Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity.

INTRODUCTION: New strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold-stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites. METHODS: Healthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m-2; VO2 max 39 [7.6] mL min-1 kg-1) participated in a 6-week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [18F]fluorodeoxyglucose positron emission tomography-magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico-thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy. RESULTS: Cold exposure increased supraclavicular BAT GU by threefold (p < 0.001), energy expenditure by 59% (p < 0.001) and plasma fatty acids (p < 0.01). Exercise training had no effect on cold-induced GU in BAT or neck muscles. Training increased aerobic capacity (p = 0.01) and decreased visceral fat (p = 0.02) and cervico-thoracic BAT mass (p = 0.003). Additionally, training decreased very low-density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high-density lipoprotein (p = 0.04). CONCLUSIONS: Although exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.

Increased insulin-stimulated glucose uptake in both leg and arm muscles after sprint interval and moderate-intensity training in subjects with type 2 diabetes or prediabetes.

We investigated the effects of sprint interval training (SIT) and moderate-intensity continuous training (MICT) on glucose uptake (GU) during hyperinsulinemic euglycemic clamp and fatty acid uptake (FAU) at fasting state in thigh and arm muscles in subjects with type 2 diabetes (T2D) or prediabetes. Twenty-six patients (age 49, SD 4; 10 women) were randomly assigned into two groups: SIT (n=13) and MICT (n=13). The exercise in the SIT group consisted of 4-6×30 s of all-out cycling with 4- minute recovery and in the MICT group 40- to 60- minute cycling at 60% of VO2peak . Both groups completed six training sessions within two weeks. GU and FAU were measured before and after the intervention with positron emission tomography in thigh (quadriceps femoris, QF; and hamstrings) and upper arm (biceps and triceps brachii) muscles. Whole-body insulin-stimulated GU increased significantly by 25% in both groups, and this was accompanied with significantly increased insulin-stimulated GU in all thigh and upper arm muscles and significantly increased FAU in QF. Within QF, insulin-stimulated GU improved more by SIT than MICT in rectus femoris (P = .01), but not differently between the training modes in the other QF muscles. In individuals with T2D or prediabetes, both SIT and MICT rapidly improve insulin-stimulated GU in whole body and in the thigh and arm muscles as well as FAU in the main working muscle QF. These findings highlight the underused potential of exercise in rapidly restoring the impaired skeletal muscle metabolism in subjects with impaired glucose metabolism.

Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD.

BACKGROUND: Insulin resistance, ß-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia. METHODS AND RESULTS: We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in ß-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity. CONCLUSIONS: In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia.

Autonomic Function Predicts Fitness Response to Short-Term High-Intensity Interval Training.

We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6×30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre-training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT.

Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives.

Obesity and diabetes are growing threats for cardiovascular diseases (CVD) and heart failure. In order to identify early and effective treatment or prevention targets, it is fundamental to dissect the role of each organ and the sequence of events leading from health to obesity, diabetes and cardiovascular diseases. The advancements in imaging modalities to evaluate organ-specific metabolism in humans in vivo is substantially contributing to the stratification of risk, identification of organ-specific culprits and development of targeted treatment strategies. This review summarizes the contribution provided by imaging of the heart, skeletal muscle, adipose tissue, liver, pancreas, gut and brain to the understanding of the pathogenesis and cardio-metabolic complications of obesity and diabetes, and to the monitoring of treatment responses in humans. We conclude by suggesting emerging fields of investigation, including the role of cardiac fat in the pathogenesis of cardiovascular disease, the conversion of white into brown adipose tissue in the treatment of obesity, the control of weight and energy balance by the brain, the integration between omics and imaging technologies to help establish biomarkers, and the characterization of gut metabolism in relation with the gut microbiome, opening a very promising preventive/therapeutic perspective.

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity.

