Cerebral hemodynamics and resistance exercise

PURPOSE: Repetitive resistance exercise with large muscle mass causes rapid fluctuations in mean arterial blood pressure (MAP). We sought to determine the effect of these fluctuations on the cerebrovasculature response determined by mean flow velocity (Vmean) of the middle cerebral artery. METHODS: Nine subjects performed 10-repetition maximum leg press exercise. MAP was estimated by finger photoplethysmography, Vmean by Doppler ultrasound, and end-tidal CO2 (PETCO2) by mass spectrometry. RESULTS: Vmean fluctuated with MAP with each repetition however averaged over the 10 repetitions, Vmean was unchanged from resting baseline values (66.9 +/- 10.8 vs 67.7 +/- 12.3 cm.s-1, baseline vs exercise, P > 0.05) despite an increased MAP (89.5 +/- 8.4 vs 105.0 +/- 4.9 Torr, P < 0.05). PETCO2 also remained unchanged from rest to exercise (37.7 +/- 2.8 vs 36.6 +/- 2.7 Torr, P > 0.05). Vmean decreased below resting levels for the first 5 s of recovery (59.8 +/- 9.1 cm.s-1, P < 0.05) as MAP returned rapidly to slightly below baseline (83.3 +/- 6.1, P > 0.05). MAP/Vmean, an index of cerebrovascular resistance, was elevated during exercise and returned to baseline after exercise. An increase in Vmean at 30 s post exercise (78.4 +/- 10.6 cm.s-1, P < 0.05) corresponded with elevated PETCO2 (43.0 +/- 4.8 Torr, P > 0.05). CONCLUSION: The results suggest that fluctuations in MAP with individual muscle contractions during resistance exercise appear to be too rapid to be countered by cerebrovascular autoregulation. However, the progressive increase in MAP over a number of contractions was effectively countered to maintain Vmean near baseline values before a decrease in Vmean immediately after exercise.     

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;?6°) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10?min) and lower body negative pressure (LBNP) tests (5?min at ?25, ?35, ?45?mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+44% before and +57% after HDBR) and LBNP exposure (+19% before and +34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP +21% before and ?8% after HDBR); LBNP was less sensitive probably because it was performed 6?h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.     

The effect of citrate loading on exercise performance,acid-base balance and metabolism

Summary Nine subjects ( 65±2 ml·kg⁻¹·min⁻¹, mean±SEM) were studied on two occasions following ingestion of 500 ml solution containing either sodium citrate (C, 0.300 g·kg⁻¹ body mass) or a sodium chloride placebo (P, 0.045 g·kg⁻¹ body mass). Exercise began 60 min later and consisted of cycle ergometer exercise performed continuously for 20 min each at power outputs corresponding to 33% and 66% , followed by exercise to exhaustion at 95% . Pre-exercise arterialized-venous [H⁺] was lower in C (36.2±0.5 nmol·l⁻¹; pH 7.44) than P (39.4±0.4 nmol·l⁻¹; pH 7.40); the plasma [H⁺] remained lower and [HCO ₃ ⁻ ] remained higher in C than P throughout exercise and recovery. Exercise time to exhaustion at 95% was similar in C (310±69 s) and P (313±74 s). Cardiorespiratory variables (ventilation, , , heart rate) measured during exercise were similar in the two conditions. The plasma [citrate] was higher in C at rest (C, 195±19 μmol·l⁻¹; P, 81±7 μmol·l⁻¹) and throughout exercise and recovery. The plasma [lactate] and [free fatty acid] were not affected by citrate loading but the plasma [glycerol] was lower during exercise in C than P. In conclusion, sodium citrate ingestion had an alkalinizing effect in the plasma but did not improve endurance time during exercise at 95% . Furthermore, citrate loading may have prevented the stimulation of lipolysis normally observed with exercise and prevented the stimulation of glycolysis in muscle normally observed in bicarbonate-induced alkalosis.     

