Thermoregulatory responses of spinal cord injured and able-bodied athletes to prolonged upper body exercise and recovery

STUDY DESIGN: Single trial, two factor repeated measures design. SETTING: England, Cheshire. OBJECTIVES: To examine the thermoregulatory responses of able-bodied (AB) athletes, paraplegic (PA) athletes and a tetraplegic (TP) athlete at rest, during prolonged upper body exercise and recovery. METHODS: Exercise was performed on a Monark cycle ergometer (Ergomedic 814E) adapted for arm exercise at 60% VO2 peak for 60 min in cool conditions ('normal' laboratory temperature; 21.5+/-1.7 degrees C and 47+/-7.8% relative humidity). Aural and skin temperatures were continually monitored. RESULTS: Mean (+/-S.D.) peak oxygen uptake values were greater (P<0. 05) for the AB when compared to the PA (3.45+/-0.45 l min-1 and 2. 00+/-0.46 l min-1, respectively). Peak oxygen uptake for the TP was 0.91 l min-1. At rest, aural temperature was similar between groups (36.2+/-0.3 degrees C, 36.3+/-0.3 degrees C and 36.3 degrees C for AB, PA and TP athletes, respectively). During exercise, aural temperature demonstrated relatively steady state values increasing by 0.6+/-0.4 degrees C and 0.6+/-0.3 degrees C for the AB and PA athletes, respectively. The TP athlete demonstrated a gradual rise in aural temperature throughout the exercise period of 0.9 degrees C. Thigh skin temperature increased by 1.3+/-2.5 degrees C for the AB athletes (P<0.05) whereas the PA athletes demonstrated little change in temperature (0.1+/-3.4 degrees C and -0.7 degrees C respectively). Calf temperature increased for the PA athletes by 1.0+/-3.6 degrees C (P<0.05), whereas a decrease was observed for the AB athletes of -1.0+/-2.0 degrees C (P<0.05) during the exercise period. During 30 min of passive recovery, the AB athletes demonstrated greater decreases in aural temperatures than those for the PA athletes (P<0. 05). Aural temperature for the TP increased peaking at 5 min of recovery remaining elevated until the end of the recovery period. Fluid consumption and weight losses were similar for the AB and PA athletes (598+/-433 ml and 403+/-368 ml; 0.38+/-0.39 kg and 0.38+/-0. 31 kg, respectively), whereas changes in plasma volume were greater for the AB athletes (-9.8+/-5.8% and 4.36+/-4.9%, respectively; P<0. 05). CONCLUSION: The results of this study suggest that under the experimental conditions PA athletes are at no greater thermal risk than AB athletes. A relationship between the available muscle mass for heat production and sweating capacity appears evident for the maintenance of thermal balance. During recovery from exercise, decreases in aural temperature, skin temperature and heat storage were greatest for the AB athletes with the greatest capacity for heat loss and lowest for the TP athlete with the smallest capacity for heat loss. Initial observations on one TP athlete suggest substantial thermoregulatory differences when compared to AB and PA athletes.     

Thermoregulatory responses to repeated warm water immersion in subjects who are paraplegic

OBJECTIVE: To compare thermoregulatory responses to repeated warm water immersion (39 degrees C) between physically active subjects who are paraplegic or able-bodied in order to gain insight into rehabilitative and adaptive processes. METHODS: Five paraplegic (P) and six able-bodied (AB) males participated. VO2 peak was determined by open-circuit spirometry using a cycle ergometer (AB) and propelling a wheelchair on a motor driven treadmill (P). Subjects sat immersed to the nipple line in 39 degrees C water for 60 min for 5 consecutive days. Pre- and post-test measurements included heart rate (HR), oesophageal temperature (Tes), sweat onset and rate (dew point hygrometry). Venous blood was obtained before, and during immersion to estimate changes in plasma volume. RESULTS: The P group was older and lighter than AB group (P<0.05). VO2max, VCO2max and VE(max) were significantly greater in AB group. HR at rest and after 60 min immersion was not significantly different between the groups pre- or post-test. Tes significantly increased after 60 min immersion in both groups, at both pre- and post-testing sessions. Post-test Tes after 60 min immersion (AB) was significantly less than Tes after 60 min of immersion pre-test. The DeltaTes (Tes 60 min-Tes 0 min) was significantly higher in AB group than the P group at pre- but not post-testing. No significant changes in sweat onset or rate were found for the AB or P groups during the pre- or post testing sessions. Significant expansion of plasma volume occurred during immersion in both groups, pre- and post-immersion sessions. CONCLUSIONS: Repeated warm water immersion (39 degrees C) for 60 min per day for a total of 5 days did not produce a significant adaptive response in P group. In the AB group, Tes at the end of 60 min immersion was significantly lower after the adaptation period.     

