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Adenosine triphosphate (ATP) has been effectively used for induced hypotension in man. Atrio-Ventricular (A-V) conduction disturbances have been observed after adenosine bolus injection and during continuous ATP i.v. infusion. The present perspective investigation was designed to determine the incidence of A-V conduction disturbances during ATP-induced hypotension. Thirty-five normotensive healthy patients (ASA I-II) with no preoperative therapy were subjected to the same anesthetic technique for orthopedic surgery. Premedication consisted of diazepam and atropine. Anesthesia was induced with thiopental and fentanyl followed by atracurium for intubation. The maintenance anesthesia consisted of isoflurane (1.5% inspired)-N2O (60%) in oxygen and incremental doses of fentanyl; the lungs were mechanically ventilated. Dipyridamole (0.15 mg kg-1) was given 15 min prior to ATP-infusion. ATP was administered by an infusion pump at a dosage of 0.025-0.05 mg kg-1 min-1. The ECG was recorded with a Mingograph 34 tape-recorder using 3 pregelled electrodes positioned to give an effective V6 lead pattern. MAP was reduced by 25% and HR increased by 6%. The mean duration of ATP-induced hypotension was 75 min +/- 50 and the mean dose of ATP infused was 200 mg +/- 161. Six patients (17%) showed A-V conduction disturbances. There was a I A-V Block (AVB) in 2 cases, a II AVB in 2 cases and a III AVB in 2 cases. In every case the arrhythmia disappeared spontaneously or after ATP-infusion suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

The glucose-6-phosphate dehydrogenase (G6PD) activity of erythroblasts, separated at different advancing stages of development, shows a marked decline of activity. A proteolytic mechanism, strictly controlled, is likely responsible of this decay, since a sufficient level of enzyme activity still remains in the circulating erythrocyte. In this report we suggest a model that could explain what triggers the mechanism of proteolytic degradation. HPLC analysis of the nucleotide content of erythroblasts and reticulocytes, showed a marked decline of adenine and pyridine nucleotides and of their catabolic products during the cell development. From thermostability tests, at fixed temperature, we have seen that ATP and NADP only, significantly protected the enzyme activity. In this light, we incubated 10 min at increasing temperatures, with and without ATP or NADP lysates of erythroblasts, separated at different stage of development and of reticulocytes. In the absence of nucleotides, we determined for all fractions a T degree break at 42 degrees C. In the presence of NADP all fractions were stabilized with no break point in the range 37-50 degrees C. On the contrary, the presence of ATP caused a progressive shift of the T degrees C break from the most immature erythroblasts (T degree break at 46 degrees C) to the reticulocytes (T degree break at 42 degrees C). Since ATP did not show any protective effect on the reticulocyte enzyme, we hypothesize the presence in these cells of a structurally modified G6PD. Furthermore, these data support our belief that the marked decline of ATP during cellular development, may represent the element responsible for the enzyme modification.

This study presents experimental data on the time dependence of the release of fibrinopeptides A and B following the interaction between thrombin and fibrinogen. It is found that the release of fibrinopeptide A is fast as compared to that of fibrinopeptide B. This process is modulated by ATP in a complex fashion. In fact, the release of fibrinopeptide A is first enhanced at low (less than 1 mM) ATP concentrations and then progressively inhibited at ATP concentrations greater than 1 mM. These results draw attention to a possible model for the in vivo modulation of thrombin activity by ATP.

Adenylate cyclase activity has been measured in segmental ganglia of the leech Hirudo m. Basal enzymatic activity was stimulated in a dose dependent fashion by serotonin. GTP is required in order to evoke maximal stimulation. The effect was blocked by methysergide, an antagonist of serotonin at receptor level. The stimulation of the enzyme was prevented by alpha beta-methy-len-ATP. In addition RMI 12330A inhibited basal as well as serotonin-stimulated adenylate cyclase activity presumably by acting at the catalytic subunit level.

New experimental methods in cellular electrophysiology allowed the identification and characterization of specific "ion channels" in the plasma membrane of cardiac cells in different regions of the heart. Function and implication of the "ion channels" have been considered in 1) the initiation of the heart-beat, 2) the chronotropic and inotropic effects of neurotransmitters (nor-epinephrine-acetylcholine), 3) the action mechanism of the steroid cardioactive drugs, 4) the cardiac repolarization, 5) the physiopathology of several arrhythmias. Moreover clinical data useful for the indirect evaluation of the ion channels function have been pointed out, stressing the ion channels models contribution for the cardiac pathology interpretation, particularly in the cardiac arrhythmias field.

In order to investigate the cardiovascular effects of ATP (15-30 mg) i.v. administration, 12 normal subjects, aged 27-55 yrs, were studied, during Arterial Pressure Monitoring and His Bundle Electrogram recording, using Sherlag's technique. ATP cardiovascular response was divided in the following four phases: Latency phase, Progressive Bra dyarrhythmic-Hypotensive, Maximal Inhibitor Phase, Tachyarrhytthmic Hypotensive Reflex Phase. Atropine (0.02-0.04 mg/Kg) i.v. injection did not significantly prevent ATP effects. Increasing dosage of atropine (0,06, pointed out a moderate competitive antagonism with ATP. These data suggest a possible direct action of ATP (purinergic receptors or direct membrane effect) but don't exclude an interaction with Parasympathetic system (probable purinergic neuromodulation).

In 10 patients with supraventricular tachycardia who underwent an electrophysiological study the ectopic atrial origin of the tachycardia could be demonstrated by the intracavitary localization of the earliest depolarized point (six cases in the right atrium and four cases in the left). Vagal stimulation and/or the i.v. infection of ATP induced or increased the degree of AV block during tachycardia; in five cases ATP interrupted the tachycardia. On the basis of their clinical and electrophysiological behavior, the patients were divided into two groups. In the first one (6 patients) tachycardia was persistent, started following late atrial beats with the same morphology of the subsequent and showed a progressive initial rate increase (warm-up phenomenon); programmed atrial stimulation failed to start and interrupt it. In the second group (4 patients) tachycardia was paroxysmal or repetitive, started following early atrial beats and could be induced and interrupted by programmed atrial stimulation. With respect to the electrophysiological characteristics of each group the authors try to define the possible mechanism responsible for the tachycardia (automaticity and micro-reentry).