Metabolic responses of the whole body, portal-drained viscera and hind quarter to acute cold exposure and feeding in sheep: Effects of nonselective and selective β-adrenoceptor blockade

1997 ◽  
Vol 77 (4) ◽  
pp. 707-714 ◽  
Author(s):  
J. O. O. Miaron ◽  
R. J. Christopherson

Two experiments were conducted to study the adrenergic regulation of thermogenesis in sheep during acute cold exposure and feeding. Propranolol, a nonselective β-blocker, metoprolol, a β1-blocker and ICI 118551, a β2-blocker, were used to investigate the β-adrenoceptor mediated whole-body and organ oxygen consumption (VO2). Whole-body oxygen consumption was measured by open circuit calorimetry. Portal-drained viscera and hindquarter oxygen consumption was the product of arterio-venous oxygen concentration difference and blood flow across the respective organs. Acute cold exposure increased (P < 0.05) whole body and hindquarters VO2 by about 60% but, not that of the portal drained viscera. Feeding induced a 41% elevation (P < 0.05) in whole body and a nonsignificant increase in the portal drained viscera VO2. The β-adrenoceptor blockers suppressed the increase in whole body VO2 associated with acute cold exposure but, only the reduction induced by the β2-adrenoceptor antagonist (ICI 118551) was significant (P = 0.02). The response to feeding was not altered by the β-blockers. This study suggests that the β-adrenoceptor system plays a role in modulating whole body but not the portal-drained viscera acute cold-induced thermogenesis, and this modulation of energy expenditure may involve a β2 receptor subtype. Key words: Calorimetry, thermogenesis, cold, feed and sheep

1997 ◽  
Vol 77 (2) ◽  
pp. 307-316 ◽  
Author(s):  
J. O. O. Miaron ◽  
R. J. Christopherson

Propranolol, a nonselective β-blocker and selective β-blockers (metoprolol a β1-blocker and ICI 118551 a β2-blocker) were used to investigate the β-adrenoceptor-mediated adrenaline-induced increase in whole-body and organ VO2 in five whether sheep. Transit time blood flow probes were chronically implanted on the portal vein and the external iliac artery and sampling catheters were placed in the mesenteric artery, iliac vein and portal vein. Oxygen consumption by the whole body was measured by open circuit calorimetry, and oxygen consumption by the portal-drained viscera and the hindquarter was determined from A-VO2 differences and organ blood flow. Absolute pre-infusion VO2 values for the whole body, portal-drained viscera and hindquarters were 236 ± 7.4, 61 ± 6.0 and 13 ± 3.1 mL min−1 respectively. The mean changes in VO2 in response to infusion were 74 vs. 11, 26, 10 and 12 mL min−1 (SE = 9.1) for whole body; 31 vs. −2, −15, 13 and −4 mL min−1 (SE = 7.3) for portal-drained viscera and 8 vs. −0.4, 2.1, 1.0 and −2.7 mL min−1; SE = 4.3) for hindquarters during adrenaline, control, propranolol, metoprolol and ICI 118551 treatments, respectively. Adrenaline increased VO2 (P < 0.05) in the whole body and portal-drained viscera, but not hindquarters relative to controls. All β-blockers suppressed (P < 0.05) the adrenaline-induced increase in VO2 except for the portal-drained viscera where metoprolol was less effective and the hindquarters where β-blockers had no effect. The blood flow pattern was similar to VO2 responses for the portal-drained viscera. The nonselective β1 and β2 blockers were effective in reducing the adrenaline-induced increases in blood flow from the portal-drained viscera and to the hindquarters, with more pronounced β-adrenoceptor-mediated haemodynamic effects. The results indicate that the β-adrenoceptor system modulates whole body VO2, clearly establishes that adrenaline induces an increased VO2 in portal-drained viscera which can be reversed by a β2 or nonselective β blocker and implicates β adrenoceptors as an influencing factor in the maintenance energy requirements of ruminants. Key words: Calorimetry, adrenaline, β blockers, blood flow, sheep


1979 ◽  
Vol 47 (1) ◽  
pp. 59-66 ◽  
Author(s):  
M. J. Fregly ◽  
D. L. Kelleher ◽  
D. J. Black

