Heterochromatin heteromorphism and variation in apolipoprotein A phenotype--a pilot study.
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Biomedical subjects
Publications and source records attributed to B W Johansson.
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Metabolic activity in cardiac tissue slices from the guinea pig (GP), the rat (RT), the nonhibernating summer and winter hedgehog (SH and WH), respectively, was determined at 20 degrees and at 37 degrees C from their rates of heat production, P, (units, W/g tissue) by direct and indirect calorimetry. Energy-linked transport of Na+ and K+ in the tissues was determined from changes in metabolic rate induced by specific inhibition of the Na/K pump, the functional expression of Na/K-ATPase, the pacemaker enzyme in energy production assigned the role of transporting Na+ and K+ out of and into the cell. The results indicate a higher rate of energy production and utilization in the cardiac tissue of the hedgehog than in that of the nonhibernators, the rat and the guinea pig, at both temperatures. At 37 degrees C the rate at which the cardiac tissue from the hedgehog consumed oxygen was as much as six times that registered for the guinea pig. The temperature coefficients of P and of the Na/K pump in the tissues from the two groups of hedgehogs were significantly higher than in the tissues from the rat and the guinea-pig (P < 0.001). The determined metabolic indices, the basal rate of heat production P, the rate of oxygen consumption, P(O2) in thermal units (W/g tissue), and the Na/K-pump capacity (PC) indicate species-specific differences between the animals. Both PC and its variation with temperature, delta PC/delta T(o)C, were in the order WH > SH > RT > GP. These results indicate that the hedgehog's cardiac tissue, in comparison with that of the nonhibernators, has a greater capacity to generate energy in general and for active transport of Na+ and K+ at 37 degrees C after exposure to a lower temperature. A role is suggested for the Na/K-ATPase and some other unique rate-limiting enzymes in the metabolic pathway for the observed differences in temperature tolerance and cardiac performance between hibernators and nonhibernators.
To study the effects of the new vasodilating beta-blocking agent carvedilol on a variety of metabolic, hemodynamic, and ECG parameters of importance for the clinical outcome of acute myocardial infarction (AMI), we infused epinephrine (EPI) in healthy male volunteers on two separate occasions to serum concentrations of the same level reached in AMI. Before the EPI infusions, the volunteers were pretreated for 2 weeks with either carvedilol or placebo in randomized order. EPI caused significant decreases in serum levels: S-potassium (0.62 mM), S-magnesium (0.07 mM), S-calcium (0.12 mM), and S-phosphate (0.26 mM). After pretreatment with carvedilol, the decreases in S-calcium and S-phosphate were partly prevented and those in S-potassium and S-magnesium were completely inhibited. Short-term treatment with carvedilol significantly decreased S-insulin and serum C-peptide and significantly attenuated the EPI-induced increase in B-glucose observed after placebo. The EPI infusion significantly increased serum concentrations of free fatty acids and glycerol. These increases were significantly attenuated by carvedilol, whereas carvedilol had no significant affects of a variety of other lipid variables. EPI infusion caused a significant (p < 0.01) increase in systolic blood pressure (SBP) from 124.8 +/- 8.1 to 135.8 +/- 12.5 mm Hg and an increase in heart rate (HR) from 71.0 +/- 11.5 to 77.2 +/- 12.2, resulting in a significant increase in rate-pressure product (RPP). This estimate of cardiac work was significantly (p < 0.05) reduced by pretreatment with carvedilol.(ABSTRACT TRUNCATED AT 250 WORDS)
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A circadian variation of symptom onset in acute myocardial infarction (AMI) with an increased frequency in the late morning and possibly also in the evening has been found in several studies. It has been suggested that different circadian rhythms may exist in various subgroups of patients. This possibility was examined in a population of 10,791 patients collected between 1973 and 1987 in a continuously operating register of patients with AMI in Malmö, Sweden. In 6,763 patients (63%) in whom a distinct symptom onset could be established, symptom onset occurred with an increased frequency between 6:01 A.M. and 12:00 noon (30.6%) and between 6:01 P.M. and 12:00 midnight (26.9%). Similar bimodal circadian rhythms were seen in patients aged greater than 70 years (n = 2,923), less than or equal to 70 years (n = 3,840), men (n = 4,528), women (n = 2,235), smokers (n = 2,458), hypertensives (n = 1,999), diabetics (n = 653), patients with (n = 1,872) and without (n = 4,891) a history of previous AMI, and in patients with recent non-Q-wave AMI (n = 333). In 455 patients receiving cardioselective beta blockers the circadian distribution did not differ from a random, whereas in patients taking nonselective beta blockers or calcium antagonists significant bimodal rhythms were found. Statistically significant interactions were found between symptom onset and age dichotomized at 70 years, and between patients with and without a history of previous AMI. In a multivariate analysis only these variables age less than or equal to/greater than 70 years; +/- history of a previous AMI) were found to modify the circadian rhythm of symptom onset in the population.(ABSTRACT TRUNCATED AT 250 WORDS)
