[Effect of Kruppel-like factor 2 on the migration of human liver sinusoidal endothelial cells].

Objective: To investigate the effect and mechanism of Kruppel-like factor 2 (KLF2) on the migration of human liver sinusoidal endothelial cells (LSEC). Methods: Cultured human LSEC were infected with different lenti-viruses to overexpress or suppress KLF2 expression (LV5-KLF2 and LV3-shKLF2, respectively), the infection efficacies were examined by real-time PCR and Western blot analysis.Transwell migration assay was used to investigate the role of KLF2 on the migration of LSEC.The mRNA and protein expression of vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by real-time PCR and Western blot analysis, respectively.The expression and phosphorylation of Src, P38 MAPK, and P44/42 MAPK were detected by Western blot. Results: The up-regulation of KLF2 expression dramatically inhibited migration of treated LSEC, compared with LV5-NC and WT control cells, fewer LV5-KLF2 cells migrated to the lower side of the filter after 12 h [ (35.6±1.4), (71.3±2.4) and (69.3±1.6), P<0.001 for all comparisons]. In contrast, the down-regulation of KLF2 expression promoted the migration of LSEC, more LV3-KLF2 cells migrated to the lower side of the filter compared with the LV3-NC and WT control cells [(189.5±5.4), (83.4±2.5) and (82.2±3.4), P<0.001 for all comparisons]. Furthermore, up-regulation of KLF2 reduced the mRNA and protein expression level of VEGFR2, while down-regulation of KLF2 significantly increased its expression in LSEC.Additionally, up-regulation of KLF2 inhibited the phosphorylation of Src, P38 MAPK, and P44/42 MAPK pathway in LSEC, whereas down-regulation of KLF2 promoted the phosphorylation of those signaling pathway proteins. Conclusions: KLF2 may inhibit the migration of human LSEC through the Src/ MAPK signaling pathway.

Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max)). EXPERIMENTAL APPROACH: After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and Q(max), using the elastance-resistance model. Physically, E(max) reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance. KEY RESULTS: Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG. CONCLUSIONS AND IMPLICATIONS: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes.

Aminoguanidine prevents fructose-induced deterioration in left ventricular-arterial coupling in Wistar rats.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties. EXPERIMENTAL APPROACH: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature. KEY RESULTS: There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. CONCLUSIONS AND IMPLICATIONS: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.

Intravenous sotalol decreases transthoracic cardioversion energy requirement for chronic atrial fibrillation in humans: assessment of the electrophysiological effects by biatrial basket electrodes.

OBJECTIVES: This study was undertaken to assess the effects of sotalol on the transthoracic cardioversion energy requirement for chronic atrial fibrillation (AF) and on the atrial electrograms during AF recorded by two basket electrodes. BACKGROUND: The effects of sotalol infusion on transthoracic electrical cardioversion for chronic atrial fibrillation in humans have not been well investigated. METHODS: We included 18 patients with persistent AF for more than three months. Atrial electrograms were recorded by two basket electrodes positioned in each atrium respectively. Transthoracic cardioversion was performed before and after sotalol 1.5 mg/kg i.v. infusion. RESULTS: In the 14 patients whose AF could be terminated by cardioversion before sotalol infusion, the atrial defibrillation energy was significantly reduced after sotalol infusion (236 +/- 74 jules [J] vs. 186 +/- 77 J; p < 0.01). Atrial fibrillation was refractory to cardioversion in four patients at baseline and was converted to sinus rhythm by cardioversion after sotalol infusion in two of them. We further divided the patients into two groups. Group A consisted of 10 patients in whom the energy requirement was decreased by sotalol while group B consisted of eight patients in whom the energy requirement was not decreased. The mean A-A (atrial local electrogram) intervals during AF were significantly increased after sotalol infusion in both groups, but the increment of A-A interval was significantly larger in group A than it was in group B patients (36 +/- 13 ms vs. 22 +/- 8 ms for the right atrium; 19 +/- 7 ms vs. 9 +/- 7 ms for the left atrium; both p < 0.05). The spatial and temporal dispersions of A-A intervals were not significantly changed after sotalol infusion in both atria in both groups. CONCLUSIONS: Sotalol decreases the atrial defibrillation energy requirement by increasing atrial refractoriness but not by decreasing the dispersion of refractoriness.

Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study.

OBJECTIVES: The objective of this study was to assess the spatial distribution of atrial ectopic foci potentially triggering recurrent atrial tachyarrhythmias after electrical cardioversion of long-standing atrial fibrillation (AF). BACKGROUND: It remains unknown whether targeted ablation of atrial ectopic foci concentrated in the pulmonary veins is feasible in patients with long-standin

Recovery of atrial function after atrial compartment operation for chronic atrial fibrillation in mitral valve disease.