Blood lactate responses in incremental exercise as predictors of constant load performance

Summary Seven trained male cyclists ( =4.42±0.23 l·min⁻¹; weight 71.7±2.7 kg, mean ± SE) completed two incremental cycling tests on the cycle ergometer for the estimation of the “individual anaerobic threshold” (IAT). The cyclists completed three more exercises in which the work rate incremented by the same protocol, but upon reaching selected work rates of approximately 40, 60 and 80% , the subjects cycled for 60 min or until exhaustion. In these constant load studies, blood lactate concentration was determined on arterialized venous ([La⁻]a_v) and deep venous blood ([La⁻]_v) of the resting forearm. The a_v-v lactate gradient across the inactive forearm muscle was −0.08 mmol·l⁻¹ at rest. After 3 min at each of the constant load work rates, the gradients were +0.05, +0.65* and +1.60* mmol·l⁻¹ (*P<0.05). The gradients after 10 min at these same work rates were −0.09, +0.24 and +1.03* mmol·l⁻¹. For the two highest work rates taken together, the lactate gradient was less at 10 min than 3 min constant load exercise (P<0.05). The [La⁻]a_v was consistently higher during prolonged exercise at both 60 and 80% than that observed at the same work rate during progressive exercise. At the highest work rate (at or above the IAT), time to exhaustion ranged from 3 to 36 min in the different subjects. These data showed that [La⁻] uptake across resting muscle continued to increase to work rates above the IAT. Further, the greater a_v-v lactate gradient at 3 min than 10 min constant load exercise supports the concept that inactive muscle might act as a passive sink for lactate in addition to a metabolic site.     

Pathologic findings in mesangiopathic glomerulonephritis in Navajo Indians

Immune complex-associated mesangiopathic glomerulonephritis was found in 64% of renal biopsies performed on Navajos over a 16-year period. It is characterized by mild mesangial expansion and predominant immunoglobulin (Ig) A and/or IgM deposits. Statistical analysis shows that glomerular deposits of IgG and C3, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and tubular atrophy are associated with renal insufficiency at the time of biopsy, and can be integrated into a pathologic index that has a high correlative value. Mesangiopathic glomerulonephritis is probably responsible for the high rates of non-diabetic end-stage renal disease seen in Navajo Indians.     

Renal cell carcinoma of end-stage renal disease: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification.

End-stage renal disease (ESRD) patients have an increased risk of carcinoma of the kidney, thought to result from development of a disproportionately high number of papillary renal cell carcinomas. This study was undertaken to discover whether these renal carcinomas have a deletion of the short arm of chromosome 3, which characterizes conventional (clear cell) carcinomas, or trisomies of chromosomes 7 and 17, which characterize the majority of sporadic papillary renal cell neoplasms. Archival specimens from 17 end-stage kidneys containing renal cell carcinomas were collected from 16 ESRD patients. DNA was extracted from paraffin blocks of tumor and nontumorous tissue. Microsatellites on the long and short arm of chromosomes 3, 7, and 17 were amplified in paired "normal" tumor samples. Heterozygous loci were analyzed for loss of heterozygosity, indicating a deletion, and for allele ratio differences, indicating a duplication. Successful microsatellite studies were obtained on 18 tumors (2 conventional carcinomas, 14 papillary carcinomas, 2 unclassified [solid, eosinophilic cell] carcinomas). Of the papillary carcinomas, none had a 3p deletion, five had trisomies of both chromosomes 7 and 17, six had no changes in chromosomes 7 and 17, and three had either trisomy 7 or trisomy 17 but not both. A 3p deletion was present in one of two conventional carcinomas. No chromosome 3, 7, or 17 changes were identified in the unclassified carcinomas. The genetic abnormalities in 6 of 18 ESRD tumors seemed to be the same as those found in sporadic papillary or conventional renal cell carcinomas. Nine of 14 papillary carcinomas did not show allelic duplications of chromosomes 7 and 17. This is uncharacteristic of the findings reported for most of the sporadic forms of the neoplasm and suggests that the genetic mechanism underlying the development of many papillary renal cell carcinomas in ESRD patients might be different than that of the general population.     

