Determination of aluminum in bone in haemodialyzed patients, using inductively coupled argon plasma emission spectrometry

We propose a new method for measuring aluminium in bone tissue, using argon plasma emission spectrophotometry. The detection limit in the bone nitric digestion liquid was 0.015 mumol/l (corresponding to 0.0075 mumol/g, i.e. 0.2 microgram/g for a tissue sample with 1.0 g wet weight). Within-run CVs were 4.66% and 1.43% for tissues containing 0.15 and 0.64 mumol/g, respectively. Other bone constituents such as calcium, phosphorus, magnesium, sodium, potassium, do not affect aluminum results. Normal values obtained in bone of subjects not suspected of aluminium intoxication were: mean +/- SD; 0.09 +/- 0.044 mumol/g (n = 24). In dialysis patients we found a mean bone aluminium content of 0.75 mumol/g for concentrations ranging between 0.16 and 3.38 mumol/g.     

The presence and molecular forms of cardiodilatin immunoreactivity in the human and rat right atrium

A sensitive and specific radioimmunoassay has been developed for cardiodilatin, the N-terminal peptide sequence of the atrial natriuretic peptide (ANP) prohormone. Cardiodilatin-immunoreactivity (-IR) concentrations in the human right atrial appendage were found to correlate with ANP-IR concentrations, determined by an established radioimmunoassay, (cardiodilatin-IR = 13.2 +/- 1.2 nmol/g, ANP-IR = 19.8 +/- 2.0 nmol/g, r = 0.80, p less than 0.001). Characterisation of the cardiodilatin-IR in the human and rat right atrium by gel permeation and fast protein liquid chromatography revealed only two cardiodilatin-IR molecular forms. The larger more hydrophobic form, the majority of the cardiodilatin-IR, contained in addition ANP-IR and therefore represents the prohormone. The smaller, less hydrophobic form, lacked ANP-IR and thus represents the cleaved N-terminal peptide sequence of the prohormone. These findings indicate that the prohormone is the major molecular form in the human and rat atrium. Furthermore, they demonstrate that a single large N-terminal peptide, cardiodilatin, derived from the prohormone, may exist as a distinct molecular form in the atrium of these species.     

Assessment of atrial regional wall motion using strain Doppler imaging during biatrial pacing in the bradycardia-tachycardia syndrome

INTRODUCTION: Biatrial pacing is expected to have preventive effects on atrial fibrillation. METHODS: We evaluated atrial regional wall motion by strain Doppler imaging (SDI) in 6 patients (62.5 +/- 11.3 [SD] years), who suffered from atrial fibrillation, with an implanted biatrial pacemaker. SDI was performed and atrial regional wall motion was estimated during biatrial (BiA) and right atrial appendage (RAA) pacing. RESULTS: There was no significant difference in the interval from the pacing spike to the peak strain of the atrium in the lateral right atrium (LRA) between BiA and RAA pacing. However, there was a significant difference in the septal atrium (SA) between BiA and RAA pacing (225.0 +/- 19.9 vs 267.2 +/- 15.7 ms, P < 0.0001) and in the lateral left atrium (LLA) between BiA and RAA pacing (216.7 +/- 21.6 vs 275.0 +/- 16.2 ms, P < 0.0001). There were significant differences in the time difference of peak strain between BiA and RAA pacing in each atrial segment (LRA-AS: 2.2 +/- 5.9 vs 45.0 +/- 11.9 ms, P = 0.0016, SA-LLA: -8.3 +/- 5.5 vs 7.8 +/- 2.7 ms, P < 0.0011, LRA-LLA: -6.1 +/- 3.9 vs 52.8 +/- 13.2 ms, P = 0.0002). There was no significant difference in the interval from the pacing spike to the inflection point of atrial strain (S-I) of LRA. However, there were significant differences in S-I of SA (83.9 +/- 24.1 vs 129.9 +/- 30.6 ms, P = 0.0086) and LLA (102.2 +/- 37.9 vs 166.1 +/- 13.4 ms, P = 0.0028). CONCLUSION: BiA pacing improved the synchronicity of regional wall motion of both atrium.     

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy.     