OBJECTIVES: We prospectively studied the recovery of atrial function after atrial compartment operation and mitral valve surgery in patients with chronic atrial fibrillation caused by mitral valve disease. BACKGROUND: Chronic atrial fibrillation is the most common arrhythmia in mitral valve disease. This arrhythmia is associated with excessive morbidity and mortality. Mitral valve surgery alone rarely eliminates it. METHODS: Twenty-two patients underwent mitral valve surgery and a new surgical method, atrial compartment operation. Doppler echocardiography was performed in all patients before operation and at 1 week and 2 and 6 months after operation in the successful cardioversion group. Peak early diastolic (E) and atrial (A) filling velocities, peak A/E velocity ratio and A/E integral ratio of the mitral and tricuspid valves were measured. RESULTS: Sinus rhythm was restored immediately after operation in 91% of patients and was maintained for > 1 week in 15 (68%) of 22 patients and > 6 months in 14 (64%) of 22. Eleven of 15 patients had left atrial paralysis (A/E integral ratio 0) at 1 week and 6 of 14 patients at 2 months. Nine of 15 patients had right atrial paralysis (A/E integral ratio 0) at 1 week and 1 of 14 patients at 2 months. Both left and right atrial contractile function (presence of an A wave on Doppler findings) was detected at 6 months in 14 patients. Mean (+/- SD) peak atrial filling velocity of the mitral valve was 15 +/- 26 cm/s at 1 week, 38 +/- 39 cm/s at 2 months and 93 +/- 32 cm/s at 6 months (p < 0.001). Mean peak atrial filling velocity of the tricuspid valve was 14 +/- 19 cm/s at 1 week, 33 +/- 19 cm/s at 2 months and 50 +/- 19 cm/s at 6 months (p < 0.001). Peak early diastolic and atrial filling velocities, peak A/E velocity ratio and A/E integral ratio of the mitral and tricuspid valves increased significantly from 1 week to 6 months. CONCLUSIONS: Chronic atrial fibrillation in mitral valve disease can often be eliminated by atrial compartment operation. No surgical mortality or significant complications were encountered. Both left and right atrial function, as manifested by Doppler findings, recover after compartment operation and improve over time. The mechanical function of the right atrium recovers earlier than that of the left.

Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling.

OBJECTIVES: We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation. BACKGROUND: Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear. METHODS: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. RESULTS: The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation. CONCLUSIONS: L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

Clinical and electrophysiologic characteristics and long-term efficacy of slow-pathway catheter ablation in patients with spontaneous supraventricular tachycardia and dual atrioventricular node pathways without inducible tachycardia.

OBJECTIVES: We sought to investigate the long-term efficacy of slow-pathway catheter ablation in patients with spontaneous, documented paroxysmal supraventricular tachycardia (PSVT) and dual atrioventricular (AV) node pathways but without inducible tachycardia. BACKGROUND: The lack of reproduction of clinical PSVT by programmed electrical stimulation, which is not uncommon in AV node reentrant tachycardia (AVNRT), is a dilemma in making the decision of the therapeutic end point of radiofrequency catheter ablation. METHODS: Twenty-seven patients (group A) with documented but noninducible PSVT and with dual AV node pathways were prospectively studied. Programmed electrical stimulation could induce a single AV node echo beat in 12 patients, double echo beats in 4 patients and none in 11 patients at baseline or during isoproterenol infusion. Of the patients in group A, 16 underwent slow-pathway catheter ablation and 11 did not. The clinical and electrophysiologic characteristics of the 27 patients were compared with those of patients with dual AV node pathways and inducible AVNRT (group B, n = 55) and patients with dual AV node pathways alone without clinical PSVT (group C, n = 47). RESULTS: During 23+/-13 months of follow-up, none of the 16 patients with slow-pathway catheter ablation had recurrence of PSVT. However, 7 of the 11 patients without ablation had PSVT recurrence at 13+/-14 months of follow-up (p < 0.03 by Kaplan-Meier analysis). Compared with groups B and C, group A consisted predominantly of men who had better retrograde AV node conduction and a narrower zone for anterograde slow-pathway conduction. CONCLUSIONS: Slow-pathway catheter ablation is highly effective in eliminating spontaneous PSVT in which the tachycardia is not inducible despite the presence of dual AV node pathways.

Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction.