Suppression of endogenous glucose production by mild hyperinsulinemia during exercise is determined predominantly by portal venous insulin

Hyperinsulinemia during exercise in people with diabetes requiring exogenous insulin is a major clinical problem. The aim of this study was to assess the significance of portal vein versus arterial insulin to hepatic effects of hyperinsulinemia during exercise. Dogs had sampling (artery, portal vein, and hepatic vein) and infusion (vena cava and portal vein) catheters and flow probes (hepatic artery and portal vein) implanted >16 days before a study. Protocols consisted of equilibration (-130 to -30 min), basal (-30 to 0 min), and treadmill exercise (0-150 min) periods. Somatostatin was infused and glucagon and insulin were replaced in the portal vein to achieve basal arterial and portal vein levels at rest and simulated levels during the first 60 min of exercise. From 60 to 150 min of exercise, the simulated insulin infusion was sustained (C; n = 7), modified to selectively create a physiologic increment in arterial insulin (Pe; n = 7), or altered to increase arterial insulin as in Pe but with a concomitant increase in portal insulin (PePo; n = 7). Euglycemic clamps were performed in all studies. Portal and arterial insulin were 15 +/- 2 and 4 +/- 1 micro U/ml (mean +/- SE of all groups), respectively, at t = 60 min in all groups. Insulin levels were unchanged for the remainder of the exercise period in C. Arterial insulin was increased from 3 +/- 1 to 14 +/- 2 micro U/ml, whereas portal insulin did not change in Pe after t = 60 min. Arterial insulin was increased from 3 +/- 1 to 15 +/- 2 micro U/ml, and portal insulin was increased from 16 +/- 3 to 33 +/- 3 micro U/ml in PePo after t = 60 min. Endogenous glucose production (R(a)) rose similarly from basal during the first 60 min of exercise in all groups (mean +/- SE of all groups was from 2.2 +/- 0.1 to 6.8 +/- 0.5 mg. kg(-1). min(-1)). The increase in R(a) was sustained for the remainder of the exercise period in C. R(a) was suppressed by approximately 40%, but only after 60 min of hyperinsulinemia, and by approximately 20% after 90 min of hyperinsulinemia in Pe. In contrast, the addition of portal venous hyperinsulinemia caused approximately 90% suppression of R(a) within 20 min and for the remainder of the experiment in PePo. Measurements of net hepatic glucose output were similar to R(a) responses in all groups. Arterial free fatty acids (FFAs), a stimulus of R(a), were increased to 1,255 +/- 258 micro mol/l in C but were only 459 +/- 67 and 312 +/- 42 micro mol/l in Pe and PePo, respectively, by 150 min of exercise. Thus, during exercise, the exquisite sensitivity of R(a) to hyperinsulinemia is due entirely to portal venous hyperinsulinemia during the first 60 min, after which peripheral hyperinsulinemia may control approximately 20-40%, possibly as a result of inhibition of the exercise-induced increase in FFA.     

Combined infusion of epinephrine and norepinephrine during moderate exercise reproduces the glucoregulatory response of intense exercise

Intense exercise (IE) (>80% O(2max)) causes a seven- to eightfold increase in glucose production (R(a)) and a fourfold increase in glucose uptake (R(d)), resulting in hyperglycemia, whereas moderate exercise (ME) causes both to double. If norepinephrine (NE) plus epinephrine (Epi) infusion during ME produces the plasma levels and R(a) of IE, this would prove them capable of mediating these responses. Male subjects underwent 40 min of 53% O(2max) exercise, eight each with saline (control [CON]), or with combined NE + Epi (combined catecholamine infusion [CCI]) infusion from min 26-40. In CON and CCI, NE levels reached 7.3 +/- 0.7 and 33.1 +/- 2.9 nmol/l, Epi 0.94 +/- 0.08 and 7.06 +/- 0.44 nmol/l, and R(a) 3.8 +/- 0.4 and 12.9 +/- 0.8 mg. kg(-1). min(-1) (P < 0.001), respectively, at 40 min. R(d) increased to 3.5 +/- 0.4 vs. 11.2 +/- 0.8 mg. kg(-1). min(-1) and glycemia 5.2 +/- 0.2 mmol/l in CON vs. 6.5 +/- 0.2 mmol/l in CCI (P < 0.001). The glucagon-to-insulin ratio did not differ. Comparing CCI data to those from 14-min IE (n = 16), peak NE (33.6 +/- 5.1 nmol/l), Epi (5.32 +/- 0.93 nmol/l), and R(a) (13.0 +/- 1.0 mg. kg(-1). min(-1)) were comparable. The induced increments in NE, Epi, and R(a), all of the same magnitude as in IE, strongly support that circulating catecholamines can be the prime regulators of R(a) in IE.     