Reduction of atrial fibrillation inducibility by radiofrequency ablation: an experimental study

A study is made of the antifibrillatory effects of radiofrequency (RF)-induced atrial lesions using nine Langendorff-perfused rabbit hearts in which the atrial electrophysiological properties and atrial fibrillation (AF) inducibility were modified by atrial stretching. Using a multiple electrode consisting of 121 unipolar electrodes, determinations were made of the atrial refractory periods, conduction velocity, wavelength of the atrial activation process, and the inducibility of sustained AF episodes (duration over 30 s) by atrial burst pacing in four situations: (a) control; (b) following dilatation of the right atrium; (c) after adding an RF linear lesion at the cava-tricuspid annulus isthmus; and (d) after adding two RF linear lesions rounding the base of the right atrial appendage and extending from the inferior zone of the sulcus terminalis to the anterior wall of the appendage. Under control conditions, AF was not induced in any of the experiments. The wavelengths were 10.5 +/- 1.2 cm for basic cycles of 250 ms and 6.6 +/- 0.5 cm for cycles of 100 ms. Following dilatation, a significant decrease was recorded in the atrial refractory periods, conduction velocity, and wavelength, which reached values of 6.1 +/- 0.7 cm (250-ms cycle, P < 0.01), and 3.9 +/- 0.3 cm (100-ms cycle, P < 0.01); AF was induced in five cases (P < 0.05). After producing the lesion at the cava-tricuspid isthmus, the electrophysiological modifications induced by atrial dilatation persisted (wavelength = 6.2 +/- 0.6 cm (250-ms cycle) and 4.3 +/- 0.3 cm (100-ms cycle); P < 0.01 vs the control) and AF was triggered in eight cases (P < 0.0001). In turn, on adding the two lesions at the right atrial free wall and appendage, AF was induced only in one experiment (P = NS vs control), and the dilatation-induced decrease in refractoriness and wavelength was attenuated. Nevertheless, differences remained significant with respect to the controls, with the exception of the functional refractory periods determined at cycles of 100 ms. In this phase, the wavelength was 6.6 +/- 0.7 cm (250-ms cycle, P < 0.01 vs control) and 4.9 +/- 0.5 cm (100-ms cycle; P < 0.05). Atrial conduction between the zones separated by the lesions was blocked at any frequency, or selectively at rapid atrial activation frequencies. In conclusion: (a) the production of three linear lesions in the right atrium (cava-tricuspid isthmus, atrial appendage, and inferior free wall) reduces AF inducibility in the experimental model used; (b) conduction block (either absolute or frequency dependent) through the lesions, reduction in tissue mass caused by lesion creation, and possibly the attenuation of the shortening of atrial refractoriness and wavelength in the zones not separated by the lesions are implicated in the reduction of AF inducibility; and (c) the single lesion in the cava-tricuspid isthmus does not impede AF inducibility.     

Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo.

Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin approximately 500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0 +/- 0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1 +/- 0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 18F-fluoro-2-deoxy-D-glucose kinetics and the three-compartment model described by Sokoloff (Sokoloff, L., M. Reivich, C. Kennedy, M. C. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara. 1977. J. Neurochem. 28: 897-916). Elevation of plasma FFA decreased whole body glucose uptake by 31 +/- 2% (1,960 +/- 130 vs. 2,860 +/- 250 mumol/min, P less than 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30 +/- 8% (150 +/- 33 vs. 200 +/- 28 mumol/min, P less than 0.02), and in skeletal muscles; both when measured in femoral (1,594 +/- 261 vs. 2,272 +/- 328 mumol/min, 25 +/- 13%) and arm muscles (1,617 +/- 411 to 2,305 +/- 517 mumol/min, P less than 0.02, 31 +/- 6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P less than 0.005), and arm muscles (r = 0.69, P less than 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans.     

Comparison of equimolar concentrations of iloprost, prostacyclin, and prostaglandin E1 on human platelet function