AIMS/HYPOTHESIS: The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants. METHODS: In the validation study, pigs were imaged using [(18)F]fluorodeoxyglucose ([(18)F]FDG) and the image-derived data were compared with corresponding ex vivo measurements in tissue samples and with arterial-venous differences in glucose and [(18)F]FDG levels. In the clinical study, GU was measured in different regions of the intestine in lean (n = 8) and morbidly obese (n = 8) humans at baseline and during euglycaemic hyperinsulinaemia. RESULTS: PET- and ex vivo-derived intestinal values were strongly correlated and most of the fluorine-18-derived radioactivity was accumulated in the mucosal layer of the gut wall. In the gut wall of pigs, insulin promoted GU as determined by PET, the arterial-venous balance or autoradiography. In lean human participants, insulin increased GU from the circulation in the duodenum (from 1.3 ± 0.6 to 3.1 ± 1.1 µmol [100 g](-1) min(-1), p < 0.05) and in the jejunum (from 1.1 ± 0.7 to 3.0 ± 1.5 µmol [100 g](-1) min(-1), p < 0.05). Obese participants failed to show any increase in insulin-stimulated GU compared with fasting values (NS). CONCLUSIONS/INTERPRETATION: Intestinal GU can be quantified in vivo by [(18)F]FDG PET. Intestinal insulin resistance occurs in obesity before the deterioration of systemic glucose tolerance.

Myocardial and peripheral vascular functional adaptation to exercise training.

Exercise training seems to restore impaired vascular function in both peripheral and myocardial vessels in patients with coronary artery and peripheral vascular disease or in patients with risk factors for these diseases. However, the results on the effects of exercise training on vascular function in apparently healthy subjects are controversial. We studied the effects of long-term volitionally increased physical activity on peripheral and myocardial vascular function in nine young healthy male monozygotic twin pairs discordant for physical activity and fitness. The brothers were divided into more (MAG) and less active groups according to physical activity and fitness. The difference between groups in VO(2max) was 18+/-10% (P<0.001). Myocardial perfusion at rest, during adenosine-induced vasodilatation and during cold-pressor test and myocardial oxygen consumption were measured with positron emission tomography. In addition, endothelial function was measured using ultrasound in brachial and left anterior descending coronary arteries, and standard echocardiographic measures were taken. No differences were observed in myocardial perfusion measurements between groups. MAG tended to have a lower oxygen extraction fraction (P=0.06), but oxygen consumption was similar between the groups. No differences were found in coronary artery, myocardial resistance vessel or peripheral endothelial function between groups. These results suggest that when the effects of heredity are controlled, myocardial perfusion reserve and endothelial function, both in peripheral arteries and myocardial vessels, are not enhanced by increased physical activity and fitness in young healthy adult men.

The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

In vivo measurements of glucose uptake in human Achilles tendon during different exercise intensities.

Muscular contraction and loading of adjacent tendons has been demonstrated to cause increased blood flow and metabolic activity in the peritendinous region. However, it is poorly known to what extent the human tendon itself takes up glucose during exercise. Thus, the purpose of this study was to measure tendon glucose uptake with increasing exercise intensity and to compare it to muscle glucose uptake at the same intensities. Eight young men were examined on three separate days during which they performed 35 min of cycling at 30, 55 and 75 % of VO2max, respectively. Glucose uptake was measured directly by positron emission tomography (PET) with 2-[ (18)F]fluoro-2-deoxyglucose ([18F]FDG). [18F]FDG was injected after 10 min of exercise that was continued for a further 25 min after the injection. PET scanning of the thigh and Achilles region was performed after the exercise. Glucose uptake of the Achilles tendon (AT) remained unchanged (7.1 +/- 1.5, 6.6 +/- 1.1, and 6.0 +/- 1.1 micromol.kg(-1).min(-1)) with the increasing workload, although the glucose uptake in m. quadriceps femoris simultaneously clearly increased (48 +/- 35, 120 +/- 35, and 152 +/- 74 micromol.kg(-1).min(-1), p < 0.05). In conclusion, the AT takes up glucose during exercise but in significantly smaller amounts than the skeletal muscle does. Furthermore, glucose uptake in the AT is not increased with the increasing exercise intensity. This may be partly explained by the cycle ergometry exercise used in the present study, which probably causes only a little increase in strain to the AT with increasing exercise intensity.

