Microinjections of 5-HT1A agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat.

1. The effects of microinjections (100 nl) into the dorsal motor vagal nucleus of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan, the 5-HT2 receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), the 5-HT3 receptor agonist phenylbiguanide (PBG), the alpha 2-adrenoceptor agonist clonidine and the excitatory amino acid glutamate on heart rate, blood pressure, tracheal pressure and phrenic nerve activity were investigated in atenolol-pretreated rats anaesthetized with sodium pentobarbitone. 2. Microinjections of glutamate (2.5 nmol) caused decreases in blood pressure, heart rate and phrenic nerve activity. In contrast, microinjections of 5-HT (1.2 nmol), 8-OH-DPAT (1.2 nmol) and flesinoxan (1.3 nmol) all caused a bradycardia but had no effect on blood pressure. In addition, 8-OH-DPAT and flesinoxan caused an increase in phrenic nerve activity. 3. Microinjections of DOI, PBG and clonidine had no significant effect on any of the variables recorded. None of the drugs used had any significant effect on tracheal pressure. 4. These results support the hypothesis that activation of 5-HT1A receptors causes excitation of cardiac vagal motoneurones and suggest that these receptors are also important in the control of central respiratory drive.

Catheter ablation of permanent atrial fibrillation: medium term results.

OBJECTIVE: To investigate the feasibility of catheter ablation as a treatment for symptomatic patients with longstanding permanent atrial fibrillation (AF). METHODS: Radiofrequency ablation was applied to encircle all pulmonary veins (PVs) and create lines from the left inferior PV to the mitral valve, along the roof of the left atrium between the PVs, and along the tricuspid valve-inferior vena cava isthmus. A seven day Holter was recorded at discharge and at follow up to assess arrhythmia burden. If patients developed a symptomatic, sustained atrial arrhythmia a repeat ablation procedure was advised. RESULTS: 42 patients underwent the procedure that took a mean of five hours with 50 minutes of fluoroscopy. After a median follow up of 8.4 months, 31 of 41 surviving patients (76%) were in sinus rhythm. Of these, 29 patients were no longer taking any antiarrhythmic drugs but 22 (52%) required more than one procedure. During follow up 49% experienced a sustained atrial tachycardia. Twenty six repeat procedures were performed. Maintenance of sinus rhythm after the first, second, or third procedure was 36% (15 of 42), 58% (11 of 19), and 71% (5 of 7), respectively. From a total of 68 procedures there were two serious complications (2.9%): a stroke from which a full recovery was made, and a PV stenosis. CONCLUSION: Catheter ablation can be used to cure longstanding permanent AF; however, there is a significant complication rate. Whether this is offset by a mortality benefit associated with sinus rhythm is unknown. Many patients will need more than one procedure to achieve success.

Ventricular arrhythmia, Cheyne-Stokes respiration, and death: observations from patients with defibrillators.

OBJECTIVE: To determine whether ventricular arrhythmia related to nocturnal hypoxaemia during Cheyne-Stokes respiration (CSR) explains the observation that CSR is an independent marker of death in heart failure. DESIGN: Prospective, observational study. PATIENTS: 101 patients at high risk of clinical serious ventricular arrhythmia fitted with an implantable cardioverter-defibrillator (ICD). MEASUREMENTS: Patients were studied at baseline for CSR during sleep. Arrhythmia requiring device discharge was used as a surrogate marker for possible sudden cardiac death. RESULTS: 101 patients (42 with CSR) were followed up for a total of 620 months. Twenty six patients experienced 432 ICD discharge episodes. Twenty four (6%), 210 (49%), 125 (29%), and 73 (17%) episodes occurred across the time quartiles 0000-0559, 0600-1159, 1200-1759, and 1800-2359, respectively. Kaplan-Meier analysis showed a relative risk of 1 (95% confidence interval 0.5 to 2.2, p = 1) for device discharge in the CSR group. The average (SED) numbers of nocturnal ICD discharges per patient per month of follow up were 0.01 (0.01) and 0.04 (0.02) for patients with and without CSR, respectively (p = 0.6). CONCLUSION: These findings refute the proposition that CSR is related to heart failure death through nocturnal serious ventricular arrhythmia.

Acute ischaemia: a dynamic influence on QT dispersion.

BACKGROUND: The aim of this study was to test the hypothesis that acute myocardial ischaemia increases QT dispersion measured from the 12-lead electrocardiogram. METHODS: Incremental atrial pacing was used to induce myocardial ischaemia in 18 patients with coronary artery disease and QT dispersion was measured. Six patients with normal coronary arteries served as the control group. FINDINGS: All the patients with coronary artery disease developed angina and/or ST depression accompanied by marked increases in QT dispersion (mean increase 38 ms, 95% CI 30 to 45 ms, p < 0.001). In contrast, in the six patients with normal coronary arteries who remained without symptoms and without ST changes, there was no significant change in QT dispersion in response to pacing. Baseline QT dispersion did not distinguish those patients with coronary artery disease from those with normal coronary arteries (44 ms [95% Cl 39-49 ms] vs 40 ms [25-55 ms]), respectively. INTERPRETATION: These results demonstrate that myocardial ischaemia induced by incremental atrial pacing in patients with coronary artery disease causes an acute increase in QT dispersion. Such "inducible" QT dispersion may prove more useful than resting QT dispersion in assessing the individual risk of arrhythmic events in patients with coronary artery disease.