Life-extending dietary restriction, but not dietary supplementation of branched-chain amino acids, can increase organismal oxidation rates of individual branched-chain amino acids by grasshoppers.

BACKGROUND: Life-extending dietary restriction increases energy demands. Branched-chain amino acids (BCAAs), at high levels, may be detrimental to healthspan by activating the mechanistic Target of Rapamycin (mTOR). Whether organismal oxidation of BCAAs increases upon dietary restriction is unknown. OBJECTIVE: Test whether dietary restriction (DR, which creates an energy deficit) or supplemental dietary BCAAs (superfluous BCAAs) increases oxidation of BCAAs, potentially reducing their levels to improve healthspan. METHODS: Grasshoppers were reared to middle-age on one of four diets, each a level of lettuce feeding and a force-fed solution: 1) ad libitum lettuce & buffer, 2) ad libitum lettuce & supplemental BCAAs, 3) DR lettuce & buffer, and 4) DR lettuce & supplemental BCAAs. On trial days, grasshoppers were force-fed one 13C-1-BCAA (isoleucine, leucine, or valine). Breath was collected and tested for 13CO2, which represents organismal oxidation of the amino acid. Additional trials re-tested oxidation of leucine (the most potent activator of mTOR) in both females and males on dietary restriction. RESULTS: Dietary restriction generally increased cumulative oxidation of each BCAA in females and hungry males over ∼8 hr. Results were consistent for isoleucine and valine, but less so for leucine. Supplementation of BCAAs, in combination with dietary restriction, increased isoleucine in hemolymph, with similar trends for leucine and valine. Despite this, supplementation of BCAAs did not alter oxidation of any BCAAs. CONCLUSIONS: Dietary restriction can increase oxidation of BCAAs, likely due to an energy deficit. The increased oxidation may decrease available BCAAs for activation of mTOR and improve healthspan.

Direct vs indirect blood pressure at rest and during isometric exercise in normal subjects.

Systolic and diastolic blood pressures were measured by intraarterial means and by auscultation. Comparisons were made with simultaneously determined intraarterial catheter and auscultation measurements. Five healthy males were measured at rest and during handgrip and deadlift isometric exercises, utilizing small and large muscle mass. The data suggest that indirect systolic blood pressure is highly correlated with the direct method at rest, during handgrip and deadlift (0.8, 0.9 and 0.91 respectively) isometric exercises. Indirect diastolic blood pressure correlates well with intraarterial at rest (0.7) and during the isometric handgrip bout which utilized small muscle mass (0.8). As for the deadlift manoeuvre, the correlation coefficients between the indirect and direct methods were low. These results suggest that when utilizing large muscle mass during isometric deadlift exercise, the indirect method is not valid for assessment of diastolic blood pressure.

Influence of muscle length and force on endurance and pressor responses to isometric exercise.

Experiments were performed to determine whether endurance time, mean arterial pressure, or heart rate was related to either muscle length or external torque production in humans during isometric knee extension. Eight men and nine women performed isometric knee extension to the endurance limit at each of three muscle lengths, determined by knee angles of 40 degrees (0.698 rad, shortest), 60 degrees (1.047 rad, intermediate), and 90 degrees (1.571 rad, longest), and at intensities of 30 and 50% maximal voluntary contraction (MVC). Knee extension forms an ascending-descending length-torque curve, and lengths were chosen to result in different external torques. MVC was greatest at a knee angle of 60 degrees (P < 0.05 vs. 40 degrees, 90 degrees), with no significant difference between 90 degrees and 40 degrees. Endurance time was inversely related to muscle length, independent of torque production, at 30% MVC [40 degrees, 395 +/- 139 (SE); 60 degrees, 237 +/- 60; 90 degrees, 165 +/- 51 s; P < 0.05 vs. each other] and 50% MVC (40 degrees, 176 +/- 64; 60 degrees, 137 +/- 40; 90 degrees, 85 +/- 23 s; P < 0.05 vs. each other). Evidence is presented that endurance is a function of internal muscle force and not resultant external torque. The experimental design allowed the relationship of external torque and cardiovascular responses to be examined independent of exercise intensity. Muscle mass was also controlled in that the same muscle group was involved in all contractions. There were no differences in mean arterial pressure, heart rate, or rating of perceived exertion at any percentage of endurance time under any condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Nasal secretions in ocular surgery under general and local anesthesia.