Previous results from our laboratory have suggested that morphine can attenuate neutrophil activation in patients with acute myocardial infarction. To elucidate if morphine preconditioning (PC) has the same effects via activation of neutrophil endopeptidase 24.11 (NEP), we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), gp100MEL14 and NEP in adult Wistar rats subjected to ten different protocols (n = 10 for each) at baseline, immediately after and 2 h after morphine PC. All groups were subjected to 30 min of occlusion and 2 h of reperfusion. Similarly, morphine-induced PC was elicited by 3-min drug infusions (100 micrograms/kg) interspersed with 5-min drug-free periods before the prolonged 30-min occlusion. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining. Pretreatment with morphine increased NEP activities (9.86 +/- 1.98 vs. 5.12 +/- 1.10 nmol/mg protein in control group; p < 0.001). Naloxone (mu-opioid receptor antagonist) (4.82 +/- 1.02 nmol/mg protein) and phosphoramidon (NEP inhibitor) (4.66 +/- 1.00 nmol/mg protein) inhibited morphine-activated NEP, whereas glibenclamide (ATP-sensitive potassium channel antagonist) and chelerythrine (protein kinase C inhibitor) had no effects. The ICAM-1 and gp100MEL14 of the third sampling were lowest for those with morphine PC (280 +/- 30 ng/ml and 2.2 +/- 0.7 micrograms/ml; p < 0.001), but naloxone (372 +/- 38 ng/ml and 3.8 +/- 0.9 micrograms/ml) and phosphoramidon (382 +/- 40 ng/ml and 4.2 +/- 1.1 micrograms/ml) abolished the above phenomenon. IS/AAR were definitely lowest for those with morphine PC (24 +/- 7%; p < 0.05). Morphine preconditioning increases NEP activities to attenuate shedding of gp100MEL14 and to ICAM-1 and, thus, provides myocardial protection.

Extracellular ATP activates calcium entry and mobilization via P2U-purinoceptors in rat lactotrophs.

Extracellular ATP has been previously shown to activate calcium signalling in pituitary cell populations [1] but the particular cell types involved have not been identified. We used video imaging of Fura-2 loaded into single rat pituitary cells and identified as lactotrophs to study the effects of extracellular ATP on [Ca2+]i. ATP does not permeabilize the cells as shown by exclusion of propidium iodide. ATP causes two types of calcium transients in lactotrophs. The most common response is a rapid increase in [Ca2+]i that decays slowly and is terminated by washout of ATP. This type of response is also seen in calcium-free medium, demonstrating mobilization of calcium stores dependent upon the presence of the agonist. ATP also stimulates calcium entry as detected by Mn(2+)-quenching of Fura-2. ATP in Mg(2+)-free medium and ATP gamma S are effective agonists suggesting ATP4- is the active form. The presence of P2-purinoceptors is apparent because ATP, ADP and AMP increase [Ca2+]i in decreasing order of potency and adenosine has no effect. ATP-induced calcium transients are reduced by the P2-purinoceptor antagonists suramin and quinidine. UTP is equipotent with ATP and defines the receptor subtype as P2U. We conclude that ATP4- acts on rat lactotrophs via P2U-purinoceptors to elevate [Ca2+]i from intracellular and extracellular sources.

Molecular variant M235T of the angiotensinogen gene is associated with essential hypertension in Taiwanese.

OBJECTIVE: To examine the association of the molecular variants of the angiotensinogen (AGT) gene with essential hypertension in Taiwanese. METHODS: We conducted a case-control study concerning 151 subjects, 102 hypertensives and 49 normotensives. We created a rapid mini-sequencing method based on dye-terminator cycle sequencing to simultaneously detect the M235T and T174M variants of the AGT gene for each subject. RESULTS: The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (chi 2 = 11.106, P = 0.004 and chi 2 = 6.453, P = 0.011, respectively), whereas those of the T174M variant did not differ (chi 2 = 0.004, P = 0.998 and chi 2 = 0.032, P = 0.858, respectively). The odds ratio for hypertension was 3.64 (95% confidence interval 1.56-8.49) for subjects with the C/C genotype of the M235T variant compared with other genotypes of 2.87 (95% confidence interval 1.76-4.68) for those carrying allele C versus those carrying allele T. CONCLUSION: The molecular variant M235T, but not T174M, of the AGT gene is associated significantly with essential hypertension in this Taiwanese population. The genotype C/C or allele C is a risk factor for hypertension. The underlying mechanism of this association needs to be elucidated further.

Attenuation of neutrophil and endothelial activation by intravenous morphine in patients with acute myocardial infarction.

