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Context: Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism, but effects on central hemodynamic function are not well established.Objective: To evaluate the effects of exercise training on left ventricular (LV) function and hemodynamic response to exercise in patients with stable chronic heart failure.Design: Prospective randomized trial conducted in 1994-1999.Setting: University department of cardiology/outpatient clinic in Germany.Patients: Consecutive sample of 73 men aged 70 years or younger with chronic heart failure (with LV ejection fraction of approximately 0.27).Intervention: Patients were randomly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day, followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70% of peak oxygen uptake (n=36) or to no intervention (control group; n=37).Main Outcome Measures: Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise; echocardiographic determination of LV diameters and volumes, at baseline and 6-month follow-up, for the exercise training vs control groups.Results: After 6 months, patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class, maximal ventilation, exercise time, and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest. In the exercise training group, an increase from baseline to 6-month follow-up was observed in mean (SD) resting LV ejection fraction (0.30 [0.08] vs 0.35 [0.09]; P=.003). Mean (SD) total peripheral resistance (TPR) during peak exercise was reduced by 157 (306) dyne/s/cm(-5) in the exercise training group vs an increase of 43 (148) dyne/s/cm(-5) in the control group (P=.003), with a concomitant increase in mean (SD) stroke volume of 14 (22) mL vs 1 (19) mL in the control group (P=.03). There was a small but significant reduction in mean (SD) LV end diastolic diameter of 4 (6) mm vs an increase of 1 (4) mm in the control group (P<.001). Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume (r=-0.76; P<.001) and in LV end diastolic diameter (r=0.45; P<.001).Conclusions: In patients with stable chronic heart failure, exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly. JAMA. 2000. [ABSTRACT FROM AUTHOR]

An abstract of the article "Activity of Radical Scavenger Enzymes in Skeletal Muscle of Patients With Chronic Heart Failure: Impact of a Metoprolol or Carvedilol Therapy," by A. Linke and colleagues is presented.

Wireless video capsule endoscopy (CE) is a modern diagnostic tool. Because of its use of digital radiofrequency, it is still relatively contraindicated in patients with implanted cardiac devices. We report the case of a patient with an Optimizer III system delivering cardiac contractility modulating signals (CCM) for heart failure therapy and an implantable cardioverter defibrillator (ICD) who underwent CE. No interferences between the devices were found.

Background: In Brugada syndrome implantable cardioverter defibrillator (ICD) therapy is associated with a high rate of inappropriate therapies, mainly due to supraventricular tachyarrhythmias (SVT) (2.7-14.1%/year). Aim of the present study was to evaluate a single ventricular fibrillation (VF) detection zone with a high cut-off rate with respect to prevention of inappropriate ICD shock due to SVT and safety of this programming., Methods: Sixty-one consecutive patients (mean age 42.6 +/- 12.9 years; 41 males) diagnosed with Brugada syndrome and implanted with an ICD were included. ICDs were prospectively programmed with a single VF detection zone and a cut-off rate of 222 beats/minute (bpm). A maximum of six shocks with the maximal shock energy were programmed. The minimal follow-up was 1 year., Results: During a follow-up of 47.6 +/- 23.1 months seven patients (2.91%/year) received appropriate ICD shocks. No patient suffered from syncope or died. Five patients (2.07%/year) received inappropriate ICD shocks: four patients due to T-wave oversensing and only one patient (0.4%/year) due to SVT (atrial fibrillation with a ventricular rate of >222 bpm)., Conclusions: Programming of a single, high-rate VF zone in patients with Brugada syndrome and an implanted defibrillator is safe. Such programming may be associated with reduced inappropriate defibrillator discharges. A single detection zone with a high VF cut-off rate can be recommended in patients with Brugada syndrome.