To investigate the etiology of nasopharyngeal secretion reflux under anesthesia, which could contaminate the conjunctiva, we photographed, after preoperative nasal instillation of fluorescein, the faces of 224 consecutive patients having cataract surgery under general (n = 78) and local (n = 146) anesthesia. In 10 patients, extension of the neck and facial contour caused fluid to drain from the nose directly into the conjunctival cul-de-sac. Nine of the 78 patients under general anesthesia had nasal secretions on the face at the end of surgery, usually due to leaking around the endotracheal tube. Adjusting head posture by moderate neck flexion and taking care to prevent leakage around the endotracheal tube, together with antiseptic preparation of the nose, may prevent contamination of the operative field by nasal secretions.

Metabolic response to graded downhill walking.

Compared with level walking or running, progressive downhill walking or running requires a decreasing energy cost to some minimum where the cost again increases with further decrements in grade. Margaria estimated this minimum occurs at a -9% grade. In this study an attempt was made to more precisely track the energy cost curve in progressive downhill treadmill walking. Ten men, mean age 22.0 +/- 2.5 yr, volunteered as subjects. After VO2max determinations the subjects attended two downhill walking sessions. Each subject performed 14 randomly ordered walking bouts of 6 min in duration, at speeds of 90 and 105 m.min-1. The grades used were 0, -3, -6, -9, -12, -15, and -18%. Gas exchange measurements were obtained by open circuit spirometry during each work bout. Heart rate was monitored continuously and the stride frequency was counted by direct observation during each walking bout. Net VO2 values decreased with decrements in grade to -9, -12% for the respective speeds of 90 and 105 m.min-1. The group mean net VO2 minimums at -9 and -12%, however, were not significantly different (P > 0.05) from the group mean values at -6 and -15% at 90 m.min-1, or between -9 and -15% grades at 105 m.min-1, Group mean net VO2 values at 0, -3, and -18% were significantly different (P < 0.05) from net VO2 values for the other grades at 90 m.min-1 walking. At 105 m.min-1, mean net VO2 values at 0, -3, -6, and -18% were significantly different (P < 0.05) from net VO2 values at the other grades.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of pedaling frequency on glycogen depletion rates in type I and type II quadriceps muscle fibers during submaximal cycling exercise.

This study was conducted to determine whether the pedaling frequency of cycling at a constant metabolic cost contributes to the pattern of fiber-type glycogen depletion. On 2 separate days, eight men cycled for 30 min at approximately 85% of individual aerobic capacity at pedaling frequencies of either 50 or 100 rev.min-1. Muscle biopsy samples (vastus lateralis) were taken immediately prior to and after exercise. Individual fibers were classified as type I (slow twitch), or type II (fast twitch), using a myosin adenosine triphosphatase stain, and their glycogen content immediately prior to and after exercise quantified via microphotometry of periodic acid-Schiff stain. The 30-min exercise bout resulted in a 46% decrease in the mean optical density (D) of type I fibers during the 50 rev.min-1 condition [0.52 (0.07) to 0.28 (0.04) D units; mean (SEM)] which was not different (P > 0.05) from the 35% decrease during the 100 rev.min-1 condition [0.48 (0.04) to 0.31 (0.05) D units]. In contrast, the mean D in type II fibers decreased 49% during the 50 rev.min-1 condition [0.53 (0.06) to 0.27 (0.04) units]. This decrease was greater (P < 0.05) than the 33% decrease observed in the 100 rev.min-1 condition [0.48 (0.04) to 0.32 (0.06) units). In conclusion, cycling at the same metabolic cost at 50 rather than 100 rev.min-1 results in greater type II fiber glycogen depletion. This is attributed to the increased muscle force required to meet the higher resistance per cycle at the lower pedal frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Rate of decline in blood lactate after cycling exercise in endurance-trained and -untrained subjects.

