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PubMed2001

Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.

OBJECTIVE: To determine the importance of rhythm regulation or rate control in patients with permanent atrial fibrillation (AF) and normal left ventricular function. PATIENTS AND INTERVENTIONS: Thirty six patients with a mixed fast and slow ventricular response rate to their AF were randomised to either His bundle ablation (HBA) and VVIR pacemaker (HBA group) or VVI pacemaker and atrioventricular modifying drugs (Med group). Outcomes assessed at one, three, six, and 12 months included exercise duration and quality of life. RESULTS: Exercise duration significantly improved from baseline in both groups. There was no difference in outcome between the groups (Med +40% v HBA +20%, p = NS). The heart rate profile on exercise was similarly slowed in both groups compared to baseline. Quality of life significantly improved in both treatment arms for the modified Karolinska questionnaire (KQ) (Med +50% v HBA +50%, p = NS) and the Nottingham health profile (NHP) (Med +40% v HBA +20%, p = NS). However, for the individual symptom scores of each questionnaire more were improved in the Med group (KQ-Med 6 improved v HBA 4, NHP-Med 3 v HBA 1). Left ventricular function was equally preserved by both treatments during follow up. CONCLUSION: In these patients control of ventricular response rate with either HBA + VVIR pacemaker or atrioventricular modifying drugs + VVI pacemaker will lead to a significant improvement in exercise duration and quality of life. Rhythm regulation by HBA did not confer additional benefit, suggesting rate control alone is necessary for the successful symptomatic treatment of these patients in permanent AF.

Aged↗
PubMed2006

Efficacy and safety of ibutilide for the conversion of monomorphic atrial tachycardia.

BACKGROUND: Ibutilide is a class III antiarrhythmic drug, frequently used for conversion of atrial fibrillation and flutter. We studied the efficacy of ibutilide for acute conversion of monomorphic atrial tachycardia (monoAT) in a prospective, open label study in the intensive care unit of a cardiological clinic. METHODS: We examined 49 episodes of monoAT in 38 patients (19 men/19 women). Thirty-three patients (87%) suffered from structural heart disease. Twenty-three episodes occurred while on antiarrhythmic therapy with class I or III drugs. Patients with prolonged QT interval (except for patients with pretreatment with class III drugs), hypokalemia, left ventricular failure, and recent myocardial infarction were excluded. All patients received one or two doses of 1 mg ibutilide fumarate under continuous rhythm monitoring. RESULTS: Conversion to sinus rhythm occurred in 19 episodes (38.8%), in 6 episodes (12.2%) after the first dose. Conversion rate was significantly higher in patients with a short history of symptoms (66.6% vs 28.6%; P < 0.05), of documented arrhythmia (0.13 (0/5.7) vs 2.6 (0.38/23.5) months, median (interquartile range); P < 0.03), higher atrial rate (272 +/- 49 vs 207 +/- 36 beats/min (means +/- SD); P < 0.004), or without preexisting antiarrhythmic therapy (53.8% vs 21.7%; P < 0.02). No differences in conversion rates were found regarding gender, age, body mass index, left ventricular function, left atrial diameter, or underlying disease. In three episodes torsade de pointes occurred after ibutilide (6.1%), requiring defibrillation in two cases (4.1%). CONCLUSIONS: Ibutilide can be used for conversion of monoAT with a similar efficacy as for atrial fibrillation, but with a considerably lower efficacy compared to typical atrial flutter.

Anti-Arrhythmia Agents↗
PubMed2002

M(3)-receptor knockout mice: muscarinic receptor function in atria, stomach fundus, urinary bladder, and trachea.