Methods for warming intravenous fluid in small volumes

PURPOSE: Laboratory experiments were performed to determine warming rates of albumin 5% at room temperature and human packed red blood cells (PRBCs) at 4 degrees C in small volumes. Four methods used in clinical practice to warm volumes appropriate for neonates were studied. METHODS: The fluids were warmed either by infusion through a fluid warmer with temperature-controlled coaxial tubing (Group I), immersion in a water bath at 37 degrees C (Group II), placing pre-filled syringes (10 and 20 ml) between a circulating water mattress and a forced-air warming blanket (Group III), or placing the same syringes between the water mattress and cotton towels (Group IV). The temperature of each fluid was recorded for the next 60 sec after the bolus injection in group I and every five minutes for a total of 30 min for the other groups. The time constant of warming for each group was calculated. The time constant and the temperature reached after the warming period were compared among groups. RESULTS: In group I 20 ml room temperature albumin 5% or 4 degrees C blood reached temperatures of 36.9 +/- 1.5 degrees C and 34.5 +/- 2.3 degrees C within 60 sec, respectively. This was faster than all other techniques used (P < 0.001). The time constants measured for the albumin and the PRBCs were 0.23 +/- 0.1 and 0.20 +/- 0.05 minutes respectively. After 15 min albumin and PRBCs in group II reached 35.5 +/- 0.4 degrees C and 33.4 +/- 0.3 degrees C, in group III reached 33.7 +/- 1.0 C and 32.8 +/- 1.7 C, and in group IV reached 29.5 +/- 0.1 degrees C and 23.3 +/- 0.8 degrees C after 15 min respectively. CONCLUSION: Warming of intravenous fluids in small volumes is accomplished most rapidly using a fluid warmer with temperature-controlled coaxial tubing and occurs more slowly in syringes, bottles, or bags exposed to various environmental conditions.     

Skeletal muscle limits the exercise tolerance of renal transplant recipients: effects of a graded exercise training program

Sixteen renal transplant recipients were studied before and after they had participated in a 24-week exercise training program to determine (1) the nature of the factors explaining their impaired exercise tolerance, and (2) their adaptative responses to exercise training. During progressive treadmill exercise to exhaustion prior to training, renal transplant recipients stopped exercising at lower peak rates of oxygen consumption (VO2max) (29.0 +/- 7.8 47.9 +/- 9.1 mL O2.kg-1.min-1; P less than 0.001) and ventilation (55.9 +/- 13.2 v 124.0 +/- 22.2 L.min-1; P less than 0.0001), and at lower peak heart rates (169 +/- 22 v 196 +/- 9 beats.min-1; P less than 0.05) and peak blood lactate concentrations (5.0 +/- 2.1 v 11.5 +/- 4.0 mmol.L-1; P less than 0.001) than did controls. None showed a plateau in oxygen consumption with increasing workload. Exercise time to exhaustion was also significantly shorter in renal transplant recipients (9.5 +/- 1.8 v 16.0 +/- 1.3 min; P less than 0.0001). After training, exercise time to exhaustion (12.0 +/- 2.0 min; P less than 0.001), VO2max (37.5 +/- 4.8 mL O2.kg-1.min-1; P less than 0.05), maximum ventilation rate (68.5 +/- 14.0 L.min-1; P less than 0.05), peak blood lactate concentrations (7.8 +/- 1.8 mmol-L-1; P less than 0.001), and the rate of oxygen consumption at a blood lactate concentration of 2.0 mmol.L-1 (22.5 +/- 2.5 v 16.5 +/- 2.2 mL O2.kg-1.min-1; P less than 0.001) had all increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial plasma histamine levels at rest, and during and after exercise in patients with asthma: effects of terbutaline aerosol.