Background: Several studies have attempted to identify risk factors for the development of an electrical storm (ES), which is defined as 3 separate ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no triggers have been found. However, little is known about the role of inflammation and NT-proBNP in patients with ES. The aim of this study was therefore to assess the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and NT-proBNP serum concentrations in ICD-patients with or without single spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES., Methods: Markers were determined in 51 patients without ICD-intervention, in 15 ICD-patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD-patients with ES (blood sampling performed within 60min after fulfilling ES criteria). VT/VF-episodes were analysed by stored ICD-electrograms., Results: All patients had idiopathic dilated cardiomyopathy (n=23) or coronary artery disease (n=63). Patients with ES revealed significantly higher mean serum concentrations of all markers (IL-6 15.19+/-10.34 pg/mL, hs-CRP 20.12+/-14.4 mg/L, NT-proBNP 4799+/-4596 pg/mL) compared to baseline values of patients with single VT/VF-events during follow-up (IL-6 8.37+/-5.8 pg/mL (p=0.03), hs-CRP 4.7+/-5.3 mg/dL (p<0.001), NT-proBNP 1913+/-2665pg/mL (p=0.04)) and compared to baseline values of ICD-patients without device intervention (IL-6 4.62+/-3.66 pg/mL (p<0.001), hs-CRP 4.1+/-3.4 mg/L (p<0.001), NT-proBNP 1461+/-2281pg/mL (p<0.001)). In 9/20 patients presenting with ES (45%) baseline values were available. All markers were significantly higher during ES compared to event-free determination (IL-6 14.54+/-10.43 vs. 7.03+/-2.83 pg/mL (p=0.04), hs-CRP 19.07+/-16.07 vs. 6.5+/-3.9 mg/L (p=0.02), NT-proBNP 4218+/-2561 vs. 2099+/-1279 pg/mL (p=0.03))., Conclusions: Electrical storm is associated with significantly elevated IL-6, hs-CRP and NT-proBNP serum concentrations in ICD-patients with structural heart disease. Thus, ES may be triggered by proinflammatory activity. Combined intraindividual elevation of determined markers might help to identify patients at risk of impending electrical storm.

N-Coumaroyldopamine and N-caffeoyldopamine are clovamide-type phenylpropenoic acid amides found in Theobroma cacao. In this article, N-coumaroyldopamine and N-caffeoyldopamine were investigated to determine their effects on P-selectin expression and platelet-leukocyte interactions in vitro and in vivo models. At the concentration of 0.05 microM, they were able to inhibit P-selectin expression on the platelets by 33 (P < 0.011) and 30% (P < 0.012), respectively. The inhibition was partially blocked by beta(2)-adrenoceptor antagonists, suggesting that beta(2) receptors are probably engaged in the inhibition. N-Caffeoyldopamine and N-coumaroyldopamine could also suppress platelet-leukocyte interactions in blood samples by 36 (P < 0.013) and 32% (P < 0.011), respectively, at the same concentration (0.05 microM). In an animal study, mice administrated orally with N-caffeoyldopamine (50 and 100 microg/35 g of body weight) also showed great reduction in the P-selectin expression and platelet-leukocyte interactions by 31 to 45% (P < 0.011) and 34 to 43% (P < 0.014), respectively. These data suggest that the clovamide-type phenylpropenoic acid amides are able to suppress platelet-leukocyte interactions via inhibiting P-selectin expression.

