Cardiorespiratory kinetics and femoral artery blood velocity during dynamic knee extension exercise

The kinetics of femoral artery mean blood velocity (MBV; measured by pulsed Doppler) and whole body oxygen uptake (VO2; measured breath by breath) were assessed from the time constant during the on (tau on) and off (tau off) transients to step changes in work rate between complete rest and dynamic knee extension (KE) exercise. Six healthy men performed 5 min of seated KE exercise, with each leg alternately raising and lowering a weight (10% maximum voluntary contraction) over a 2-s duty cycle. Because kinetic analysis of VO2 kinetics during KE exercise is a new approach, the VO2 responses were also evaluated during the on and off transitions to the more familiar upright cycling exercise in which the magnitude of increase in VO2 and cardiac output was similar to that during KE exercise. During KE exercise, VO2 tau on [mean 72.2 +/- 11.2 (SE) s] was slower than VO2 tau off (33.3 +/- 1.8 s; P < 0.01). Cardiac output, measured with impedance cardiography, was not different for tau on (67.1 +/- 20.0 s) compared with that for tau off (52.9 +/- 7.6 s). Likewise, MBV tau on (34.5 +/- 3.9 s) was not different from tau off (35.3 +/- 3.2 s). During cycling, the VO2 tau on (18.0 +/- 2.4 s) and tau off (30.7 +/- 1.2 s) were both faster than KE VO2 tau on (P < 0.01). Even though the MBV kinetics indicated a rapid adaptation of blood flow during KE exercise, there was a slow adaptation of VO2. A transient hyperemia immediately on cessation of KE exercise, indicated by both MBV and calculated systemic vascular conductance responses, suggested that blood flow might have been inadequate and could have contributed to the delayed adaptation of VO2 at the onset of exercise, although other explanations are possible.     

Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension

The redistribution of blood flow (BF) in the abdominal viscera during right-legged knee extension-flexion exercise at very low intensity [peak heart rate (HR), 76 beats/min] was examined by using Doppler ultrasound. While sitting, subjects performed a right-legged knee extension-flexion exercise every 6 s for 20 min. BF was measured in the upper abdominal aorta (Ao), right common femoral artery (RCFA), and left common femoral artery (LCFA). Visceral BF (BFVis) was determined by the equation [BFAo - (BFRCFA + BFLCFA)]. A comparison with the change in BF (DeltaBF) preexercise showed a greater increase in DeltaBFRCFA than in DeltaBFAo during exercise. This resulted in a reduction of BFVis to 56% of its preexercise value or a decrease in flow by 1,147 +/- 293 (+/-SE) ml/min at the peak workload. Oxygen consumption correlated positively with DeltaBFAo, DeltaBFRCFA, and DeltaBFLCFA but inversely with DeltaBFVis during exercise and recovery. Furthermore, BFVis (% of preexercise value) correlated inversely with both an increase in HR (r = -0.89), and percent peak oxygen consumption (r = -0.99). This study demonstrated that, even during very-low-intensity exercise (HR <90 beats/min), there was a significant shift in BF from the viscera to the exercising muscles.     

Reliability of eccentric isokinetic knee flexion and extension measurements

This study assessed the test-retest reliability of knee isokinetic eccentric muscle performance in subjects with and without a history of tibio-femoral pathology. Nineteen adults were tested at 60 degrees/sec and 180 degrees/sec on three occasions using a standardized protocol that incorporates a same-session learning phase. Results revealed moderate to excellent reliability for average peak torque test-retest ICC (2,1) = .58 to .96, total work ICC = .63 to .93, and power ICC = .67 to .93. Joint angle at peak torque was unreliable (ICC = .01 to .69) for both muscle groups at both angular velocities. Knee flexion reliability was higher than extension reliability at both 60 degrees/sec and 180 degrees/sec. Subjects with tibio-femoral pathologies had ICC values lower than the healthy subjects. Reliable eccentric isokinetic measurements can be obtained for average peak torque, total work, and power. Clinicians should not assume the same degree of reliability in testing patients as in testing healthy subjects.     

Alternatives for measuring knee extension strength of the elderly at home

The objective of this study was to determine whether pregnancy is associated with an acceleration of human immunodeficiency virus (HIV) disease progression in women who have a pregnancy while HIV infected. A retrospective review of all women aged 15-35 years who attended an HIV outpatient program from January 1989 through August 1995, was undertaken. The 192 women who had a term pregnancy after testing positive for HIV were compared with 164 women who were not pregnant during the same period. The main outcome measures were death, the occurrence of a first acquired immunodeficiency syndrome (AIDS)-defining condition, or a condition indicative of symptomatic HIV. Disease progression was assessed using the Kaplan-Meier method and multivariate proportional hazards models. Compared with nonpregnant women, women with a term pregnancy were significantly more likely to be African-American (88% vs. 78%, p < 0.05), younger than 22 years of age (51 % vs. 11%, p < 0.001), and to have entered the clinic with a higher median CD4 count (519 vs. 433 cells/microl, p < 0.001). After adjusting for entry CD4 count and other factors, pregnancy was not associated with progression to any of the study outcomes. Thus, in women attending a publicly funded clinic, pregnancy does not appear to accelerate the progression of HIV disease.     

