RESPONSES OF HUMAN SUBJECTS TO INTRA-ARTERIAL ADENOSINE
INJECTIONS 
Adenosine, a vasodilator metabolite, is produced in many tissues, and
its release is enhanced when the local demand for oxygen exceeds the
supply. It is an agent with several actions, and its physiological role
is controversial, especially regarding its participation in the
exercise pressor reflex. MacLean and associates (p. 1045) examined the
responses of muscle sympathetic nerve activity to femoral arterial
injections of adenosine under several conditions in human volunteers.
The results suggest that adenosine does not directly stimulate
afferents in the leg muscles but exerts its reflex actions by
baroreceptor unloading and by stimulation of chemosensitive afferents
elsewhere. The report is discussed in an Invited Editorial by Kaufman
(p. 1043).
DEHYDRATION AND HEAT LOSS IN EXERCISING HORSES
Does progressive dehydration alter sweat production or composition
during prolonged exercise? Kingston et al. (p. 1133) examined this
question in horses during more than 3 h of low-intensity exercise (40%
of maximal oxygen consumption). Fluid loss averaged 33.8 liters,
resulting in a 21% decrease in plasma volume and an 11% decrease in
total body water. This hypohydration did not alter sweat rate, sweat
composition, or heat storage, as determined by changes in body
temperature. Respiratory and cutaneous evaporative heat loss
represented 23 and 70%, respectively, of the total heat dissipated.
ALCOHOL AND REHYDRATION AFTER EXERCISE
Despite the well-known diuretic action of alcohol, many recreational
athletes rehydrate with beer or other weakly alcoholic beverages
after exercise. Shirreffs and Maughan (p. 1152) studied the effects of
alcohol ingestion on fluid and electrolyte balance after
exercise-induced dehydration. Subjects rehydrated after exercise on 4 different days with beverages containing 0, 1, 2, and 4% alcohol.
Urine production over the 6 h following rehydration did not
differ among the trials, but the peak urine flow rate occurred later,
and the increases in blood and plasma volumes with rehydration were
slower with the 4% beverage. The results indicate that alcohol has a
negligible diuretic effect in this setting. Rehydration is equivalent
with beverages that are alcohol free or contain up to 2% alcohol, but
the recovery process is delayed with 4% alcohol.
CONDITIONED VENTILATORY RESPONSES?
Despite considerable interest in the possibility that classic
conditioning may modify the chemical control of breathing, little experimental evidence supports this possibility. In this issue, Nsegbe
et al. (p. 1174) report the results of a controlled experiment in which
a conditioned stimulus (1-min tone) was paired with an unconditioned
ventilatory stimulus (hypercapnia). An experimental group received the
conditioned-unconditioned sequence of stimuli, and then the
subjects were tested for conditioning of ventilation by receiving the
conditioned stimulus alone. A control group also received both
conditioned and unconditioned stimuli, but these were not temporally
linked. In the experimental group, the conditioned stimulus alone
increased breath duration and decreased ventilation, leading the
authors to conclude that the conditioning paradigm produced inhibitory conditioning of the respiratory controller.
ORIGINS AND MECHANISMS OF CHEYNE-STOKES BREATHING
Nonobstructive periodic breathing during sleep (Cheyne-Stokes
respiration) is strongly associated with heart failure and
cerebrovascular insufficiency. The pathogenesis of such respiratory
instability is unknown, but increases in controller gain and in
circulatory delay have been postulated to be causative factors.
Franklin et al. (p. 1184) report the results of a study of 10 patients,
with Cheyne-Stokes respiration secondary to heart failure or previous stroke, during sleep. The observed respiratory periodicity was accompanied by periodic changes in cerebral blood flow, blood pressure,
and heart rate, such that the values of these variables reached maxima
during hyperpnea and minima in apnea. Oxygen administration diminished
apnea-induced oxygen desaturations but left respiratory and hemodynamic
periodicities unaltered, suggesting that periodic fluctuations in
arterial PO2 do not play a key
pathogenic role.
ENDOTHELIN RECEPTORS AND PULMONARY HYPERTENSION
Does endothelin-receptor stimulation participate in the pathogenesis of
pulmonary hypertension? Hill et al. (p. 1209) addressed this question
by treating rats with monocrotaline and studying them for 3 wk
thereafter. Bosentan, an endothelin-receptor blocker, was given on
several different schedules. Bosentan treatment for the full 3 wk or
the last 11 days resulted in less right ventricular hypertrophy, lower
right ventricular systolic pressure, and less pulmonary vascular
thickening, but treatment only for the first 10 days after
monocrotaline provided no protection. These findings suggest that the
pathogenic role of endothelin-receptor stimulation is not immediate
but, rather, comes into play after the acute inflammatory phase of the
monocrotaline response.
MYOGENIC REGULATORY FACTORS DURING REGENERATION OF SKELETAL MUSCLE
IN YOUNG, ADULT, AND OLD RATS
The effect of aging on regeneration and myogenic factor expression was
examined by Marsh et al. (p. 1270) in skeletal muscle after
intramuscular bupivacaine injection in young, adult, and old rats. In
young rats, the mass of injected muscles was fully recovered by 21 days, whereas muscle mass was not normalized over the same period in
adult and old rats. In regenerating muscles, myogenin mRNA levels
increased in all groups of rats and returned to baseline levels after
21 days only in young animals. Qualitatively similar results were
observed for MyoD mRNA expression. The age-related impairment in muscle
mass recovery appears to be associated with an age-dependent inability
to downregulate myogenin and MyoD mRNA expression. Alternatively,
elevated expression of these mRNAs may reflect ongoing and perhaps
ineffective myogenic activity in muscles of older animals.
ENDURANCE TRAINING IN THE ELDERLY
Normal aging reduces blood volume and total body water and increases
water imbalance. Pickering and colleagues (p. 1300) asked whether 4 mo
of individualized physical training would affect these age-related
changes in body fluids and whether concomitant effects on
cardiovascular function would be seen. Physical training in 10 elderly
subjects increased the maximal oxygen uptake substantially (16%),
expanded plasma volume by 10%, and reduced body fat; however, there
were no training effects on total body water, fat free mass, or body
weight. Resting echocardiography showed that these changes were
associated with improvement in left ventricular function. The results
are in the same direction as those found with training in younger
subjects. However, all gains in plasma volume and left ventricular
function were reversed with 4 mo of detraining.
OXYGEN UPTAKE KINETICS AT EXERCISE ONSET
That oxygen uptake (
O2) does
not rise immediately as exercise is initiated but somewhat
exponentially with a half time of ~20-30 s continues to provoke
controversy: the slow O2
response could be due to inertia in the oxygen transport system or in
the muscle metabolic processes that generate ATP. MacDonald et al. (p.
1318) report that breathing 70% oxygen does not accelerate the kinetics at low workloads but does so at higher workloads (above the ventilatory threshold). The findings are interpreted as
oxygen transport limitation of kinetics at high but not low workloads.
These results must, however, be interpreted with care, since in the
absence of simultaneous muscle blood flow measurements the effects of
altering inspired oxygen fraction on muscle oxygen availability remain
uncertain.
RESPONSES OF HUMAN SUBJECTS TO INTRA-ARTERIAL ADENOSINE
INJECTIONS