Background: Exercise intolerance and early muscle fatigue are key symptoms in patients with chronic heart failure (CHF). In advanced stages of the disease, profound metabolic abnormalities have been described finally leading to a catabolic state with progressive loss of muscle bulk. The aim of this study was to investigate morphological, functional and electromyographical parameters of the skeletal muscle in CHF., Methods: We included 17 patients with CHF and 12 age-matched healthy controls (left ventricular ejection fraction 25+/-2 versus 68+/-1%, body mass index 26.6+/-0.8 versus 28.0+/-1.0 kg/m2; P=NS) in this study. Cross-sectional area (CSA) of the thigh was assessed by computed tomography. Under electromyographical control, maximal and submaximal (30%) isometric strength as well as the relative decrease of muscle strength of the quadriceps muscle over a period of 20 s were determined., Results: Patients with CHF showed a significant reduction of muscle CSA (134.8+/-5.3 versus 165.2+/-7.4 cm2, P=0.002) as compared with healthy controls. The maximal quadriceps muscle strength was found to be significantly reduced in patients with CHF (226.7+/-22.3 versus 286.9+/-17.1 N, P<0.05) who also exhibited a higher extent of muscular fatigability (-2.18+/-0.33 versus -0.54+/-0.20 N/s, P<0.01). Electromyographic activity at 30% submaximal contraction showed a lower increase in patients with CHF (66+/-22 versus 114+/-36%; P<0.05) indicating impaired muscle fibre recruitment. Furthermore, a significant correlation between muscular fatigability and reduced electromyographic activity was found in CHF (r=0.84; P<0.001)., Conclusions: Our findings demonstrate an impaired electromyographic activity and muscular function in patients with CHF suggesting a new pathomechanism contributing to functional abnormalities of the skeletal muscle in advanced stages of this disease.

N-Cinnamoyltyramine, N-caffeoyltyramine, N-feruloyltyramine, and N-sinapoyltyramine were synthesized and investigated to identify the most potent compound with anti-proliferation effect on HL-60, U937 and Jurkat cells. N-Caffeoyltyramine was the most potent with GI(50)=10 microM. The treatment of the cells with N-caffeoyltyramine activated caspase-3 activity, and inhibited the growth of cells via decreasing in protein tyrosine kinase activity including epidermal growth factor receptor. These data indicate that N-caffeoyltyramine is most potent compound, inducing cell death of the cancer cells by inhibiting protein tyrosine kinases and activating caspase-3 activity.

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or 14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.

Anthocyanin-rich extracts, potent antioxidants and commercially available food coloring agents, have been reported to inhibit growth of various cancer cell lines. We investigated the effect of semipurified anthocyanin-rich extract from fruits of Aronia meloncarpa, on normal colon and colon cancer cell lines. A 24-h exposure to 50 mg monomeric anthocyanin/ml of Aronia extract resulted in 60% growth inhibition of human HT-29 colon cancer cells. The treated cells showed a blockage at G1/G0 and G2/M phases of the cell cycle. The cell cycle arrest coincided with an increased expression of the p21WAF1 and p27KIP1 genes and decreased expression of cyclin A and B genes. Prolonged exposure to the extract resulted in no further change in the cell number, indicating a cytostatic inhibition of cell growth. NCM460 normal colon cells demonstrated <10% growth inhibition at the highest concentration of 50 mg/ml extract. A 35% decrease in the cyclooxygenase-2 gene expression was observed within 24 h of exposure of HT-29 cells but did not translate into decreased protein levels or protein activity. These results support the need for further research to identify the specific component(s) in this extract that suppress cancer cell growth and the genes affected by these natural compounds.

Background: Mean platelet volume (MPV) is increased in patients at high risk for athero-thrombotic diseases. Thus, an elevated MPV may be a risk marker for platelet activation., Methods: Healthy subjects with normal triglyceride (TG) levels (90+/-6 mg/dl; n = 40) or mild hypertriglyceridemia (161+/-79 mg/dl; n = 32) were studied. MPV was measured in fasting blood samples before and after stimulation with collagen (10 micro g/ml), and exposure to 4 or 37 degrees C. Samples from the normotriglyceridemic subjects were tested again 4 h after consuming a high-fat drink., Results: Collagen and exposure to 4 degrees C increased MPV, whereas incubation at 37 degrees C lowered MPV regardless of TG level. There was no significant difference in unstimulated MPV between the fasting and the fed states in the normotriglyceridemic subjects (both 7.2+/-0.1 fl; mean+/-SEM), nor between the latter group and hypertriglyceridemic subjects (7.0+/-0.1 fl). There was a significant negative relation between MPV and fasting TG level., Conclusions: This study suggests that MPV response to low-dose collagen may be a useful indicator of platelet propensity to activation. Further studies are warranted to correlate MPV with classical platelet aggregation tests and with the use of platelet-active drugs.