The purpose of this study was to compare the rate of decline in blood lactate (La) levels in nine trained men [maximal O2 consumption (VO2max) 65.5 +/- 3.3 ml.kg-1.min-1] and eight untrained men (VO2max 42.2 +/- 2.8 ml.kg-1.min-1) during passive recovery from a 3-min exercise bout. Trained and untrained subjects cycled at 85 and 80% VO2max, respectively, to produce similar peak blood La concentrations. Twenty samples of arterialized venous blood were drawn from a heated hand vein during 60 min of recovery and analyzed in an automated La analyzer. The data were then fitted to a biexponential function, which closely described the observed data (r = 0.97-0.98). There was no difference in the coefficient expressing the rate of decline in blood La for trained and untrained groups (0.0587 +/- 0.0111 vs. 0.0579 +/- 0.0100, respectively). However, trained subjects demonstrated a faster time-to-peak La (P = 0.01), indicative of a faster efflux of La from muscle to blood. Thus the rate of decline in blood La after exercise does not appear to be affected by training. The faster decline previously reported for trained subjects may be due to the use of a linear rather than a biexponential curve fit.

Heat regulation during exercise with controlled cooling.

During heavy sustained exercise, when sweating is usually needed to dissipate the extra metabolic heat, controlled cooling caused heat loss to match total heat production with little sweating. The total heat produced and metabolic rate were varied independently by having subjects walk uphill and down. Heat loss was measured directly with a suit calorimeter; other measurements included metabolic energy from respiratory gas exchange and body temperatures. Thermoregulatory sweating was minimized by adjusting cooling in the calorimeter suit. Heat loss rose to match total heat, not metabolic rate, and there was a slow rise in rectal temperature. In the absence of major thermoregulatory response rectal temperature correlated most closely with total heat; it also correlated with the relative oxygen cost of exercise. Heat flow or heat content appeared to be the controlled variable and body temperature rise a secondary event resulting from thermal transport lag.

Energy exchange in downhill and uphill walking: a calorimetric study.

Energy balance can be written as 1) M = sigma Q +/- W +/- S, expressed as power (W), where M is the rate of metabolic energy transformation, sigma Q the rate of heat loss, W the work rate, and S the rate of body heat storage. When submaximal treadmill exercise continues long enough, body temperature stops changing, S becomes zero, and the heat storage term is dropped from equation 1. For uphill walking the equation becomes 2) M = sigma Q + Wvert, and for downhill walking it becomes 3) M = sigma Q - Wvert. This study tested the energy balance equations with direct measurements of heat exchange using a suit calorimeter and M from standard measurements of respiratory gas exchange. Ten healthy men walked on a motor driven treadmill at 1.5 m.s-1 at grades of 0, 5, 10, -5, and -10% for 70-90 min to ensure a thermal steady state. As expected, +Wvert was identified as a power output, whereas -Wvert was accounted for as a power input, totally transformed to heat in the downhill walking subject. There also appeared to be a quantity of non-thermal energy, Wwalk, needed to satisfy the energy balance equation. This was significant at 0, 5, and 10% grades (P less than 0.01) but not significant at -5 and -10% grades (P greater than 0.05). The data confirm previous results for level walking and extend them to include uphill walking. While it had been suggested that Wwalk represents an externalization of energy at the foot, the present data suggest an alternative explanation.(ABSTRACT TRUNCATED AT 250 WORDS)

Time to fatigue during isometric exercise using different muscle masses.

