Svein Golf

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris ☆: Clinical results from The Norwegian Randomized Trial

OBJECTIVES The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Stenting in small coronary arteries (SISCA) trial. A randomized comparison between balloon angioplasty and the heparin-coated beStent.

OBJECTIVES The purpose of this study was to assess the clinical and angiographic benefits of elective stenting in coronary arteries with a reference diameter of 2.1 to 3.0 mm, as compared with traditional percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND The problems related to small-vessel stenting might be overcome using modern stents designed for small vessels, combined with effective antiplatelet therapy. METHODS In five centers, 145 patients with stable or unstable angina were randomly assigned to elective stenting treatment with the heparin (Hepamed)-coated beStent or PTCA. Control angiography was performed after six months. The primary end point was the minimal lumen diameter (MLD) at follow-up. Secondary end points were the restenosis rate, event-free survival and angina status. RESULTS At follow-up, there was a trend toward a larger MLD in the stent group (1.69 +/- 0.52 mm vs. 1.57 +/- 0.44 mm, p = 0.096). Event-free survival at follow-up was significantly higher in the stent group: 90.5% vs. 76.1% (p = 0.016). The restenosis rate was low in both groups (9.7% and 18.8% in the stent and PTCA groups, respectively; p = 0.15). Analyzed as treated, both the MLD and restenosis rate were significantly improved in patients who had stents as compared with PTCA. CONCLUSIONS In small coronary arteries, both PTCA and elective stenting are associated with good clinical and angiographic outcomes after six months. Compared with PTCA, elective treatment with the heparin-coated beStent improves the clinical outcome; however, there was only a nonsignificant trend toward angiographic improvement.

Effects of chronic pindolol treatment on human myocardial ß1- and ß2-adrenoceptor function

SummaryTo evaluate the effects of chronic pindolol treatment on human myocardial ß-adrenoceptor, membrane preparations from right atrial auricles from patients on chronic pindolol treatment and from patients not treated with ß-blocker were compared with respect to specific binding of [125I]-iodocyanopindolol ([125I]-ICYP) and adenylate cyclase (AC) activity. Pindolol treatment was associated with a 25% increase in total ß-adrenoceptor density (72.3 vs. 58.3 fmol/mg protein). This increase was due a 40% increase of the ß1-adrenoceptor subtype (62.2 vs. 44.3 fmol/mg protein), while ß2-adrenoceptor density was decreased by about 25% (10.0 vs. 14.0 fmol/mg). Isoprenaline 5 μmol/l (9.7 vs. 14.2 pmol/min/mg) and terbutaline 50 gmol/l (4.9 vs. 8.3 pmol/min/mg protein) stimulated adenylate cyclase activity was reduced, whereas fluoride (10 mmol/l) stimulated cAMP production to the same extent in both groups (9.4 vs. 9.4 pmol/min/mg protein). Thus, chronic treatment with pindolol was associated with upregulation of the ß1-adrenoceptors and a down-regulation of the ß2-adrenoceptors. The total level of ß-adrenoceptors was slightly increased. In spite of this, adenylate cyclase activity and response was reduced.

Catecholamine Responsive Adenylate Cyclase in Human Myocardial Preparations Properties and Optimalization of Assay Conditions