Negative chronotropic and smooth muscle contractile responses to the nonselective muscarinic agonist carbamylcholine were compared in isolated tissues from M(3)-muscarinic receptor knockout and wild-type mice. Carbamylcholine (10(-8)-3.0 x 10(-5) M) induced a concentration-dependent decrease in atrial rate that was similar in atria from M(3)-receptor knockout and wild-type mice, indicating that M(3) receptors were not involved in muscarinic receptor-mediated atrial rate decreases. In contrast, the M(3) receptor was a major muscarinic receptor involved in smooth muscle contraction of stomach fundus, urinary bladder, and trachea, although differences existed in the extent of M(3)-receptor involvement among the tissues. Contraction to carbamylcholine was virtually abolished in urinary bladder from M(3)-receptor knockout mice, suggesting that contraction was predominantly due to M(3)-receptor activation. However, approximately 50-60% maximal contraction to carbamylcholine occurred in stomach fundus and trachea from M(3)-receptor knockout mice, indicating that contraction in these tissues was also due to M(2)-receptor activation. High concentrations of carbamylcholine relaxed the stomach fundus from M(3)-receptor knockout mice by M(1)-receptor activation. Thus M(3)-receptor knockout mice provided unambiguous evidence that M(3) receptors 1) play no role in carbamylcholine-induced atrial rate reduction, 2) are the predominant receptor mediating carbamylcholine-induced urinary bladder contractility, and 3) share contractile responsibility with M(2) receptors in mouse stomach fundus and trachea.

Animals↗
PubMed2002

Differences in protective profiles of diltiazem isomers in ischemic and reperfused guinea pig hearts.

The effects of L-cis and D-cis diltiazem on the extracellular potassium concentration ([K(+)]e), pH and cardiac function were compared in ischemic guinea pig hearts. Before inducing ischemia, L-cis diltiazem (10 and 30 microM) reduced the left ventricular developed pressure (LVDP) with a marginal inhibition of heart rate (HR), whereas lower doses of the D-cis isomer decreased both LVDP and HR. L-cis Diltiazem only slightly inhibited the increase in [K(+)]e and the decrease in pH but significantly inhibited ischemic contractures in contrast to the marked inhibition of these parameters produced by even low doses of the D-cis isomer. Notably, at equipotent doses for the ischemic parameters, L-cis diltiazem restored the left ventricular end-diastolic pressure (LVEDP) and HR after reperfusion to a greater extent than the D-cis isomer. These results suggest that the L-cis isomer may specifically improve postischemic function, in addition to the modest action on [K(+)]e and pH, in guinea pig hearts.

Animals↗
PubMed1998

Synthesis, rotamer orientation, and calcium channel modulation activities of alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates.

A group of racemic alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates (13a-q) was prepared using a modified Hantzsch reaction that involved the condensation of a 3- or 6-substituted-2-pyridinecarboxaldehyde (7a-j) with an alkyl or 2-phenethyl 3-aminocrotonate (11a-d) and nitroacetone (12). Nuclear Overhauser (NOE) studies indicated there is a significant rotamer fraction in solution where the pyridyl nitrogen is oriented above the 1,4-dihydropyridine ring, irrespective of whether a substituent is located at the 3- or 6-position. A potential H-bonding interaction between the pyridyl nitrogen free electron pair and the suitably positioned 1,4-dihydropyridine NH moiety may stablize this rotamer orientation. In vitro calcium channel antagonist and agonist activities were determined using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays, respectively. Compounds having an i-Pr ester substituent acted as dual cardioselective calcium channel agonists (GPLA)/smooth muscle-selective calcium channel antagonists (GPILSM), except for the C-4 3-nitro-2-pyridyl compound which exhibited an antagonist effect on both GPLA and GPILSM. In contrast, the compounds with a phenethyl ester group, which exhibited antagonist activity (IC50 = 10(-5)-10(-7) M range) on GPILSM, were devoid of cardiac agonist activity on GPLA. Structure-activity relationships showing the effect of a substituent (Me, CF3, Cl, NO2, Ph) at the 3- or 6-position of a C-4 2-pyridyl moiety and a variety of ester substituents (Me, Et, i-Pr, PhCH2CH2-) upon calcium channel modulation are described. Compounds possessing a 3- or 6-substituted-2-pyridyl moiety, in conjuction with an i-Pr ester substituent, are novel 1,4-dihydropyridine calcium channel modulators that offer a new drug design approach directed to the treatment of congestive heart failure and may also be useful as probes to study the structure-function relationships of calcium channels.

Animals↗
PubMed1990

Cardiorespiratory interactions in patients with an artificial heart.