Eight asthmatic patients and two normal subjects performed two identical exercise tests 140 minutes apart (first test preceded by inhalation of saline and the second by terbutaline sulphate). A ninth asthmatic patient exercised twice after placebo 40 minutes apart. Arterial plasma levels of histamine and cyclic AMP, expiratory flow rates and volumes were measured at rest and during and after exercise. After the first test the mean +/- SEM fall in PEFR was 45.2 +/- 2.6%. In five asthmatics there was an increase in plasma histamine (mean +/- SEM 14.8 +/- 3.3 pmol ml-1) coinciding with exercise-induced asthma (EIA). Histamine levels returned to pre-exercise values within 30 minutes. After terbutaline these five patients had histamine levels greater than those observed before, during, or after the first test. This effect may have been the result of changes in pulmonary microcirculation. After the second test the levels decreased indicating no further release of histamine in response to exercise. No EIA occurred in these patients after terbutaline. The other patients and the two normal subjects had little or no change in histamine throughout the study. The one patient in whom exercise was repeated after placebo demonstrated less histamine release and less EIA after the second test.     

A comparison of enflurane with alfentanil anaesthesia for gynaecological surgery

Forty patients undergoing gynaecological surgery were randomly assigned to receive either alfentanil and thiopentone for induction of anaesthesia, followed by alfentanil-N2O/O2 (60%/40%) for maintenance of anaesthesia, or low-dose fentanyl and thiopentone, followed by enflurane-N2O/O2 (60%/40%). More patients given enflurane developed a tachycardia (P less than 0.03) and 20% decreases in systolic and diastolic blood pressure. Times to recovery were significantly shorter after alfentanil than after enflurane. Plasma concentrations of alfentanil during induction suggested that haemodynamic and catecholamine responses were either less than, or did not differ from, baseline levels when the plasma concentration of the drug exceeded 150 ng ml-1. At extubation and the beginning of spontaneous breathing, the plasma concentration was 278 +/- 129 ng ml-1. Values for pharmacokinetic parameters of alfentanil were as follows: clearance, 5.2 +/- 2.0 ml kg-1 min-1; volume of distribution, 0.63 +/- 0.20 1 kg-1; and elimination half-life, 96.9 +/- 52.5 min. Two patients who had extended surgery had significantly lower plasma clearance of alfentanil and increased half-life. The authors conclude that the alfentanil technique was preferable to maintenance with enflurane.     

Impaired exercise performance after successful liver transplantation

BACKGROUND: Recipients of heart, lung, and kidney transplants have impaired peak exercise performance (peak Vo2 40% to 60% predicted, reduced anaerobic threshold [AT]) without evidence of ventilatory or cardiac limitations. The aim of this study was to determine whether similar exercise impairment occurs in liver transplant recipients. METHODS: We studied eight healthy liver transplant recipients (age 42+/-9 [SD] years, 6 male, 31+/-13 months posttransplant). Immunosuppression included FK506 or cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Subjects underwent lung function testing and cardiopulmonary exercise testing on a cycle ergometer. RESULTS: Peak exercise oxygen consumption (Vo2) was 22+/-8 ml/min/kg (66+/-20% predicted maximum). No subject demonstrated exercise desaturation or ventilatory limitation (peak minute ventilation 55+/-8% predicted maximum voluntary ventilation). Peak heart rate was 87+/-8% of predicted maximum. Early AT was evident (1.2+/-0.34 L/min, 48+/-11% predicted Vo2max). CONCLUSIONS: Liver transplant recipients exhibit impaired peak exercise performance similar to that observed after other solid organ transplants, possibly as a result of chronic deconditioning or myopathy related to immunosuppressive medications.     

Pharmacokinetics and dynamics of endogenously released and therapeutically administered adrenaline in resuscitation. A comparative animal experimental study

In this study, catecholamine plasma levels and hemodynamic response were measured to compare the effects of endogenously released (group A; n = 8), intravenously injected (group B; 10 micrograms/kg; n = 8), and endobronchially instilled (e.b.) epinephrine (group C; 100 micrograms/kg; n = 8) on resuscitation. Although the endogenous release of epinephrine produced peak plasma concentrations of 214 +/- 86 ng/ml (mean +/- SEM) during cardiac massage, only 5 animals were successfully resuscitated in group A. Mean arterial pressure and cardiac output were significantly lower in the first hour of restored spontaneous circulation compared to groups B and C. Endobronchial and intravenous epinephrine administration proved equally effective with regard to resuscitability and hemodynamic response during cardiac massage. All animals in groups B and C were successfully resuscitated and peak plasma concentrations of epinephrine were achieved with comparable onset times (317 +/- 53 ng/ml after 2.5 min in group B, 634 +/- 202 ng/ml after 3 min in group C). The tenfold epinephrine dose administered endobronchially was able to generate only a twofold increase in peak plasma epinephrine concentrations. The mean bioavailability with this route of administration, however, was 40% (5-71%). The ongoing absorption and therefore significantly longer half life of e.b. epinephrine compared to i.v. administration improved the hemodynamic situation of group C animals during the early postresuscitation period. More extensive use of e.b. epinephrine administration can be recommended, especially in out-of-hospital resuscitation, when intubation is achieved before an intravenous line can be established.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial protection: efficacy of a novel magnesium-based cardioplegia (RS-C) compared to St Thomas' Hospital cardioplegic solution