Twelve healthy male volunteers were given adrenaline infusions, 0.05 microgram/kg body weight/min over 120 minutes in order to achieve serum adrenaline concentrations comparable with those seen in acute myocardial infarction. The infusions were given on four occasions, at intervals of at least 4 weeks. Before the infusions the subjects were given, in random order, 14 days of pretreatment with placebo, hydrochlorothiazide 50 mg once daily, amiloride 10 mg once daily, or lisinopril 20 mg once daily. The adrenaline infusion induced a drop in serum potassium of the same magnitude in all four groups, with the lowest absolute value after hydrochlorothiazide because of the lowest pre-adrenaline level. The infusion-induced decreases in serum calcium and magnesium were of the same magnitude in all groups, with the absolute calcium being least low in the hydrochlorothiazide group because of the highest preinfusion value. Preinfusion serum urate was highest after hydrochlorothiazide and fell during the adrenaline infusion in all groups, although not significantly. Blood glucose increased during the adrenaline infusion in all groups, but significantly more after hydrochlorothiazide and amiloride than after lisinopril. Heart rate increased during the adrenaline infusion in all groups but least after lisinopril. QTc preinfusion was longer after hydrochlorothiazide than after amiloride and placebo, but the infusion-induced prolongation of QTc was of the same magnitude in all pretreatment groups. Since our results were obtained in short-term experiments in normal subjects, their clinical relevance is questionable, but they support the view that ACE inhibitors may have certain metabolic advantages over diuretics.
Three-hundred and ninety-four 68-year-old men, representing 60.3% of a cohort of men born in 1914, were examined with ambulatory ECG during 24 h in 1982-83. Ninety-eight (24.8%) men had one or more episodes of ischaemic type ST segment depression (greater than or equal to 0.10 mV), 79 of whom had no history of previous ischaemic heart disease (IHD). During 63 months follow-up, 17 of the 98 suffered a cardiac event, i.e. fatal or non-fatal myocardial infarction (MI) or death due to chronic IHD. The objective of this study was to assess the influence of psychosocial factors, such as social network and social support, on cardiac event rate in men with ischaemic ST segment depression. A higher risk was found among men with little material and informational support (i.e. access to practical services and material resources and access to guidance, advice and information (crude relative risk 4.8; 95% CI; 1.6-14.8) and men with low availability of emotional support (i.e. opportunity for care, encouragement of personal value and feelings of confidence and trust) (crude relative risk 4.3; 95% CI: 1.4-13.3). This association was independent of history of IHD and other known risk factors for myocardial infarction (MI).
Based upon community myocardial infarction (MI) records in five Swedish cities, geographical variation and time trends in the attack rate of fatal and non-fatal MI have been evaluated. During the study period 1975-1982, a total of 7699 events were registered among men and 1823 events among women. The mean annual mortality was highest in the north, and a declining gradient in mortality was observed from the northern to the southern part of the country. The out-of-hospital death rate was highest in the north, while no difference in in-hospital mortality was observed. However, the geographical variation in the morbidity of MI was less consistent. Changes over time generally followed the same pattern in all cities. The attack rate of fatal and non-fatal MI tended to decline among women and men aged 60-64 years. The pattern was less consistent among younger men. Among women aged 50-59 years the mortality remained unchanged, but the attack rate of non-fatal MI increased in all cities. This increase was not explained by inclusion of less severe infarctions. A considerable proportion, about 85%, were recorded as primary events, emphasizing the possible role of primary prevention in obtaining a decrease in the incidence of the disease. The results of this study support previous findings of an important regional difference in the mortality of MI in Sweden. However, the magnitude of the regional variation in the incidence of coronary heart disease might be overestimated if only the mortality pattern is studied.
