(1/91) Uptakes and images of 38K in rabbit heart, kidney, and brain.
The purpose of this study was to evaluate the kinetics and image quality of positron-emitting 38K (half-life, 7.6 min) and high-resolution small-animal PET in the heart, kidney, and brain of rabbits. METHODS: Studies were performed with 18 closed-chest anesthetized rabbits at baseline and during infusions of adenosine (0.2 mg/kg/min) and propranolol (0.5-1.0 mg/kg intravenously) using high-resolution small-animal PET. 38K was injected intravenously and dynamic PET imaging of the heart, kidney, or brain was performed for 3 min. Colored microspheres were injected into the left ventricle to measure organ blood flow. Arterial blood was withdrawn directly from the femoral artery, and, after the animals were killed, 38K activities in each organ were measured directly with a well counter. Uptake of 38K was calculated by dividing the 38K activities in each organ by the integral of the input function. The extraction fraction of 38K was estimated by dividing the uptake of 38K in each organ by the organ blood flow, measured by microspheres. RESULTS: The left ventricular myocardium and kidney were clearly visualized, but there was no visual 38K uptake in the brain. For the heart, kidney, and brain, respectively, average blood flow was 2.91 +/- 1.29, 5.49 +/- 0.71, and 0.57 +/- 0.11 mL/min/g, and the extraction fraction of 38K at baseline was 0.55 +/- 0.13, 0.48 +/- 0.13, and 0.022 +/- 0004. The Renkin-Crone model fit the relation between myocardial extraction and flow under a wide range of myocardial blood flow (r = 0.89). CONCLUSION: 38K is a suitable tracer for noninvasively showing the potassium kinetics of the heart, kidney, and brain by PET imaging. (+info)
(2/91) The role of K+ channels in the force recovery elicited by Na+-K+ pump stimulation in Ba2+-paralysed rat skeletal muscle.
The present experiments were performed to assess the role of K+ channels in hormonal stimulation of the Na+-K+ pump and to determine the contribution of Na+-K+ pumps to the recovery of excitability and contractility in depolarized skeletal muscle. In soleus muscle, Ba2+ (0.02 and 1 mM) was found to inhibit 42K+ efflux and 42K+ influx. Both in the absence and the presence of Ba2+ (1 mM), salbutamol and calcitonin gene-related peptide (CGRP) induced a marked decrease in intracellular Na+ and stimulation of 42K+ uptake. In soleus muscles Ba2+ (0.1 and 1.0 mM) decreased twitch and tetanic force. Subsequent stimulation of the Na+-K+ pumps by salbutamol, CGRP or repeated electrical stimulation produced a highly significant restoration of force development, which was suppressed by ouabain, but not by glibenclamide. Also, in extensor digitorum longus muscles Ba2+ (0.1 mM) produced a considerable force decline, which was partly restored by salbutamol and CGRP. The area of compound action potentials (M-waves) elicited by indirect stimulation was decreased by Ba2+ (0.1 mM). This was associated with a concomitant decrease in tetanic force and depolarization. Salbutamol, CGRP or repeated electrical stimulation all elicited marked recovery of M-wave area, force and membrane potential. All recordings showed close correlations between these three parameters. The data add further support to the concept that due to its electrogenic nature and large transport capacity, the Na+-K+ pump is a rapid and efficient mechanism for the maintenance of excitability in skeletal muscle, acting independently of Ba2+- or ATP-sensitive K+ channel function. (+info)
(3/91) Comparison of total body potassium with other techniques for measuring lean body mass in men and women with AIDS wasting.
BACKGROUND: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. DESIGN: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. RESULTS: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P: < 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting. (+info)
(4/91) Voltage dependence of the apparent affinity for external Na(+) of the backward-running sodium pump.
The steady-state voltage and [Na(+)](o) dependence of the electrogenic sodium pump was investigated in voltage-clamped internally dialyzed giant axons of the squid, Loligo pealei, under conditions that promote the backward-running mode (K(+)-free seawater; ATP- and Na(+)-free internal solution containing ADP and orthophosphate). The ratio of pump-mediated (42)K(+) efflux to reverse pump current, I(pump) (both defined by sensitivity to dihydrodigitoxigenin, H(2)DTG), scaled by Faraday's constant, was -1.5 +/- 0.4 (n = 5; expected ratio for 2 K(+)/3 Na(+) stoichiometry is -2.0). Steady-state reverse pump current-voltage (I(pump)-V) relationships were obtained either from the shifts in holding current after repeated exposures of an axon clamped at various V(m) to H(2)DTG or from the difference between membrane I-V relationships obtained by imposing V(m) staircases in the presence or absence of H(2)DTG. With the second method, we also investigated the influence of [Na(+)](o) (up to 800 mM, for which hypertonic solutions were used) on the steady-state reverse I(pump)-V relationship. The reverse I(pump)-V relationship is sigmoid, I(pump) saturating at large negative V(m), and each doubling of [Na(+)](o) causes a fixed (29 mV) rightward parallel shift along the voltage axis of this Boltzmann partition function (apparent valence z = 0.80). These characteristics mirror those of steady-state (22)Na(+) efflux during electroneutral Na(+)/Na(+) exchange, and follow without additional postulates from the same simple high field access channel model (Gadsby, D.C., R.F. Rakowski, and P. De Weer, 1993. Science. 260:100-103). This model predicts valence z = nlambda, where n (1.33 +/- 0.05) is the Hill coefficient of Na binding, and lambda (0.61 +/- 0.03) is the fraction of the membrane electric field traversed by Na ions reaching their binding site. More elaborate alternative models can accommodate all the steady-state features of the reverse pumping and electroneutral Na(+)/Na(+) exchange modes only with additional assumptions that render them less likely. (+info)
(5/91) Correlation of the glycoside response, the force staircase, and the action potential configuration in the neonatal rat heart.