Cardiac surgery patients now tend to be sicker with more severe disease; consequently, improved protection is important. We compared St Thomas' Hospital solution (STH2: hyperkalaemia and hypermagnesaemia) to a hypermagnesaemia-alone cardioplegia (RS-C) based on a novel non-phosphate buffered crystalloid solution (AqixRS-I). Isolated Langendorff-perfused rat hearts were used (function measured). Initial studies established optimal magnesium concentration as 25 mmol/l (LVDP recovery after 50 min at 37 degrees C global ischaemia (GI) for 16, 25, 35, 50 mmol/l magnesium vs. STH2 was 48+/-3, 50+/-2, 50+/-3, 30+/-3 and 51+/-2%, respectively). Contracture-related measurements (onset time, peak) for 25 mmol/l RS-C (32+/-1 min, 35+/-1 mmHg) compared favourable (P<0.05) to STH2 (26+/-1 min, 43+/-2 mmHg). LVDP recovery after a single 2-min cardioplegic infusion (with RS-C-25 or STH2) and 20, 30, 40 or 50 min GI was higher for RS-C-25 than STH2 after 20 min GI (81+/-1% vs. 74+/-1%; [P<0.05]) but similar at other GI durations. Subsequent multi-infusion studies (60 min GI, 3x2 min infusions every 20 min) demonstrated significantly improved recovery with RS-C-25 vs. STH2 (LVDP: 73+/-2%, 44+/-1% [P<0.001]; LVEDP: 9+/-2 mmHg, 45+/-2 mmHg [P<0.001]). We conclude that single RS-C infusion with optimal 25 mmol/l magnesium improved protection after short (20 min) GI durations, or after multi-infusions during prolonged (60 min) GI durations. Magnesium-based cardioplegia may be a useful alternative to hyperkalaemic cardioplegia under certain specific conditions.     

S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children

BACKGROUND: It has been suggested that nasal administration of s-ketamine may be used to improve sedation or premedication in combination with nasal midazolam in pediatric patients. In this study we measured and compared plasma concentrations of s-ketamine and its main metabolite s-norketamine after nasal and i.v. administration in preschool children. METHODS: During sevoflurane anaesthesia, 20 children, aged 1-7 years, weight 11-25 kg, received s-ketamine 2 mg x kg(-1) either intranasally (Group IN, n = 10), or i.v. (Group IV, n = 10). Six venous blood samples were obtained up to 60 min after drug administration for measurement of s-ketamine and s-norketamine plasma concentrations. RESULTS: Plasma concentrations [mean +/- sd] of s-ketamine in group IN peaked at 355 +/- 172 ng x ml(-1) within 18 +/- 13 min vs. 1860 +/- 883 ng x ml(-1) within 3 +/- 1 min in group IV (P < 0.01). Plasma concentrations of s-norketamine in group IN peaked at 90 +/- 128 ng x ml(-1) within 50 +/- 11 min vs. 429 +/- 277 ng x ml(-1) within 40 +/- 16 min in group IV (P < 0.01). One child in group IN experienced rapid and high level s-ketamine absorption with a peak plasma concentration of 732 ng x ml(-1) after 2 min, which decreased to 274 ng x ml(-1) after 60 min. Systolic blood pressure and heart rate remained unaltered in both study groups after s-ketamine administration. CONCLUSIONS: Nasal administration of s-ketamine 2 mg x kg(-1) results in a wide spread of plasma concentrations and absorption times. Rapid and high level drug absorption after nasal drug administration is possible. The use of a pulse oximeter and continuous observation after nasal administration of s-ketamine for pediatric premedication is recommended.     

