Omega-3 fatty acids and lipoprotein associated phospholipase A(2) in healthy older adult males and females.

PURPOSE: Lipoprotein associated phospholipase A(2) (Lp-PLA(2)) is a novel inflammatory factor that has been independently associated with stroke and cardiovascular disease (CVD). Omega-3 fats have been implicated in reducing inflammation associated with CVD. The aim of this study was to determine if an 8-week isocaloric diet supplemented with eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) in the form of fish oil or α-linolenic acid (ALA) in the form of flaxseed oil would alter Lp-PLA(2) among healthy adults ages 50 years and older. METHODS: Fifty-nine healthy adults (~75% female, average age 61 years) were randomized to one of three groups with equal amounts of total fat intake. All capsules contained ~1 g of fat. The control group (n = 19) consumed olive oil capsules (~11 g/day); the ALA group (n = 20) consumed flaxseed oil capsules (~11 g/day) and the EPA/DHA group (n = 20) consumed fish oil capsules (~2 g/day + 9 g/day of olive oil). Fasting blood samples were obtained before and after the 8-week intervention for determination of Lp-PLA(2) mass and activity as well as lipid values. RESULTS: We did not find any significant changes in Lp-PLA(2) mass or activity after the intervention in any of the groups; however, change in oxidized LDL was associated with change in Lp-PLA(2) mass (r = 0.37, p < 0.01). CONCLUSION: Supplementing the diet with omega-3 fatty acids for 8-weeks did not influence Lp-PLA(2) activity or mass among older adults; altering oxidized LDL may be necessary to see changes in Lp-PLA(2) levels.

Vanadate stimulation of 2-deoxyglucose transport is not mediated by PI 3-kinase in human skeletal muscle.

Glucose transport in mammalian skeletal muscle is stimulated by insulin, hypoxia and tyrosine protein phosphatase inhibitors such as vanadate. However, it is unknown whether the vanadate signaling mechanism shares a common or separate pathway with insulin or hypoxia. Therefore, experiments were conducted on incubated human muscle strips to compare the effects of vanadate with insulin and hypoxia stimulated 2-deoxyglucose transport (2-DOG). We also used the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin to examine whether PI 3-kinase is a common step by which each stimulate glucose transport. Results demonstrate that whereas the effects of vanadate and hypoxia were additive with insulin stimulated glucose transport, the effect of vanadate plus hypoxia was not. In addition, wortmannin significantly (P < 0.05) reduced insulin but not vanadate or hypoxia stimulated 2-DOG transport. Moreover, PI 3-kinase activity was significantly elevated (P < 0.05) in the presence of insulin but not vanadate. In conclusion, these data suggest that vanadate and hypoxia stimulate glucose transport via a similar signaling pathway which is distinct from insulin and that the vanadate signaling pathway is not mediated by PI 3-kinase in human skeletal muscle.

Skeletal muscle GLUT4 protein concentration and aging in humans.

The insulin resistance of aging has been attributed to a postreceptor defect in skeletal muscle. The present study examined whether a reduction in the concentration of the insulin-stimulated glucose transporter (GLUT4) in skeletal muscle was associated with advancing age in men (n = 55) and women (n = 29). Insulin sensitivity (minimal model) was negatively associated (P < 0.001) with age (range, 18-80 years) in men (r = -0.44) and women (r = -0.58). GLUT4 protein concentration in the vastus lateralis was also negatively associated (P < 0.05) with age (men, r = -0.28; women, r = -0.51). There was no relation (P > 0.15) between GLUT4 content in the gastrocnemius and age. GLUT4 concentration in the vastus lateralis was positively associated (P < 0.01) with insulin sensitivity in both sexes (r = 0.42); this relationship persisted in the men after adjusting for overall adiposity, regional adiposity, and cardiorespiratory fitness. These findings suggest that a decrement in GLUT4 protein concentration in skeletal muscle may at least partially contribute to the insulin resistance of aging in humans.

Outcome probabilities and life history after surgical mitral commissurotomy: implications for balloon commissurotomy.

