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Spread and modulation of electrical activity in cardiac tissue requires intercellular transfer of current via gap junctions, specialised regions of densely packed ionic channels. Electrotonic interaction is determined not merely by intercellular electrical resistance (Rj) but rather by the interplay of Rj and sarcolemmal passive and active electrical properties (Zaniboni et al., Spitzer et al.). In this work we combined a well established protocol to measure Rj in cell pairs (Weingart e Maurer) with a stimulation protocol which allowed to simultaneously study parameters relative to action potential transfer during sequential stimulation. Current clamp experiments, performed on cardiomyocyte pairs held in double-patch configuration, allowed to simultaneously monitor, at a relatively high frequency (1 Hz), membrane resistance (Rm), resting potential (Vm), maximum depolarization rate (dv/dtmax) and time to peak of dv/dtmax in both cells as well as Rj. Spontaneous electrical uncoupling was observed in guinea pig cell pairs with little or no effect on action potential transfer. Pharmacological uncoupling with 40 microM beta-glycyrrhetinic acid reached, in one case, a much higher level of Rj and dramatically increased time delay for action potential appearance. When only Rj was measured over a short time interval after approximately two minutes from cell-attachments, values of Rj approximately 40 M omega in rat cell pairs (n = 20) and Rj approximately 15 M omega in guinea pig cell pairs (n = 24) were obtained. The possibility of monitoring simultaneously active and intercellular/cellular passive electrical properties makes this protocol particularly suitable to study dynamic changes in Rj during action potential transfer.

Unlabelled: Simulations of cardiac tissue bidomain model indicate that point cathodal stimulation gives rise to a dog-bone depolarized region (virtual cathode) extending across fibers, limited by two symmetric hyperpolarized regions (virtual anode) extending along fibers. These predictions were experimentally confirmed by optical mapping studies of transmembrane potentials while no direct validation is reported at the extracellular level. The present study aims at defining the influence of the virtual cathode on extracellular potentials by means of high-density epicardial mapping., Methods: Epicardial potentials were measured in seven exposed rat hearts by means of a 11 x 11 electrode array with 360 x 540 microns resolution. Cathodal current pulses, 100-200 microA intensity and 1 ms duration, to avoid superposition of stimulus and activation potentials, were delivered from one of the electrode array and unipolar potentials were measured from all other electrodes., Results and Discussion: a) During stimulus, negative equipotential lines were elliptic along fibers, as expected, but for a 2 mm circular region at the pacing site. b) During 1-2 ms interval between stimulus offset and start of activation, equipotential lines became elliptic across fibers in the presence of the region directly excited by the stimulus field. Start of activation was either symmetric with isochrones initially circular around the pacing site and then elliptic along fibers, or asymmetric initiating at only one side of the pacing site across fibers with isochrones elliptic along fibers. In the latter case, the wave front was blocked through the refractory region directly excited by the stimulus field, subdivided into two wings which collided and merged at the opposite side, giving rise to a plane wave front propagating across fibers away from the pacing site., Conclusions: High spatial resolution epicardial potential mapping reveals the existence of the virtual cathode and its influence on impulse initiation and conduction. The unexpected existence of a region of conduction block at the pacing site, due to spatial asymmetry of normal cardiac tissue which enhances activation threshold at one of the two sides of the virtual cathode, is intriguing since it is one of the requirements for reentry of conduction in the presence of a circuit with decreased conduction velocity and short duration of refractory period.

Ceftriaxone effectively inhibited 332 out of 452 (73.45%) bacterial strains in vitro tests. 291 out of 365 (79.69%) gram negative and 41 out of 87 (47.12%) gram positive strains were inhibited. The tests showed ceftriaxone to be more effective than cephalothin, cephotaxime, cephuroxime, cephamandol and cephoxitin. Kinetic tests showed that cephtriaxone has a plasmatic half life of 7.25 hrs. 24 hours after administration of a 1000 mg venous bolus the drug was still present in the blood. Urinary elimination over a 24 hr. period amounted to means 486.8 mg (48.68%). The drug has liquor transfer capacity. 37 of the 38 patients treated showed complete clinical or clinicobacteriological cure. Improvement was noted in the 38th.

Microbiological, kinetic and clinical studies were conducted on a new cephamycin, cephotetan. In vitro the antibiotic was found to be very effective against all strains tested. It had a particularly strong action against Gram negative bacteria too. Kinetically speaking, an intravenous bolus produced a high plasmatic concentration with a half life of about 4 hours. Elimination via the kidneys was fastest in the first 3 hours after administration (49.82%) and the slowed down. 82.76% of the dose administered was excreted within 24 hours. This antibiotics is particularly indicated in cases of urinary, respiratory and biliary infections.