Effect of temperature on blood flow and metabolism in a neurovascular island skin flap

Using the buttock flap in 29 white Yorkshire pigs, blood flow and O2 consumption were measured at dermal temperatures between 35 degrees C and 15 degrees C. Flow was measured with an electromagnetic flowmeter and O2 consumption was calculated as the product of blood flow and the difference in flap A-VO2. Baseline flow was 6.6 +/- .9 (SE) ml/100 g/min at 35 degrees C and 3.1 +/- .02 (SE) ml/10 g/min at 15 degrees C. Blood flow through the flap stopped completely at a dermal temperature of 14 degrees C. Oxygen consumption was 0.16 +/- .02 (SE) ml/100 g/min at 35 degrees C and 0.04 +/- 0.01 (SE) ml/100 g/min at 15 degrees C. At 20 degrees C blood flow was 4.3 ml/100 g/min and metabolism was .04 ml/100 g/min. In other words, blood flow was 65% of baseline, while O2 consumption was only 25% of baseline. The therapeutic effect of local cooling at 20 degrees C deserves further investigation. The cessation of flow at 14 degrees C may be caused by increased plasma viscosity.     

The effect of 30% nitrous oxide on thermoregulatory responses in humans during hypothermia.

Clinical studies have reported that body core temperature decreases during prolonged surgery and anesthesia. Although this finding has been attributed primarily to increased heat loss resulting from exposure of body cavities and infusion of cold solutions, it is generally recognized that anesthesia interferes with the thermoregulatory system. The present study examined the effects of mild narcosis induced by 30% N2O on shivering thermogenesis and cutaneous thermoregulatory vasoconstriction in humans, during exposure in a much more intense peripheral thermal stimulus than the ones often used in clinical studies. Nine male subjects were immersed in 15 degrees C water on two separate occasions. During one occasion subjects inspired air (control condition), and during the other occasion the inspired gas mixture contained 20% O2, 30% N2O, and 50% N2 (N2O condition). On both occasions, subjects were immersed to the neck for 60 min, or until their core temperature decreased by 2 degrees C from the preimmersion value. Following the cooling phase, subjects rewarmed via endogenous thermogenesis while lying in a well-insulated bed for 48 min. In the N2O condition, subjects continued to inspire the anesthetic gas mixture during the 48-min period of recovery. O2 uptake (VO2), esophageal temperature (Tes), mean skin temperature (Tsk), mean heat flux (Q) and forearm-fingertip temperature gradient (Tsk-gr) were recorded at 1-min intervals. Tsk and Q in both conditions stabilized within 10 and 25 min of immersion, respectively, and were not significantly different between the two conditions. The cooling rate of Tes was greater during the N2O than the control condition. VO2 increased during the immersion in both conditions and was greater in the control than in the N2O condition. In both conditions, VO2 increased linearly with decreasing Tes, but at any given Tes, VO2 was higher in the control than in the N2O condition. No significant difference was observed in cutaneous thermoregulatory vasoconstriction between the two experimental conditions, as indicated by the Tsk-gr values. The estimated Tes threshold for shivering (estimated from the O2 consumption vs. delta Tes regression) was reduced by 0.95 +/- 0.26 (SE) degrees C during the immersion phase and by 0.39 +/- 0.05 (SE) degrees C during the rewarming phase in the N2O condition compared to the control conditions. Although the thermosensitivity (gain) of shivering appeared preserved during the immersion phase, it was reduced during the N2O rewarming phase.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-CoA carboxylase-2 expression

Endurance training has been shown to increase fat oxidation both at rest and during exercise. However, most exercise training studies have been performed at high exercise intensity in well-trained athletes, and not much is known about the effect of a low-intensity training program on fat oxidation capacity in lean sedentary humans. Here, we examine the effect of 3-month low-intensity training program on total and intramuscular triglyceride (IMTG)- and/or VLDL-derived fat oxidation capacity and skeletal muscle mRNA expression. Six healthy untrained subjects (aged 43 +/- 2 years, BMI 22.7 +/- 1.1 kg/ m(2), V(O)(2max) 3.2 +/- 0.2 l/min) participated in a supervised 12-week training program at 40% V(O)(2max) three times weekly. Total and plasma-derived fatty acid oxidation at rest and during 1 h exercise was measured using [(13)C]palmitate, and in a separate test, [(13)C]acetate recovery was determined. Muscle biopsies were taken after an overnight fast. Total fat oxidation during exercise increased from 1,241 +/- 93 to 1,591 +/- 130 micromol/min (P = 0.06), and IMTG- and/or VLDL-derived fatty acid oxidation increased from 236 +/- 84 to 639 +/- 172 micromol/min (P = 0.09). Acetyl-CoA carboxylase-2 mRNA expression was significantly decreased after training (P = 0.005), whereas lipoprotein lipase mRNA expression tended to increase (P = 0.07). In conclusion, a minimal amount of physical activity tends to increase fat oxidation and leads to marked changes in the expression of genes encoding for key enzymes in fat metabolism.     

