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A dual-component positive inotropic effect of endothelin-1 in guinea pig left atria: a role of protein kinase C.

This study was designed to analyze the mechanism(s) underlying the positive inotropic effect (PIE) of endothelin-1 (ET-1) in the guinea pig left atrium. ET-1 exhibited a greater PIE at lower frequencies of pacing and potentiated significantly the postrest contraction similar to isoproterenol. However, ET-1 prolonged the duration of a single contraction, whereas isoproterenol shortened it. ET-1 was similar to methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate in the prolonged duration of a single contraction but different from this drug in the force-frequency relationship. ET-1 at concentrations of 10 nM and higher caused a dual-component PIE composed of an initial increasing phase (early component) and a second greater positive inotropic phase (late component). The early component was correlated to the ET-1-induced prolongation of the duration of the action potential in the time course. Both nifedipine and ryanodine suppressed the late component much more than the early component. ET-1 (> or = 3 nM) produced significant stimulation of phosphoinositide hydrolysis as measured by [3H]inositol monophosphate accumulation. ET-1 was found to activate protein kinase C (PKC) instantaneously but transiently (evaluated by the translocation of PKC activity to the particulate fraction). Pretreatment with 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine and staurosporine, PKC inhibitors, markedly inhibited the late component of the PIE of ET-1 without affecting the early component. These data indicate that the two components of the PIE induced by ET-1 in the guinea pig left atrium may be mediated by different mechanisms. The early component may be attributed to the increased Ca++ influx as a result of the prolongation of the duration of the action potential, whereas the late component may be linked to stimulation of phosphoinositide hydrolysis and subsequent PKC activation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[The "flickering" phenomenon in the right atrium].

To specify characteristics and reasons of flickering in the right auricle (FRA) detected at two-dimensional ECG, 278 patients with innocent cardiac murmur (ICM) and 93 patients with congenital heart disease (CHD) underwent clinical and ECG examinations. FRA was found in 34.5% of ICM and 57.0% of CHD patients. Topographic-anatomical, ECG, intraoperative comparative investigations suggested that FRA may result from the eustachian valve movements and fenestration-filament structure of the endocardium at the opening of the inferior vena cava, interatrial septum, coronary sinus valve, base of the atrioventricular cusps. The movement of the eustachian valve was followed through the cardiac cycle. It is thought advisable that FRA characteristics should be taken into consideration for valid understanding of right atrial circulation in normal and CHD conditions.

Adult↗

Influence of regression of left ventricular hypertrophy on left atrial size and function in patients with moderate hypertension.

OBJECTIVES: The aim of the study was to evaluate the effect of regression of left ventricular (LV) hypertrophy on left atrial (LA) size and function in patients treated with telmisartan, an angiotensin II receptor blocker. METHODS: Patients population included 80 patients with mild-moderate LV hypertrophy treated with telmisartan. Patients were followed over a period of 12 months from the start of telmisartan treatment. LA size was measured during systole from the parasternal long-axis view from M-mode. Atrial function was assessed by Doppler-echocardiography and the following parameters were measured: transmitral peak A velocity, atrial filling fraction, atrial ejection force (AEF), peak E velocity, deceleration time and isovolumic relaxation time, LA maximal and minimal volume, and LV cardiac mass index (LVMI). RESULTS: All patients had an increased LVMI and decrease during follow-up. LA dimensions were greater at baseline and reduced after 1 year of treatment. LA volume indexes maximal volume, minimal volume and P volume were reduced compared with baseline value (maximal volume from 35+/-5 to 32+/-5, p<0.05; minimal volumes from 14+/-2 to 10+/-4, p<0.05). AEF, a parameter of atrial systolic function, increased from 12+/-3 to 15+/-2.4 (p<0.01). The reduction of LA volumes correlate with reduction of LVMI (LA maximal volume and LVMI r = 0.45; p<0.01; LA minimal volume and LVMI r = 0.34; p<0.05). A positive correlation was also found between LV mass index and P volume (r = 0.41; p<0.01), LV mass index and LA active emptying volume (r = 0.39; p<0.01), and LV mass index and LA total emptying volume (r = 0.38; p<0.05). CONCLUSIONS: The present study suggests that regression of LV hypertrophy due to telmisartan is associated with reduction of LA volumes that expresses variation of LV end-diastolic pressure. The reduction of LV end-diastolic pressure is associated with an increase in diastolic filling and with a significant reduction of active and passive emptying contribution of left atrium to LV stroke volume.

