for this cerebral activation. The rCBF was measured at +5.0 and +9.0 cm above the orbitomeatal (OM) plane in 13 subjects during 1) rest; 2) dynamic left-hand contractions; 3) postcontraction ischemia (metaboreceptor afferents); and 4) biceps brachii tendon vibration (muscle spindles). The rCBF increased only during dynamic hand contraction; contralateral MS1 (OM +9) by 15% to 64 +/- 8.6 ml.100 g-1.min-1 (P < 0.05); supplementary motor area (OM +9) by 11% to 69 +/- 9.8 ml.100 g-1.min-1 (P < 0.05); and there were also bilateral increases at MS2 (OM +5) [by 16% to 64 +/- 8.6 ml.100 g-1.min-1 (P < 0.05)]. These findings suggest that the rCBF increase during dynamic hand contraction does not require neural input from muscle spindles or metabolically sensitive nerve fibers, although the involvement of mechanoreceptors (group III or Ib) cannot be excluded.

Arterial blood gases and acid-base status of dogs during graded dynamic exercise.

The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady-state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional distribution of blood flow of dogs during graded dynamic exercise.

The regional blood flow response to progressive treadmill exercise was measured with radioactive microspheres in 25 untrained mongrel dogs. Incremental increases in work intensity resulted in corresponding increases in blood flows to the gracilis, gastrocnemius, semimembranosus, and semitendinosus muscles of the hindlimb and to the heart. During maximal exercise, blood flow was greatest in the semimembranosus muscle and lowest in the semitendinosus muscle (342 and 134 ml-1.100 g tissue-1.min-1, respectively). Exercise produced a decrease in blood flow to the temporalis muscle, which was classified as nonlocomotive in function. Blood flows to the stomach, pancreas, and large intestine decreased at the lowest exercise work load and remained diminished throughout the continuum to maximal exercise. Blood flows to the small intestine and spleen were maintained during submaximal exercise but were reduced by 50% at maximal O2 consumption (VO2max). No changes in blood flows to the kidneys, adrenal glands, liver, and brain were found. These results demonstrate that 1) renal blood flow is maintained at resting levels during exercise in untrained dogs; 2) blood flow changes in the various organs of the splanchnic region of dogs during exercise are heterogeneous; and 3) blood flows to the working skeletal muscles of dogs progressively increase with increasing work loads up to VO2max.

Traumatic myocardial infarction during competitive volleyball: a case report.

A previously asymptomatic physically active 41-yr-old Caucasian male was hit in the chest by a spiked volleyball. Following the impact of the ball he developed substernal chest pain, which persisted during and after the game. Despite the administration of thrombolytic therapy, he suffered an extensive anteroapical myocardial infarction; subsequent cardiac catheterization revealed the presence of a 70% occlusion in his mid left anterior descending coronary artery. We hypothesize that this patient sustained a traumatic coronary artery thrombosis resulting in acute myocardial infarction. The presence of underlying coronary artery disease may predispose an individual to traumatic myocardial infarction.

Cardiovascular responses to active and passive cycling movements.

Ten healthy subjects were evaluated at rest and at 5 min of unloaded active (AC) and passive (PC) cycling. Passive limb movements were accomplished using a tandem bicycle with a second rider performing the movements. We measured heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), oxygen uptake (VO2), rating of perceived exertion (RPE), and electrical activity (EMG) of lower limbs muscles. Values for stroke volume (SV) and peripheral vascular resistance (PVR) were calculated. EMG, RPE, and VO2 were higher during AC than during PC (P < 0.001). CO increased during both modes of cycling, but during AC it resulted from a HR acceleration (73 +/- 2 at rest to 82 +/- 2 beats.min-1 at 60 rpm; P < 0.001) with no change in SV whereas during PC, SV increased from rest (65 +/- 4 at rest to 71 +/- 3 ml at 60 rpm; P = 0.003) along with no change in HR. PVR remained constant during PC, but decreased by 13% during AC (P < 0.001) and MAP increased only during PC (93 +/- 2 at rest to 107 +/- 2 mm Hg at 60 rpm). These results supports the concept that central command determines the HR response to dynamic exercise. The increase in SV and consequently in MAP during PC was probably due to increased venous return and/or to muscle mechanoreceptor-evoked increased myocardial contractility.

The effect of normoxic or hypobaric hypoxic endurance training on the hypoxic ventilatory response.

Cross-sectional studies in endurance athletes have demonstrated a diminished hypoxic ventilatory response (HVR) compared with mountaineers or sedentary controls. Conversely, short-term altitude acclimatization may increase the HVR. The longitudinal effect of training, either at sea level or altitude, on HVR has not been previously reported. We therefore studied 21 untrained men and women before and after 5 wk of cycle ergometer training at either sea level or 2,500 m. HVR was determined using the steady-state method (16). Minute ventilation (VE) was measured with a Tissot spirometer during the last minute of 5 min breathing room air, 8% and 12% O2, administered in random order. CO2 was added at the mouth in an effort to maintain end-tidal CO2 at baseline levels. Oxyhemoglobin saturation was measured directly from arterial blood with a hemoximeter (OSM 3). HVR was defined as the positive slope of the line relating VE to O2 saturation in l.min-1%-1. One group of subjects trained at sea level at 70% maximal oxygen uptake (VO2max; N = 7). A second group trained at 2,500 m in a hypobaric chamber, at the same relative exercise intensity (i.e., 70% altitude VO2max) or same absolute intensity (same power output) as group 1 (N = 14). Both groups trained on a bicycle ergometer for 45 min.d-1, 5 d.wk-1 for 5 wk.(ABSTRACT TRUNCATED AT 250 WORDS)