Nitric oxide synthase inhibition reduces glucose uptake during exercise in individuals with type 2 diabetes more than in control subjects

Nitric oxide (NO) synthase inhibition reduces leg glucose uptake during cycling without reducing leg blood flow (LBF) in young, healthy individuals. This study sought to determine the role of NO in glucose uptake during exercise in individuals with type 2 diabetes. Nine men with type 2 diabetes and nine control subjects matched for age, sex, peak pulmonary oxygen uptake (VO(2) peak), and weight completed two 25-min bouts of cycling exercise at 60 +/- 2% VO(2) peak, separated by 90 min. N(G)-monomethyl-L-arginine (L-NMMA) (total dose 6 mg/kg) or placebo was administered into the femoral artery for the final 15 min of exercise in a counterbalanced, blinded, crossover design. LBF was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous glucose difference. During exercise with placebo, glucose uptake was not different between control subjects and individuals with diabetes; however, LBF was lower and arterial plasma glucose and insulin levels were higher in individuals with diabetes. L-NMMA had no effect on LBF or arterial plasma glucose and insulin concentrations during exercise in both groups. L-NMMA significantly reduced leg glucose uptake in both groups, with a significantly greater reduction (P = 0.04) in the diabetic group (75 +/- 13%, 5 min after L-NMMA) compared with the control group (34 +/- 14%, 5 min after L-NMMA). These data suggest a greater reliance on NO for glucose uptake during exercise in individuals with type 2 diabetes compared with control subjects.     

ATP-dependent K(+) channels contribute to local metabolic coronary vasodilation in experimental diabetes

This study tested whether ATP-dependent K(+) channels (K(ATP) channels) are an important mechanism of functional coronary hyperemia in conscious, instrument-implanted diabetic dogs. Data were collected at rest and during exercise before and after induction of diabetes with alloxan monohydrate (40-60 mg/kg intravenously). K(ATP) channels were inhibited with glibenclamide (1 mg/kg intravenously). In nondiabetic dogs, arterial plasma glucose concentration increased from 4.8 +/- 0.3 to 21.5 +/- 2.2 mmol/l 1 week after alloxan injection. In nondiabetic dogs, exercise increased myocardial oxygen consumption (MVO(2)) 3.4-fold, myocardial O(2) delivery 3.0-fold, and heart rate 2.4-fold. Coronary venous PO(2) decreased from 19.9 +/- 0.8 mmHg at rest to 14.8 +/- 0.8 mmHg during exercise. Diabetes significantly reduced myocardial O(2) delivery and lowered coronary venous PO(2) from 16.3 +/- 0.6 mmHg at rest to 13.1 +/- 0.9 mmHg during exercise. Glibenclamide did not alter the slope of the coronary venous PO(2) versus MVO(2) relationship in nondiabetic dogs. In diabetic dogs, however, glibenclamide further reduced myocardial O(2) delivery; coronary venous PO(2) fell to 9.0 +/- 1.0 mmHg during exercise, and the slope of the coronary venous PO(2) versus MVO(2) relationship steepened. These findings indicate that K(ATP) channels contribute to local metabolic coronary vasodilation in alloxan-induced diabetic dogs.     

Effect of cardiopulmonary bypass on cortical cerebral oxygenation during coronary artery bypass grafting.