Comparison between flutter valve drainage bag and underwater seal device for pleural drainage after lung surgery.

AIM OF THE STUDY: The purpose of the present study was to compare the use of a conventional underwater seal device with suction and a flutter valve drainage bag for pleural drainage after lung surgery. PATIENTS AND METHODS: Altogether 59 patients undergoing elective lung surgery except pneumonectomy between February 2001 and April 2002 were prospectively randomized to receive postoperative pleural drainage by 28F chest tube(s) attached to underwater seal device placed on negative pressure of 15 cm of water or flutter valve drainage bag. Following withdrawal of four patients from the study, 55 patients were evaluated (31 patients in the underwater seal device group and 24 patients in the flutter valve drainage bag group). RESULTS: In the conventional underwater seal device group the mean drainage time was 2.6 (SD +/- 2.0) days and in the flutter valve drainage bag group the mean drainage time was 3.3 days (SD +/- 4.0); difference -0.8, 95% confidence interval (CI) -2.4 to 0.9. The mean length of hospitalization in the surgical ward was 3.6 (SD +/- 2.7) and 4.1 (SD +/- 4.4) days respectively (difference -0.5, 95% CI -2.5 to 1.4). CONCLUSIONS: The results of this study suggest that flutter valve drainage system is a safe and feasible alternative in managing postoperative air leaks and haemorrhage after lung surgery other than pneumonectomy if air leaks are not extremely massive.

Flutter valve drainage bag is a useful device for the pleural drainage.

BACKGROUND AND AIMS: The purpose of the present study was to compare the use of the flutter valve pleural drainage bag and the conventional underwater seal system for the pleural drainage in the treatment of pneumothorax and pleural effusion. PATIENTS AND METHODS: Altogether fifty patients who needed the pleural drainage at our hospital between February and October 1999 were randomized to this prospective study either into the flutter valve pleural drainage group or into the conventional underwater seal pleural drainage group, 25 patients in each. RESULTS: In the conventional underwater seal system group, the mean drainage time was 4.1 (SD +/- 4.0) days and in the flutter valve drainage bag group 4.8 (SD +/- 4.9) days (difference -0.7, 95% confidence interval (CI) -3.3 to 1.8). The mean length of hospitalization was 16.3 (SD +/- 20.9) days and 18.7 (SD +/- 27.0) respectively (difference -2.4, 95% CI -16.1 to 11.3). CONCLUSIONS: The results of this study suggest that flutter valve drainage bag is a safe and feasible system in the most cases when pleural drainage is needed in the treatment of pneumothorax and pleural effusion.

Percutaneous dilational tracheostomy or conventional surgical tracheostomy?

OBJECTIVE: Percutaneous dilational tracheostomy (PDT) is increasingly used in intensive care units (ICU), and it has a low incidence of complications. The aim of this study was to compare the costs, complications, and time consumption of PDT with that of conventional surgical tracheostomy (ST) when both procedures were performed in the ICU. DESIGN: The study was a prospective, randomized trial. SETTING: The procedures were performed routinely in the ICU of Satakunta Central Hospital. PATIENTS: During a 23-month period from December 1995 to November 1997, 30 patients underwent PDT and 26 patients had ST. In one patient, PDT was converted to ST. All patients were receiving ventilation in the ICU, and all tracheostomies were performed at the patient's bedside in the ICU. The Portex percutaneous tracheostomy kit was used for all PDTs. RESULTS: The mean time to perform PDT was 11 mins (SD, 6; range, 2-40), and the mean time to perform ST was 14 mins (SD, 6; range, 3-39). In the PDT group, five patients had moderate bleeding during the procedure. In three patients, the bleeding was resolved with compression; in one patient, it was resolved with ligation of the vessel; and in one patient, it was resolved with electrocoagulation. Bleeding did not cause any complications afterward. In the PDT group, one patient had minimal oozing from the wound edge on the first postoperative day and it was resolved spontaneously. In the ST group, there were no intraprocedural complications. One patient had bleeding from the wound on first postoperative day. The sutures were removed, and the bleeding vessel was ligated. The mean cost (in U. S. dollars) of PDT was $161 (SD, 10.4; range, $159-$219), and the mean cost of ST was $357 (SD, $74; range, $239-$599). The cost of PDT was significantly lower than the cost of ST (p < .001). CONCLUSION: We found that PDT is a cost-effective procedure in critically ill ICU patients. Although we performed ST at the bedside in the ICU to avoid the risks associated with moving critically ill patients to the operating room, we found PDT to be a simple and safe procedure.