Comparison of a 4-day confinement and head-down tilt on endocrine response and cardiovascular variability in humans

The aim of this study was to determine the effects of a 4-day head-down tilt (HDT; – 6°) and 4-day confinement on several indicators that might reflect a state of cardiovascular deconditioning on eight male subjects. Measurements were made of endocrine responses, heart rate variability and spontaneous baroreflex response (SBR) slope before, during and after each intervention. Plasma volume decreased by 10% after the 4-day HDT. The concentration of active renin was increased and that of urinary atrial natriuretic peptide decreased during the 4-day experiment in both groups. Plasma arginine vasopressin concentration decreased significantly only after 4-day confinement. After the 4-day HDT, one of the spectrum analysis parameters was statistically changed: the parasympathetic indicator decreased significantly (P < 0.05) whereas the sympathetic indicator and the total power spectrum were unaltered. After 4-day confinement spectrum analysis parameters were not statistically altered. A significant decrease of SBR (P < 0.05) was noticed only after the 4-day HDT. These data would suggest that exposure to a 4-day HDT was sufficient to induce a cardiovascular deconditioning which may have been induced by confinement and inactivity.     

Ramp work tests with three different beta-blockers in normal human subjects

Summary The effects of-blockade on the responses of oxygen uptake ( ), heart rate (HR) and blood lactate (La^–) were examined during ramp cycle ergometer tests (50 W·min^–1 ramp slope) in 8 healthy male volunteers. Each subject took placebo, or one of four different doses of three different-blockers (propranolol, metoprolol or oxprenolol) 2 h prior to each test for a total of 15 exercise tests. ( ) was measured breath-by-breath, HR was sampled once per breath, and La^– was obtained every minute. Linear regression analysis was applied to and HR data to obtain the kinetic parameter total lag time (TLT) and a slope value. La^– was analyzed by a continuous exponential model with the lactate slope index (LSI) being derived from the individual response curves. Submaximal exercise HR was significantly depressed at the baseline as well as during the ramp tests by-blockade. TLT for HR was significantly affected by-blockade, with a dose dependent shift from a placebo value of 16 to 26 s with placebo to a value of -40 to -60 s at the highest dose. Slope of HR was significantly depressed relative to placebo. kinetics assessed by TLT were not significantly affected by-blockade. This slope of the vs work rate relationship was significantly less than placebo only at the highest dose of-blocker. The LSI was not significantly affected by-blockade. In contrast with the clear impairment of HR response to exercise during-blockade, both the and La^– responses appear to be relatively unaffected by-blockade during ramp exercise tests. However, the significant change in slope of the vs work rate relationship at the highest dose level indicates that the oxygen transport system is in fact impaired by-blockade. It is concluded that the ramp exercise test is not a sensitive means of detecting changes in oxygen transport kinetics during exercise with-blockade. Further, there were no differences between the three-blocking drugs.Supported by the Heart and Stroke Foundation of Ontario, and the Natural Sciences and Engineering Research Council of Canada     

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R–R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R–R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r=0·76 and r=0·85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean ± SEM; 3·5 ± 0·3 versus 11·2 ± 1·4 ms mmHg^–1; P<0·01) and spontaneous sequence analysis (10·3 ± 0·8 versus 31·5 ± 2·3 ms mmHg^–1; P<0·001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7·9 ± 1·4 versus 6·7 ± 0·8 ms mmHg^–1; P=0·27) or spontaneous sequence methods (21·8 ± 2·7 versus 20·0 ± 2·1 ms mmHg^–1; P=0·24). BRG was correlated during RB and SB protocols (r=0·80; P<0·0001). ARMA and spontaneous BRG estimates were correlated (r=0·79; P<0·0001), with spontaneous sequence values being consistently larger (P<0·0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.     

Regulation of blood flow at the onset of exercise by feed forward and feedback mechanisms.

Blood flow adapts quickly after the onset of exercise to meet the metabolic demands of skeletal muscle. This review approaches the issue of how rapidly blood flow adapts and what the mechanisms for adaptation are primarily from a control theory perspective. Several recent papers have suggested that O2 transport proceeds at a rate that anticipates the metabolic demand over a very wide range of work rates. When considered from a control theory perspective, this implies involvement of feed forward control. Although there is one very important feed forward mechanism in the muscle pump that is activated with the onset of exercise, other evidence suggests that adjustment of blood flow to match the metabolic demand relies on feedback control from local dilator factors released in proportion to the metabolic demand. These distinct mechanisms with different onset times mean that blood flow adapts to the exercise demand with at least two distinct phases. The time course of the adaptation varies greatly between work rates, showing that blood flow control cannot be described by a linear control system and that the mechanisms responsible for vasodilation are dependent on work rate.