The purpose of this study was to test the hypothesis that differences in the pressor response to static exercise using varying muscle masses are due to differences in endurance time. i.e., time to fatigue. Ten healthy, male subjects (mean age 24 +/- 3 years) participated in the study. With no knowledge of the purpose of the study, the subjects were instructed to maintain static contractions for as long as possible during 30% maximal voluntary contraction (MVC) in handgrip (HG), two-leg extension (LE), and dead lifting (DL). Inability to sustain a contraction within 10% of the designated force (30% MVC) marked the endurance time end point. During sustained contractions, heart rate, blood pressure, and time to fatigue were measured. Times to fatigue were 3.39 +/- 0.92, 3.61 +/- 1.67, and 3.68 +/- 1.34 min for HG, LE, and DL, respectively. These differences were not significant (p greater than 0.05). Heart rate and blood pressure increased progressively with sustained contractions, DL greater than LE greater than HG. LE and DL responses were consistently and significantly (P less than 0.05) higher than HG responses reflecting the magnitude of absolute force of contractions. The magnitude of the pressor response to the three sustained static contraction maneuvers was not related to the time to fatigue. The data affirm the view that the pressor response is a function of muscle mass activated and the absolute force developed during static exercise.

Cardiovascular responses to military antishock trouser inflation during standing arm exercise.

Military antishock trousers (MAST) inflated to 50 mmHg were used with 12 healthy males (mean age 28 +/- 1 yr) to determine the effects of lower-body positive pressure on cardiac output (Q), stroke volume (SV), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), total peripheral resistance (TPR), and O2 uptake (VO2) during graded arm-cranking exercise. Subjects were studied while standing at rest and at 25, 50, and 75% of maximal arm-cranking VO2. At each level, rest or work was continued for 6 min with MAST inflated and for 6 min with MAST deflated. Order of inflation and deflation was alternated at each experimental rest or exercise level. Measurements were obtained during the last 2 min at each level. Repeated-measures analysis of variance revealed significant increases (P less than 0.001) in Q, SV, and MABP and a consistent decrease in HR with MAST inflation. There was no apparent change in Q/VO2 between inflated and control conditions. There was no effect of MAST inflation on VO2 or TPR. MAST inflation counteracts the gravitational effect of venous return in upright exercise, restoring central blood volume and thereby increasing Q and MABP from control. HR is decreased consequent to increased MABP through arterial baroreflexes. The associated decrease in TPR is not observed, being offset by the mechanical compression of leg vasculature with MAST inflation.

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

Carnitine supplementation and depletion: tissue carnitines and enzymes in fatty acid oxidation.

Sixty-two male rats were randomly assigned into a 3 X 2 X 2 factorial design containing 12 groups according to carnitine treatment, exercise training (treadmill, 1 h, 5 times/wk, 8 wk, 26.8 m/min, 15% grade), and physical activity [rested for 60 h before they were killed or with an acute bout of exercise (1 h, 26.8 m/min, 15% grade) immediately before they were killed]. Isotonic saline was injected intraperitoneally 5 times/wk in the controls, whereas 750 mg/kg of L- or D-carnitine, respectively, were injected in the supplemented and depleted treatment groups. A significant increase in free and short-chain acyl carnitine concentration in skeletal muscle and heart was observed in L-carnitine supplemented rats, whereas a significant reduction in skeletal muscle, heart, and liver occurred in rats depleted of L-carnitine. Long-chain acyl carnitine in all tissues was not altered by carnitine treatment; training increased plasma and liver concentrations, whereas acute exercise decreased skeletal muscle and increased liver concentrations. An acute bout of exercise significantly increased short-chain acylcarnitine in liver, regardless of carnitine and/or training effects. beta-Hydroxyacyl-CoA dehydrogenase activity in skeletal muscle was induced by training but reduced by depletion. Carnitine acetyltransferase (CAT) was significantly increased in heart by L-carnitine supplementation, whereas it was reduced by depletion in skeletal muscle. Exercise training significantly increased CAT activity in skeletal muscle but not in heart, whereas acute exercise significantly increased activity in both tissues. Carnitine palmitoyltransferase activity was increased by acute exercise in the heart in only the supplemented and exercise-trained rats.

Isometric exercise: cardiovascular responses in normal and cardiac populations.

