Previous small clinical trials have suggested that treatment with nitric oxide donors in suspected myocardial infarction can reduce mortality by 30-35%. To confirm this finding in a large-scale trial, we compared molsidomine and its active metabolite linsidomine (a nitric oxide donor) with placebo in 4017 patients with acute myocardial infarction.In our trial, patients without signs of overt heart failure (Killip III/lV) were randomly assigned in a double-blind design within 24 h of symptom onset to receive linsidomine 1 mg/h intravenously for 48 h, followed by 16 mg molsidomine by mouth daily for 12 days (n = 2007), or an identical placebo (n = 2010). All other treatments could be used at the responsible physician's discretion with the exception of systematic vasodilator treatment. The molsidomine and placebo groups showed similar all-cause 35-day mortality (168 [8.4%] vs 176 [8.8%] deaths, p = 0.66), and adjustment for baseline variables in a Cox model had no effect. Similarly, we found no difference for long-term mortality(mean follow-up 13 months; 294 [14.7%] vs 285 [14.2%] deaths, p = 0.67). The two groups showed similar frequencies of major and minor adverse events; only headache was significantly more common in the molsidomine group.Changes in treatment practices and the lower risk profile of our study subjects than of participants in previous trials may explain the results. It is still not clear whether nitric oxide donors can improve survival in higher-risk myocardial infarction patients.

A combination of oral flecainide and mexiletine was given to 11 patients in whom monotherapy with one of these drugs was ineffective for the suppression of inducible ventricular tachycardia or fibrillation. In eight of 11 studies, combination therapy prevented inducibility of a sustained ventricular tachycardia or resulted in induction of only nonsustained tachycardia (P = 0.0003, when compared to monotherapy). In one patient, a slow ventricular tachycardia was induced. During exercise testing ventricular tachycardia occurred in two of these nine patients, and ventricular fibrillation in another patient. Seven patients received combination on the long term, for a mean of 18 months. One patient had recurrences of ventricular tachycardia which was well tolerated. Another patient had a recurrent episode of ventricular fibrillation, but was successfully resuscitated. Severe congestive heart failure occurred in two patients. ACE inhibitors were given to them and to another four patients. No other important unwanted effects occurred. The combination of mexiletine and flecainide is very effective in suppressing inducible sustained ventricular tachycardia. The efficacy of this combination to prevent recurrences of ventricular tachyarrhythmias is acceptable. Exercise testing is of importance to unmask proarrhythmic effects before discharge from hospital.

The incidence of sustained atrial, pacemaker-mediated and ventricular rhythm disturbances was studied retrospectively in a consecutive series of 112 patients without a history of preexisting atrial tachyarrhythmias, receiving an atrial or dual-chamber pacemaker. Early atrial fibrillation (during the first week) was recorded twice. Late atrial fibrillation was seen in seven patients, flutter in one, yielding a total incidence of 8.9% for 22 months. There were no significant differences with respect to age, aetiology, electrocardiographic diagnosis, pacing history, or the measured intracardiac P wave between the group with and the group without atrial fibrillation. Treatment with digoxin reverted three patients to sinus rhythm, association of digoxin and amiodarone, six patients. One patient with congestive heart failure remained in atrial fibrillation. Pacemaker-mediated tachycardia was not a major problem. One patient of a subgroup with known ventricular arrhythmia had a non-sustained ventricular tachycardia during programming at follow-up; sustained ventricular tachycardia was not recorded. Reprogramming to VDD, DVI or VVI was done in 6/100 patients. The incidence of atrial fibrillation or flutter in highly selected patients with dual-chamber or atrial pacing is moderately low. It is not possible to identify patients with a high risk for development of atrial fibrillation; when it occurs, it is easily controlled with drugs. DDD pacing seems to be safe in patients with a history of serious ventricular arrhythmias, treated with appropriate drugs.

SummaryInfections with B-haemolytic streptococci, especially Lancefield’s group A, may be complicated with a nowadays rare syndrome in which various organs may be involved. This syndrome emerges from a review of ancient autopsy reports in patients dying of scarlet fever or other severe infections with Bhaemolytic streptococci. Analysis of 21 recent cases (two being described in detail in this article) reveals that, after a variable delay, lesions are seen prominently in the kidneys and the liver, but also other organs as spleen, adrenals and the haematopoietic system may be involved. These organs, when affected, arc usually enlarged and infiltrated by predominantly lymphoplasmocytic cells in the intcrstitium. This can lead to acute renal failure due to acute interstitial nephritis and to icterus due to acute interstitial hepatitis. The pathogenetic rnechanisms remain unclear but have probably an immunological basis or depend on the action of circulating bacterial toxins. When, like in the two described cases, a scarlatiniform rash accompanies the syndrome, similarities with toxic shock syndrome are so striking that one wonders how often both syndromes in the past have been confounded.

In this randomized, double-blind, placebo-controlled trial the renal function was studied in 60 patients recovering from coronary artery bypass surgery treated with a daily dose of 800 mg sulphinpyrazone (SP) or 880 mg acetylsalicylic acid (ASA) or placebo. Serum creatinine level increased (p less than 0.05) during the first 2 days of SP treatment, but returned to its baseline level within 4 days under maintained therapy; during ASA and placebo therapy no significant changes occurred. Serum urea levels decreased (p less than 0.01) during ASA and placebo treatments as time from surgery subsided; the decrease of serum urea level was delayed in the SP group compared with the ASA and placebo groups. Urinary excretion of prostaglandin E2 (PGE2) was significantly decreased (p less than 0.01) during ASA treatment; in the SP group, urinary PGE2 excretion tended also to decrease during the first days of treatment, the decrease being significant only on the 4th day (p less than 0.01). The urinary excretion of kallikrein decreased significantly only in the SP group (p less than 0.01), while the changes in the ASA and placebo group were not significant. We suggest that the rapidly reversible acute renal impairment during SP therapy was probably due to a transient renal ischemia caused by a drug-related decrease in urinary kallikrein excretion rather than by renal prostaglandin inhibition.