From 1967 to 1988, 339 patients with mitral stenosis underwent surgical commissurotomy, 103 with a closed and 236 with an open technique. The 1 month and 1, 5, 10 and 20 year overall survival rate was 99.7%, 99%, 95%, 87% and 59%, respectively, and the technique (open versus closed) was not a risk factor. Technique was also not a risk factor for a second mitral commissurotomy, subsequent mitral valve replacement, thromboembolism or poor functional status. Risk factors were older age at commissurotomy, black race, higher pulmonary vascular resistance, mitral leaflet calcification, left ventricular enlargement and postcommissurotomy mitral incompetence. The closed technique was a risk factor for mitral incompetence immediately after commissurotomy, but important incompetence developed in only 2 of the 103 patients undergoing closed commissurotomy. Mitral valve replacement was not required within 10 years in 78% of patients and within 20 years in 47%. Despite some increased prevalence of postcommissurotomy mitral incompetence and particularly in view of the considerable long-term likelihood of mitral valve replacement, initial therapy for most patients with mitral stenosis should probably be surgical closed (or percutaneous balloon) mitral commissurotomy. The equations developed in the present study can be used to predict and compare outcome probability after percutaneous balloon commissurotomy with that after surgical commissurotomy and to compare these with outcome probability after mitral valve replacement.

A clinical comparison of mitral valve repair versus valve replacement in ischemic mitral regurgitation.

Severe mitral regurgitation caused by acute myocardial infarction has been a particularly difficult management problem with disappointing clinical results. Over a 75-month period, ending March 31, 1987, 611 patients underwent mitral valve operations at Duke University Medical Center. Within this group, 55 patients had clearly defined ischemic mitral regurgitation, and 37 of these required emergency operations. Thirty-one of the 55 patients had isolated posterior papillary muscle dysfunction, nine had papillary muscle rupture, and 15 had severe ventricular dysfunction and generalized annular dilatation. Thirty-two patients were treated with primary mitral valve replacement, and 23 had mitral valve repair. In 18, repair was accomplished by a transventricular approach, combining the techniques of commissural annuloplasty, papillary muscle shortening or reimplantation, and infarct exclusion. Transventricular mitral valve repair proved to be safe, expeditious, and effective in restoring valve competence. Although the repair and replacement groups were similar with respect to all relevant baseline characteristics, improved operative survival was observed after valve repair, as compared to replacement, both for the overall group (p = 0.03) and for acute papillary muscle dysfunction (p = 0.05). These data suggest that a policy of predominant mitral valve repair, when appropriately applied in patients with ischemic mitral regurgitation, offers the potential for improving therapeutic results.

Seven days of exercise increase GLUT-4 protein content in human skeletal muscle.

Insulin-responsive glucose transporter (GLUT-4) content increases by 1.8-fold in skeletal muscle with 14 wk of exercise training [Houmard et al. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E896-E901, 1993]. The purpose of this study was to determine whether more short-term training (7 days) increases GLUT-4 protein content in human skeletal muscle. Seven sedentary men [25.0 +/- 1.1 (SE) yr, 44.1 +/- 2.2 ml.kg-1.min-1 maximal O2 uptake, 14.9 +/- 2.1% body fat] were examined before and after 7 days of cycle ergometer training (1 h/day, 76 +/- 2% maximal heart rate). Needle biopsy samples from the vastus lateralis were used to determine GLUT-4 protein content. Muscle GLUT-4 increased (P < 0.05) by an average of 2.8 +/- 0.5-fold with 7 days of training. GLUT-4 content in skeletal muscle thus increases substantially with short-term exercise training.

Impact of hyperinsulinemia on myosin heavy chain gene regulation.

The purpose of this study was to determine whether hyperinsulinemia alters myosin heavy chain (MHC) gene expression in human skeletal muscle. A biopsy from the vastus lateralis was obtained in young, lean [age 24.6 +/- 1.0 (SE) yr, body fat 11.9 +/- 1.9%, body mass index 26.1 +/- 1.1 kg/m2; n = 10] men before and after 3 h of hyperinsulinemia (hyperinsulinemic-euglycemic clamp). Muscle was analyzed for mRNA of type I, IIa, and IIx MHC isoforms. Hyperinsulinemia (mean of 1,065.7 +/- 9.8 pmol/l during minutes 20 to 180) did not change (P > 0.05) the mRNA concentration of either the type I MHC or type IIA MHC isoforms. In contrast, type IIX MHC mRNA increased (P < 0.05) with hyperinsulinemia compared with the fasted condition. These data indicate that hyperinsulinemia rapidly increases type IIx MHC mRNA in human skeletal muscle.

Effect of fat emulsion infusion and fat feeding on muscle glycogen utilization during cycle exercise.

