Blood lactate clearance during active recovery after an intense running bout depends on the intensity of the active recovery

High-intensity exercise training contributes to the production and accumulation of blood lactate, which is cleared by active recovery. However, there is no commonly agreed intensity or mode for clearing accumulated blood lactate. We studied clearance of accumulated blood lactate during recovery at various exercise intensities at or below the lactate threshold after high-intensity interval runs that prompted lactate accumulation. Ten males repeated 5-min running bouts at 90% of maximal oxygen uptake ([Vdot]O2max), which increased blood lactate concentration from 1.0 ± 0.1 to 3.9 ± 0.3 mmol · l-1. This was followed by recovery exercises ranging from 0 to 100% of lactate threshold. Repeated blood lactate measurements showed faster clearance of lactate during active versus passive recovery, and that the decrease in lactate was more rapid during higher (60-100% of lactate threshold) than lower (0-40% of lactate threshold) (P < 0.05) intensities. The more detailed curve and rate analyses showed that active recovery at 80-100% of lactate threshold had shorter time constants for 67% lactate clearance and higher peak clearance rates than 40% of lactate threshold or passive recovery (P < 0.05). Finally, examination of self-regulated intensities showed enhanced lactate clearance during higher versus lower intensities, further validating the intensity dependence of clearance of accumulated blood lactate. Therefore, active recovery after strenuous exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner. Maximum clearance occurred at active recovery close to the lactate threshold

Inert gas clearance from tissue by co-currently and counter-currently arranged microvessels

To elucidate the clearance of dissolved inert gas from tissues, we have developed numerical models of gas transport in a cylindrical block of tissue supplied by one or two capillaries. With two capillaries, attention is given to the effects of co-current and counter-current flow on tissue gas clearance. Clearance by counter-current flow is compared with clearance by a single capillary or by two co-currently arranged capillaries. Effects of the blood velocity, solubility, and diffusivity of the gas in the tissue are investigated using parameters with physiological values. It is found that under the conditions investigated, almost identical clearances are achieved by a single capillary as by a co-current pair when the total flow per tissue volume in each unit is the same (i.e., flow velocity in the single capillary is twice that in each co-current vessel). For both co-current and counter-current arrangements, approximate linear relations exist between the tissue gas clearance rate and tissue blood perfusion rate. However, the counter-current arrangement of capillaries results in less-efficient clearance of the inert gas from tissues. Furthermore, this difference in efficiency increases at higher blood flow rates. At a given blood flow, the simple conduction-capacitance model, which has been used to estimate tissue blood perfusion rate from inert gas clearance, underestimates gas clearance rates predicted by the numerical models for single vessel or for two vessels with co-current flow. This difference is accounted for in discussion, which also considers the choice of parameters and possible effects of microvascular architecture on the interpretation of tissue inert gas clearance

Blood lactate clearance after maximal exercise depends on active recovery intensity

AIM: High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise.<p></p> METHODS: We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration >10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold.<p></p> RESULTS: Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05).<p></p> CONCLUSION: Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold

The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents

Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss. In 34 obese adolescents (median age 15.7 years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7 months, and again after 12 months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24 kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (- 1.08 (- 1.40-- 0.79) mL/min) was noticed compared with nocturnal values (0.75 (- 0.89-- 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day - 1.24 (- 1.44-1.05) mL/min and night - 0.98 (- 1.09-- 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72 mL/min (0.59-0.77) and nighttime clearance was 0.46 mL/min (0.41-0.51). After weight loss, daytime clearance increased to 0.99 mL/min (0.85-1.17) and nighttime clearance increased to 0.78 mL/min (0.64-0.93). Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.What is Known:center dot Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.What is New:center dot In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.center dot Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss

Cyclosporine Absorption Following Orthotopic Liver Transplantation

Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9–21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2–7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: (1) cyclosporine clearance is highly variable between patients, (2) pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, (3) cyclosporine is poorly and variably absorbed in liver transplant patients, and (4) cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI.

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin

Studies on hepatic blood flow and the rate of Bromsulphalein clearance in dogs with portacaval transposition

Hepatic plasma and blood flows were determined in dogs with modified portacaval transposition. Mean hepatic blood flow was 43 ml. per kilogram per minute, approximately that expected in a normal dog. Similarly, the rate of Bromsulphalein clearance was in the range expected for normal dogs. © 1962

Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis

The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion. We utilize a mathematical model to illustrate that electrolyte-free water clearance results in a greater reduction in IF volume compared to blood volume, and that this difference may be mediated by peripheral sequestration of osmotically inactive sodium. By coupling the model with data on plasma and urinary sodium and water in healthy subjects administered either the SGLT2i dapagliflozin or loop diuretic bumetanide, we predict that dapagliflozin produces a 2-fold greater reduction in IF volume compared to blood volume, while the reduction in IF volume with bumetanide is only 78% of the reduction in blood volume. Heart failure is characterized by excess fluid accumulation, in both the vascular compartment and interstitial space, yet many heart failure patients have arterial underfilling due to low cardiac output, which may be aggravated by conventional diuretic treatment. Thus, we hypothesize that by reducing IF volume to a greater extent than blood volume, SGLT2 inhibitors might provide better control of congestion without reducing arterial filling and perfusion

Administration of liposomal agents and blood clearance capacity of the mononuclear phagocyte system

As liposomes are cleared from the circulation to a substantial extent by the phagocytic cells of the mononuclear phagocyte system (MPS), there is a question whether administration of liposome-based therapeutic agents interferes with clearance of infectious organisms by the MPS from blood. In the present study, at first the effect of administration of three types of empty liposomes (devoid of drug), differing in blood residence time, on carbon clearance and bacterial clearance from blood was studied with mice. Classical liposomes (LIP A) and placebo liposomes with lipid composition as in AmBisome (LIP B) or as in Doxil (LIP C) were used. Liposomes were administered intravenously as a single dose. Second, the effect of multiple-dose administration of AmBisome on bacterial blood clearance was studied with rats. AmBisome was administered with two different dosage schedules. The blood clearance capacity of the MPS was monitored at different time points after the last liposome injection. It was shown that the carbon blood clearance capacity of the MPS was impaired only at a high lipid dose of empty classical liposomes. The bacterial blood clearance capacity was never impaired, not even after prolonged treatment with AmBisome administered in a clinically relevant regimen

Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection.

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection