Donor-specific cytotoxic T cells recovered from transvenous biopsies after clinical heart transplantation.
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Biomedical subjects
Publications and source records attributed to S Simonsen.
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Monophasic action potentials were recorded in the outflow tract of the right ventricle in patients with coronary artery disease during ventricular pacing at different basic cycle lengths and programmed stimulation. During continuous pacing (basic cycle length 600 ms) the time for 90% repolarisation (MAP90) and the QTa interval decreased exponentially during the first 1.5-2 min of pacing to 90% of control values. The reproducibility of the monophasic action potential signals and the ventricular effective refractory period were assessed as good when studied after repetitive trains of 8 beats for more than 1.5 min. The reproducibility of conduction, however, was less good. Electrical restitution of MAP90 duration of the premature beats determined at three different basic cycle lengths was different from that in single muscle preparations. The curves showed two phases with unchanged MAP90 durations despite longer coupling intervals. The first phase was close to the ventricular effective refractory period, probably because subnormal conduction left the diastolic interval constant for the earliest premature beats. This indicates that subnormal conduction may influence the premature dispersion of repolarisation.
A transplanted (Tx) heart will probably compensate its sympathetic denervation by increasing the sensitivity to adrenergic stimulants. To evaluate whether this also engages the myocardial adenylate cyclase (AC) system, small endomyocardial biopsies were collected at right heart catheterization both from patients with heart Tx with no signs of rejection and from a group of patients serving as controls. In crude homogenates from these biopsies, AC activity was measured at basal conditions and following in vitro stimulation with optimal concentrations of beta-receptor agonists, histamine and sodium fluoride (NaF). The Tx group exhibited a 75% (p = 0.01) higher activation of AC with isoproterenol, and a 62% (p less than 0.05) higher AC activation with terbutaline compared with the control group. The differences in AC activation by histamine and NaF were insignificant. Thus, sympathetic denervation leads to increased activation of the beta-adrenoceptor-coupled AC system, leaving the histaminergic system unaltered. The upregulation does probably engage the receptor part of the receptor-AC system exclusively, since no elevation of NaF stimulation of AC was found in the Tx hearts.
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A series of 125 consecutive patients with isolated ventricular septal defect (VSD) aged 10 or over, were followed until death or beyond the age of 30 (31-73) years. A prospective restudy was performed after a mean follow-up of 15 (3-21) years. Forty-one patients (group 1) were treated with surgical repair of VSD at a mean age of 23 (10-51) years, and early mortality was 10%, i.e. 3 with severe aortic insufficiency and one with systemic pulmonary artery pressure. Surgery was initially not regarded indicated in 70 patients with small defects (group 2). A further 14 patients were judged inoperable (group 3). Long-term mortality was 5% in group 1, 9% in group 2 and 71% in group 3. When restudied, group 2 patients had significantly higher (p less than 0.01) and group 1, lower (p less than 0.01) pulmonary artery pressures than initially. A moderate deterioration in NYHA-rating was noted in group 2 (p less than 0.05) vs. a slight improvement in group 1 (p less than 0.05). The non-operated patients had a higher incidence of valvular lesions (19% vs. 13%) and bacterial endocarditis (4.3% vs. 2.7%) than the operated but not to a statistically significant level. Spontaneous closure was 6% in group 2 whereas mostly small residual defects were found in 34% of the operated. Patients with uncomplicated VSDs (absence of valvular lesions or coronary heart disease) had subnormal exercise tolerance as judged from a standardized ergometer bicycle test. These patients also had impaired left ventricular function based upon haemodynamic studies during moderate supine exercise. No major differences were noted between groups 1 and 2, but operated patients with residual VSDs tended to have the poorest cardiac performance. Non-cardiac disease represented only a minor problem and no significant differences in psychosocial function were observed between groups 1 and 2. Only 50% in group 1 and 60% in group 2 attended a regular medical clinic. Antibiotic prophylaxis had only been practiced by 50% in both groups. Although small, but differences between groups 1 and 2 favour surgery. This must be regarded as a positive result of surgical treatment since those operated on had basically larger and thus more severe defects than the others. In view of the very low operative risk associated with modern surgical technique one should direct patients with significant shunts to operative treatment.
The immediate haemodynamic and electrophysiologic effects of intravenous prenalterol 2.5-75 micrograms/kg in patients with coronary heart disease without clinical heart failure were investigated during fixed rate atrial pacing. Right ventricular peak dP/dt increased pronounced and serum concentration dependent after prenalterol concomitant with an increase in stroke volume and a moderate decrease in peripheral vascular resistance. The effects on haemodynamics after prenalterol were thus serum concentration dependent but with marked interindividual variation. AV nodal conduction velocity increased significantly. It is concluded that prenalterol possess pronounced inotropic properties. The haemodynamic response to prenalterol intravenously is to a lesser degree dependent on the chronotropic effects of the drug and it is often unpredictable.