To investigate the effects of morphine on neutrophil and endothelial activation, we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), L-selectin, and neutrophil endopeptidase 24.11 (NEP) in 38 patients with acute myocardial infarction (group 1) and 16 control subjects (group 2). In group 1, all the patients underwent blood sampling at initial presentation and 10 minutes later. Twenty of them had 3 mg of morphine administered intravenously immediately after the first sampling (group 1A) and the other 18 after a second sampling (group 1B). The serum levels of ICAM-1 and L-selectin were both significantly higher in groups 1A and 1B than in group 2. In group 1A, the ICAM-1 decreased significantly at second blood samplings (310 +/- 28 vs 368 +/- 30 ng/ml; p <0.001), whereas in group 1B there was no significant change in ICAM-1 (357 +/- 33 vs 359 +/- 26 ng/ml; p = NS). In group 1A, the L-selectin decreased significantly at second blood samplings (2.3 +/- 1.2 mg/L, p <0.001 vs baseline), whereas in group 1B there was no significant change in L-selectin (3.9 +/- 1.0 mg/L, p = NS vs baseline). There was no significant difference in baseline NEP activities between groups 1A and 1B (4.89 +/- 1.22 vs 5.14 +/- 1.57 nmol/mg protein; p = NS). However, the NEP activities at second blood samplings decreased significantly in group 1A (9.88 +/- 1.86 nmol/mg protein, p <0.001 vs baseline), whereas no significant changes were observed in group 1B (5.09 +/- 1.62 nmol/mg protein, p = NS vs baseline). In conclusion, morphine increased NEP activities and thus attenuated shedding of L-selectin and ICAM-1.

Effects of percutaneous mitral valvuloplasty on left atrial appendage flow velocity.

This study shows an increase in LAA flow after PTMV in both normal sinus rhythm and atrial fibrillation. These results suggest that relief of mitral stenosis may not only confer hemodynamic benefits for the improvement of symptoms but also have a favorable influence on future thromboembolism.

Importance of left atrial appendage function as a risk factor for systemic thromboembolism in patients with rheumatic mitral valve disease.

One hundred fifty-six patients with rheumatic mitral valve disease were studied with transesophageal echocardiography to assess the influence of left atrial (LA) appendage size and contractile function on the occurrence of systemic embolism. LA appendage function, represented by peak emptying velocity, was found to be a better indicator than LA spontaneous echo contrast as a risk factor for systemic thromboembolism.

Influence of additional partition on the recovery of atrial function after atrial compartment operation for atrial fibrillation.

Chronic atrial fibrillation can be eliminated by an atrial compartment operation, but additional partition on the right atrium impairs the recovery of right atrial mechanical function. Thus, it is important to appropriately divide the atria for both maintaining sinus rhythm and maximizing atrial mechanical function.

Percutaneous balloon pericardiotomy for patients with recurrent pericardial effusion: using a novel double-balloon technique with one long and one short balloon.

Percutaneous balloon pericardiotomy is effective and less invasive for the treatment of recurrent pericardial effusion. This study suggests that the double-balloon method with 1 longer and 1 shorter balloon is the procedure of choice for percutaneous balloon pericardiotomy.

Relation of Chlamydia pneumoniae infection in Taiwan to angiographically demonstrated coronary artery disease and to the presence of acute myocardial infarction or unstable angina pectoris.

Reports of the association of Chlamydia pneumoniae (C. pneumoniae) infection with coronary artery disease (CAD) are scarce in the Oriental population. We therefore conducted a case-control study to explore this issue in Taiwan. There were 242 consecutive subjects (166 men and 76 women) who underwent cardiac catheterization at the National Taiwan University Hospital Cardiac Catheterization Laboratory. Patients with CAD (n = 156) had > or = 1 coronary artery lesion of > 50% diameter stenosis on angiography. Controls (n = 86) had no demonstrable CAD angiographically. Antibodies to C. pneumoniae were tested by using an enzyme-linked immunosorbent assay. The prevalence of antibodies to C. pneumoniae was as follows: immunoglobulin-G (IgG), 50% (122 of 242 patients); immunoglobulin-A (IgA), 72% (176 of 242 patients); and either IgG or IgA, 79% (192 of 242 patients ). The odds ratio (OR) for CAD with either IgG or IgA was 1.4 (95% confidence interval [CI] 0.7 to 2.7, p = 0.31). After adjusting for the known CAD risk factors, the OR decreased to 0.8 (95% CI 0.3 to 2.1, p = 0.60). The OR for unstable angina or acute myocardial infarction with the presence of either IgG or IgA was 0.5 (95% CI 0.2 to 1.1, p = 0.08) and 0.4 ( 95% CI 0.1 to 1.0, p = 0.049) after adjusting for other risk factors. These results suggest a high prevalence of C. pneumoniae infection in Taiwan. However, C. pneumoniae infection is not associated with angiographically documented CAD, and, in contrast, is a negative predictor for the development of acute coronary syndromes.