Isometric exercise produces a characteristic pressor increase in blood pressure which may be important in maintaining perfusion of muscle during sustained contraction. This response is mediated by combined central and peripheral afferent input to medullary cardiovascular centers. In normal individuals the increase in blood pressure is mediated by a rise in cardiac output with little or no change in systemic vascular resistance. However, the pressor response is also maintained during pharmacologic blockade or surgical denervation by increasing systemic vascular resistance. Left ventricular function is normally maintained or improves in normal subjects and cardiac patients with mild impairment of left ventricular contractility. Patients with poor left ventricular function may show deterioration during isometric exercise, although this pattern of response is difficult to predict from resting studies. Recent studies have shown that patients with uncomplicated myocardial infarction can perform submaximum isometric exercise such as carrying weights in the range of 30 to 50 lb without difficulty or adverse responses. In addition, many patients who show ischemic ST depression or angina during dynamic exercise may have a reduced ischemic response during isometric or combined isometric and dynamic exercise. Isometric exercises are frequently encountered in activities of daily living and many occupational tasks. Cardiac patients should be gradually exposed to submaximum isometric training in supervised cardiac rehabilitation programs. Specific job tasks that require isometric or combined isometric and dynamic activities may be evaluated by work simulation studies. This approach to cardiac rehabilitation may facilitate patients who wish to return to a job requiring frequent isometric muscle contraction. Finally, there is a need for additional research on the long-term effects of isometric exercise training on left ventricular hypertrophy and performance. The vigorous training regimens currently utilized by international class and professional athletes should stimulate longitudinal studies of physiologic and pathophysiologic outcomes of intense isometric exercise training programs.

The effects of beta-adrenergic blockade on body composition in free-fed and diet-restricted rats.

The effects of the non-selective beta-adrenergic blocking agent propranolol (known for its anti-lipolytic activity) on body composition were investigated in growing male rats on normal unrestricted diet (N = 7) and on diet restriction (N = 7, 95% of controls). Three animals in each group were injected i.p. with 30 mg propranolol per kg body weight (bw) dissolved in saline, 5 days/week. This dose attenuates exercising heart rate by 25% and exercise training-induced enzyme activity. The remaining animals received saline. Fat, glycogen, moisture and non-ether extractable residue were determined in the homogenized residue of the whole animal. After 9 weeks on the experimental regimen, bw gain was significantly lower in the diet restricted rats, whereas propranolol had no effect on the bw gain. The percentage of fat, moisture and non-ether extractable residue were unchanged by either propranolol or diet restriction. However, glycogen content was significantly lower in the beta-blocked rats either with or without diet restriction. These data indicated that neither beta-adrenergic blockade nor minimal diet restriction influences the percentage body fat, whereas body glycogen content is decreased under both conditions.

Thermoregulatory responses to skin wetting during prolonged treadmill running.

We examined the physiological responses to skin wetting during a 120-min level treadmill run to assess whether skin wetting would reduce the dehydration and the increase in core temperature associated with prolonged exercise. Testing was conducted in an environmental chamber (T = 29.5 degrees C, wind velocity = 3 m X sec-1) under two different humidity conditions (33 or 66% relative humidity). Ten male subjects performed two runs in each humidity condition; one served as a control run. The other included spraying the body with 50 ml of water (T = 29.5 degrees C) every 10 min. Spraying had no effect on rectal temperature (Tre), heart rate, oxygen consumption, perceived exertion, sweat loss, or percent change in plasma volume in both the humid and the dry conditions. Spraying produced a significant reduction in mean skin temperature (Tsk), which increased the (Tre - Tsk) gradient. At the same time, overall skin conductance (K) was decreased, presumably as a result of cutaneous vasoconstriction due to the low Tsk. Since heat transfer from the body's core to the skin is expressed by the equation: heat transfer = K X (Tre - Tsk) the spraying had no effect on heat transfer away from the core, and Tre remained unchanged.

Enzymatic adaptation to physical training under beta-blockade in the rat. Evidence of a beta 2-adrenergic mechanism in skeletal muscle.