Female rats treated chronically with ethynylestradiol (36 micrograms/kg per day) alone, and in combination with the progestational agent, norethynodrel (253 micrograms/kg per day), cooled significantly faster than controls when lightly restrained and exposed to air at 5 degrees C. Rate of cooling of rats given only norethynodrel was similar to that of the control group. In other studies, rate of oxygen consumption was determined for all groups during acute exposure to cold (14 degrees C). All estrogen-treated groups achieved the same maximal rate of oxygen consumption as control and norethynodrel-treated groups during cold exposure, but cooled significantly faster. Two groups of female rats were treated chronically with ethynylestradiol at two separate doses (36 and 61 micrograms/kg per day). An untreated group served as controls. Rate of oxygen consumption of all animals were measured during restraint and exposure to cold (18 degrees C). The estrogen-treated groups again achieved the same maximal rate of oxygen consumption as the control group, but also cooled significantly faster despite the fact that the cold stress was less severe than in the previous experiment. That estrogen-treated rats cooled faster than controls in both studies despite achieving a maximal rate of heat production which did not differ from controls suggests that reduced cold tolerance of estrogen-treated rats may be related to increased heat loss.


1965 ◽  
Vol 209 (1) ◽  
pp. 227-230 ◽  
Author(s):  
Tetsuo Nagasaka ◽  
Loren D. Carlson

Oxygen consumption, heart rate, and colonic, pinna, and paw temperatures were recorded continuously in warm-adapted (W-A) and cold-adapted (C-A) dogs anesthetized with pentobarbital sodium (30 mg/kg), paralyzed with Flaxedil (5 mg/kg per hr), and mechanically ventilated. The dogs were infused with norepinephrine (1.25 µg/kg per min) for 20 min at 30 C and after 45 min of acute cold exposure to 5 C. Oxygen consumption of C-A dogs increased with a slight increase in the heart rate during the initial 18–20 min of body cooling. O2 consumption decreased continuously during cold exposure in W-A dogs. Calorigenic effects of infused noradrenaline were similar in C-A and W-A dogs at 30 C and 5 C. Heart rate increased in W-A dogs at 30 and 5 C. These results show that nonshivering thermogenesis is well developed by cold acclimation in dogs, and suggest that the increase may be due to an increase in noradrenaline in blood rather than to increased sensitivity of the animals to the calorigenic effects of noradrenaline.


2020 ◽  
Author(s):  
Takuya Nishikawa ◽  
Kazunori Uemura ◽  
Yohsuke Hayama ◽  
Toru Kawada ◽  
Keita Saku ◽  
...  

Abstract Background: Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. Although the use of β-blockers in the acute phase of HF can be expected to be beneficial, the negative chronotropic and inotropic effects limit their use due to the risk of circulatory collapse (cardiogenic shock, and/or pulmonary congestion). A safe method to administer β-blockers in the acute phase of HF is in great need. In this study, we developed an automated drug delivery system that controls the infusion of landiolol, an ultra-short-acting β-blocker, while preventing circulatory collapse. Method: We designed a system that simultaneously regulates cardiac function and volume status to control haemodynamics. The system monitors arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of haemodynamics, the system controls mean AP and mean PLA by administering landiolol, dextran, and furosemide. We applied the system for 60 min to 5 mongrel dogs with rapid pacing-induced HF, and assessed haemodynamics, MVO2 and lactate.Results: In all dogs, the system successfully adjusted delivery of the drugs resulting in accurate control of mean AP and mean PLA. From 15 to 60 min after the system was activated, median of absolute performance error (index of precision of control) was small for mean AP (median [interquartile range], 2.5 [2.1 – 3.7] %) and mean PLA (4.1 [1.8 – 6.2] %). Although the system decreased mean AP compared to baseline, mean and systolic AP were maintained not lower than 70 and 100 mmHg, respectively, and lactate did not increase. Furthermore, the system significantly decreased PLA and MVO2 (3.6 [3.3 – 4.0] to 2.7 [2.5 – 3.3] ml·min-1·100 g left ventricular weight-1) compared to baseline. Consequently, the automated drug delivery system successfully reduced MVO2 without inducing circulatory collapse.Conclusion: We developed an automated landiolol delivery system that achieved safe administration of landiolol in a canine model of acute HF. The system controlled AP and PLA accurately and stably, and reduced MVO2. With further development for clinical application, the automated drug delivery system may be the key tool to improve management of patients with HF.