Use of the Heimlich valve for treating pneumothorax.

BACKGROUND AND AIMS: The aim of this retrospective study was to compare the use of a small caliber tube connected to Heimlich flutter valve with a conventional thoracic drainage system in the treatment of pneumothorax. MATERIALS AND METHODS: Patients with simple pneumothorax during the years 1991-1995 in Satakunta Central Hospital were included in this study. Nineteen patients were treated with the Heimlich flutter valve and 57 patients were treated with the standard drainage tube connected to an underwater seal device. The data were collected from hospital records focusing on the duration of chest drainage, the number of chest roentgenograms and the length of hospital stay. RESULTS: In the Heimlich valve group the mean drainage time was 2,2+/-0.9 days and in the standard thoracic drainage group 3.4+/-3.8 days (p <0.05) respectively. The mean length of hospitalization in the Heimlich valve group was 3.3+/-2.2 days and in the standard thoracic drainage group 5+/-4.9 days (p < 0.01). The number of chest roentgenograms in the Heimlich valve group was 3+/-1.1 and in the standard thoracic drainage group 4.6+/-2.7 (p < 0.001). CONCLUSION: We believe that the treatment with a small caliber tube and Heimlich valve is a safe and effective procedure. It also reduces the duration of chest drainage and the length of hospital stay.

Deep hypothermia and circulatory arrest in the surgical management of renal cell carcinoma with vena caval involvement.

Six patients operated on for renal cell carcinoma with vena caval involvement were prospectively studied. The mean age of the four men and two women was 58 (range 51-77) years. In four of them the tumour was excised during cardiopulmonary bypass and deep hypothermic circulatory arrest. The operation was radical in three of these patients and palliative in one. There were no major complications or deaths during hospitalisation averaging 9 (7-17) days. The mean follow-up was 9 (4-14) months, during which two patients had died of metastatic disease. The surgical approach with cardiopulmonary bypass and deep hypothermic circulatory arrest is well tolerated and can be used to facilitate complete tumour thrombectomy, with low operative risk. Need for caval tumour thrombectomy was found in 5% of all patients with renal cell carcinoma during the study period.

Open management with mesh and zipper of patients with intra-abdominal abscesses or diffuse peritonitis.

OBJECTIVE: To evaluate the open management of intra-abdominal abscesses and persistent peritonitis by the "mesh and zipper" technique, and to assess the predictive value of the APACHE II score. DESIGN: Prospective open study. SUBJECTS: 21 consecutive patients with life-threatening peritonitis. INTERVENTIONS: Insertion of mesh and zipper and lavage once or twice daily with several litres of warmed saline. MAIN OUTCOME MEASURE: Mortality. RESULTS: Eleven of the 21 patients died (52%). The APACHE II score accurately predicted outcome, in that no patient who scored less than 20 points died, and no patient who scored more than 26 points lived. CONCLUSION: The mesh and zipper technique with daily intraperitoneal lavage is effective in the treatment of life-threatening peritonitis and the APACHE II score is an accurate predictor of survival.

Aortic graft--enteric fistula.

Aortic graft infection is a serious complication in vascular surgery. We present a series of three cases with aortoenteric fistula. In two patients an emergency operation was necessary and one underwent elective surgery. The infected Dacron aortobifemoral graft was removed and the aorta was sutured with monofilament sutures. An axillobifemoral bypass graft was inserted after the laparotomy closure and second skin preparation. Two patients are alive 2.5 years and six months postoperatively. One patient died 45 days postoperatively.