Prostaglandins E1 and I2 (PGE1 and PGI2) have been shown to be potent inhibitors of platelet aggregation. We compared the antiaggregatory effect of equimolar concentrations of these two agents with that of a newly synthesized prostacyclin analogue, iloprost, and measured the effects of these agents on intracellular levels of cyclic adenosine monophosphate (cAMP) in human platelets. In addition, because the platelet inhibitory properties of prostanoids are associated with increased vasoactivity, we assessed the effects of each prostanoid on coronary flow in isolated perfused rat hearts. Concentrations ranging from 0.0001 mumol/L to 1 mumol/L of iloprost, PGI2, and PGE1 were incubated with either platelet-rich plasma or gel-filtered platelets. Greater than 90% inhibition of platelet aggregation in response to threshold concentrations of adenosine diphosphate (n = 6) and epinephrine (n = 6) was observed in all donors when 0.01 mumol/L iloprost, 0.1 mumol/L PGI2, and 1 mumol/L PGE1 were added to platelet-rich plasma. In gel-filtered platelets, at threshold concentrations of thrombin (n = 6), 90% inhibition was observed with 0.01 mumol/L iloprost. In contrast, similar inhibition to thrombin required 0.1 mumol/L PGI2, and with PGE1 it was never achieved in two donors. At 0.01 mumol/L of prostanoid, cAMP levels (n = 6) rose from a baseline value of 439 +/- 99 pmol/10(9) platelets to 1857 +/- 454 pmol/10(9) platelets for iloprost, 758 +/- 99 pmol/10(9) platelets for PGI2, and 692 +/- 199 pmol/10(9) platelets for PGE1. In addition, at 6 mumol/L, alterations in coronary flow (P greater than 0.05) were noted to be 127% of baseline values for iloprost (n = 5) and 153% for PGI2 (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs

Plasma ammonia and total and free carnitine were measured in 84 children requiring anticonvulsant drugs: 32 patients (group A) on valproic acid alone, 28 children (group B) on polytherapy including valproic acid, and 24 patients (group C) on polytherapy without valproic acid. The other anticonvulsant drugs used in groups B and C were carbamazepine and phenobarbital. Plasma ammonia concentrations were elevated in both group A and B compared with controls. Group B patients showed significantly higher hyperammonemia than group A (59.9 +/- 16.3 micrograms/dl vs. 36.7 +/- 12.4 micrograms/dl; P < 0.05). Group C patients had plasma ammonia levels similar to those of controls (31.1 +/- 14.7 micrograms/dl vs. 29.7 +/- 12.1 micrograms/dl; NS). In both group A and group B patients, plasma ammonia levels were correlated with the valproic acid dosage (r = 0.32, P < 0.01) and with serum concentrations of valproic acid (r = 0.41, P < 0.001). Moreover, a significant correlation between plasma ammonia and duration of valproic acid therapy was found in the patients as a whole (r = 0.31, P < 0.01). Plasma total and free carnitine concentrations were significantly reduced in groups A and B (total carnitine 36.9 +/- 6.9 mumol/l vs. 32.9 +/- 9.7 mumol/l; free carnitine 28.9 +/- 5.1 mumol/l vs. 25.7 +/- 4.3 mumol/l, respectively) compared with group C patients who did not receive valproic acid and in whom values were similar to controls (total carnitine 46.1 +/- 9.0 mumol/l vs. 47.7 +/- 10.1 mumol/l; free carnitine 40.1 +/- 7.1 mumol/l vs. 42.9 +/- 8.0 mumol/l, respectively). Twenty-eight patients (18 of group A and 10 of group B) were re-evaluated and showed a complete normalization of plasma ammonia, and total and free carnitine levels which were similar to controls. Our data suggest that hyperammonemia is an important problem in patients receiving valproic acid, particularly in association with other anticonvulsant drugs. This increase of plasma ammonia and the concomitant reduction of carnitine seem to be transient and completely reversible.     

Comparative penetration of cefonicid and cefazolin into the atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentrations of cefonicid in serum and the atrial appendage were at least twice those observed for cefazolin at a given time after a dose. The mean (+/- standard deviation) atrial appendage-serum ratio was 0.47 +/- 0.14 for cefonicid and 0.34 +/- 0.06 for cefazolin (P less than 0.005). Pericardial fluid concentrations of cefonicid were slightly lower than those observed in patients receiving cefazolin (P greater than 0.05). A single intravenous dose of cefonicid provides high and sustained concentrations in serum and cardiac tissue and thus may be useful in antibiotic prophylaxis of certain surgical procedures; however, further study of the efficacy of this agent in the prevention and treatment of infections associated with Staphylococcus spp. is needed.     

Interest of zinc determination in leucocyte fractions for the assessment of marginal zinc status.