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In the present study we have examined adenylate cyclase (AC) activity, the stimulation by isoproterenol and inhibition by propranolol, in endomyocardial biopsies from eleven patients with suspected cardiomyopathy. Biopsies were obtained by heart catheterization from the right endomyocardial surface of the interventricular septum. Three biopsies were taken from each patient (mean weight, 2.1 mg; range, 1.2-4.0 mg). One biopsy was studied by light microscopy. The two other biopsies were homogenized and AC activity in the homogenates was determined in the presence of different concentrations of isoproterenol and isoproterenol (5 micrograms/ml) combined with different concentrations of propranolol. Thus stimulation and inhibition curves were established for a pair of biopsies from each patient. Appropriate biopsy material was obtained in triplicate from only seven patients. In these patients the variance in maximal receptor stimulation (by isoproterenol) and inhibition (by propranolol) was significantly smaller in pairs of biopsies compared to the variance between all biopsies (p values from less than 0.05 to less than 0.025). Hence it is possible to determine AC activity, and adrenergic receptor function, in very small endomyocardial biopsies. New diagnostic possibilities could thereby be introduced.
Fifty-two patients with isolated congenital ventricular septal defects (VSDs), studied for the first time at age 10 or older, were restudied an average of 16 years later (range 4 to 21). The study protocol included a symptom-limited bicycle ergometer test, M mode echocardiographic examination, and hemodynamic studies at rest and during mild supine exercise. Of the 52, 17 had been operated on an average of 19 years earlier (range 11 to 21) (group 1) and 35 with smaller defects were not operated on (group 2). Although more pronounced findings were made in group 1, a similar pattern was observed in group 2: In most subjects in both groups a subnormal working capacity was observed. A subnormal left ventricular fractional shortening and circumferential shortening velocity was noted in a high proportion at echocardiography. A number of hemodynamic aberrations were observed in a high proportion of patients during exercise but not at rest. Thus a subnormal increase in left and right ventricular cardiac output was found in addition to pathologic increase in right and left ventricular end-diastolic, pulmonary arterial, and pulmonary capillary wedge pressures. In group 1, elevated pulmonary arterial pressures before operation and/or small residual VSDs were associated with a poor hemodynamic outcome. In neither group could significant correlations be observed between hemodynamic aberrations, shunt size, and/or age. Among patients who underwent surgery, the earlier surgical trauma might have contributed to the functional aberrations, but in group 2 the only likely explanation for the findings seems to be the VSD itself. Possibly a long-standing VSD--found unnecessary to repair according to commonly accepted criteria--may lead to disturbed systolic function and increase in compliance of both ventricles via a chronic pressure and volume overload.
Eight patients underwent orthotopic heart transplantation in Norway during 1984, with retransplantation in one case. The age range of the 5 men and 3 women was 19-53 years. The preoperative diagnosis was cardiomyopathy in 6 patients, ischaemic heart disease in one, and a combination of the two disorders in one patient. The immunosuppressive regimen, with cyclosporin A and low-dose prednisolone, and the treatment of graft rejection, followed the Stanford University protocol. There was no operative mortality. Three patients died shortly after the transplantation, 2 of them after about a week from acute rejection; in one of these 2 cases a second transplant was made, but was followed by pulmonary and renal complications. The third death occurred about 10 weeks postoperatively, from donor heart failure due to Toxoplasma myocarditis. The 5 survivors are clinically in good condition.
In a consecutive series, 125 patients with isolated ventricular septal defect (VSD) and age 10 or more were observed until death or beyond the age of 30 (31-73) years. Reinvestigation was performed after a mean observation time of 15 (4-21) years. Among the 41 patients who primarily underwent surgery (group 1) there were four postoperative deaths--three patients with severe aortic insufficiency and one with systemic pulmonary artery pressure. Surgery was not initially regarded as indicated in 70 patients with small defects (group 2). The remaining 14 patients were judged to be inoperable (group 3). The long-term mortality was 5% in group 1, 9% in group 2 and 71% in group 3. At the reinvestigation, the pulmonary artery pressure was significantly higher than the initial level in group 2 and significantly lower than that level in group 1. As compared with the surgically treated patients, group 2 showed higher incidence of valvular lesions (22% v. 14%) and of bacterial endocarditis (4.3% v. 2.7%), but not to statistically significant level. Spontaneous closure occurred in 6% of the group 2 cases. Residual defects were found in 34% of group 1, but were small. The intergroup differences, though of minor degree, favour surgical treatment, and patients with significant shunt should be recommended operation.
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Doppler echocardiography and cardiac catheterization were undertaken in 70 consecutive patients, 31-68 years of age (mean 39), who had isolated congenital ventricular septal defects (VSD), 28 of whom had been operated upon. In 50 patients with invasively proven VSD, 37 had a correct Doppler diagnosis of VSD (group 1) and in 13 a false negative result was obtained (group 2); i.e. a sensitivity of 74%. No false positive Doppler diagnosis was made in the 20 patients without evidence of shunt. Left to right ventricular systolic pressure difference (delta P) ranged between 55 and 142 mm Hg, with a mean value of 103 mm Hg in group 1 and 99 mm Hg in group 2. There was good correlation between delta P obtained by continuous wave Doppler and catheterisation in 17 group 1 patients with moderate and large shunts (r = 0.81, P less than 0.001). There was no correlation in the remaining 20 patients in group 1 with small shunts (r = 0.20, P greater than 0.1). Doppler echocardiography in the adult with isolated VSD has good sensitivity and excellent specificity. Doppler prediction of delta P is reasonably correct in patients with moderate and large shunts, but of no value in patients with small shunts.