Elevated plasma fatty acids have been shown to spare muscle glycogen during exercise. However, on the basis of recent findings, the saturation of fatty acids may influence this response. The purpose of this study was to determine whether saturated or unsaturated fatty acids affected muscle glycogenolysis to varying degrees during cycle exercise. Five healthy men completed three 60-min cycle ergometer trials (EX) at approximately 70% maximal O2 uptake (VO2max). Triglyceride levels were elevated by a fat feeding (FF) composed of 90% saturated fatty acids (heavy whipping cream, 90 g) or by the infusion of Intralipid (IL; Clintec Nutrition; 45 ml/h of 20% IL, 9.0 g), which was 85% unsaturated. A control trial (CON) consisted of a light breakfast (43 g carbohydrate and 1 g fat). Heparin (2,000 U) was administered 15 min before EX in FF and IL trials, resulting in one- and threefold increases in free fatty acid (FFA) levels in IL and FF, respectively. Pre-EX muscle glycogen did not differ. The utilization of muscle glycogen during 60 min of EX was less (P < 0.05) during the FF (60.0 +/- 5.2 mmol/kg wet wt) and IL (58.6 +/- 6.2 mmol/kg wet wt) compared with CON (81.8 +/- 7.5 mmol/kg wet wt). There was no difference between FF and IL in the amount of glycogen utilized. Serum triglyceride levels were greater (P < 0.05) at preheparin in FF (1.58 +/- 0.37 mmol/l) and IL (0.98 +/- 0.13 mmol/l) compared with CON (0.47 +/- 0.14 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate feedings and exercise performance: effect of initial muscle glycogen concentration.

To determine whether the ergogenic benefits of carbohydrate (CHO) feedings are affected by preexercise muscle glycogen levels, eight cyclists performed four self-paced time trials on an isokinetic ergometer over a simulated distance of 70 km. Trials were performed under the following preexercise muscle glycogen and beverage conditions: 1) high glycogen (180.2 +/- 9.7 mmol/kg wet wt) with a CHO beverage (HG-CHO), 2) high glycogen (170.2 +/- 10.4 mmol/kg wet wt) with a non-CHO beverage (HG-NCHO), 3) low glycogen (99.8 +/- 6.0 mmol/kg wet wt) with a CHO beverage (LG-CHO), and 4) low glycogen (109.7 +/- 5.3 mmol/kg wet wt) with a non-CHO beverage (LG-NCHO). The CHO drink (ingested at the onset of exercise and every 10 km thereafter) provided 116 +/- 6 g CHO/trial and prevented the decline in serum glucose observed during both NCHO trials. Performance times ranged from 117.93 +/- 1.44 (HG-CHO) to 122.91 +/- 2.46 min (LG-NCHO). No intertrial differences (P > 0.05) were observed for O2 consumption (75% of maximal O2 consumption), power output (237 W), or self-selected pace (8.44 min/5 km) during the initial 71-79% of exercise. Over the final 14% of the time trial, power output and pace (231 W and 8.62 min/5 km) were similar for the HG-CHO, HG-NCHO, and LG-CHO conditions, but both variables were significantly lower during the LG-NCHO trial (198 W and 9.67 min/5 km, P < 0.05 vs. all other trials).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of resistance exercise on glucose tolerance in normal and glucose-intolerant subjects.

This study was conducted to determine whether improvements in glucose tolerance could be observed after a single bout of resistance exercise in young (27.1 +/- 1.24 yr) control subjects, older (53.3 +/- 1.7 yr) patients with non-insulin-dependent diabetes mellitus (NIDDM), and older (50.7 +/- 1.9 yr) age-matched control subjects. Each subject was screened for fitness level and any contraindications to exercise before inclusion in the study. A 75-g oral glucose tolerance test was administered 2 wk after the subjects were screened, and the subjects were familiarized with the exercise equipment. The maximum weight that could be lifted with one repetition was determined on seven Nautilus machines that utilized the upper and lower body. After a 48-h rest period, a 3-set x 10-repetition protocol based on the subject's one repetition maximum was completed by each participant on each machine. Eighteen hours after the lifting protocol, a second oral glucose tolerance test was administered. There was no change in the pre- to post-exercise glucose levels in any of the treatment groups, but the total insulin responses (area under the curve) of the young control and NIDDM groups were significantly lower after exercise: from 6.93 +/- 0.8 x 10(3) to 5.38 +/- 0.65 x 10(3) pM in the young control group and from 9.83 +/- 1.95 x 10(3) to 7.77 +/- 1.50 x 10(3) pM in the NIDDM group. The postexercise C-peptide levels were unchanged in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid antagonism alters blood glucose homeostasis during exercise in humans.