The rat heart demonstrates marked alterations in its responses to ouabain and increased frequencies of stimulation and in the duration of its action potential during the initial 21 days of life. At an age of 6.2 days 5 times 10- minus 5M ouabain produced a 158.2% increase in dP/dt compared with a 17.2% increase at 21.1 days (P less than 0.001). At 6.2 days dP/dt increased by 53.4% when the heart rate was accelerated from 30 to 90 beats/min compared with an increase of 12.2% at 21.1 days (P less than 0.005). The positive glycoside and staircase responses at the younger age were virtually eliminated when the hearts were perfused with a solution containing 50% [Na+]o and 25% [Ca-2+]o ([Ca-2+]o/[Na+]o-2 maintained constant). The duration of the ventricular action potential progressively decreased from 350-400 msec at birth to 100-150 msec at 21 days of life. This decrease was due to a shortening and a decrease in the potential level of the plateau phase. The prominent plateau typical of the early neonatal period was significantly diminished by perfusion with 50% [Na+]o. The results suggest that Na+ flux through a slow membrane channel plays a significant role in the positive staircase and glycoside responses of the early neonatal rat heart. As the heart matures and becomes functionally anomalous relative to other mammalian species, the slow channel progressively closes. (+info)
(6/91) Perturbation of the pump-leak balance for Na(+) and K(+) in malaria-infected erythrocytes.
In human erythrocytes infected with the mature form of the malaria parasite Plasmodium falciparum, the cytosolic concentration of Na(+) is increased and that of K(+) is decreased. In this study, the membrane transport changes underlying this perturbation were investigated using a combination of (86)Rb(+), (43)K(+), and (22)Na(+) flux measurements and a semiquantitative hemolysis technique. From >15 h postinvasion, there appeared in the infected erythrocyte membrane new permeation pathways (NPP) that caused a significant increase in the basal ion permeability of the erythrocyte membrane and that were inhibited by furosemide (0.1 mM). The NPP showed the selectivity sequence Cs(+) > Rb(+) > K(+) > Na(+), with the K(+)-to-Na(+) permeability ratio estimated as 2.3. From 18 to 36 h postinvasion, the activity of the erythrocyte Na(+)/K(+) pump increased in response to increased cytosolic Na(+) (a consequence of the increased leakage of Na(+) via the NPP) but underwent a progressive decrease in the latter 12 h of the parasite's occupancy of the erythrocyte (36-48 h postinvasion). Incorporation of the measured ion transport rates into a mathematical model of the human erythrocyte indicates that the induction of the NPP, together with the impairment of the Na(+)/K(+) pump, accounts for the altered Na(+) and K(+) levels in the host cell cytosol, as well as predicting an initial decrease, followed by a lytic increase in the volume of the host erythrocyte. (+info)
(7/91) Age-related differences in fat-free mass, skeletal muscle, body cell mass and fat mass between 18 and 94 years.
OBJECTIVE: To determine (1) lean and fat body compartments, reflected by fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), body cell mass (BCM), total body potassium (TBK), fat mass and percentage fat mass, and their differences between age groups in healthy, physically active subjects from 18 to 94 y of age; and (2) if the rate of decrease in any one of the parameters by age might be accelerated compared to others. METHODS: A total of 433 healthy ambulatory Caucasians (253 men and 180 women) aged 18--94 y were measured by dual-energy X-ray absorptiometry (DXA) and whole body scintillation counter (TBK counter) using a large sodium iodide crystal (203 mm diameter). RESULTS: The ASMM change (-16.4 and -12.3% in men and women, respectively) in >75 y-old compared to 18 to 34-y-old subjects was greater than the FFM change (-11.8 and -9.7% in men and women, respectively) and this suggests that skeletal muscle mass decrease in older subjects was proportionally greater than non-skeletal muscle mass. BCM (-25.1 and -23.2% in men and women, respectively) and TBK differences were greater than the differences in FFM or ASMM suggesting altered composition of FFM in older subjects. Women had lower peak FFM, ASMM, BCM and TBK than men. CONCLUSIONS: The decline in FFM, ASMM, BCM and TBK is accelerated in men and women after 60 y of age and FFM, ASMM, BCM and TBK are significantly lower than in younger subjects. Fat mass continued to increase until around 75 y. (+info)
(8/91) Coincidence and noncoincidence counting (81Rb and 43K): a comparative study.
This paper compares the accuracy of imaging and resolution obtained with 81Rb and 43K using coincidence and noncoincidence counting. Phantoms and isolated infarcted dog hearts were used. The results clearly show the superiority of coincidence counting with a resolution of 0.5 cm. Noncoincidence counting failed to reveal even sizable defects in the radioactive source. (+info)