Effect of 5-HT4 receptor stimulation on the pacemaker current I(f) in human isolated atrial myocytes.

OBJECTIVE: 5-HT4 receptors are present in human atrial cells and their stimulation has been implicated in the genesis of atrial arrhythmias including atrial fibrillation. An I(f)-like current has been recorded in human atrial myocytes, where it is modulated by beta-adrenergic stimulation. In the present study, we investigated the effect of serotonin (5-hydroxytryptamine, 5-HT) on I(f) electrophysiological properties, in order to get an insight into the possible contribution of I(f) to the arrhythmogenic action of 5-HT in human atria. METHODS: Human atrial myocytes were isolated by enzymatic digestion from samples of atrial appendage of patients undergoing coeffective cardiac surgery. Patch-clamped cells were superfused with a modified Tyrode's solution in order to amplify I(f) and reduce overlapping currents. RESULTS AND CONCLUSIONS: A time-dependent, cesium-sensitive increasing inward current, that we had previously described having the electrophysiological properties of the pacemaker current I(f), was elicited by negative steps (-60 to -130 mV) from a holding potential of -40 mV. Boltzmann fit of control activation curves gave a midpoint (V1/2) of -88.9 +/- 2.6 mV (n = 14). 5-HT (1 microM) consistently caused a positive shift of V1/2 of 11.0 +/- 2.0 mV (n = 8, p < 0.001) of the activation curve toward less negative potentials, thus increasing the amount of current activated by clamp steps near the physiological maximum diastolic potential of these cells. The effect was dose-dependent, the EC50 being 0.14 microM. Maximum current amplitude was not changed by 5-HT. 5-HT did not increase I(f) amplitude when the current was maximally activated by cAMP perfused into the cell. The selective 5-HT4 antagonists, DAU 6285 (10 microM) and GR 125487 (1 microM), completely prevented the effect of 5-HT on I(f). The shift of V1/2 caused by 1 microM 5-HT in the presence of DAU 6285 or GR 125487 was 0.3 +/- 1 mV (n = 6) and 1.0 +/- 0.6 mV (n = 5), respectively (p < 0.01 versus 5-HT alone). The effect of 5-HT4 receptor blockade was specific, since neither DAU 6285 nor GR 125487 prevented the effect of 1 microM isoprenaline on I(f). Thus, 5-HT4 stimulation increases I(f) in human atrial myocytes; this effect may contribute to the arrhythmogenic action of 5-HT in human atrium.

[Changes in pacemakers and the wearers of pacemakers as a result of the use of different electromagnetic energy sources]. / Alterazioni nei pacemaker e nei portatori dei pacemaker in conseguenza dell'uso di varie sorgenti di energia elettromagnetica.

Over the past decade there have been considerable advances in cardiac electrostimulation technologies. However, there are still reports of electromagnetic interference with pacemakers and pacemaker patients. We have studied the effects of various electromagnetic sources (short-wave diathermy, electrosurgical knives, electrotherapy and radiofrequencies) on both humans and animals. The results of the studies were completely negative and, therefore, we are convinced that today's pacemakers are much more reliable and hence less subject to interference from external electromagnetic sources. We performed the following tests: (a) Short-wave diathermy: various electrode positions in pigs and 8 patients with pacemakers. (b) Electrosurgical knives: several tests on pigs with unipolar electrosurgical knife; 6 tests on humans during automatic defibrillator implantation using two-pole electrosurgical knives; 23 pacemaker patients underwent abdominal surgery (3 inguinal hernias, 12 gastric resections; 6 cholecystotomies, 2 aortic aneurysms-with two-pole electrosurgical knives). (c) Electrotherapy (TENS): on pigs. (d) Radiofrequency (RF) for transcatheter ablation-several tests on pigs.

[Heterotopic heart transplantation in the rat: an experimental method for evaluating myocardial protection]. / Il trapianto eterotopico del cuore di ratto: una metodica sperimentale per la valutazione della protezione miocardica.

This research represents the first part of a project finalized to prolong the ischemic time of the explanted heart. Our experimental model utilizes rat hearts heterotopically transplanted into the abdomen of a recipient: a denervated heart but perfused by blood as to permit a good evaluation of the reperfusion damage. We used 3 different types of cardioplegic solutions to achieve cardiac arrest: the first of the intracellular fluid type, the second of the extracellular type and the third one as a standard cardioplegic solution supplemented by Ca++ antagonist. Cold saline 4 degrees C was used as control. Histological patterns, birefringence index and intracellular content of high energy phosphates were evaluated. Specimens were taken after 1 hour of ischemic time and after 1 hour of reperfusion. Early results show that administration of cardioplegic solution maintains birefringence index and preserve high energy phosphates: among the 3 different types of solution the intracellular type seems to achieve better results although the number of experiments is too small to show any statistical significance. These data show that this model is appropriate to test cardioplegic solutions and their effectiveness.

[Mitral valve replacement with the Björk-Shiley monostrut prosthesis: a 4-year clinical experience]. / Sostituzione valvolare mitralica con la protesi Björk-Shiley monostrut. Esperienza clinica di 4 anni.

Mitral valve replacement with Björk-Shiley monostrut prostheses was performed in 142 patients, aged 18 to 73 (mean age: 53.8). A group of 101 patients underwent isolated mitral replacement (group A), while both mitral and aortic (in one case tricuspid) valves were replaced in 41 (group B). In 19 of group A patients and in 9 of group B patients a tricuspid annuloplasty was added. Hospital mortality was one case in each group (group A: 1%; group B:2.4%). The cause of death was low output in both cases (i.e. not valve-related). Late mortality occurred in 4 cases (4%) in group A, and in 3 cases (7.3%) in group B (follow-up: 6 to 58 months; mean follow-up: 24 months). Actuarial survival was 93.79% in group A and 89.94% in group B one year after surgery; it was 93.79% in group A and 81.76% in group B after 3 years. All deaths from undetermined causes, as well as any new unexplained neurological deficit or peripheral emboli, were considered to be valve-related: 84.18% of group A patients, as well as 67.90% of group B, were event free after 3 year (actuarial). most valve-related events occurred in the first year after surgery. We observed thromboembolism in 3 cases for each group: one patient in group B had pannus formation over the prosthetic annulus; prosthetic valve endocarditis in 1 case of group A and 2 of group B; significant hemorrhage due to anticoagulant therapy in 1 (group A); one patient in each group died suddenly, 4 and 7 months postoperatively. One group A patient and 2 group B patients were reoperated: a new valve prosthesis was implanted in two patients. Mean transvalvular gradient, as determined by echocardiography, was 3.8 +/- 2.3 (SD) mmHg in the case of isolated mitral replacement. In conclusion, we believe these results are highly encouraging, especially in the isolated mitral replacement group. Björk-Shiley monostrut prosthesis has been demonstrated to be a reliable valve substitute, with an acceptable incidence of complications. No Björk-Shiley monostrut prosthesis structural deterioration was seen, and its hemodynamic behaviour may be considered satisfactory.