Adult↗

Targeted modification of atrial electrophysiology by homogeneous transmural atrial gene transfer.

BACKGROUND: Safe and effective myocardial gene transfer remains elusive. Heterogeneous ventricular gene delivery has been achieved in small mammals but generally with methods not readily transferable to the clinic. Atrium-specific gene transfer has not yet been reported. We hypothesized that homogeneous atrial gene transfer could be achieved by direct application of adenoviral vectors to the epicardial surface, use of poloxamer gel to increase virus contact time, and mild trypsinization to increase virus penetration. METHODS AND RESULTS: We "painted" recombinant adenovirus encoding the reporter gene Escherichia coli beta-galactosidase directly onto porcine atria. Investigational variables included poloxamer use, trypsin concentration, and safety. Using the painting method, we modified the atrial phenotype with an adenovirus expressing HERG-G628S, a long-QT-syndrome mutant. Our results showed that application of virus with poloxamer alone resulted in diffuse epicardial gene transfer with negligible penetration into the myocardium. Dilute trypsin concentrations allowed complete transmural gene transfer. After trypsin exposure, echocardiographic left atrial diameter did not change. Left atrial function decreased on postoperative day 3 but returned to baseline by day 7. Tissue tensile strength was affected only in the 1% trypsin group. HERG-G628S gene transfer prolonged atrial action potential duration and refractory period without affecting ventricular electrophysiology. CONCLUSIONS: We show complete transmural atrial gene transfer by this novel painting method. Adaptation of the method could allow application to other tissue targets. Use with functional proteins in the atria could cure or even prevent diseases such as atrial fibrillation or sinus node dysfunction.

Action Potentials↗

Atrial BNP endocrine function during chronic unloading of the normal canine heart.

The goal of the study was to define the effect of chronic unloading of the normal heart on atrial endocrine function with a focus on brain natriuretic peptide (BNP), specifically addressing the role of load and neurohumoral stimulation. Although produced primarily by atrial myocardium in the normal heart, controversy persists with regard to load-dependent vs. neurohumoral mechanisms controlling atrial BNP synthesis and storage. We used a unique canine model of chronic unloading of the heart produced by thoracic inferior vena caval constriction (TIVCC), which also resulted in activation of plasma endothelin (ET-1), ANG II, and norepinephrine (NE), known activators of BNP synthesis, compared with sham. TIVCC was produced by banding of the inferior vena cava for 10 days (n = 6), whereas in control (n = 5) the band was not constricted (sham). In a third group (n = 7), the band was released on day 11, thus acutely reloading the heart. Chronic TIVCC decreased cardiac output and right atrial pressure with a decrease in atrial mass index consistent with atrial atrophy. Atrial BNP mRNA decreased compared with sham. Immunoelectron microscopy revealed an increase in BNP in atrial granules consistent with increased storage. Acute reloading increased cardiac filling pressures and resulted in an increase in plasma BNP. We conclude that chronic unloading of the normal heart results in atrial atrophic remodeling and in suppression of atrial BNP mRNA despite intense stimulation by ET, ANG II, and NE, underscoring the primacy of load in the control of atrial endocrine function and structure.

Animals↗

Persistent atrial standstill in a cat.

A domestic shorthaired cat was presented with a 1-month history of cardiomegaly and recurrent chylothorax. The heart rate was 130 beats/min and no P waves were present on a surface electrocardiogram. Thoracic radiographs and an echocardiogram demonstrated severe biatrial dilatation, pleural effusion and restrictive pleural disease. Permanent atrial standstill was suspected. Pleurocentesis was performed and therapy was started with enalapril, frusemide and aspirin. Intracardiac electrograms revealed no atrial activity, and atrial pacing failed to elicit atrial or ventricular depolarisations. The patient was euthanased. Necropsy showed severe atrial wall thinning with marked cardiocyte loss. Persistent atrial standstill is a rare disease in the cat. Clinical signs may have been due to loss of atrial function, ventricular diastolic dysfunction, bradycardia, neurohormonal activation and reduced atrial natriuretic peptide plasma concentrations.