A retrospective analysis of the influence of respiration was carried out in three patients with artificial hearts. During spontaneous ventilation, large swings in intrathoracic pressure can produce a pattern reminiscent of pulsus paradoxus in the systemic arterial pressure. A decrease in intrathoracic pressure decreased biventricular filling and enhanced biventricular emptying. An increase in intrathoracic pressure increased biventricular filling, but acting as an increased afterload, impeded biventricular emptying. The influence of respiration on the artificial heart can be considered the result of the artificial ventricles' functioning effectively as extrathoracic pumps, such that changes in intrathoracic pressure produce gradients for biventricular filling and ejection relative to atmospheric pressure (which serves as the reference pressure for the artificial ventricles). Respiratory-induced variation in ventricular performance is clearly present with the artificial heart, but the mechanisms producing these changes appear to be markedly different from normal conditions, in which the ventricles are functionally within the thorax and have a compliant common septum allowing ventricular interaction.

Atrial Function↗
PubMed1993

Echocardiographic findings in mild and severe forms of sickle cell anemia.

M-mode echocardiographic findings were compared between sickle cell anemic and healthy children. Patients were composed of two groups; Group 1: mild group with no crises, no blood transfusions at the ages of 5.0 to 13.0, total of 12 children; Group 2: severe group, with frequent crises with requirement of blood transfusions at the ages of 3.0 to 13.0 years, total of 18 children. Control group was composed of 12 healthy children aged 5.0 to 13.0. When M-mode echocardiographic findings were compared, important findings were as follows: Mean left atrium dimension was increased both in the mild and severe groups (P < 0.001) compared with controls. This finding also supports the increase in the left ventricle end-diastolic dimension in both the severe and mild groups as compared with controls (P < 0.001). The increase in end-diastolic left ventricle dimension could be due to anemia present in the patients, but there was no difference between the two patient groups. Posterior left ventricle thickness and left ventricle mass was increased in both the mild and severe groups compared with controls (P < 0.001, P < 0.05), respectively. Left ventricular fractional shortening was more or less the same with controls. In spite of left ventricular volume load and dilatation, left ventricular contraction was good and systolic function was normal, and there was no correlation between the ECHO findings and hematological indices.

Adolescent↗
PubMed1990

Atrial natriuretic factor constitutes an intrinsic functional unit within superior cervical ganglia of the rat.

The molecular forms of atrial natriuretic factor were studied in the sympathetic ganglia of the rat. The peptide atrial natriuretic factor was also tested for its ability to induce intracellular changes in ganglionic elements. Chromatographic evaluation of extracted ganglionic atrial natriuretic factor revealed the presence of proatrial natriuretic factor together with lower molecular weight peptides. Atrial natriuretic factor induced a maximal six-fold increase of cGMP accumulation within ganglia in vitro, most probably in principal ganglionic cells. Its effect on cGMP was not mediated by acetylcholine or any other neurotransmitter because it persisted after muscarinic receptor blockade and in a calcium-free medium and was not affected by ganglia decentralization. Thus, atrial natriuretic factor appears to be produced by a structural neural component of ganglia (in preganglionic cholinergic neurons or small intensely fluorescent cells?) and has receptors at sites different from its source. It is suggested that atrial natriuretic factor may be locally involved in the process of neurotransmission and may be yet another peptide neurotransmitter and/or neuromodulator.

Animals↗
PubMed1987

Effect of alpha-human atrial natriuretic polypeptide on anterior pituitary function in men.

In order to examine the effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on the basal plasma concentrations of GH, TSH, LH, FSH and PRL in humans, synthetic alpha-hANP was infused into 10 normotensive, euvolemic, healthy volunteers. There were observed marked hypotensive, diuretic and natriuretic effects during the alpha-hANP infusion. The basal plasma concentrations of GH, TSH, LH and FSH, showed no significant change following the alpha-hANP infusion. However, significant suppression of the plasma PRL concentration was observed with the alpha-hANP administration. The mean plasma PRL concentration tended to be decreased during 20 min of alpha-hANP infusion, however, there the differences were not statistically significant. A significant reduction in the mean plasma PRL concentration (-20%, P less than 0.5) was observed 10 min after the end of infusion, following the reversion to the preinfusion level at 70 min after the end of infusion. Such a significant and delayed suppression was not seen in the case of placebo infusion. The data suggest that the circulating hANP may reduce the release of PRL.