In an attempt to clarify the role of endogenous opioid peptides in substrate mobilization and hormonal responses to dynamic exercise, eight trained cyclists completed exercise trials at 90% of maximal O2 consumption (VO2max) until exhaustion and at 70% VO2max for 90 min. Trials were conducted after intravenous administration of the opiate antagonist naloxone (NAL, 0.1 mg/kg bolus + 0.1 mg.kg-1.h-1) or volume-matched saline (SAL) at each intensity. Serum glucose was maintained at significantly higher levels at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and at all points during exercise and at 30 and 60 min of recovery in the 90%-NAL than in the 90%-SAL trial. The serum insulin response to exercise was not altered by NAL administration at either intensity. Serum C-peptide was approximately 50% higher at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial but was significantly lower during exercise in the 90%-NAL than in the 90%-SAL trial. The plasma glucagon response to exercise at 70% VO2max was not altered by NAL administration but was significantly elevated in the 90%-NAL vs. the 90%-SAL trial. Plasma epinephrine was 50-150% (approximately 2-3 nM) higher during exercise from 30 to 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and was higher at termination (4.9 +/- 2.1 vs. 2.7 +/- 1.7 nM) in the 90%-NAL than in the 90%-SAL trial, although the difference in the 90% trial was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of reduced training and training cessation on insulin action and muscle GLUT-4.

This study examined the impact of a 50% reduction in training frequency or training cessation on insulin action and muscle GLUT-4 protein concentration. Middle-aged individuals were tested before and after 12 wk of exercise training (4 days/wk, 40-45 min/day). Subjects then either maintained training (n = 9), reduced training frequency by 50% (n = 11), or stopped exercising (n = 10) for the ensuing 2 wk. GLUT-4 protein concentration and insulin action (insulin sensitivity index, as determined by the minimal model) increased (P < or = 0.05) by an average of 1.6- and 1.9-fold, respectively, with the 12 wk of training. Insulin action and GLUT-4 did not increase further with the additional 2 wk of training in the maintained training group. Similarly, insulin sensitivity index and GLUT-4 concentration remained at trained levels when training frequency was reduced by 50% for 2 wk. GLUT-4 concentration and insulin action, however, were not different from sedentary values after 14 days of training cessation. These findings indicate that a 14-day 50% reduction in exercise frequency maintains the improvements in GLUT-4 protein concentration and insulin action gained with endurance training in moderately trained middle-aged adults; in contrast, these adaptations are largely lost with training cessation.

Substrate utilization during exercise in formerly morbidly obese women.

The purpose of this study was to compare substrate utilization during fasting and submaximal exercise in morbidly obese women after weight loss (WL) with that in weight-matched controls (C). WL were studied in the weight-stable condition approximately 24 mo after gastric bypass surgery. Energy intake (self-reported) and expenditure ((2)H(2)(18)O) were also compared. The respiratory exchange ratio during exercise at the same absolute (15 W) workload was significantly (P < or = 0.05) elevated in WL vs. C (0.90 +/- 0.02 vs. 0.83 +/- 0.03); this was reflected as lower fat utilization in WL (29.7 +/- 4.8 vs. 53.2 +/- 9.7% of energy from fat). Respiratory exchange ratio during exercise at the same relative (65% of maximal O(2) uptake) intensity was also significantly (P < 0.05) elevated in WL (0.96 +/- 0.01 vs. 0.89 +/- 0.02), and fat use was concomitantly depressed (12.4 +/- 3.0 vs. 34.3 +/- 9.9% of energy from fat). Resting substrate utilization, daily energy expenditure, and self-reported relative macronutrient intake did not differ between groups. These data suggest that lipid oxidation is depressed during physical activity in WL. This defect may, at least in part, contribute to a propensity for the development of morbid obesity.

Insulin activation of phosphatidylinositol 3-kinase in human skeletal muscle in vivo.