A 44-year-old man suffered from recurrent episodes of unconsciousness, without any other concomitant manifestations. After routine workup, EEG and CT had proven nondiagnostic, prolonged Holter monitoring revealed a single episode of asystole, lasting 7.6 seconds. A pacemaker was inserted but did not abolish his episodic syncope. Subsequently, long-term EEG recording revealed epileptiform activity with independent foci in both temporal lobes. Antiepileptic treatment relieved the patient of his symptoms. This case illustrates the intimate relationship between the heart and the brain that sometimes lies behind syncope.
To assess the effects of current treatments with beta-blockers or calcium antagonists on the clinical outcome of acute myocardial infarction (MI), enzymatically estimated infarct sizes, circulatory arrests from ventricular tachyarrhythmias, ventricular tachycardia (VT)/ventricular fibrillation (VF), and in-hospital mortality were analyzed retrospectively from 7,922 citizens of Malmö, Sweden, hospitalized due to a first MI between 1973 and 1987. Of these patients, 296 were on treatment with calcium antagonists, 393 on treatment with a beta 1-selective beta-blocker, 482 with a nonselective beta-blocker, and 95 on combined treatment with beta-blockers and calcium antagonists at the time of admission to hospital. In a set of multivariate analyses including several clinical characteristics, patients on treatment with a nonselective beta-blocker had a significantly lower peak aspartate aminotransferase (ASAT; difference -0.70 mukat/l, 95% CL: -1.24 to -0.16), whereas no significant relations between peak ASAT and treatment with cardioselective beta-blockers or calcium antagonists were found. Treatment with cardioselective beta-blockers or calcium antagonists, in contrast to treatment with a nonselective beta-blocker, were significant predictors of the occurrence of circulatory arrests from VT/VF. The relative risk of VT/VF in patients on cardioselective beta-blockers was 1.51 (95% CI: 1.12-2.03), and in patients on calcium antagonists 1.44 (95% CI: 1.03-2.02). None of the treatments were significantly associated with in-hospital mortality. In patients on beta-blockers or calcium antagonists when suffering their first MI, nonselective beta-blockade may reduce infarct size. Treatment with beta-blockers or calcium antagonists identified patients with an increased risk of circulatory arrests from VT/VF, but neither of the treatments were significantly associated with in-hospital mortality. We suggest that only minor differences exist between the effects of chronic treatment with beta-blockers and calcium antagonists on the outcome of an acute MI.
A case of acute cardiac insufficiency in a 26 year old woman is described. Ultrasound examination of the pericardium was suspect for an pericardial tumor with pericardial effusion and solid masses of tumor in the fluid. Magnetic resonance imaging (MRI) gave the impression of tumor in the pericardium. Pericardiocentesis showed neither malignant cells nor growth of microorganisms. The patient recovered completely on steroid therapy and control MRI showed anatomic normalisation of the cardiac region. It is concluded that idiopatic peracarditis can mimic pericardial tumor on ultrasound and MRI investigation.
Mortality from coronary heart disease has declined for more than 20 years in several industrialized countries. Partly because of a lack of morbidity data, the reasons for the decline are not satisfactorily established. This community-wide survey of coronary heart disease morbidity and mortality in Malmö, Sweden, showed declining mortality rates beginning in the mid-1970s. Between the 3-year intervals 1975-1977 and 1984-1986, coronary heart disease mortality declined by 17% (2,610/100,000 inhabitants in 1984-1986) in men aged greater than or equal to 70 years and by 8% (938/100,000 inhabitants in 1984-1986) in men aged 60-69 years, while coronary heart disease mortality in men aged 50-59 years increased by 7% (355/100,000 inhabitants in 1984-1986). In women aged greater than or equal to 70 years, coronary heart disease mortality decreased by 12% between 1975-1977 and 1984-1986 (1,609/100,000 inhabitants in 1984-1986), while the decrease in women aged 60-69 years was 5% (242/100,000 inhabitants in 1984-1986). The decline in mortality was associated with a decline in both incidence rates and in-hospital case fatality rates for myocardial infarction. The authors suggest that the declining coronary heart disease mortality in Malmö was due partly to prevention of coronary heart disease but that improved medical care for acute and chronic coronary heart disease may also have contributed.
