Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end-stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and beta-2-microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice-weekly, in-center, 8-hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45+/-7 years). Serum creatinine levels decreased from 9.2+/-1.9 to 3.0+/-1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7+/-1.9 to 2.5+/-0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8+/-5.5 mg/L predialysis to 14.9+/-7.0 mg/L at 8 hours (P<0.01). Dialysate-side clearances of phosphorus and creatinine were 136+/-13 and 143+/-27 cm(3)/min, respectively. Phosphorus clearances were steadily maintained during the 8-hour session. A total of 904+/-292 mg of phosphorus was removed during the 8-hour treatment, with 501+/-174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one-half of the session. The overall calculated B2M clearance was 55.1+/-40.3 cm(3)/min using the immediate post-B2M value and 28.4+/-34.2 mg/L using the 30-minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8-hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.
The thalamus may be the critical brain area involved in sensory gating and the relay of respiratory mechanical information to the cerebral cortex for the conscious awareness of breathing. We hypothesized that respiratory mechanical stimuli in the form of tracheal occlusions would modulate the gene expression profile of the thalamus. Specifically, it was reasoned that conditioning to the respiratory loading would induce a state change in the medial thalamus consistent with a change in sensory gating and the activation of molecular pathways associated with learning and memory. In addition, respiratory loading is stressful and thus should elicit changes in gene expressions related to stress, anxiety, and depression. Rats were instrumented with inflatable tracheal cuffs. Following surgical recovery, they underwent 10 days (5 days/week) of transient tracheal occlusion conditioning. On day 10, the animals were sacrificed and the brains removed. The medial thalamus was dissected and microarray analysis of gene expression performed. Tracheal obstruction conditioning modulated a total of 661 genes (p < 0.05, log2 fold change ≥0.58), 250 genes were down-regulated and 411 up-regulated. There was a significant down-regulation of GAD1, GAD2 and HTR1A, HTR2A genes. CCK, PRKCG, mGluR4, and KCJN9 genes were significantly up-regulated. Some of these genes have been associated with anxiety and depression, while others have been shown to play a role in switching between tonic and burst firing modes in the thalamus and thus may be involved in gating of the respiratory stimuli. Furthermore, gene ontology and pathway analysis showed a significant modulation of learning and memory pathways. These results support the hypothesis that the medial thalamus is involved in the respiratory sensory neural pathway due to the state change of its gene expression profile following repeated tracheal occlusions.
Respiratory related evoked potentials (RREP) elicited by inspiratory mechanical loads have been demonstrated in humans and lambs. However, it was unknown if an occlusion paradigm can also elicit a RREP in chronically instrumented, awake, spontaneously breathing rats. Rats were instrumented with electrodes on the surface of the cortex and an occluder was sutured around the trachea. After recovery, the tracheal cuff was inflated for 3 to 5 breaths. Occlusions were presented approximately every 30 seconds for approximately 10 to 18 minutes. Occlusion‐elicited evoked potentials (EP) were obtained by computer‐signal averaging the ECoG activity. A short‐latency peak was observed on the averaged occlusion‐elicited evoked potentials in all animals for Day 1 and 2. A long‐latency peak was observed in all animals from Day 3 to 11. The result demonstrated that inspiratory occlusion elicits an evoked potential in the cortex of awake, spontaneously breathing rats. The waveform of the EP changes with chronic occlusion conditioning.
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