In order to test the sensitivity of leucocyte zinc determination in the assessment of zinc status, an isolation procedure of mononuclear (MNC) and polymorphonuclear (PMNC) cell fractions was developed. Zinc concentrations in cells from healthy subjects were (mean +/- SD, in mumol/10(10) cells): 0.81 +/- 0.24 in MNC and 0.55 +/- 0.06 in PMNC. In patients suffering from several diseases known to be associated with a marginal impairment in zinc status (cirrhosis, cancer, obesity, endocrine and rheumatic diseases), these concentrations did not differ from those in controls except in rheumatic patients in whom MNC zinc was increased (1.05 +/- 0.42 mumol/10(10) cells) and correlated with erythrocyte sedimentation rate (r = 0.41, P less than 0.01). This relation was also significant in the whole study population (r = 0.39, P less than 0.01). Leucocyte zinc therefore appears to have a limited value in the assessment of marginally impaired zinc status, except in inflammatory states.     

Correlation between quantitative left atrial spontaneous echocardiographic contrast and intact fibrinogen levels in mitral stenosis.

An association between left atrial spontaneous echocardiographic contrast (LASEC) and thromboembolic events has been recognized. However, the appearance of LASEC and the assessment of its intensity are gain dependent. To evaluate the relation between LASEC intensity and coagulation activity, 11 patients with mitral stenosis underwent transesophageal echocardiography with quantitative integrated backscatter assessment of LASEC. Right and left atrial blood samples were evaluated for concentrations of coagulation markers, including intact fibrinogen, fibrinopeptide A, D-dimer, prothrombin fragment 1+2, and thrombin-antithrombin III complex. The patients were found to have significantly higher mean left atrial concentrations compared with right atrial concentrations of thrombin-antithrombin III (28.46 +/- 21.05 versus 3.21 +/- 7.16 ng/mL, respectively; P =.001) and fibrinopeptide A (32.78 +/- 17.54 versus 7.42 +/- 8.27 nmol/L, respectively; P <.001). Intact fibrinogen levels were similar in both atria, and a strong, direct correlation existed between left and right atrial intact fibrinogen levels (r = 0.78, P =.005). Quantitative integrated backscatter of LASEC correlated directly with left atrial fibrinogen level (r = 0.78, P =.013) but not with markers of thrombin generation (thrombin-antithrombin III) or activity (fibrinopeptide A). Our results confirm that patients with mitral stenosis have evidence of a regional hypercoagulable state in the left atrium. However, the intensity of LASEC assessed by quantitative integrated backscatter correlates with both right and left atrial intact fibrinogen level, a systemic marker of coagulation.     

Characteristic P wave morphology in patients undergoing the atrial compartment operation for chronic atrial fibrillation with mitral valve disease

The P wave in the surface ECG represents atrial electrical activation and may be altered in certain pathological conditions. Atrial compartment operation has been used to convert chronic AF to sinus rhythm. However, this procedure may result in changes of impulse conduction in various atrial compartments and alters the P wave morphology. This study sought to elucidate the P wave changes after the atrial compartment operation for AF. Fifteen patients undergoing the atrial compartment operation for chronic AF were studied. In the operation, the atrium was divided into three compartments, namely the left atrium, the atrial septum including sinus and AV nodes, and the right atrial compartment. The anatomic connection between adjacent compartments were preserved at the posterior lower margin of incisions. The surface lead P waves were correlated with intracardiac recording and stimulation in various atrial compartments. Fifteen age- and sex-matched control patients without structural heart diseases were compared. The results showed that patients undergoing the atrial compartment operation had a prolonged P wave duration (190 +/- 27 v s95 +/- 14 ms, P < 0.001), a prolonged PR interval (207 +/- 23 vs 155 +/- 20 ms, P < 0.001), and a shortened PR segment (17 +/- 19 vs 60 +/- 17 ms, P < 0.001). The increase in P wave duration was primarily due to a conduction delay from the sinus node to the other atrial compartments as the conduction time from the high right atrium to the right atrial appendage was 132 +/- 57 ms(vs 21 +/- 6 ms for control,P < 0.001), and the conduction time from the high right atrium to the distal coronary sinus was 140 +/- 55 ms(vs 70 +/- 15 ms, P < 0.001). However, the conduction from the high right atrium to the low septal right atrium, which were located in the same compartment, was not impaired. Also, the conduction in the AV node and His-Purkinje system were not impaired. The mean axis of P waves varied greatly, but was not statistically different from that of the control group (60 +/- 48 degrees vs 52 +/- 18 degrees,P > 0.05). Although the patients undergoing atrial compartment operation had a larger left atrial size, their P wave amplitude was smaller (1.0 +/- 0.3 vs 1.3 +/- 0.3 mm, P < 0.01), and an increased negative terminal force in V1 was not seen (0.02 +/- 0.02 vs 0.02 +/- 0.01 mm/s, P > 0.05). Alteration in P wave morphology was seen in 14 patients. All the P waves showed a biphasic configuration with an initial positive and a terminal slurred negative deflection in leads II, III, and aVF. The terminal components represented the activation of right atrial appendage in 5 patients, the left atrium in 1, and the combined activation of right atrial appendage and the left atrium in 8 patients. The P wave morphology suggested that activation of both the right atrial appendage and the left atrial compartments proceeded in a caudocranial direction as a result of the atrial incisions. In conclusion, atrial compartment operation altered the conduction time and direction in the atria and resulted in characteristic P wave changes.     