Cardiac transmembrane potentials and Na and Ca currents were recorded at different temperatures in rat and hedgehog ventricular muscle. At 35 degrees C in both species resting potential was about -80 mV and upstroke velocity (Vmax) of the action potential above 100 V/s. The shape of the action potential in hedgehog ventricular cells at 35 degrees C was similar to that in the rat showing a fast repolarization phase. When temperature was decreased, the membrane resting potential depolarized and action potential amplitude and Vmax declined. In rat ventricular cells at 10 degrees C, the resting potential was about -40 to -50 mV and Vmax was reduced to about 5 V/s. In hedgehog ventricular cells, however, the transmembrane potentials and Vmax were better maintained at low temperature. Phase 3 of the action potential was markedly prolonged below 20 degrees C in hedgehog but not in rat ventricular cells. When temperature was decreased to 10 degrees C the availability curve of the Na current shifted toward more negative potentials and ICa.peak declined in rat ventricular cells. In hedgehog cardiac preparations, the Na current was less influenced by the cooling and ICa.peak did not change very much at low temperatures. A transient inward current usually considered to induce cardiac arrhythmias could be recorded in rat ventricular cells below 20 degrees C but not in hedgehog preparations. These features of hedgehog cardiac membranes may contribute to the cold tolerance and the resistance to ventricular fibrillation during the hypothermia in mammalian hibernators.
The objective of this long-term ECG (LTER) study in 394 68-year-old men, selected at random from the general population of Malmö, Sweden, was to determine the prevalence and occurrence of cardiac arrhythmias and their impact on morbidity and mortality from IHD. According to Lown classification, 29.4% (116 men) had ventricular arrhythmia (VA) group 4-5. Serious ventricular arrhythmia (Lown group 4-5) was more common in men with asymptomatic ischaemic type ST-segment depression (STD) than in those without it (37.8% vs. 26.7%: P less than 0.05). During the mean follow-up period of 53.1 months there were seven IHD deaths (6%) among the 116 patients with VA, Lown 4-5, and nine IHD deaths (3.2%) among the 278 patients without serious VA, Lown 0-3, (P = 0.26). Six and three of these deaths, respectively, were considered to be sudden (P = 0.022). The increased cardiac event rate (fatal or non-fatal MI or deaths due to chronic IHD) associated with a serious ventricular arrhythmia disappeared when history of IHD at baseline and occurrence of STD during LTER were taken into account. The study did not provide any evidence to suggest that ventricular arrhythmia was triggered by myocardial ischaemia. Five of 9 (56%) deaths due to IHD in men with STD occurred among the 38% (37/98) of patients who belonged to Lown class 4-5. It is concluded that the prognostic information derived from LTER can be improved by combined monitoring of STD and ventricular arrhythmias.
In order to study the effects of treatment with class 1 antiarrhythmics on the metabolic, hemodynamic, and electrocardiographic responses to adrenaline, 12 healthy volunteers were infused on four occasions, after pretreatment with placebo, disopyramide, mexiletine, and flecainide, respectively, with adrenaline at a rate producing serum adrenaline concentrations comparable with those seen in acute myocardial infarction. After pretreatment with placebo adrenaline caused significant falls in serum potassium, serum magnesium, serum calcium, and serum phosphate and a significant increase in blood glucose. Adrenaline also caused a significant increase in heart rate and systolic blood pressure and a significant fall in diastolic blood pressure. On the electrocardiogram a significant prolongation of QTc duration and a flattening of the T-wave amplitude were seen. Pretreatment with disopyramide had no effect on the hemodynamic response to adrenaline but caused a significant prolongation of Qtc duration before the adrenaline infusion. Pretreatment with mexiletine was associated with a significantly greater fall in serum potassium during adrenaline infusion, and pretreatment with flecainide with a greater fall in serum magnesium, as compared with placebo pretreatment Flecainide also caused a significant prolongation of the QRS duration before adrenalin infusion, and after all the active pretreatments a prolongation of QRS duration was seen during adrenaline infusion. The metabolic and hemodynamic changes during adrenaline infusion may not only reduce the antiarrhythmic efficacy of antiarrhythmics but may also increase the risk of proarrhythmic effects in a clinical setting. These results may help to explain why treatment with antiarrhythmics seems to be without beneficial effect on mortality in post-myocardial infarction patients.