A mean plasma concentration curve, with peaks within the first hour and moderate individual variations, was obtained after a single administration of 800 mg of bacampicillin to 5 healthy volunteers. An adequate antibiotic transfer from the circulation to the bronchial apparatus was demonstrated. Treatment of 34 patients suffering from ampicillin-sensitive bacterial diseases permitted clinical cure of all patients, without onset of side-effects. It is concluded that bacampicillin is preferable to oral ampicillin because of its kinetic and tolerance features.

Kinetic and clinical evaluation of cefotiam, a new cephalosporin, is reported. It was found that the drug is rapidly distributed to the tissues. Equilibrium between tissues and plasma is reached in about an hour. Some 90-91% of the dose administered is excreted in the urine, and accumulation does not occur. A clinical cure was obtained in 27 of a series of 35 patients (77.1%). Improvement was observed in 7 cases (20%). The antibiotic proved ineffective in the remaining cases (2.8%). Tolerance was excellent and there were no side-effects worthy of note.

A microbiological and clinical study of the action of piperacillin is presented. The drug showed an excellent in vitro antibacterial action on gram positive and gram negative microorganisms. Its in vitro action on Ps. aeruginosa (70.8% of strains inhibited) was also extremely interesting, making it the second most effective of the antibiotics tested after polymyxin B and colistin, polypeptides unsuitable for clinical use. In vivo, the administration of piperacillin achieved a clinical and bacteriological cure in 35 out of 40 patients and a clinical cure in 2 out of 40. It was only therapeutically unsuccessful in 3 cases. It is concluded that its microbiological, kinetic and tolerance features make piperacillin suitable for a wide range of therapeutic purposes.

Previous work on the spread of excitation on the dog's ventricular surface enabled us to locate up to 30 breakthrough points (BKTPs) where excitation reaches the ventricular surface. In particular the equipotential contour maps enabled us to detect 3 to 5 BKTPs on the anterior right ventricular surface, near the a-v groove when a large part of ventricular surface was still at rest. With a view to investigating the mechanism underlying the early excitation of these basal regions, we stimulated the heart at several right ventricular BKTPs and in other points located at a distance from the BKTPs. The instantaneous equipotential maps showed that after stimulation most right ventricular BKTPs remained in the same position as observed the normal beats. The early appearance of epicardial wavefronts in the basal region and generally in other areas of the right ventricle was attributed to the rapid propagation of excitation waves through the Purkinje network, probably associated to a short transmural crossing time, due to a local thinness of the ventricular wall.

The effects of Verapamil on main haemodinamic parameters and on Max sigma pos., sigma Q15, Max sigma pos./Max sigma neg. and sigma ST, studied by automatic recording of thoracic maps, were evaluated in 11 patients with acute myocardial infarction within 6 hours from pain onset. Verapamil was given at the dose of 0.1 mg/Kg followed by infusion of 0.035 mg/min. Hemodynamic measurements were made before and 15 minutes after Verapamil; the maps were recorded before and 5, 15 and 30 minutes after Verapamil. Heart rate and sistolic arterial pressure were reduced, though not significantly: right atrial pressure, pulmonary pressures and capillary pulmonary pressure remained unchanged. On the contrary, the reduction of diastolic arterial pressure (from 94 +/- 4.2 to 88 +/- 4.5 mmHg; P less than 0.05) and of cardiac index (from 3.1 +/- 0.11 to 3 +/- 0.11; P less than 0.05) was important. Max sigma pos. increased after 15 minutes from 11619 +/- 1970 to 12349 +/- 2151 microV (P less than 0.01), but il decreased after 30 minutes to 11037 +/- 2042 microV (P less than 0.05). Max sigma pos./Max sigma neg. ratio increased significantly after 5 and 15 minutes. Sigma Q15 increased significantly only after 30 minutes (from 7198 +/- 1643 to 8688 +/- 1541 microV; P less than 0.05). Sigma ST showed a transient, non significant increase after 5 minutes, but decreased significantly after 30 minutes (from 76664 +/- 19505 to 67157 +/- 18581 microV; P less than 0.05). The results show that Verapamil does not cause worsening of main haemodinamic parameters during acute, non complicated myocardial infarction and reduces significantly ST segment elevation. The Authors discuss also a possible electrophysiological effect of Verapamil on action potential of ischemic cells, responsible for early increase of sigma ST observed in some patients.