In the present study we have investigated the conditions for optimal adenylate cyclase (AC) activity in preparations of human myocardial biopsies, with emphasis on both basal enzyme activity and isoproterenol response. Different preparation procedures (homogenates, membrane particles) of the same biopsy showed no difference in relative response to isoproterenol, although absolute activities, using protein concentration for normalization, showed some variance. The AC-receptor complexes of the preparations were also stable when stored on ice for 3 h, and both basal and stimulated AC activities were constant at a wide range of protein concentrations (2.9-31.9 micrograms/tube), and throughout 92 min incubation. The effects of varying Mg2+, guanyl nucleotides (GTP, GMP-P(NH)P), and ATP concentrations on myocardial AC activities were also investigated under both basal conditions as well as after isoproterenol stimulation. The apparent Km for the substrate (Mg X ATP) binding to the AC was approximately 0.1 mmol/l. Isoproterenol stimulated the AC activity by increasing Vmax (41 to 142 pmol/mg protein X min) without any change in the apparent Km. Maximal relative activation by isoproterenol was achieved at pH 6.5-7.0. The concentration of isoproterenol causing half maximal AC stimulation was approximately 0.1 micrograms/ml (2 X 10(-4) mmol/l). Half maximal inhibition of isoproterenol (4 micrograms/ml) stimulated AC activity was obtained by 0.025 micrograms/ml propranolol (8 X 10(-5) mmol/l). The sensitivity and precision of this assay should make it possible to measure AC activity as well as isoproterenol response in very small quantities of myocardial tissue. This could provide a method for studying receptor functions of sick hearts by endomyocardial biopsies.

Clinical Benefit of Small Vessel Stenting: One-year Follow-up of the SISCA Trial

Objective : To assess the long-term clinical benefit of elective stenting as compared with percutaneous transluminal coronary angioplasty (PTCA) in small coronary arteries. Design : The Stenting in Small Coronary Arteries (SISCA) trial was a randomized trial comparing elective stenting with PTCA in coronary arteries with a reference diameter of 2.1-3.0 mm. The heparin-coated beStent was used. Control angiography was performed after 6 months, and the patients were followed clinically for 12 months. Results : At 6 months the clinical outcome was significantly better in the stent group as compared with the PTCA group, with an event-free survival in 90.5 and 76.1% ( p = 0.016), respectively. From 6 to 12 months, event-free survival was unchanged in both groups, demonstrating a sustained long-term clinical benefit of elective stenting. Conclusion : Angioplasty in small coronary arteries is associated with a favorable clinical outcome after 1 year. The clinical benefit of elective stenting using the Hepamed ® -coated beStent is maintained beyond 6 months, without any tendency towards late events. Thus, elective stenting should be considered as an option when treating small coronary arteries.

Congenital Swallowing‐induced Symptomatic Heart Block: A Case Report of a Probably Hereditary Disorder

A 15‐year‐old girl had had syncope induced by swallowing since infancy. An ECG recorded during food intake revealed SA block with very slow functional and ventricular escape rhythms. No symptoms or signs of other cardiac disorders or gastrointestinal diseases were present. Activation of a strong vagal reflex, able to inhibit impulse formation and propagation in an otherwise normal heart, is the most likely explanation of the disorder in this patient. Furthermore, EGGs of her close relatives which were recorded during food intake as compared with the findings in a reference group (n = 20), indicated that a genetic factor could be involved.

Increased β-adrenoceptor-coupled adenylate cyclase response in transplanted human hearts

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.

Relative selectivity of different β-adrenoceptor antagonists for human heart β1- and β2-receptor subtypes assayed by a radioligand binding technique

The affinity constants of inhibition (Ki values) for both β1- and β2-receptor subtypes were determined for four different β-adrenoceptor antagonists by a radioligand binding technique in a human myocardial membrane preparation. The radioligand was the high affinity antagonist [125I]-(—)-iodocyanopindolol (ICYP), and the drugs tested were atenolol, metoprolol, ICI 141 292 and ICI 118 551. Different concentrations of the drugs at test were allowed to compete with a constant concentration of ICYP for the specific binding sites (β-receptors). Ki values for β1- and β2-receptors for each β-adrenoceptor antagonist were developed from these data by computer calculations. Atenolol and metoprolol were found to differ slightly regarding potency (absolute Ki values) and to be practically equal regarding relative selectivity (approx. 40; i.e. ratio between high and low Ki values), while ICI 141 292 was found to have slightly higher relative selectivity (approx. 60) and much higher potency. All these drugs exhibited hi...

Catecholamine-responsive adenylate cyclase activity in human endomyocardial biopsies: Individual sensitivity to isoproterenol stimulation and propranolol inhibition

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.