Effect of cardiac tamponade on atrial natriuretic peptide concentrations: influence of stretch and pressure

1. In order to study the role of atrial pressure and atrial stretch on the release of atrial natriuretic peptide we have measured plasma atrial natriuretic peptide concentration, urine output and haemodynamic variables in eight patients during and 30 min after the relief of cardiac tamponade. This condition is characterized by high atrial pressure with little or no atrial stretch. 2. Relief of tamponade was associated with a rise in urine output (53 +/- 27.9 to 101 +/- 24.5 ml/h, mean +/- SEM; P = 0.09), systolic blood pressure (95 +/- 9.6 to 126 +/- 7.0 mmHg, P less than 0.0001), and plasma atrial natriuretic peptide concentration (369.5 +/- 70.9 to 490.3 +/- 94.7 pg/ml, P less than 0.05) despite a large fall in right atrial pressure (18.6 +/- 1.6 to 9.5 +/- 1.3 mmHg, P less than 0.001). 3. These results suggest, therefore, that an increase in atrial stretch, rather than in atrial pressure, stimulates the release of atrial natriuretic peptide.     

Effects of magnesium sulfate on lipid peroxidation and blood pressure regulators in preeclampsia

OBJECTIVES: To investigate the status of lipid peroxidation and serum levels of several vasoactive substances in preeclamptic (PE) pregnant women before and during treatment with magnesium sulfate (MgSO(4)). DESIGN AND METHODS: The study population included 16 PE women. Circulating levels of malondialdehyde (MDA), endothelin 1 (ET-1), nitric oxide (NO) metabolites, and calcitonin gene-related peptide (CGRP) were measured before (at admission) and during MgSO(4) treatment (at delivery and 24 h postpartum). RESULTS: At admission systolic and diastolic blood pressures were 157 +/- 3 mm Hg and 106 +/- 2 mm Hg, respectively, and decreased significantly during treatment at delivery and 24 h postpartum (P < 0.0001). Before treatment, serum MDA concentrations were 0.383 +/- 0.037 micromol/L, and decreased significantly during MgSO(4) administration at delivery and 24 h postpartum (P < 0.0001). In contrast, serum ET-1 levels at 24 h postpartum were significantly higher as compared with those observed before treatment (79 +/- 3 versus 65 +/- 2 pg/mL, P = 0.002). Serum NO metabolite concentrations were 26 +/- 3 micromol/L, and no significant changes were observed during treatment. Serum levels of CGRP were 50 +/- 3 pg/mL at admission, and increased significantly at partum (P < 0.001). Serum ET-1 correlated negatively with NO metabolites before treatment (r = -0.69, P = 0.002), but not during treatment. In contrast, ET-1 correlated positively with serum CGRP levels during treatment (r = 0.73, P = 0.002 and r = 0.71, P = 0.002, at delivery and 24 h postpartum, respectively), but not before treatment. CONCLUSIONS: This study demonstrates that MgSO(4) administration to PE pregnant women induced significant changes in lipid peroxidation, production of ET-1 and CGRP.     

