Lennart Jorfeldt

Echocardiography Doppler in pulmonary embolism: Right ventricular dysfunction as a predictor of mortality rate ☆ ☆☆ ★

To test the hypothesis that right ventricular (RV) systolic dysfunction at the time of diagnosis of pulmonary embolism (PE) is a predictor of mortality rate, 126 consecutive patients with PE were examined with echocardiography Doppler (ED) on the day of diagnosis. RV function was assessed by evaluation of wall motion on a four-point scale. The material was divided into two groups: group A (n = 56) with normal or slightly reduced RV function and group B (n = 70) with moderately or severely reduced RV function. The overall mortality rate was 7.9% in the hospital and 15.1% within 1 year. Four deaths occurred in group A and 15 in group B (p = 0.04). All in-hospital deaths (n = 10) occurred in group B (p = 0.002). The variables associated with mortality rate were RV dysfunction and cancer (in-hospital, p = 0.002 and 0.004; 1 year, p = 0.04 and < 0.001, respectively). Nine (7.1%) deaths (all in-hospital) were caused by PE. Five of these patients had advanced-stage cancer. The in-hospital mortality rate in patients without cancer was 4%, all from PE and all in group B. In conclusion, RV dysfunction when diagnosis of PE is established is associated with mortality rate. A strategy for risk stratification of patients with PE with ED may be of clinical usefulness.

Pulmonary Embolism: One-Year Follow-Up With Echocardiography Doppler and Five-Year Survival Analysis

BACKGROUND The long-term prognosis for patients with pulmonary embolism (PE) is dependent on the underlying disease, degree of pulmonary hypertension (PH), and degree of right ventricular (RV) dysfunction. A precise description of the time course of pulmonary artery pressure (PAsP)/RV function is therefore of importance for the early identification of persistent PH/RV dysfunction in patients treated for acute PE. Other objectives were to identify variables associated with persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients alive 1 month after inclusion. METHODS AND RESULTS Echocardiography Doppler was performed in 78 patients with acute PE at the time of diagnosis and repeatedly during the next year. A 5-year survival analysis was made. The PAsP decreased exponentially until the beginning of a stable phase, which was </=38 days. The recovery of RV function occurred during the same time period. Risk factors for persistent PH/RV dysfunction and the 5-year mortality rate were analyzed using multiple logistic regression models. A PAsP of >50 mm Hg at the time of diagnosis of acute PE was associated with persistent PH after 1 year. The 5-year mortality rate was associated with underlying disease. Only patients with persistent PH in the stable phase required pulmonary thromboendarterectomy within 5 years. CONCLUSIONS An echocardiography Doppler investigation performed 6 weeks after diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and may be of value in planning the follow-up and care of these patients.

Interstitial glucose and lactate balance in human skeletal muscle and adipose tissue studied by microdialysis.

1. Microdialysis was used to gain insight into the substrate exchanges in the interstitial space of skeletal muscle and adipose tissue. Probes were inserted in the quadriceps femoris muscle and para‐umbilical subcutaneous adipose tissue of thirteen subjects and microdialysis was performed at different flow rates (1‐4 microliters min‐1) and during changes in tissue blood flow. 2. When ethanol (5 mM) is included in the perfusion solution, the ethanol clearance from the probe is a measure of tissue blood flow. Blood flow changes induced by adenosine or vasopressin perfusion, by exercise or by circulatory occlusion resulted in ethanol clearance values of 69‐139% of the basal level. The ethanol clearance was higher in skeletal muscle than in adipose tissue (32‐62%, P < 0.001), a difference compatible with a higher blood flow in muscle tissue. 3. The fraction of the interstitial glucose concentration that was recovered with the microdialysis was similar in skeletal muscle (the absolute values being 1.70 +/‐ 0.14 mM at 1 microliter min‐1 and 0.59 +/‐ 0.05 mM at 4 microliters min‐1) and adipose tissue (1.89 +/‐ 0.20 mM at 1 microliter min‐1; 0.54 +/‐ 0.05 mM at 4 microliters min‐1) and correlated inversely with the tissue ethanol clearance, both in the basal state and during changes in tissue blood flow (muscle: r = ‐0.56 to ‐0.67; adipose tissue r = ‐0.72 to ‐0.95). Coefficients of variation were 6‐8% (glucose) and 11‐16% (lactate) and were similar during isometric exercise. The reproducibility of the technique (comparison of two contralateral probes; perfusion flow rate 4 microliters min‐1) was 5.3‐8.3% (ethanol) and 23.9‐20.8% (glucose) in muscle (n = 6) and adipose tissue (n = 4) respectively. 4. The skeletal muscle dialysate lactate concentration (1 microliter min‐1: 1.16 +/‐ 0.2 mM) was higher than in adipose tissue (0.76 +/‐ 0.08 mM, P < 0.05), where the absolute amount of lactate that could be removed from the tissue (at 4 microliters min‐1) was only half of that in skeletal muscle (0.8 +/‐ 0.11 vs. 1.76 +/‐ 0.23 nmol min‐1, P < 0.05). The dialysate lactate level was not affected in either tissue by large changes in the interstitial glucose concentration indicating that in neither tissue is blood glucose a significant source of lactate formation. 5. The blood flow effects on the dialysate glucose concentration are the likely consequence of probe glucose drainage artificially shifting the balance between the supply and consumption of interstitial glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Exercise and insulin cause GLUT-4 translocation in human skeletal muscle.

Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocation phenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic-hyperinsulinemic clamp (0.8 mU ⋅ kg-1 ⋅ min-1). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (V˙o 2 max), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin (44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological conditions, moderate intensity exercise and physiological hyperinsulinemia ∼56 μU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle.Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocation phenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic-hyperinsulinemic clamp (0.8 mU. kg(-1). min(-1)). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (VO(2 max)), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin (44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological conditions, moderate intensity exercise and physiological hyperinsulinemia approximately 56 microU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle.

The influence of ethanol on splanchnic and skeletal muscle metabolism in man.

Splanchnic and leg exchange of ethanol, acetate, glucose, lactate, pyruvate, glycerol, and free fatty acids was studied in five healthy volunteers before and after a 60-min infusion of ethanol. Leg and splanchnic blood flows were determined simultaneously using a modified indicator dilution technique. The blood alcohol concentration obtained was 1.88 mmoles/liter and splanchnic uptake of ethanol was calculated to be 1.18 mmoles/min. All subjects showed an acetate uptake over the legs with a mean of 0.25 mmole/min. Splanchnic glucose production was attenuated in four of five subjects after ethanol treatment, and glucose uptake by the legs was significantly reduced. The normal splanchnic uptake of lactate was changed by ethanol to a release, and the arterial concentration was nearly doubled. Net leg release of lactate decreased significantly. Splanchnic blood flow and oxygen uptake were uninfluenced by ethanol, whereas leg blood flow decreased from a mean of 0.77 to 0.65 liter/min. It is concluded that, following ethanol treatment, (1) a major part of acetate released from the splanchnic region is taken up by the muscles, (2) leg glucose uptake is decreased by a reduction of the same magnitude as the actate uptake, and (3) leg blood flow is reduced, probably owing to a constriction of muscle vessels.

Influence of Age on the Local Circulatory Adaptation to Leg Exercise

Blood flow and oxygen uptake of the leg and release of lactate were studied in a group of 7 healthy well-trained 52–59-year-old men at rest and during bicycle exercise at work loads that were increased in steps to near maximal levels of work intensity. The results were compared with those for 7 healthy subjects 25–30 years of age studied previously (11). Blood flow to the leg rose in linear proportion to pulmonary oxygen uptake at submaximal work intensities but tended to level off at the heaviest work loads. The rise in leg blood flow during exercise was less in the middle-aged group and was largely compensated for by a larger arterial-femoral venous oxygen difference during exercise. Leg release of lactate rose approximately exponentially in relation to work load. No difference was observed between the two age groups with regard to arterial lactate or net release of lactate during exercise. It is concluded that blood flow to the leg in middle-aged men rises in a curvilinear manner in response to exercis...

Interstitial lung disease in polymyositis and dermatomyositis: Longitudinal evaluation by pulmonary function and radiology

OBJECTIVE To estimate predictors and long-term outcome of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM). METHODS We conducted a prospective study in which newly diagnosed PM/DM patients, regardless of clinical symptoms of pulmonary disease, were investigated with repeated chest radiography, high-resolution computed tomography (HRCT) of the lungs, and pulmonary function test (PFT). Clinical, radiologic, and lung function outcome was based on the last followup results. RESULTS Twenty-three patients with a mean followup period of 35 months were included. Findings on radiographic examination and/or PFT compatible with ILD were recorded in 18 patients (78%). Patients with ILD had lower lung function, higher radiologic scores, and higher creatine kinase values than those without ILD. All patients were treated with high-dose glucocorticoids and other immunosuppressive agents. Two patients died due to ILD, both with active myositis. During the followup, total lung capacity (TLC) improved in 33%, remained stable in 39%, and deteriorated in 28%. Changes in TLC correlated only partially with HRCT findings, which persisted even after normalizing for lung function. CONCLUSION ILD associated with PM/DM is in most cases mild, chronic, and has a nonprogressive course during immunosuppressive treatment. PFT can be normalized during treatment with immunosuppressive therapy, even if radiologic signs of ILD persist. The course of ILD could not be predicted on the first examination. Therefore, myositis patients with ILD need careful evaluation of clinical features as well as PFT and radiologic features during followup.