Nonselective and beta 1-selective adrenergic antagonists were tested for their effects on enzymatic adaptation to exercise training in rats as follows: trained + placebo (TC); trained + propranolol (TP); trained + atenolol (TA); and corresponding sedentary groups, SC and SP. Trained rats ran 1 h/d at 26.8 m/min, 15% grade, 5 d/wk, 10 wk. Both beta-antagonists were given at doses that decreased exercise heart rates by 25%. Training increased skeletal muscle citrate synthase, cytochrome c oxidase (Cyt-Ox), carnitine palmitoyltransferase (CPT), beta-hydroxyacyl coenzyme A dehydrogenase, mitochondrial malate dehydrogenase (MDH), and alanine aminotransferase (ALT) activities significantly in the TC group, but not in TP. These enzyme activities, except Cyt-Ox and CPT, were also significantly increased in TA. Hepatic phosphoenolpyruvate carboxykinase activity did not alter with training or beta-blockade. Fructose 1,6-bisphosphatase activity was lower in TC than in SC, but unchanged in TP or TA. Hepatic mitochondrial MDH and ALT activities increased with training only in TC. It is concluded that beta 2-adrenergic mechanisms play an essential role in the training-induced enzymatic adaptation in skeletal muscle.

Carnitine status, plasma lipid profiles, and exercise capacity of dialysis patients: effects of a submaximal exercise program.

Carnitine status, blood lipid profiles, and exercise capacity were evaluated in a combined group of hemodialysis (N = 4) and continuous ambulatory peritoneal dialysis (N = 6) patients before and after an 8-week submaximal exercise program. Maximal aerobic capacity (VO2max) was only 18.5 +/- 5.9 (mean +/- SD) mL O2/kg/min, well below the expected 30 to 35 mL O2/kg/min for age-matched sedentary controls. Plasma short-chain acylated carnitine levels, which were two to three times normal values, were reduced after the exercise program, but the long-chain acylcarnitines were significantly reduced during acute exercise. Muscle biopsies of the vastus lateralis were performed at rest in five patients prior to and after the 8-week exercise program. Total carnitine in skeletal muscle was 3.09 (.076 SD) mumol/g ww, with only 11.3% acylated prior to the exercise program, which was much lower than the 4.25 +/- 1.27 mumol/g ww, with 28.5% acylated in a group of healthy athletic subjects (N = 28). Muscle free carnitine concentrations decreased significantly following the 8-week training period, with only a slight reduction in total carnitine. The percent of acylated carnitine was therefore significantly increased (P less than 0.05) from 11.3% to 25.2% after the experimental period. Pretraining carnitine palmitoyl transferase activity at rest was 0.57 +/- 0.28 nmol palmitoyl carnitine formed/5 min/mg mitochondrial protein, which was not changed by exercise training v 1.80 +/- 0.51 nmol/5 min/mg protein in 28 healthy normals (P less than 0.001). Free fatty acid concentrations were reduced significantly during acute exercise as a result of the exercise training program whereas other plasma lipids were not altered. (ABSTRACT TRUNCATED AT 250 WORDS)

Dietary carnitine intake related to skeletal muscle and plasma carnitine concentrations in adult men and women.

The purpose of this investigation was to determine if there was any relationship between dietary carnitine intake and the concentrations of carnitine in skeletal muscle and blood plasma in healthy adult men and women. Subjects (14 men, 14 women, fasted 8 h) reported to the Biodynamics Laboratory where they completed a 24-h diet recall questionnaire. Resting muscle biopsy (vastus lateralis) and blood plasma samples were taken and assayed for free, short-chain, and long-chain acyl carnitine concentrations. Dietary carnitine intake was estimated from data on concentrations in food. There was no significant relationship between either protein or carnitine intake with skeletal muscle carnitine concentrations. There was a significant relationship between both dietary carnitine (r = 0.50) and protein (r = 0.48) intake with blood plasma total acid soluble carnitine concentrations (p less than 0.01) in all subjects.