Animals↗

Phentolamine and hypoxia: modulation of contractility and alpha 1-adrenoceptors in isolated rat atria.

The hypoxia-induced effects on the binding sites and affinity constant of adrenoceptors, in the presence and absence of phentolamine, were determined for atrial membranes of hearts from normal and genetically hyperlipidaemic Yoshida (YOS) rats. Atrial function was also measured during normoxia and hypoxia, in the presence and absence of phentolamine. Hypoxia increased alpha 1-adrenoceptor density in atrial membranes of normal rats (Bmax 10.6 to 26.7 fmoles/mg protein). Phentolamine prevented the increase in the Bmax of alpha 1-adrenoceptors and increased the equilibrium dissociation constant of these receptors (KD 0.17 to 0.53 nmol/l). Beta-adrenoceptors did not change during hypoxia, but the Bmax was slightly increased (26%) in the presence of phentolamine. Thus, the alpha 1/beta ratio increased from 0.40 in normoxia to 1.06 in hypoxia. In normoxic atria from YOS rats, the alpha 1/beta ratio was already elevated (0.86) in comparison to control rats (mainly due to a higher density of alpha 1-adrenoceptors in atrial membranes from YOS rats). This ratio was not modified by hypoxia (0.84), but decreased when phentolamine was present (0.30). Hypoxia reduced the force of contraction and increased diastolic tension of atria of normal rats, while the sinus rate was not significantly modified. Phentolamine abolished the increase in diastolic tension and reduced the negative effect of hypoxia on contractile force. In YOS rat atria, functional parameters were modified by hypoxia in a qualitatively similar way to that of normal rat atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial and ventricular electromechanical function in 1-ventricle hearts: influence of atrial flutter and Fontan procedure.

OBJECTIVE: Echocardiography was used to study electromechanical atrial and ventricular function in adult patients with a 1-ventricle heart who were in sinus rhythm to better understand the recurrence of atrial flutter in these conditions. Patients who had recent atrial flutter, with and without the Fontan procedure, were compared with those who had no arrhythmia. METHODS: This was a prospective study that used M-mode and 2-dimensional Doppler echocardiography and electrocardiography. Conventional measurements were used to evaluate ventricular long-axis function. Basic data were drawn from case notes. The setting was a designated quaternary service for grown-up congenital heart patients (GUCH) in a tertiary referral center for cardiology and cardiac surgery. From January 1997 to February 1998, 26 consecutive adult patients (aged >16 years) with a heart with one functioning ventricle and a history of atrial flutter were studied: group 1, with non-Fontan palliative surgery or no surgery (10 patients), and group 2, with Fontan-type repair (16 patients). Also studied were 20 patients with a 1-ventricle heart but no history of atrial flutter. These 20 patients were divided into 2 groups: control 1, which comprised 14 patients with previous shunts or no surgery, and control 2, which consisted of 6 patients with Fontan repair. RESULTS: P-wave duration on the electrocardiogram was similar in the 4 patient groups, but the amplitude was reduced in group 2 and control 2 (patients with Fontan surgery) (P <.016). Bifid P wave was seen in 5 (50%) of 10 patients in group 1 and in 6 (43%) of 14 patients in control 1, but it was not seen in patients with Fontan (P <.01). Ventricular systolic and diastolic dimensions and fractional shortening were not different between patients and controls. Right atrial transverse dimensions were greater in group 2 patients compared with those in controls. Significant atrioventricular valve regurgitation was seen in 9 of 10 group 1 patients but in none of the others. Right-sided total long-axis excursion and atrial A-wave amplitude were depressed in group 2 patients compared with the values in the others. The onset of right atrial shortening was delayed by 50 ms in group 2 compared with control 2, whereas the left atrial shortening was delayed by 30 ms in group 1 compared with control 1. This particular disturbance remained 6 months after cardioversion. CONCLUSION: In 1-ventricle hearts, significant atrioventricular valve regurgitation is commonly associated with atrial flutter in patients who did not undergo the Fontan procedure, and with electromechanical disturbances in those who did. Recognition of disturbances in ventricular long-axis function may thus assist in the identification of patients with a 1-ventricle heart who are prone to atrial flutter.