Alveolar oxygen uptake and blood flow dynamics in knee extension ergometry

The relationship was studied between the increase in oxygen uptake (VO2) measured breath-by-breath at the mouth, and the increase in femoral artery blood flow measured continuously with pulsed and echo Doppler methods. Five men exercised at 50 W on a knee extension ergometer in both the supine and the upright posture. The kinetics of the responses were determined by curve fitting to obtain the mean response time (MRT = 63% of the time required to achieve steady state). In the upright position, the increase in blood flow (MRT = 12.4 +/- 9.4 s, mean +/- SD) was faster than the increase in VO2 (29.6 +/- 9.3 s). Likewise in the supine position, blood flow increased more rapidly (25.1 +/- 9.7 s vs. 36.7 +/- 9.6 s). It should be noted that the increase in blood flow appeared to be faster than VO2, yet when blood flow adapted more slowly in the supine posture, it had an impact on the adaptation of VO2. This suggests that blood flow might have important effects on metabolism at the onset of submaximal exercise.     

The slump test: the effects of head and lower extremity position on knee extension

Maitland's slump test is a widely used neural tissue tension test. During slump testing, terminal knee extension is assessed for signs of restricted range of motion (ROM), which may indicate impaired neural tissue mobility. A number of refinements that modify hip and ankle position has been added to the basic slump test procedure, but no research to date has measured the effects of ankle and hip position on knee extension ROM during testing. The purpose of this study was to examine the effect of neural tension-producing movements of the cervical spine and lower extremity on knee extension ROM during the slump test. Thirty-four males with no significant history of low back pain were tested in the slump position with the cervical spine flexed and extended in each of three lower extremity test positions: neutral hip rotation with the ankle in a position of subject comfort (neutral), neutral hip rotation with ankle dorsiflexion (ankle dorsiflexion), and medial hip rotation with ankle dorsiflexion. Results showed significant decreases in active knee extension ROM (F1,198 = 29.53, p < 0.0001) in the cervical flexion compared with the cervical extension conditions. Subjects also exhibited significant decreases in active knee extension ROM (F2,198 = 56.76, p < 0.0001) as they were progressed from neutral to the ankle dorsiflexion to the medial hip rotation with ankle dorsiflexion positions of the lower extremity. The results of our study indicate that limitations in terminal knee extension ROM may be considered a normal response to the inclusion of cervical flexion, ankle dorsiflexion, or medial hip rotation in the slump test in young, healthy, adult males. In addition, the presence of a cumulative effect on knee extension ROM with the simultaneous application of these motions is noted. These findings may assist clinicians when assessing knee extension ROM during slump testing.     

Systemic leakage during isolated limb perfusion for melanoma

A hazard of regional perfusion for melanoma is incomplete isolation, resulting in leakage of the cytostatic drug into the systemic circulation. Data were analysed retrospectively on 438 melphalan perfusions performed for melanoma of the extremities during the period 1978-1990; continuous isotopic measurement of systemic leakage was carried out. The cumulative systemic leakage after 60 min perfusion was 0.9 per cent (95 per cent confidence interval 0.7-1.1 per cent). Systemic leakage of > or = 1 per cent was detected in 12.6 per cent of perfusions, > or = 5 per cent in 6.2 per cent and > or = 10 per cent in 1.4 per cent. In 2.3 per cent of patients, systemic side-effects in the form of mild transient bone marrow depression occurred. Six variables related to the perfusion technique were assessed by multivariate analysis for their influence on systemic leakage. The level of isolation and diameter of the venous cannula emerged as significant factors. In addition, ligation of the internal iliac vein provided optimal isolation during iliac perfusion.     

Anterior knee laxity and loss of extension after anterior cruciate ligament injury

This study was performed to examine the relationship between knee extension loss and the length of time after injury. We also wanted to compare anterior laxity in anterior cruciate ligament-injured knees in the early and late stages of injury. Loss of knee extension was measured in 81 patients with anterior cruciate ligament injury using lateral radiography with the injured leg relaxed and elevated. Extension loss was defined as the difference in maximal extension angle between the injured and uninjured knees. Average loss of extension was 3.6 degrees in the 17 knees in which the anterior cruciate ligament had been torn 3 weeks or less before examination (the acute injury group) and 0.6 degree in the 64 knees in which the anterior cruciate ligament had been torn more than 3 weeks before examination (the chronic injury group). The extension loss in the acutely injured knees was significantly greater compared with that in the uninjured knees and in the chronically injured knees. Arthrometric measurements using the KT-1000 arthrometer were reliable to diagnose an acute tear. There was no correlation between the degree of extension loss and arthrometric anterior knee laxity measurements. In 12 patients, the initial extension deficit in the early stage of injury significantly resolved with time, and manual maximum arthrometric measurements of anterior knee laxity improved spontaneously with time.     