Diagnostic accuracy of transesophageal echocardiography for detecting left atrial thrombi in patients with rheumatic heart disease having undergone mitral valve operations.

Transesophageal echocardiography (TEE) has emerged as an efficient method for detecting left atrial (LA) thrombi in recent years, but its accuracy has not been fully evaluated. A prospective clinicopathologic study in 213 consecutive patients with chronic rheumatic mitral valve disease over a period of 39 months was undertaken. All patients underwent open heart surgery within 3 days after the TEE study. The presence or absence of LA thrombi was confirmed at surgery by direct inspection of the left atrium and proven by histopathologic examination. Of the 213 patients, 147 had predominant mitral stenosis, and the remaining 66 patients had significant mitral regurgitation. Twenty-eight patients had LA thrombi by TEE criteria. These findings were all confirmed at surgicopathologic studies (specificity 100%). However, in 2 patients, LA thrombi were present but could not be detected by TEE (sensitivity 93.3%). Therefore, the positive predictive value was 100%, the negative predictive value was 98.9% and the diagnostic accuracy was 99.1%. No thrombi were found in patients with significant mitral regurgitation. The frequency of LA thrombi in patients with predominant mitral stenosis was 20% (30 of 147), and most of these patients had chronic atrial fibrillation (28 of 30, 93%). Only 16 patients (16 of 30, 53%) were found to have LA thrombi by transthoracic echocardiography. Furthermore, our data showed poor correlation between the echogenicity of LA thrombi and the degree of thrombus organization. Thus, TEE is excellent for detecting LA thrombi in patients with rheumatic heart disease severe enough to warrant mitral valve operations.

Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.

1. In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identified as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10(-7) g kg(-1). The aim of this study was to determine whether liriodenine at its effective anti-arrhythmic dose of 10(-7) g kg(-1) had effects on the left ventricular (LV)-arterial coupling in Wistar rats. 2. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E(es)) and effective arterial volume elastance (E(a)), respectively. The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the optimality of energy transmission from the left ventricle to the arterial system. 3. Liriodenine at the dose of 10(-7) g kg(-1) showed no significant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (P(es)), E(a), E(es), and Q(load). 4. By contrast, liriodenine at the dose of 10(-6) g kg(-1) produced a significant fall of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in P(es). Moreover, liriodenine administration of 10(-6) g kg(-1) to rats significantly decreased E(es) by 8.5% and E(a) by 10.6%, but did not change Q(load). 5. We conclude that liriodenine at the dose of 10(-7) g kg(-1) has no effects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects on the efficiency of energy transferred from the left ventricle to the arterial system.

Clinical significance of fibrillatory wave amplitude. A clue to left atrial appendage function in nonrheumatic atrial fibrillation.

Seventy-eight patients with chronic nonrheumatic atrial fibrillation were studied by transesophageal echocardiography with regard to the left atrial appendage function and its relation to the coarseness of atrial fibrillation on electrocardiogram. These 78 patients (52 men and 26 women; mean age, 66 +/- 10 years; range, 40 to 94 years) were classified into two groups according to the presence of coarse (group 1, n = 46; those with the greatest amplitude of fibrillatory wave in lead V1 > or = 1 mm) or fine (group 2, n = 32; those without the coarse fibrillatory wave in lead V1) atrial fibrillation on a standard 12-lead electrocardiogram within 1 month of echocardiographic studies. There were no significant differences in age, sex, mean duration of atrial fibrillation, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, and left atrial dimension between the two groups. In group 1, however, the left atrial appendage ejection fraction (24.4 +/- 14.2% vs 32.6 +/- 14.8%; p < 0.05) and the peak emptying velocity (21.7 +/- 12.6 cm/s vs 30.4 +/- 14.3 cm/s; p < 0.01) were lower than those in group 2. There were higher incidences of left atrial appendage spontaneous echo contrast (26/46 vs 7/32; p < 0.005) and thrombus (8/46 vs 0/32; p < 0.05) in group 1 patients. The coarse atrial fibrillation revealed a sensitivity of 80.0%, a specificity of 58.1%, a positive predictive value of 60.9%, and a negative predictive value of 78.1% for the presence of left atrial appendage spontaneous echo contrast and/or thrombus formation. In conclusion, in patients with coarse nonrheumatic atrial fibrillation, the left atrial appendage function is usually poor and the incidence of spontaneous echo contrast and thrombus formation appears to be higher in these patients.