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Head-up tilt testing demonstrates vasovagal mechanisms as a cause for syncope, but the pathophysiology underlying this condition remains unclear. The aim of this study was (i) to measure plasma beta-endorphins, adrenocorticotrophic hormone, cortisol, catecholamines, and brain natriuretic peptide during head-up tilt, and (ii) to assess the effect of naloxone infusion during head-up tilt in subjects with reproducible vasovagal syncope. During the assessment of unexplained syncope, 71 subjects underwent a total of 93 tilt tests (60-70 degrees head upwards for 40-45 min or until syncope occurred) during which frequent blood sampling was performed. Subjects with a positive tilt test (n = 56) (mean duration to syncope 23.6 min) showed a larger rise in beta-endorphin levels prior to syncope (baseline 4.7 +/- 2.2 vs syncope onset 6.9 +/- 3.2 pmol.l-1, P = 0.0001) than those with a negative test (n = 37) (baseline 3.9 +/- 3.9 vs end of test 4.9 +/- 2.3 pmol.l-1, P = 0.03). During tilting, adrenocorticotrophic hormone, cortisol, and noradrenaline increased; adrenaline and brain natriuretic peptide remained unchanged; and these responses were similar in positive and negative test groups. Naloxone (2.6 mg.kg-1 i.v. bolus followed by 20 micrograms.kg-1.min-1 infusion), administered in a double-blind fashion during head-up tilt in nine subjects, failed to modify either the time to syncope or the vasodepressor response. Thus, endogenous opioids appear not to be an important trigger for vasovagal syncope, and other pathophysiological mechanisms should be considered.

The class III antiarrhythmic drug dofetilide is known to prolong action potential duration by specific blockade of the delayed rectifier potassium channel Ik. As dofetilide is likely to be used in the treatment of atrial arrhythmias it is important to determine the relative sensitivity of the atrium and ventricle in man. Twelve male patients underwent monophasic action potential and refractory period recordings from the high right atrium and right ventricular septum. The patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously. The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD 6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo group. There was no significant difference in effect between the two chambers. The change in QTc did not accurately reflect acute changes in refractory period or monophasic action potential duration. This has important implications for the use of QT prolongation to assess the acute effect of class III drugs.

Paroxysmal atrial fibrillation is a common, poorly understood and difficult-to-treat arrhythmia. Although it tends to be treated in a similar fashion to chronic atrial fibrillation, its pathophysiology is different, and drugs commonly used for chronic atrial fibrillation may have only limited value in treating paroxysmal atrial fibrillation. A broad range of presenting clinical symptoms may be associated with this arrhythmia, and even in the asymptomatic patient, there may be a risk of serious thromboembolic events. In symptomatic patients, effective control of paroxysms with antiarrhythmic therapy can often be difficult, and the role of anticoagulation remains controversial. This review attempts to clarify these issues, by surveying the range of therapies available.

The incidence, amplitude, mechanism and relationship to prior exposure to streptococcal antigen of blood pressure changes to streptokinase-containing thrombolytic agents were investigated in 125 patients treated with either 1.5 x 10(6) IU streptokinase over 60 min or 30 U anistreplase over 5 min, within 6 h of onset of acute myocardial infarction. Twenty-one of 52 patients with anterior and 34 of 73 with inferior myocardial infarction had a hypotensive response. There were no significant differences in the incidence, duration or amplitude of hypotension between the two treatment groups. The maximum mean fall in systolic blood pressure was 16.9 mmHg (95% confidence limits, CL 12.2 to 24.5 mmHg), and the maximum mean fall in diastolic blood pressure was 13.7 mmHg (CL 10.3 to 17.1 mmHg), starting 4 min after start of therapy and resolving within 34 min. Blood pressure changes were well tolerated. Hypotension was not related to pretreatment streptokinase resistance titre, or anti-SK IgG concentration, to changes in plasma fibrinogen, B-beta 15-42 peptide, D-dimer--as indices of thrombin activation and fibrin (-ogen) breakdown--to plasma viscosity. The blood pressure changes following treatment with streptokinase-containing thrombolytic agents in acute myocardial infarction are frequent but well tolerated. The mechanism of hypotension remains unclear, but is not related to prior exposure to streptococcal antigen.

A comparison of verapamil with adenosine for the immediate treatment of supraventricular tachycardia was made from a retrospective review of 164 spontaneous episodes of paroxysmal tachycardia in 43 patients. Verapamil administered to 33 patients restored sinus rhythm in 91 of 112 episodes (81 per cent). Hypotension occurred in 9 per cent of episodes. Adenosine terminated 94 per cent of episodes of supraventricular tachycardia in 25 patients. The arrhythmia recurred shortly after adenosine restored sinus rhythm in 20 episodes. Transient side effects were common. Fifteen patients were treated with both agents. Adenosine was successful in all, but verapamil failed to restore sinus rhythm at least once in seven of the 15 patients. Early recurrence of tachycardia occurred in five of these after adenosine, but in only one after verapamil. Verapamil and adenosine are both effective in the treatment of supraventricular tachycardia; adenosine has the higher success rate and is safer, but transient symptoms are common and arrhythmias may recur.

The antihypertensive effect and a non-invasive cardiovascular assessment of indapamide in patients with idiopathic hypertension have been investigated in an uncontrolled study. Indapamide was found to be an effective antihypertensive agent in a dose of 2.5 mg per day with a mean fall in blood pressure of 25/18 mmHg. Apart from the development of impotence in one patient, no side effects were encountered. Its effect on heart rate and cardiac output suggest that vasodilatation may contribute to its mode of action. Exercise performance is well maintained and cardiac performance appears to improve when blood pressure is lowered with this drug.