2008 ◽  
Vol 147 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. SANO ◽  
H. SAWADA ◽  
A. TAKENAMI ◽  
M. AL-MAMUN

SUMMARYDilution of [1-13C]leucine (Leu) and open-circuit calorimetry were used to determine the effects of diet and cold exposure on rates of plasma Leu turnover, Leu oxidation, and whole body protein synthesis (WBPS) in sheep. The experiment was designed as a crossover design for two 23-day periods. Six adult sheep were assigned to two dietary treatments, medium (Me-diet) and high (Hi-diet) intake, and were fed either 515 or 830 kJ/kg BW0·75per day of metabolizable energy intake, respectively. The temperature in the chamber was changed from a thermoneutral environment (23°C) to a cold environment (2–4°C) for 5 days (the 18th to 23rd day of the experiment). Turnover rate of both plasma Leu and WBPS were greater (P<0·01) for the Hi-diet compared with the Me-diet and increased (P<0·01) during cold exposure. Leucine oxidation rate was numerically greater (P=0·10) for the Hi-diet compared with the Me-diet and increased (P=0·03) during cold exposure. No significant diet×environment interaction was detected in the rates of plasma Leu turnover, Leu oxidation or WBPS. It is concluded that plasma Leu kinetics and WBPS were influenced by intake level and increased during cold exposure, but the responses to cold exposure were not modified by intake level in sheep under the conditions of the present experiment.


Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1748
Author(s):  
Kohei Watanabe ◽  
Shideh Narouei

Surface electromyography (EMG) has been used to estimate muscle work and physiological burden of the whole body during human movements. However, there are spatial variations in surface EMG responses within individual muscles. The aim of this study was to investigate the relation between oxygen consumption and surface EMG responses of lower leg muscles during walking at various speeds and to quantify its spatial variation within an individual muscle. Nine young males walked on a treadmill at four speeds: preferred minus 1 km/h, preferred, preferred plus 1 km/h, and preferred plus 2 km/h, and the metabolic response was measured based on the expired gas. High-density surface EMG of the tibialis anterior (TA), medial gastrocnemius (MG), lateral gastrocnemius, and soleus muscles was performed using 64 two-dimensional electrode grids. Correlation coefficients between oxygen consumption and the surface EMG amplitude were calculated across the gait speeds for each channel in the electrode grid and for individual muscles. Mean correlation coefficients across electrodes were 0.69–0.87 for the four individual muscles, and the spatial variation of correlation between the surface EMG amplitude and oxygen consumption within an electrode grid was significantly greater in MG muscle than in TA muscle (Quartile deviations: 0.24 for MG and 0.02 for TA, p < 0.05). These results suggest that the physiological burden of the whole body during gait at various speeds can be estimated from the surface EMG amplitude of calf muscles, but we need to note its spatial distribution within the MG muscle.


Catalysts ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 503
Author(s):  
Morten Gundersen ◽  
Guro Austli ◽  
Sigrid Løvland ◽  
Mari Hansen ◽  
Mari Rødseth ◽  
...  

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.


Author(s):  
Takuya Nishikawa ◽  
Kazunori Uemura ◽  
Yohsuke Hayama ◽  
Toru Kawada ◽  
Keita Saku ◽  
...  

AbstractBeta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.


1984 ◽  
Vol 246 (3) ◽  
pp. R380-R383 ◽  
Author(s):  
C. Martinez-Torres ◽  
L. Cubeddu ◽  
E. Dillmann ◽  
G. L. Brengelmann ◽  
I. Leets ◽  
...  

Twenty-one Venezuelan peasants were segregated into three groups on the basis of measurements of iron status: seven normal subjects, six iron-deficient subjects with normal hemoglobin and eight iron-deficient subjects with a hemoglobin concentration of less than 9 g/dl. All subjects were placed in a water bath at an initial temperature of 36 degrees C. The water temperature was then rapidly lowered to 28 degrees C, and observations were made over the period of 1 h. Mean oral temperature of the first group fell 0.2, the second group 0.5, and the third group 0.9 degrees C. Mean plasma norepinephrine levels in both groups of iron-deficient subjects were significantly higher at 36 degrees C and during cold exposure compared with control subjects. Oxygen consumption was also significantly increased in both groups of iron-deficient subjects after cold exposure.


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