OBJECTIVE: To investigate the changes in cerebral oxygenation during coronary artery bypass grafting (CABG) with normothermic cardiopulmonary bypass (CPB) using near infrared spectroscopy. METHODS: Measurement of cerebral cortical oxygenation changes included concentration of deoxygenated haemoglobin [HHb], oxygenated haemoglobin [O(2)Hb], changes in the redox status of the cytochrome c oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation index (TOI), and cerebral blood volume (CBV) as expressed by tissue haemoglobin index (THI). Measurements were performed in 19 consecutive patients undergoing normothermic (34-36 degrees C) CPB. Data were recorded at 0.5s intervals and averaged into 30 s epochs. Data analysis was carried at baseline, 1, 20, and 40 min after start of CPB, at rewarming, on weaning from CPB, and at closing of chest. RESULTS: There were no in-hospital death, neurological deficits, or myocardial infarcts. Compared to baseline, during the entire CPB duration, there was a marked reduction in [O(2)Hb] and CBV which reached their worst level 40 min after initiation of CPB (from -3.03+/-5.1 to -9.25+/-7.20 micromol/l for [O(2)Hb], and a 24% reduction for CBV (both P<0.0001). The deterioration in [O(2)Hb] was recovered by the end of surgery, while the changes in CBV persisted. No significant changes occurred with respect to [HHb], [Cyt-Ox], and TOI. CONCLUSIONS: Conventional CABG is responsible for deterioration in [O(2)Hb], and CBV, which peak at 40-60 min following initiation of CPB. The changes in [O(2)Hb] are reversible whereas the reduction of CBV persists to the end of the surgery. This suggests a transient impairment in the autoregulatory mechanisms controlling cerebral blood flow following discontinuation of cardiopulmonary bypass.     

Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise

The present study was intended to investigate the different components of fatty acid utilization during a 60-min period of moderate-intensity cycling exercise (50% of VO2max) in eight male type 2 diabetic subjects (aged 52.6 +/- 3.1 years, body fat 35.8 +/- 1.3%) and eight male obese control subjects (aged 45.1 +/- 1.4 years, body fat 34.2 +/- 1.3%) matched for age, body composition, and maximal aerobic capacity. To quantitate the different components of fatty acid metabolism, an isotope infusion of [U-13C]-palmitate was used in combination with indirect calorimetry. In separate experiments, the 13C label recovery in expired air was determined during infusion of [1,2-13C]-acetate (acetate recovery factor). There were no differences in energy expenditure or carbohydrate and total fat oxidation between the groups. The rate of appearance (Ra) of free fatty acid (FFA) (P < 0.05) and the exercise-induced increase in Ra of FFA were significantly lower (P < 0.05) in type 2 diabetic subjects compared with control subjects (baseline vs. exercise [40-60 min]; type 2 diabetes 11.9 +/- 0.9 vs. 19.6 +/- 2.2 micromol x kg(-1) fat-free mass [FFM] x min(-1) and control 15.8 +/- 1.8 vs. 28.6 +/- 2.1 micromol x kg(-1) FFM x min(-1)). The oxidation of plasma-derived fatty acids was significantly lower in type 2 diabetic subjects during both conditions (P < 0.05, baseline vs. exercise [40-60 min]; type 2 diabetes 4.2 +/- 0.5 vs. 14.1 +/- 1.9 micromol x kg(-1) FFM x min(-1) and control 6.2 +/- 0.6 vs. 20.4 +/- 1.9 micromol x kg(-1) FFM x min(-1)), whereas the oxidation of triglyceride-derived fatty acids was higher (P < 0.05). It is hypothesized that these impairments in fatty acid utilization may play a role in the etiology of skeletal muscle and hepatic insulin resistance.     

Evaluation of myocardial preservation using 31P NMR

The purpose of this study was (1) to monitor myocardial high-energy phosphate content and recovery of left ventricular (LV) contractile function following normothermic graded cardiac ischemia and single-dose hypothermic potassium cardioplegia, and (2) to assess the temporal limits of LV functional recovery during single-dose cardioplegia maintained at 17 degrees C. Rabbit hearts (30) were perfused, equipped with an LV balloon, paced at 240 beats/min, and placed in a nuclear magnetic resonance (NMR) magnet. Hearts underwent either graded, global normothermic ischemia or potassium cardioplegia arrest maintained at 17 degrees C for 1 hr. Myocardial high-energy phosphate level, LV contractility, and temperature were monitored continuously. Phosphocreatine (PCr) fell to 10 +/- 2, 2 +/- 1, and 0% of control and ATP to 70 +/- 3, 19 +/- 7, and 0% of control at 10, 40, and 60 min of 37 degrees C ischemia. After 1 hr of reperfusion, regression analysis of final developed pressure (DP) on end ischemic ATP (EIATP) content revealed: DP = 1.02 EIATP + 18 (r = 0.95). Following single-dose cardioplegia, maintained at 17 degrees C, PCr fell to 16 +/- 3% of control at 60 min while ATP fell only to 92 +/- 5% control. With reperfusion, recovery of DP was 100%. It was concluded that (1) PCr serves as an energy buffer for ATP, (2) EIATP predicts recovery of LV function, (3) single-dose cardioplegia maintained at 17 degrees C provides complete myocardial preservation for up to 60 min.