Adult↗
PubMed1997

[A correlation between atrial natriuretic peptide, brain natriuretic peptide, and perioperative cardiac and renal functions in open heart surgery].

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are homeostatic hormones secreted from the human heart which protect both cardiac and the renal function. It is well known that these hormones increase in patients along with increases in the severity of congestive heart failure or acute myocardial infarction. However, as yet there are no reports in the literature on changes of the secreted level of ANP or BNP in surgical patients undergoing cardiopulmonary bypass (CPB). We evaluated the relationship between ANP, BNP, and perioperative cardiac and renal functions in patients with heart failure caused by CPB. We selected 45 patients of elective open heart surgery. We measured plasma level of ANP in all 45 cases, and BNP in 18 cases at preoperation, postoperation, and postoperatively three days after, respectively. At the same time, the cardiac index (CI) was measured. These cases were divided into the following groups. Group A1 (n = 23): cases in which the preoperative ANP was less than 40 pg/ ml. Group A2 (n = 22): cases in which the preoperative ANP was more than 40. Group B1 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as mach as the normal level. Group B2 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as much as the normal level. Group B2 (n = 10): cases in which the preoperative BNP was more than that of 10 times as mach as normal level. We then carried out a comparative study of the perioperative cardiac and renal functions in group A1 and A2, and group B1 and B2, respectively. In the terms of preoperative cardiac and renal function, there were no significant differences between groups A1 and A2, and there were no significant differences in urinary volume during CPB or post operative CI. However, the urinary volume during CPB of group B1 was significantly more than that of B2. Furthermore, the incidence of postoperative CI in group B1. Furthermore, the incidence of postoperative CI in group B1 was significantly higher than in B2. The preoperative and post operative third day BNP level had significant negative correlations with postoperative CI and postoperative third day CI, respectively (r = -0.641, -0.514, p = 0.008, 0.012). The postoperative ANP and BNP levels tend to a mean level roughly similar to one another because of the easing of cardiac stress by surgery and postoperative management. According to these results and several instances in the literature, a preoperative high BNP is considered to suggest a potential perioperative risk for cardiac and renal function. We conclude that determination of the plasma BNP level can be helpful for decisions related to CPB flow and measures taken to enhance cardiac and renal protection during surgery, and therefore is a useful reference for perioperative management.

Aged↗
PubMed1999

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure.

BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. AIMS: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. METHODS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. CONCLUSION: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function.

Aged↗
PubMed1994

Diagnosis of atrial arrhythmias using the Holter function of a new DDD pacemaker.

UNLABELLED: The extension of random access memory now makes it possible to store electrocardiographic (ECG) information, referred to here as Holter function (HF), in the memories of new pacemakers, which can be used as diagnostic tools during long-term follow-up. This report describes our experience in 26 consecutive patients for whom the device was used to detect episodes of atrial arrhythmias (AA). An illustrative case is also presented to describe in detail the device's analytical method. RESULTS: Fourteen AA profiles were successfully recorded in 10 patients by the pacemaker HF and correlated with confirmatory simultaneous surface ECG tracings. Three additional profiles were recorded in three other patients without simultaneous ECG recordings. A diagnosis of AA is established when the following findings are combined: (1) in all cases a large number of short interatrial intervals (A INT); (2) in presence of AV block, interventricular intervals (V INT) stored between the lower programmed pacing rate and the upper rate limit or the fallback rate; (3) in absence of AV block, V INT stored between the basic rate and the AV node refractory period; (4) in case of fallback, (VVI function) no stored AV INT; and (5) in absence of fallback, great variability of AV INT (Wenckebach function). CONCLUSIONS: (1) Diagnoses of AA can be made with the pacemaker HF; (2) The homogeneity of the HF profiles makes them useful for long-term follow-up and will probably contribute and clarify the natural history of AA in DDD patients; (3) HF may also serve to monitor the safety and efficacy of antiarrhythmic drug therapy during long-term follow-up.

Aged↗
PubMed1994

The effect of residual strain on the diastolic function of the left ventricle as predicted by a structural model.