Acute Effects of Different Atrial Pacing Sites in Patients with Atrial Fibrillation: Comparison of Single Site and Biatrial Pacing

It has been reported that a trial single site or biatrial pacing can suppress the occurrence of AF. However, its mechanism remains unclear. The study population included 32 patients with AF (n = 20: AF group), or without paroxysmal AF (n = 12: control group). The mechanism and efficacy of atrial pacing were investigated by electrophysiological studies to determine which was more effective for suppressing AF induction; single site pacing of the right atrial appendage (RAA) or distal coronary sinus (CS-d), or biatrial (simultaneous BAA and CS-d) pacing. In the AF group, AF inducibility was significantly higher with BAA extrastimulus during RAA (12/20; P < 0.0001) or biatrial paced drive (7/20; P < 0.01) than during CS-d paced drive (0/20). In the control group, AF was not induced at any site paced. In the AF group, the conduction delay and other parameters of atrial vulnerability significantly improved during CS-d paced drive. The atrial recovery time (ART) at RAA and CS-d was measured during each basic pacing mode. ART was defined as the sum of the activation time and refractory period, and the difference between ARTs at RAA and CS-d was calculated as the ART difference (ARTD). The ARTD was significantly longer during BAA pacing in the AF group than in control group (155.0 +/- 32.8 vs 128.8 +/- 32.9 ms, P < 0.05). In the AFgroup, ARTDs during biatrial (52.0 +/- 24.2 ms) and CS-d pacing (51.7 +/- 26.0 ms) were significantly shorter than ARTD during RAA pacing. The CS-d paced drive was more effective for suppressing AF induction than biatrial or RAA paced drive by alleviating conduction delay. CS-d and biatrial pacing significantly reduced ARTD compared with RAA pacing.     

The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired insulin-stimulated muscle glycogen synthase activation in vivo in man is related to low fasting glycogen synthase phosphatase activity.

Insulin-mediated glycogen synthase activity in skeletal muscle correlates with the rate of insulin-mediated glycogen deposition and is reduced in human subjects with insulin resistance. To assess the role of glycogen synthase phosphatase as a possible mediator of reduced glycogen synthase activity, we studied 30 Southwestern American Indians with a broad range of insulin action in vivo. Percutaneous biopsies of the vastus lateralis muscle were performed before and during a 440-min euglycemic clamp at plasma insulin concentrations of 89 +/- 5 and 1,470 +/- 49 microU/ml (mean +/- SEM); simultaneous glucose oxidation was determined by indirect calorimetry. After insulin stimulation, glycogen synthase activity was correlated with the total and nonoxidative glucose disposal at both low (r = 0.73, P less than 0.0001; r = 0.68, P less than 0.0001) and high (r = 0.75, P less than 0.0001; r = 0.74, P less than 0.0001) plasma insulin concentrations. Fasting muscle glycogen synthase phosphatase activity was correlated with both total and nonoxidative glucose disposal rates at the low (r = 0.48, P less than 0.005; r = 0.41, P less than 0.05) and high (r = 0.47, P less than 0.05; r = 0.43, P less than 0.05) plasma insulin concentrations. In addition, fasting glycogen synthase phosphatase activity was correlated with glycogen synthase activity after low- (r = 0.47, P less than 0.05) and high- (r = 0.50, P less than 0.01) dose insulin stimulations. These data suggest that the decreased insulin-stimulated glucose disposal and reduced glycogen synthase activation observed in insulin resistance could be secondary to a low fasting glycogen synthase phosphatase activity.     

Impaired activity and gene expression of hexokinase II in muscle from non-insulin-dependent diabetes mellitus patients.

After entering the muscle cell, glucose is immediately and irreversibly phosphorylated to glucose-6-phosphate by hexokinases (HK) I and II. Previous studies in rodents have shown that HKII may be the dominant HK in skeletal muscle. Reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate concentrations in muscle have been found in non-insulin-dependent diabetes mellitus (NIDDM) patients when examined during a hyperglycemic hyperinsulinemic clamp. These findings [correction of finding] are consistent with a defect in glucose transport and/or phosphorylation. In the present study comprising 29 NIDDM patients and 25 matched controls, we tested the hypothesis that HKII activity and gene expression are impaired in vastus lateralis muscle of NIDDM patients when examined in the fasting state. HKII activity in a supernatant of muscle extract accounted for 28 +/- 5% in NIDDM patients and 40 +/- 5% in controls (P = 0.08) of total muscle HK activity when measured at a glucose media of 0.11 mmol/liter and 31 +/- 4 and 47 +/- 7% (P = 0.02) when measured at 0.11 mmol/liter of glucose. HKII mRNA, HKII immunoreactive protein level, and HKII activity were significantly decreased in NIDDM patients (P < 0.0001, P = 0.03, and P = 0.02, respectively) together with significantly decreased glycogen synthase mRNA level and total glycogen synthase activity (P = 0.02 and P = 0.02, respectively). In the entire study population HKII activity estimated at 0.11 and 11.0 mM glucose was inversely correlated with fasting plasma glucose concentrations (r = -0.45, P = 0.004; r = -0.54, P < 0.0001, respectively) and fasting plasma nonesterified fatty acid concentrations (r = -0.46, P = 0.003; r = -0.37, P = 0.02, respectively). In conclusion, NIDDM patients are characterized by a reduced activity and a reduced gene expression of HKII in muscle which may be secondary to the metabolic peturbations. HKII contributes with about one-third of total HK activity in a supernatant of human vastus lateralis muscle.     

