Functional analysis of rabbit anti-peptide antibodies which mimic autoantibodies against the beta 1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy.

A synthetic peptide corresponding to the second extracellular loop of the beta 1-adrenergic receptor was used as an antigen for antibody production in three rabbits. Antibodies of high titers were obtained in all rabbits. Only one rabbit yielded antibodies which decreased radioligand binding on the receptor in a similar way to that described for autoantibodies in patients with dilated cardiomyopathy. These antibodies recognized the receptor protein in immunoblots. Epitope mapping indicated that the N-terminal sequence of the loop used as antigen was the target of the major antigen fraction. Incubation of antibodies with C6 glioma cell membranes or inner membranes of E. coli, which express the human beta 1-adrenergic receptor, resulted in a decrease in number of radioligand binding sites. This decrease was dependent on the concentration of antibody and of Mg++ ions. It was not affected by the GTP analog GppNHp or the beta 1 subtype-specific antagonist metoprolol. The agonist, isoproterenol, also induced a decrease but the effects of antibody and agonist were not additive. These results suggest that the antibodies induce a Mg(++)-dependent, 'active', labile conformation of the receptor, independent from coupling to the GTP regulatory protein, but similar to that induced by the agonist isoproterenol. This interpretation was corroborated by the beta 1-adrenergic receptor agonist-like effect of the antibodies on cardiomyocytes in culture.     

Long-term prognosis in relation to ECG findings in acute myocardial infarction

In 680 patients with acute myocardial infarction the prognosis during the following 5 years was related to observations made in a standard electrocardiogram (ECG) and 24 precordial chest leads. Patients with a Q-wave infarction (based on a 12-lead standard ECG) had a mortality rate during hospitalization of 10.2% which was much higher than that in patients with a non-Q-wave infarction (1.9%, p less than 0.001). At 5 years' follow-up 33.6% of those with a Q-wave infarction had died versus 28.4% of those with a non-Q-wave infarction (p greater than 0.2). Corresponding mortality rate among patients with no previous infarction (n = 587) was 32.1% and 25.2%, respectively (p = 0.17). In patients with anterior infarction and no previous infarction there was no correlation between Q- and R-wave changes in the 24 chest leads 4 days after admission to hospital and 5-year mortality rate. We thus conclude that patients with a Q-wave infarction had a higher in-hospital mortality compared with non-Q-wave infarction as judged from standard ECG, whereas 5-year mortality was similar. Similarly, there was no correlation between Q- and R-wave changes in an increased number of chest leads and 5-year mortality rate.     

G?teborg Metoprolol Trial: effects on arrhythmias

During the initial hospitalization, ventricular fibrillation (VF) developed in 6 metoprolol-treated patients (0.9%) vs 17 placebo-treated patients (2.4%) after inclusion in the study (p = 0.035). There were 6 episodes of VF in the metoprolol group compared with 41 episodes in the placebo group (p less than 0.001). During the same period, 14 metoprolol-treated patients had treated ventricular tachycardia vs 26 placebo-treated patients (p = 0.076). Similar favorable results were found when the incidence of severe ventricular arrhythmias during the first rehospitalization within the 3-month double-blind treatment period was analyzed.     

Abnormal lung function in healthy preterm infants.

The aim of this study was to assess the consequences of preterm birth for the functional development of the lungs. We studied 32 healthy preterm infants (gestational age 25 to 33 wk at birth) and 53 healthy full-term infants (37 to 42 wk) at the same mean postmenstrual age of 40 wk with a multibreath nitrogen washout technique to assess functional residual capacity (FRC), gas mixing efficiency, and dead space and with the single-breath occlusion technique to calculate compliance and resistance of the respiratory system. Twenty of the preterm infants were also assessed with the same methods at 34.2 (32 to 37) wk. At the same postmenstrual age the preterm infants had lower FRC/kg body weight, lower specific compliance, impaired gas mixing efficiency, and higher total and dead space ventilation/kg than the full-term infants. Specific compliance and specific conductance decreased but gas mixing efficiency increased from 34 to 40 wk. We conclude that premature exposure to extrauterine conditions changes lung function. Preterm infants showed signs of dysfunction of the terminal respiratory units and higher elastic recoil than infants who spent the corresponding time for development in utero. It is suggested that preterm birth per se affects alveolarization and formation of elastic tissue in the lungs.     

Long-term morbidity in patients where the initial suspicion of myocardial infarction was not confirmed

The morbidity and mortality during a 5-year follow-up in patients admitted to the coronary care unit with chest pain presenting an initial suspicion of acute infarction, but in whom the diagnosis could not be confirmed, is reported. They were divided into four groups: Possible myocardial infarction (29%), angina pectoris (24%), chest pain of uncertain origin (32%), and nonischemic cause of chest pain (15%). The overall 5-year mortality rate was 13.3% and did not differ substantially between the four groups. During the 5-year follow-up a confirmed myocardial infarction developed in 28% and 22% among patients with the diagnosis possible infarction and angina pectoris, respectively, and in about 10% of the remaining patients. Stroke developed in 4% of patients with possible infarction and in 2-3% in the remaining subgroups. In all, 59% of the patients were rehospitalized for a mean duration of 30 days in hospital. Among survivors at 5 years, 54% reported chest pain equivalent to angina pectoris and 25% had chest pain daily. A high prevalence of angina pectoris, a high frequency of rehospitalization due to chest pain, and a high consumption of cardiovascular drugs could be found in all four groups.     

Adverse effects of beta-blockade withdrawal in patients with congestive cardiomyopathy

Fifteen patients with congestive cardiomyopathy who had improved conspicuously on chronic administration of a beta-blocker were studied after withdrawal of the drug. In six patients there was a pronounced deterioration of their clinical condition, and in all of the remaining patients there was a significant decrease in ejection fraction, and signs of compromised diastolic function with pathological apex curves and an increase in third heart sound. All these changes were reversed within a few weeks to a few months after readministration of beta-blocking drugs. This study supports the idea that an aetiological factor in congestive cardiomyopathy may be a pathological response to sympathetic stimulation which could be partly controlled by administration of beta-blocking drugs.     

Treatment of pain in acute myocardial infarction.

The treatment of pain in acute myocardial infarction varies with local practice. Narcotic analgesics are still the usual treatment in many hospitals. Knowledge of optimal doses, duration of pain relief, and time between drug administration and pain relief is inadequate. Many studies indicate that the relief of pain is often incomplete after treatment with narcotic analgesics. There is often a need for alternative treatments. Large randomised studies consistently show that beta blockade, initially given intravenously and then orally, relieves pain and reduces the need for analgesics. Studies also indicate that early administration of streptokinase and glyceryl trinitrate relieves pain. There is evidence that drugs that limit ischaemic damage also relieve pain.     

Immediate effects on lung function of instilled human surfactant in mechanically ventilated newborn infants with IRDS

We have studied the effects on lung volume, respiratory mechanics and ventilation during the first hours after instillation of 60 mg/kg of human surfactant into the trachea of 4 very preterm, newborn infants with severe IRDS under mechanical ventilation. Measurements were made with a "face-out" body plethysmograph and a modified nitrogen wash-out method. In addition to a transient decrease in total and alveolar ventilation immediately after the instillation we found an immediate rise in lung volume, but respiratory compliance decreased. These changes lasted less than two hours. Oxygen requirements fell in 3 out of 4 infants. The changes in lung volume and compliance are explained in terms of changes in the shape of the static recoil pressure characteristics of the diseased lungs after treatment. Mechanisms behind the short duration are sought in mode of instillation, dosage, age at treatment, and severity of disease.