The unloaded heart is not stress-free. It is subjected to residual stress and strain. Their extent and influence on the global performance of the left ventricle and on local phenomena in the ventricular wall are studied by model simulation. The analysis focuses on the equatorial region of the ventricle, with an approximate thick-walled cylindrical geometry. The in vivo myocardium is considered to be incompressible, consisting of fibers embedded in a fluid matrix, with transmurally varying anisotropic microstructure in accordance with morphological characteristics. The results show that residual strain is transmurally distributed with a pattern and magnitude which agree well with measurements. The calculated residual strains are within mean +/- one standard deviation of the measured ones. Their magnitude was found to increase with increasing opening angle and with increasing wall thickness. The residual strain was found to have several effects on ventricular function: At volumes higher than the reference one it gives rise to more uniform transmural distributions of stress and intramyocardial pressure; it causes about 50% increase in the ventricular compliance at high volumes and doubles the suction of atrial blood at low volumes, thus facilitating the diastolic filling. In addition, residual strains cause bias of in vivo measured strains from their true values. This may significantly affect physiological interpretation of measured ventricular deformations. In conclusion, the present structural analysis predicts that residual strain has favorable effect on left-ventricular diastolic performance, and gives rise to more uniform ventricular stress distribution.

Atrial Function, Left↗
PubMed2006

Pulmonary vein vestibule ablation for the control of atrial fibrillation in patients with impaired left ventricular function.

INTRODUCTION: Congestive heart failure (CHF) and atrial fibrillation (AF) are frequently linked, and when associated produce additive deleterious effects. In this prospective study, the effects of catheter ablation for AF in patients with impaired left ventricular (LV) function are presented. METHODS: Baseline data and clinical outcome have been prospectively collected in 105 consecutive patients who underwent pulmonary vein ablation for the control of AF. We evaluated 40 patients affected by LV dysfunction with ejection fraction (EF)<40% and compared them to the remaining 65 patients with normal ventricular function in terms of changes in LV function, maintenance of sinus rhythm, and quality of life during follow-up. RESULTS: After a mean follow-up of 14+/-2 months, 87% of patients with impaired LV function and 92% of patients with normal ventricular function were in sinus rhythm, with or without antiarrhythmic therapy (P=NS). A significant improvement in LVEF and fractional shortening was documented in patients with CHF (33+/-2% vs 47+/-3%, and 19+/-4% vs 30+/-3%, P<0.01 for both comparisons). Evaluation of exercise capacity and quality of life documented better improvements in patients with CHF compared to patients without CHF. CONCLUSIONS: Catheter ablation in patients with LV dysfunction is feasible, not associated with higher procedural complications, and provides a significant improvement in LV performance, symptoms, and quality of life during follow-up.

Atrial Fibrillation↗
PubMed2003

ECG mapping and imaging of cardiac electrical function.

Inverse electrocardiography has been developed for several years. By coupling electrocardiographic mapping and 3D-time anatomical data, the electrical excitation sequence can be imaged completely non-invasively in the human heart. In this study, a bidomain theory based surface heart model activation time imaging approach was applied to single beat data of atrial and ventricular depolarization. For sinus and paced rhythms, the sites of early activation and the areas with late activation were estimated with sufficient accuracy. In particular for focal arrhythmias, this model-based imaging approach might allow the guidance and evaluation of antiarrhythmic interventions, for instance, in case of catheter ablation or drug therapy.

Adult↗
PubMed1993

Similar atypical beta-adrenergic receptors mediate in vitro rat adipocyte lipolysis and colonic motility inhibition.

We investigated the putative common nature of the rat atypical beta-adrenoceptors mediating white adipocyte lipolysis and proximal colon motility inhibition, using the non-selective antagonist alprenolol and agonist isoprenaline and the selective agonists SR 58611A and BRL 37344. Results in either isolated intestinal and fat tissues were consistent with: isoprenaline acting through both typical (beta 1, beta 2) and typical beta-adrenoceptors; SR 58611A and BRL 37344 acting solely through the latter. The identical pA2 values obtained with alprenolol, irrespective of the tissue and the selective agonist (SR 58611A or BRL 37344) used, support the high functional homology of the atypical beta-adrenoceptors in rat colon and adipocytes.

Adipocytes↗