Background: In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies., Methods and Results: In 10 CHF patients with normal serum uric acid (UA) levels (315+/-42 micromol/L) and 9 patients with elevated UA (535+/-54 micromol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 microg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (P<0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558+/-21 micromol/L, range 455 to 743 micromol/L), treatment reduced UA by >120 micromol/L in all patients (mean reduction 217+/-15 micromol/L, P<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (P<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (r=0.63, P<0.05)., Conclusions: In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.

Numerous phytochemicals are believed to have beneficial effects on human health. N-Coumaroyltyramine accumulates in plants in response to wounding and pathogen attack. Due to the scarcity of N-coumaroyltyramine, its biological activities have not been studied in human cells. In this study, N-coumaroyltyramine was chemically synthesized and then purified by an HPLC with a UV-visible absorbance detector. Retention times of major peaks were 14.3 and 20.7 min, and the peak at 20.7 min was confirmed by LC-MS as N-coumaroyltyramine with a mass/charge (m/z) unit of 284.1. The synthesis procedure was relatively easy and had an acceptable yield (approximately 55%). The compound exhibited a new activity, suppression of growth of human tumor cells such as U937 and Jurkat cells. In addition, the suppressed growth of the cells was strongly associated with an increased percentage of cells in the S phase of the cell cycle progression. Furthermore, N-coumaroyltyramine was able to inhibit the protein tyrosine kinases including epidermal growth factor receptor (EGFR). This is the first report of the growth suppressing activity of N-coumaroyltyramine and its arrest of cells at the S phase of the cell cycle, possibly by inhibition of protein tyrosine kinases.

This overview focuses on recent evidence in support of vitamin E and omega-3 fatty acids as positive effectors of cardiovascular health through their ability to influence signaling processes in platelets. Special emphasis is placed on vitamin E actions independent of antioxidant activity. The sometimes discordant findings among observational studies, clinical trials, and in vitro cellular studies have been scrutinized for clues to explain possible mechanisms of actions and suggest strategies for future work to define appropriate intakes of these two nutrients.

Objectives: We sought to analyze the systemic effects of lower-limb exercise training (ET) on radial artery endothelial function in patients with chronic heart failure (CHF)., Background: Local ET has the potential to improve local endothelial dysfunction in patients with CHF. However, it remains unclear whether the systemic effects can be achieved by local ET., Methods: Twenty-two male patients with CHF were prospectively randomized to either ET on a bicycle ergometer (ET group, n = 11; left ventricular ejection fraction [LVEF] 26 +/- 3%) or an inactive control group (group C, n = 11; LVEF 24 +/- 2%). At the beginning of the study and after four weeks, endothelium-dependent and -independent vasodilation of the radial artery was determined by intra-arterial infusion of acetylcholine (ACh-7.5, 15 and 30 microg/min) and nitroglycerin (0.2 mg/min). The mean internal diameter (ID) of the radial artery was assessed using a high resolution ultrasound system (NIUS-02, Asulab Research Laboratories, Neuchâtel, Switzerland) with a 10-MHz probe., Results: After four weeks of ET, patients showed a significant increase in the baseline-corrected mean ID in response to ACh (30 microg/min), from 33 +/- 10 to 127 +/- 25 microm (p < 0.001 vs. control group at four weeks). In the control group, the response to ACh (30 microg/min) remained unchanged. Endothelium-independent vasodilation was similar in both groups at the beginning of the study and at four weeks. In the training group, increases in agonist-mediated, endothelium-dependent vasodilation correlated to changes in functional work capacity (r = 0.63, p < 0.05)., Conclusions: In patients with stable CHF, bicycle ergometer ET leads to a correction of endothelial dysfunction of the upper extremity, indicating a systemic effect of local ET on endothelial function.

Objectives: The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF)., Background: Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise., Methods: Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 microg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%., Results: At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 microg/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 microg/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg. +/- T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study., Conclusions: Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation.