Adolescent↗

Dose-related cardiac electrophysiological effects of intravenous magnesium. A double-blind placebo-controlled dose-response study in patients with paroxysmal supraventricular tachycardia.

AIMS: The role of magnesium as an antiarrhythmic drug is yet not conclusive. Therefore, we performed a double-blind, randomized, placebo-controlled dose-response study of cardiac electrophysiological effects of intravenous magnesium. METHODS AND RESULTS: Thirty-six patients undergoing an electrophysiological evaluation for paroxysmal supraventricular tachycardia were randomized to one of the following dosages of intravenous magnesium (0, 5, 10 or 20 mmol). Conventional electrophysiological variables for sinus node function, atrial, atrioventricular node and ventricular conduction and refractoriness were measured before and after magnesium administration. Prolongation of the atrial-His interval was found at 5 mmol of magnesium compared with placebo and no further prolongation was observed at higher doses (-3 +/- 8, 11 +/- 9, 7 +/- 15, 11 +/- 16, for the dosages of 0, 5, 10 and 20 mmol of magnesium, respectively, P < 0.05). Measures of sinus node function, intra-atrial conduction and conduction through the Purkinje system were unaffected by magnesium. Male gender was associated with prolongation in atrial effective refractory period, in contrast to shortening in females: 2 +/- 43, 35 +/- 44, 36 +/- 33, 13 +/- 12 ms for males and 3 +/- 6, -12 +/- 11, -13 +/- 12, 0 +/- 23 ms for females, respectively (P < 0.001). CONCLUSION: Atrioventricular node conduction was prolonged by 5 mmol intravenous magnesium and no further prolongation was observed at higher dosages. At dosages of 5 and 10 mmol magnesium the atrial effective refractoriness was prolonged in males and shortened in females.

Adolescent↗

Maternal cardiac systolic function and total body water estimation in normal and gestational hypertensive women.

We assessed total body water (TBW) content and cardiac function in 25 normotensive (N) and 22 gestational hypertensive (GH) women matched for age, gestational age, and prepregnancy body mass index (BMI) during the third trimester of gestation. Patients underwent maternal echocardiography, bioelectrical impedance analysis (BIA), and hematocrit (Hct %) evaluation. The TBW:Hct ratio (water balance index, WBI) was calculated. Hct was significantly lower in N vs. GH women (31.9+/-2.2% vs. 36.2+/-2.5; p<0.001). There was no difference in TBW between the two groups. WBI was higher in N vs. GH women (1.35+/-0.20 l.kg(-1) x m(-2) vs. 1.19+/-0.18; p<0.001). N subjects showed a higher stroke volume than GH patients (78.0+/-9.7 ml vs. 67.9+/-10.2; p=0.001). Atrial function was higher in N vs. GH women (left atrial fractional area change 57.4+/-5.1% vs. 42.5+/-7.5; p<0.001). A correlation was found between stroke volume and WBI ( r=0.93, p<0.0001). Maternal cardiac function and WBI are strongly related and might help in understanding the mechanisms of adaptation in normal and hypertensive pregnancy.

Adult↗

Rate dependent far-field R wave sensing in an atrial tachyarrhythmia therapy device.

A case is reported of far-field R wave (FFRW) oversensing resulting in inappropriate atrial tachycardia (AT) detection by a dual chamber pacemaker incorporating atrial autoadjusting sensitivity (AAS). FFRW oversensing occurred during periods of functional atrial undersensing (FAU) with PR interval prolongation. Limitations of the pacemaker's ability to reject FFRWs and programming considerations for addressing this unique behavior are discussed.

Aged↗

Differential responses accompanying sequential stimulation and ablation of vagal branches to dog heart.