The incidence of large venous emboli during total knee arthroplasty without pneumatic tourniquet use

The T4 phage capsid accessory protein genes soc and hoc have recently been developed for display of peptides and protein domains at high copy number (Ren et al., 1996. Protein Science 5, 1833-1843; Ren et al., 1997. Gene 195, 303-311). That biologically active and full-length foreign proteins can be displayed by fusion to SOC and HOC on the T4 capsid is demonstrated in this report. A 271-residue heavy and light chain fused IgG anti-EWL (egg white lysozyme) antibody was displayed in active form attached to the COOH-terminus of the SOC capsid protein, as demonstrated by lysozyme-agarose affinity chromatography (>100-fold increase in specific titer). HOC with NH2-terminal fused HIV-I CD4 receptor of 183 amino acids can be detected on the T4 outer capsid surface with human CD4 domain 1 and 2 monoclonal antibodies. The number of molecules of each protein (10-40) bound per phage and their activity suggest that proteins can fold to native conformation and be displayed by HOC and SOC to allow binding and protein-protein interactions on the capsid.     

Imaging of myocardial perfusion and metabolism with positron emission tomography

Positron emission tomography (PET) has been providing new information in the diagnosis and the pathophysiological assessment of heart diseases. The PET tracers commonly used in Japan are 13N-ammonia, 18F-fluorodeoxyglucose (FDG) for imaging of myocardial perfusion and metabolism, respectively. Measurement of regional myocardial blood flow by 13N-ammonia dynamic PET scan and a compartment model analysis is applied to the functional estimation of coronary stenotic lesions and the detection of perfusion abnormalities in hypertrophic heart diseases, familial hyperchlesterolemia and other diseases with possible microvascular lesions. 18F-FDG is commonly used to differentiate ischemic but viable tissue from myocardial scar in coronary artery disease and also used to detect cardiac tumor and the cardiac involvement in sarcoidosis. In addition to these two tracers, 11C-acetate is now expected to provide the clinical analysis of pathophysiology of heart failure by estimating the efficiency of energy conversion of the heart into external work.     

Immunogenicity studies with haptenated melittin peptides: implication for membrane involvement during the recognition step

The specific recognition of elicitors produced by plant pathogenic bacteria carrying avirulence (avr) genes is postulated to initiate cellular defense responses in plants expressing corresponding resistance genes. The biochemical functions of most avr genes, however, are not known. A heterologous system was developed to phenotypically express Pseudomonas syringae avr genes in Escherichia coli cells that required the P. syringae hrp cluster. E. coli MC4100 transformants carrying the plasmic-borne P. syringae pv. syringae Pss61 hrp cluster and p. syringae pv. glycinea avrB expressed from a triple lacUV5 promoter gained the ability to elicit the hypersensitive response in soybean cultivars expressing Rpg1 and in an Arabidopsis thaliana accession expressing RPM1. Inactivation of energy transducing or outer membrane components of the hrp-encoded secretion system blocked phenotypic expression expression of avrB in E. coli, but deletions abolishing harpinPSS production had little effect on the production of the AvrB phenotype by the E. coli transformants. Phenotypic expression of avrA, AvrPto, avrRpm1, avrRpt2, and avrPph3 in E. coli was also shown to require the hrp cluster. The results indicate that generation of the Avr phenotype in P. syringae strains is specifically dependent on the secretion activities of the hrp cluster.     

The use of a novel monitoring apparatus and modified Belzer hydroxyethyl starch perfusate for analysis of glomerular filtration during hypothermic perfusion preservation