The purpose of this investigation was to determine whether insulin-stimulated phosphatidylinositol 3-kinase (PI3-kinase) activity is detectable in needle biopsies of human skeletal muscle. Sixteen healthy nonobese males matched for age, percent fat, fasting insulin, and fasting glucose participated in one of two experimental protocols. During an intravenous glucose tolerance test (IVGTT) protocol, insulin-stimulated PI3-kinase activity was determined from percutaneous needle biopsies at 2, 5, and 15 min post-insulin administration (0.025 U/kg). In the second group, a 2-h, 100 mU . m-2 . min-1 euglycemic hyperinsulinemic clamp was performed, and biopsies were obtained at 15, 60, and 120 min after insulin infusion was begun. Insulin stimulated PI3-kinase activity by 1.6 +/- 0.2-, 2. 2 +/- 0.3-, and 2.2 +/- 0.4-fold at 2, 5, and 15 min, respectively, during the IVGTT. During the clamp protocol, PI3-kinase was elevated by 5.3 +/- 1.3-, 8.0 +/- 2.6-, and 2.7 +/- 1.4-fold above basal at 15, 60, and 120 min, respectively. Insulin-stimulated PI3-kinase activity at 15 min post-insulin administration was significantly greater during the clamp protocol vs. the IVGTT (P < 0.05). These observations suggest that insulin-stimulated PI3-kinase activity is detectable in needle biopsies of human skeletal muscle, and furthermore, that the euglycemic, hyperinsulinemic clamp protocol may be a useful tool to assess insulin signaling in vivo.

Fiber type and citrate synthase activity in the human gastrocnemius and vastus lateralis with aging.

The purpose of this study was to determine whether enzymatic and histochemical characteristics of human skeletal muscle are altered with aging. Tissues from the vastus lateralis (VL) and gastrocnemius were analyzed for citrate synthase (CS) activity and fiber type in 55 sedentary men (age range 18-80 yr). In this population, CS activity in the gastrocnemius was negatively related to age (r = -0. 32, P < 0.05); there was no relationship in the VL. Treadmill-determined maximal oxygen consumption was positively related (r = 0.40, P < 0.05) to CS in the gastrocnemius but not in the VL. CS activity in the gastrocnemius was 24% lower in the oldest (>/=60 yr, n = 10) vs. the youngest (

Pulmonary artery sling with tracheal stenosis: one-stage repair.

Pulmonary artery sling with tracheal stenosis is a difficult management problem. We describe the use of cardiopulmonary bypass as a method to facilitate one-stage repair.

A simple method of treating coronary air embolism after cardiopulmonary bypass.

Coronary air embolism is a potential complication of cardiac operations performed with cardiopulmonary bypass, especially open heart operations. There are many recommended methods described in the literature to treat the sequelae of coronary air embolism, none universally effective. We describe a simple and safe method to treat the condition, which we have found very effective in our practice.

Arterial switch operation: successful bilateral internal thoracic artery grafting.

Internal thoracic artery grafting in arterial switch operations for transposition of great arteries has been reported for salvage of myocardial ischemia after initial coronary transfer. We report a situation where we opted for primary coronary bypass grafting to avoid an obviously difficult coronary transfer, with successful outcome.

Absorbable pulmonary artery band.

Absorbable pulmonary artery banding may be a useful method of avoiding further operation or angioplasty in patients whose underlying lesion has a natural history of resolution. We report 2 cases of absorbable pulmonary artery banding using braided Dexon. In both cases the bands functioned well initially and were completely resorbed after 2 years and 6 months, respectively.

Plasma leptin and exercise: recent findings.

The cloning of murine and human obese genes in 1994, and the subsequent identification that the product of the obese gene, leptin, is secreted from adipose tissue, stimulated a tremendous amount of interdisciplinary interest in adipose tissue endocrinology and the potential role of this tissue in the regulation of energy balance. Exercise, with concomitant changes in fuel flux, systemic hormone levels and energy expenditure, may contribute to the regulation of plasma leptin levels and presumably, leptin action. The initial work characterising the leptin-exercise relationship was equivocal. Cross-sectional studies provided some mixed evidence regarding the relationship between aerobic capacity or habitual physical activity and plasma leptin. In contrast, studies on acute bouts of exercise and exercise training interventions have, with few exceptions, suggested that exercise does not alter systemic leptin independent of changes in fat mass. In general, these studies did not carefully control for energy balance, and sampled only a single fasting plasma leptin level. Two recent studies utilising experimental designs in which energy balance was controlled and 24-hour profiles of plasma leptin were determined have provided the most compelling evidence to date of the interaction between exercise, energy balance and systemic leptin in humans. These studies provide a clear explanation for the apparent lack of an acute effect of exercise on systemic leptin and underscore the importance of clearly defining the balance between energy intake and energy expenditure when studying the physiology of leptin. The aim of this brief review is to provide an overview of the interaction between energy expenditure during physical activity and systemic leptin level. Special emphasis will be placed on those studies in which energy intake/balance was carefully controlled.