Electrical excitation of small thoracic vagal branches elicited highly localized responses in the canine heart. Specific pathways to the sinoatrial nodal (SAN) regions were identified from negative chronotropic responses to stimulation (20 Hz, 5.0 ms, 3.0-5.0 V) of these branches. Pathways to the atrioventricular nodal (AVN) region were determined from changes in A-H interval (His bundle electrogram) and incidence of heart block as vagal branches were stimulated during concurrent atrial pacing. A few small branches influenced a single cardiac function (atrial rate, contractile force, or AV conduction). More commonly, activation of such branches elicited simultaneous chronotropic and dromotropic effects. However, many branches failed to elicit any detectable cardiac change. The major outflow from the left vagus to SAN and AVN regions is by way of cardiac branches from the recurrent laryngeal nerve at its reflection around the aorta. Activation of the left recurrent nerve reduced atrial rate by 43% and doubled A-H interval 84 to 167 ms. The right thoracic vagus or its branches induced A-H prolongation from 78 to 131 ms. H-V intervals remained constant at a mean of 35 ms. Outflows from the right thoracic vagus to SAN and/or AVN regions originated just below the middle cervical ganglion and at all levels down to the azygos vein.

Animals↗

Left atrial geometric and functional remodeling in athletes.

The aim of this study was to evaluate left atrial (LA) volume and its changes with the phases of atrial filling, and to examine the effect of exercise capacity on these parameters. Using two-dimensional echocardiography, LA volumes were measured in 30 male endurance runners and 30 age-matched sedentary men (controls). Maximal oxygen consumption (VO2max) was measured using a metabolic chart during exercise. LA reservoir, pump, and conduit functions, kinetic energy and force were calculated. We found that athletes had higher LA volume and volume index (except the conduit volume), LA passive emptying fraction, and LA total emptying fraction compared to control subjects. We observed positive correlations between: VO2max and LA passive emptying fraction (r=0.49, p<0.05); VO2max and LA active emptying fraction (r=0.54, p<0.05); VO2max and LA kinetic energy (r=0.61, p<0.05); and VO2max and LA force (r=0.57, p<0.05). These findings suggest that atrial function reflects exercise capacity in athletes.

Adult↗

Total body water estimation and maternal cardiac systolic function assessment in normal and gestational hypertensive pregnant women.

BACKGROUND: The importance of establishing correlations between cardiac function (cardiac output and stroke volume) and total body water (TBW) content in normal and hypertensive pregnancy focuses primarily on their potential relevance in treatment. Total body water content and cardiac function were evaluated in 25 normotensive (N) and 22 gestational hypertensive (GH) pregnant women matched for age, gestational age, and pre-pregnancy body mass index (BMI) during the third trimester of gestation. MATERIAL/METHODS: Patients underwent maternal echocardiography, bioelectrical impedance analysis (BIA), and hematocrit (Hct) evaluation, and the water balance index (WBI), i.e. the ratio of total body water to hematocrit, was computed. Hematocrit showed significantly lower values in normal than in GH women (31.9+/-2.2% vs. 36.2+/-2.5%; p<0.001). RESULTS: There was no difference in TBW between the two groups. The WBI was higher in normal than in GH women (1.35+/-0.20 l.kg-1.m-2 vs. 1.19+/-0.18 l.kg-1.m-2; p<0.001). Normal subjects showed a higher stroke volume than GH patients (78.0+/-9.7 ml vs 67.9+/-10.2 ml; p=0.001). Atrial function was also higher in normal than in GH women (left atrial fractional area change: 57.4+/-5.1% vs. 42.5+/-7.5%; p<0.001). Correlation was found between stroke volume and WBI (r=0.93, p<0.0001). CONCLUSIONS: Maternal cardiac function and the water balance index are strongly related and might help in comprehending the mechanisms of adaptation in physiologic and hypertensive pregnancy.

Adaptation, Physiological↗

[Incidence and dynamic behavior of spontaneous echocardiographic contrast and atrial thrombi in the transplanted heart].