Pulmonary embolism: Relation between the degree of right ventricle overload and the extent of perfusion defects☆☆☆★★★

BACKGROUND Inasmuch as the presence of right ventricle (RV) overload in patients with pulmonary embolism (PE) is associated with a bad prognosis, evaluation of RV function in PE is of importance. This study was done to establish if the degree of RV overload can be predicted from the extent of perfusion defects (PDf). METHODS One hundred twenty-one consecutive patients with PE diagnosed by lung scintigraphy (LS) were examined by echocardiography Doppler (ED) immediately after diagnosis. PDf were graded visually in categories (LS score 1 = < or =20%, 2 = >20% of total lung area) and on a continuous scale (normal perfusion = 0, no perfusion = 1). The reproducibility of both methods was tested. RV wall motion was assessed on a four-point scale (0 = normal to 3 = severely hypokinetic). The distance from LV posterior wall to RV anterior wall and dimensions of RV and LV were measured. Pulmonary artery systolic pressure (PAsP) was calculated by using the maximum velocity of tricuspid regurgitation. RESULTS There were 51 patients with LS score 1 and 70 (58%) with score 2. In comparison with patients with LS score 1, those with score 2 more often had RV hypokinesis 2+ or 3+ (n = 49 vs n = 16) (p < 0.001), larger RV (34 +/- 6 mm [22 to 48] vs 29 +/- 5 [17 to 38]) (SD [range]) (p < 0.001) and higher PAsP (51 +/- 13 mm Hg [21 to 83] vs 42 +/- 14 [20 to 81]) (p < 0.001). The variability in both groups was large. With continuous scaling, PDf averaged 0.3. This was also the value that best discriminated RV hypokinesis 2+ or 3+ in a receiver operating characteristic curve. However, the variability for this scan scoring method was SD 0.073, giving a 95% confidence limit of +/-0.15. CONCLUSION There is a significant correlation between RV overload and PDf, but the variability is large; therefore, an estimate of the size of perfusion defects in LS cannot replace ED in the assessment of PAsP and the degree of RV overload in PE.

Effects of high-dose glucose–insulin–potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes

The effects of glucose-insulin-potassium (GIK) on cardiac metabolism have been studied previously in non-diabetic patients after cardiac surgery. Although patients with diabetes mellitus can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery remains unexplored. Therefore the present study investigates the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with Type II diabetes. A total of 20 patients with Type II diabetes undergoing elective coronary surgery were randomly allocated to either post-operative high-dose GIK or standard post-operative care, including insulin infusion if necessary to keep blood glucose below 10 mmol/l. Myocardial substrate utilization was studied using the coronary sinus catheter technique. Haemodynamic state was assessed with the aid of Swan-Ganz catheters. High-dose GIK caused a shift towards carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of non-esterified fatty acids and beta-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with high-dose GIK. A decrease in systemic vascular resistance was found both in the control group and in the high-dose GIK group. We conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of non-esterified fatty acids and beta-hydroxybutyric acid. This could have implications for treatment of the diabetic heart in association with surgery and ischaemia.

The influence of ethanol on human splanchnic and skeletal muscle metabolism during exercise.

Arterial concentrations and splanchnic and leg exchange of ethanol, acetate, glucose, pyruvate, lactate, glycerol, free fatty acids and ketone bodies were determined in sixteen healthy male volunteers after administration of small doses of ethanol. Measurements were made at rest and during 40 min work (50% of max V·o2). Two doses of ethanol were administered, giving blood concentrations at which the ethanol elimination capacity was not saturated (2·5 mmol/l) and where ethanol was eliminated with maximal velocity (8·5 mmol/l).Splanchnic blood flow and oxygen uptake were not influenced by ethanol during exercise. Ethanol uptake in the liver was restricted by the arterial inflow during exercise when the smaller dose was administered but when the larger dose was infused, hepatic uptake was not influenced by exercise. Most of the acetate released from the liver after ethanol treatment was taken up by skeletal muscle. Splanchnic output of glucose was reduced by ethanol but the leg uptake was not influenced duri...