Evidence for increased atrial sympathetic innervation in persistent human atrial fibrillation

OBJECTIVE: In this study, we aimed to compare the level of atrial sympathetic innervation in human atrial fibrillation (AF) to that in sinus rhythm (SR). BACKGROUND: Histological studies of atrial tissue obtained from animals with experimentally induced AF indicate that sympathetic hyperinnervation could play a role in the pathogenesis of AF. METHODS: In 24 patients (12 in SR and 12 in AF) undergoing bypass surgery, we collected right atrial appendage tissue. In AF patients, left atrial appendage tissue was also acquired. The degree of sympathetic innervation was quantified by measuring the amount of staining for tyrosine hydroxylase (TH) and tissue norepinephrine (NE). In conjunction, nerve growth factor (NGF) mRNA expression was assessed by real-time polymerase chain reaction (PCR). Growth-associated protein 43 (GAP43) immunostaining was used to assess degree of new neural growth. RESULTS: When corrected for differences in tissue fibrosis, the expression of both TH (AF 0.45 +/- 0.1%, SR 0.09 +/- 0.03%, P = 0.02) and tissue NE (AF 358 +/- 49 pg/mg, SR 225 +/- 39 pg/mg, P = 0.04) was greater in atrial tissue of the AF cohort. The degree of atrial TH staining (P = 0.01) and NE content (P < 0.001) was also significantly greater in the right compared with left atrial samples in the AF cohort. There were no differences in NGF mRNA expression or GAP43 staining. CONCLUSION: This study provides evidence for the presence of heightened atrial sympathetic innervation in patients with persistent AF, suggesting autonomic remodeling may be part of atrial substrate for AF.     

Impaired natriuretic response to atrial natriuretic peptide in the isolated kidney of rats with experimental cirrhosis

1. Sodium retention in cirrhosis may be partly attributable to resistance to a putative circulating natriuretic factor. In cirrhosis, plasma concentrations of atrial natriuretic peptide are often increased in the presence of sodium retention. 2. In order to determine whether the kidney of cirrhotic animals may be insensitive to atrial natriuretic peptide, isolated perfused kidneys from six cirrhotic and five control rats were exposed to increasing concentrations of atrial natriuretic peptide. Cirrhosis had been induced by carbon tetrachloride administration. 3. Excretion in vivo of a 2 mmol sodium load, administered by gavage, was impaired in cirrhotic animal for up to 4 h as compared with control animals (4.2 +/- 1.9 vs 34.9 +/- 13.4% P less than 0.05). 4. During perfusion at 110 mmHg in the absence of atrial natriuretic peptide, sodium excretion by isolated kidneys of cirrhotic animals tended to be lower than in control animals, but the difference was not significant (4.93 +/- 1.01 vs 8.41 +/- 1.48 mumol min-1 g-1 kidney weight, P = 0.09). There was a smaller increase in urinary sodium excretion by the kidneys of cirrhotic rats compared with control rats in the presence of atrial natriuretic peptide at 10, 50 and 200 pmol/l (respectively: 0.06 +/- 0.08 vs 1.29 +/- 0.35 mumol/min-1 g-1 kidney weight, P less than 0.02; 0.49 +/- 0.08 vs 1.82 +/- 0.42 mumol min-1 g-1 kidney weight, P less than 0.03; 1.42 +/- 0.16 vs 3.23 +/- 0.73 mumol min-1 g-1 kidney weight, P less than 0.05), but not at 1000 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)