BACKGROUND: Standard orthotopic heart transplantation produces important anatomic and functional atrial alterations with subsequent thrombotic risk. Therefore the aim of this study was to analyze the prevalence and evolution of spontaneous echocardiography, atrial thrombi and embolic events. PATIENTS AND METHOD: 52 consecutive transplanted patients were analyzed with transesophageal echocardiography and hemodynamic studies performed at 15 days and one year after transplantation. RESULTS: Spontaneous echocardiography contrast was present in 27 patients (52%). Ten atrial thrombi were observed (19.2%), 9 with spontaneous echocardiography contrast. Six atrial thrombi appeared on day 15 and 4 after one year (with spontaneous echocardiography contrast on the previous study). Using multiple logistic regression analysis left atrial size was the only independent predictor factor for spontaneous echocardiography contrast (OR = 1.27; 95% CI, 1.09-1.54) and was an important predictor factor of atrial thrombi formation (OR = 1.19; 95% CI, 1.04-1.42). Likewise, the main predictor of atrial thrombi was the presence of spontaneous echocardiography contrast (OR = 116; 95% CI, 8.4-999). The hemodynamic pattern did not predict either the presence of spontaneous echocardiography contrast or atrial thrombi. The global incidence of embolic events was 4% less than previously described. CONCLUSIONS: The incidence of atrial thrombi and spontaneous echocardiographic contrast after standard orthotopic heart transplantation was 19.2% and 52%, respectively. An enlarged atrium and/or spontaneous echocardiography contrast was found to increase the risk of atrial thrombi. Considering the dynamic nature of atrial thrombi formation, periodical transesophageal echocardiography studies are recommended after heart transplantation.

Analysis of Variance↗

Appearance of atrial sound after reversion of atrial fibrillation.

To determine the incidence and time of onset of the atrial sound after reversion of atrial fibrillation in patients with myocardial disease, 12 patients with arteriosclerotic heart disease and 4 patients with primary myocardial disease were followed with serial auscultation as well as daily simultaneous apical phonocardiogram, apex cardiogram, and lead II electrocardiogram. Their average age was 52.3 years. Each patient had been in atrial fibrillation for 6 months to 2 years' duration; 13 were reverted to sinus rhythm with DC capacitor discharge and 3 with quinidine sulphate. All 16 patients developed an atrial sound when in sinus rhythm, but only 2 on the day of reversion; the other 14 patients developed an atrial sound on the first to the sixth day after reversion (average third day). The atrial sound persisted in each patient. This study indicates that the atrial sound as a manifestation of diminished ventricular compliance may be absent in patients with myocardial disease immediately after reversion of atrial fibrillation and may later appear as left atrial function improves.

Adult↗

Is left atrial appendage flow a predictor for outcome of cardioversion of nonvalvular atrial fibrillation? A transthroacic and transesophageal echocardiographic study.

Accurate echocardiographic parameters for predicting the success of cardioversion or maintenance of sinus rhythm are poorly defined. This prospective transthoracic and transesophageal echocardiographic study was conducted to test the hypothesis that the left atrial appendage flow pattern could be a predictive parameter of the success of cardioversion and maintenance of sinus rhythm in patients with nonvalvular atrial fibrillation. Eighty-two consecutive patients with nonvalvular atrial fibrillation of <6 months' duration underwent transesophageal examination after transthoracic echocardiography. After exclusion of left atrial thrombus, pharmacologic (n = 18) or electrical (n = 64) cardioversion was successful in 75 of 82 patients. In the group that underwent successful cardioversion, maintenance of sinus rhythm (n = 35) or recurrence of arrhythmia (n = 40) was assessed during a 1-year follow-up. During transesophageal examination, five left atrial appendage thrombi were found, spontaneous echo contrast was present in 26 (32%) patients, and mean peak left atrial appendage emptying velocity was 35 +/- 18 cm/sec. Peak left atrial appendage emptying velocity was found to be statistically related to parameters of left ventricular and left atrial function but not to long-term maintenance of sinus rhythm. No other echocardiographic parameter was identified as a predictor for either the success of cardioversion or the maintenance of sinus rhythm at follow-up. In patients with nonvalvular atrial fibrillation of recent onset, peak left atrial appendage emptying velocity appears to be a complex parameter depending on left atrial and left ventricular function but that does not predict either the success rate of cardioversion or long-term maintenance of sinus rhythm after successful cardioversion.

Aged↗