Background: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease., Methods: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography., Results: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group)., Conclusions: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.

Differences in growth characteristics, phosphatase activity, and hydrogen peroxide generation in two clones of a T-cell leukemic line are described in this communication. Wurzburg cells had significantly shorter population doubling times compared with the parental Jurkat cells (16.6 +/- 2.0 h and 20.7 +/- 2.2 h, respectively; mean +/- SD, p < .0001, n = 20). In addition, total phosphatase activity was significantly decreased (p < .006) and hydrogen peroxide production was significantly increased (p < .002) in Wurzburg cells compared to Jurkat cells. That the cell line with the faster growth rate should have these latter two properties is entirely consistent with the positive effects of increased kinase activity and hydrogen peroxide on proliferative cellular responses in T cells. As originally described, Wurzburg cells were distinguished from Jurkat cells by their lack of CD45, a membrane protein tyrosine phosphatase, and their positive response to hydrogen peroxide-stimulation of NF-kappaB activation. We propose that these two clones, with their distinguishing characteristics, can be used to advantage in experiments designed to study the effects of antioxidants on signaling pathways that control cell life and death.

A randomized, double-blind study was conducted with 12 healthy adult males to determine the effects of oral pyridoxine supplementation on in vitro platelet aggregation. Following a 4-wk baseline period, half the subjects received 100 mg/day of pyridoxine X HCl while the remaining subjects received a placebo for 6 wk. In vitro platelet responses to ADP and collagen and the plasma pyridoxal 5'-phosphate (PLP) concentrations were measured at biweekly intervals. Plasma PLP concentrations increased significantly (p less than 0.001) for those receiving the vitamin B6 compared to baseline values or compared to those receiving the placebo. However, there was no significant effect of increased levels of plasma PLP on collagen-stimulated platelet aggregation and only a slight effect on ADP-stimulated aggregation. Acute administration of 100 mg pyridoxine X HCl failed to alter the in vitro response of platelets to either ADP or collagen. Reevaluation of conclusions based solely on in vitro studies suggesting the use of pyridoxine as an effective in vivo antithrombotic agent may be warranted.

Thrombin, within seconds after its addition, stimulated the release of 1-14C-20:4n-6 from the platelet phospholipids, phosphatidylcholine and phosphatidylinositol. Although inhibitors of prostaglandin cyclooxygenase did not inhibit this PLA2 activity, the anti-malarial drug, quinacrine, did. The location of the PLA2 that furnishes 20:4n-6 for the cyclooxygenase is not clear, but if it were in or near membranes containing the cyclooxygenase, phospholipids in the vicinity might serve as the source of 20:4n-6. How substrate specificity relates to the asymmetric distribution of the various phospholipid classes in membranes is yet to be determined.

Three strains of rats were fed a fish oil diet to verify their ability to incorporate and convert dietary eicosapentaenoic acid (20:5 omega 3) into trienoic prostaglandins. Our results show that such conversion indeed occurs in kidney medullae homogenates. Specifically, the presence of prostaglandin E3 (PGE3) was established by gas chromatographic-mass spectrometric (GC-MS) analysis. That compound was conclusively identified by comparison of fragment ions and their relative intensities with those obtained from authentic PGE3. Further evidence was provided by studying the recovery of exogenously added PGE3. Further evidence was provided by studying the recovery of exogenously added PGE3. The crude ethyl acetate extracts of the medullary homogenates were methylated and cleaned up by liquid-gel chromatography with Lipidex-5000 prior to conversion to PGB3 for GC-MS analysis. The PGE3 was quantified by selected ion monitoring (SIM) with [3,3,4,4-2H4] PGE2 as internal standard. The levels of PGE3 were similar, about 3 ng/mg of wet tissue, in the 3 strains of rats. Identical in vivo conversion of the 2.0:5 omega 3 fatty acid to PGE3 could not be positively established by analysis of pooled urine specimens.