The present study describes an experimental model for measurement of glomerular filtration during hypothermic perfusion preservation (HPP). To facilitate glomerular filtration during HPP, perfusate oncotic pressure was reduced by lowering the concentration of hydroxyethyl starch. Lewis rats underwent HPP at a mean perfusion pressure of 40-46 mmHg. An isograft model was used to demonstrate that retrieval and preparation for HPP did not impact adversely on renal function. Total cold ischemic time (CIT) consisted of the time from retrieval and preparation for perfusion (2 hr) added to the time of HPP. Tubular function studies demonstrated identical concentrations of Na+ and iohexol in ureteral effluent (UE) compared with circulating perfusate and, as such, established that UE flow represented a direct measure of glomerular filtration. Glomerular filtration rate (GFR) was then monitored during HPP by collecting UE in a beaker housed within a computerized Mettler balance system. GFR evolved in a characteristic, biphasic pattern during HPP, increasing from baseline values to reach a peak level at 4.8+/-0.3 hr of CIT and declining progressively thereafter. At 2.5 hr, time of peak values, 10 hr, 19.5 hr, and 24 hr of CIT, GFR values were 29+/-6 microl/min, 39+/-7 microl/min, 20+/-4 microl/min (n=15; P<0.01), 7+/-2 microl/min (n=14; P<0.001), and 14+/-6 microl/min (n=5), respectively. Intrarenal perfusate flows at the same time intervals were 4180+/-292 microl/min, 4083+/-290 microl/min, 3577+/-294 microl/min (P=NS), 1948+/-393 microl/min (P<0.001), and 2175+/-743 microl/min, respectively. Filtration fraction (FF) initially changed in parallel to glomerular filtration. Thereafter, FF either declined at a disproportionately slow rate compared with GFR (n=8) or increased rapidly (n=7). The data suggest that (1) primary change(s) in glomerular dynamics occur during HPP and (2) declining perfusate flow during the later stages of HPP reflects increasing renal vascular resistance localized at a postglomerular level. The data provide an experimental basis for investigating the clinical utility of monitoring glomerular filtration during HPP.     

Reductions in cardiac output in hypoxic young pigs: systemic and regional perfusion and oxygen metabolism

We tested the hypotheses that, in hypoxic young pigs, reductions in cardiac output restrict systemic oxygen transport to a greater extent than does hypoxia alone and that compensatory responses to this restriction are more effective in higher than in lower priority vasculatures. To study this, 10- to 14-day-old instrumented awake hypoxic (arterial oxygen tension = 39 Torr) pigs were exposed to reduced venous return by inflation of a right atrial balloon-tipped catheter. Blood flow was measured with radionuclide-labeled microspheres, and oxygen metabolism was determined with arterial and venous oxygen contents from appropriate vessels. Hypoxia resulted in a reduction in oxygen tension; increases in cardiac output and perfusion to brain (72% over baseline), heart, adrenal glands, and liver without reductions to other organs except for the spleen; reductions in systemic and intestinal oxygen delivery; and increases in systemic and intestinal oxygen extraction without changes in systemic, cerebral, or intestinal oxygen uptake. During hypoxia, decreasing venous return was associated with increases in arterial lactic acid concentration and central venous pressure; attenuation of the hypoxia-related increase in cardiac output; sustained increases in brain (72% over baseline) and heart perfusion; reductions in lung (bronchial artery), pancreatic, renal, splenic, and intestinal (-50% below baseline) perfusion; decreases in systemic and gastrointestinal oxygen delivery; sustained increases in systemic and intestinal oxygen extraction; and decreases in intestinal oxygen uptake, without changes in cerebral oxygen metabolism. We conclude that when venous return to the heart is reduced in hypoxic young pigs, the hypoxia-related increase in cardiac output was attenuated and the relative reduction in cardiac output was associated with preserved cerebral oxygen uptake and compromised intestinal oxygen uptake. Regional responses to hypoxia combined with relative reductions in cardiac output differ from that of hypoxia alone, with the greatest effects on lower priority organs such as the gastrointestinal tract.     

Muscle metabolism in uremia and the effect of amino acid supplementation

Molecular cloning of calcium channel subunit genes has identified an unexpectedly large number of genes and splicing variants, and a central problem of calcium channel biology is to now understand the functional significance of this genetic complexity. While electrophyisological, pharmacological, and molecular cloning techniques are providing one level of understanding, a complete understanding will require many additional kinds of studies, including genetic studies done in intact animals. In this regard, an intriguing variety of episodic diseases have recently been identified that result from defects in calcium channel genes. A study of these diseases illustrates the kind of insights into calcium channel function that can be expected from this method of inquiry.     

Gender and fat metabolism during exercise: a review

We examined the evidence for greater fat utilization by women during exercise and the potential gender differences in specific cellular processes. Results from well-controlled studies show that, compared to men, women oxidize more fat during submaximal exercise, resulting in the relative sparing of muscle glycogen. Mature female rats use less muscle glycogen during running and can run longer than male counterparts. Circulating estrogen is critical to these observations, as shown by studies where male rats were treated with estrogen. Estrogen-treated male rats use less muscle glycogen during exercise and can run longer than untreated males. The cellular mechanisms and factors underlying these findings are unknown and certainly multifactorial. We offer some information that, unfortunately, does not lead to any natural conclusion. However, this area is certainly ripe for research.