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Biomedical subjects

P Jaillon

Publications and source records attributed to P Jaillon.

At least 145 records · Page 8Linked to original sources
PubMed1980

Intravenous N-acetylprocainamide disposition kinetics in coronary artery disease.

N-Acetylprocainamide (NAPA) disposition kinetics was studied in eight patients with coronary artery disease. NAPA was given over a 45-min period by intravenous infusion, and blood samples were drawn at specified times for 24 hr. NAPA plasma levels were determined by a specific high-pressure liquid chromatography (HPLC) procedure and the concentration-time data were fit to a three-compartment model. Mean (+/- SD) values for the elimination half-life, the total body clearance, and the steady-state volume of distribution were 9.53 +/- 3.22 hr, 1.98 +/- 0.40 ml/min/kg, and 1.30 +/- 0.18 1/kg. There was moderate intersubject variability in disposition. The data reported here differ from those reported for normal subjects.

Acecainide↗
PubMed1980

Time dependency of ventricular fibrillation thresholds determined using trains of stimuli.

When determining ventricular fibrillation threshold (VFT), considerable time elapses from beginning a VFT measurement until the actual occurrence of ventricular fibrillaion (VF). We have defined this elapsed time as the "time to VF" and examined the effect of varying time to VF on the measured value of VFT. We induced VF in anesthetized dogs with a 100-Hz train of 16 4-ms stimuli applied to the right ventricular epicardium. The time to VF was varied by changing either the increment of fibrillation current increase (0.5, 1.0, or 2.0 mA) from one train to the next and/or the number of atrial paced beats between trains (6-192 beats). For 0.5-mA current increments, as time to VF increased from 66 to 454 s, VFT fell progressively from 15.3 +/- 4.8 to 6.7 +/- 1.1 mA. When time to VF exceeded 454 s, VFT increased again. Current increments of 1.0 and 2.0 mA had a similar time dependency of VFT. For any time to VF the VFT was lower when small current increments (i.e., more trains) were used to induce VF. Pretreatment with reserpine in six dogs abolished the time dependency. We conclude that time elapsed from the beginning of a VFT determination until VF actually occurs and the total number of trains used are important determinants of the VFT, probably because of local catecholamine release by the stimuli.

Animals↗
PubMed1980

A model to describe myocardial drug disposition in the dog.

A model, employing open-chested, anesthetized dogs, was developed to facilitate the study of myocardial drug disposition. Propranolol was employed as a model compound for initial investigation. Propranolol was administered as either a single i.v. bolus of 0.5 mg/kg or by a stepwise infusion protocol employing three rates: 2.6, 6.5 and 12.0 micrograms/kg/min. Blood and myocardial biopsy samples were obtained at specified times and the concentration of propranolol in tissue homogenates and plasma was determined by a high-pressure liquid chromotographic procedure. The concentration-time data obtained from the i.v. bolus studies were fitted to a three-compartment model where one of the compartments represented the myocardium. The model predicts that plasma and myocardial concentrations achieve distribution equilibrium within 2 min after administration. The myocardial-to-plasma concentration ratios ranged from 6.2 to 20.3 and were constant with time for each dog. The myocardial-to-plasma concentration ratios also remained constant during the infusion protocol, indicating linear accumulation up to myocardial concentrations of 6.7 micrograms/ml. To assess regional myocardial concentration differences, the concentration of drug in the right atrium was compared with the concentration of drug in the right atrium was compared with the concentration in the left ventricle at the end of the infusion protocol. The concentrations were not significantly different. The model developed will be used to study the myocardial disposition of several antiarrhythmic drugs and the factors which affect their rate and extent of accumulation.

Animals↗
PubMed1979

Effects of the beta-adrenergic blocking agents propranolol and timolol on canine cardiac refractory periods.

The effects of d,1-propranolol and 1-timolol on cardiac refractory periods (RP) were compared in 14 phentobarbital-anesthetized dogs using endocavitary His bundle electrograms and programmable electrical stimulation. Beta-blocking agents were injected at cumulative doses in each dog at 3 day intervals. A control group (6 dogs) received 4 successive saline injections at the same time intervals. RP measurements at a constant drive rate were done before and 10 minutes after each dose of either drug or saline. Propranolol and timolol produced a dose-dependent increase of atrial and atrioventricular nodal refractory periods; dose-response curves were parallel. Depending on the parameter chosen timolol exerted an 8--36 times more potent effect than propranolol. The effects of propanolol and timolol on ventricular effective (VERP) and functional (VFRP) RP were measured in 6 dogs. Both drugs increased VFRP significantly, but saline had the same effect. Only the higher doses of timolol increased VERP significantly. These data confirm that blockade of myocardial beta-adrenergic receptors exerts predominant effects on supraventricular refractoriness and that in anesthetized dogs timolol has more potent beta-blocking properties than does propranolol.

Animals↗
PubMed1979

Influence of congestive heart failure on prazosin kinetics.

The kinetics of oral prazosin was studied in 10 healthy normal subjects (NS) and in 9 patients with congestive heart failure (CHF). NS received a single 5-mg dose, and blood concentrations of prazosin (CB) were measured, using a specific HPLC assay, during an 8-hr period. CHF patients received a 2-mg dose after which CB was measured for 10 hr. These patients then received 2 to 5 mg prazosin every 8 hr for 48 hr. After the last dose of prazosin, CB was measured for 24 hr. After the initial dose, time to peak CB did not differ significantly between that of the NS (123 +/- 19 SEM min) and of patients with CHF (132 +/- 31.3 min). AUC/mg prazosin was greater (p less than 0.001) in patients with CHF (3,385 +/- 380 Ng x min/ml) than in NS (1,603 +/- 208 ng x min/ml). Elimination of prazosin from blood was slower in CHF patients (t1/2 = 374 +/- 33.4 min) than in NS (t1/2 = 144.5 +/- 4.3 min) (p less than 0.001). These data suggest that in patients with CHF the elimination of prazosin is substantially slower than in NS and therefore higher steady-state prazosin concentrations can be expected in CHF patients than in NS.

Administration, Oral↗
PubMed1978

[Merits of the assay of plasma catecholamines in a glucagon test to diagnosis of pheochromocytoma (author's transl)].

In one female patient suffering from an extra-adrenal pheochromocytoma, a stimulation test with glucagon was performed. In spite of the absence of an increase in heart rate and blood pressure, a pronounced increase in plasma catecholamines showed this test to be positive. The authors discuss the reliability criteria of this test, and confirm its good tolerance.

Adrenal Gland Neoplasms↗
PubMed1978

Comparative dromotropic activity of timolol and propranolol in anesthetized dogs.

The comparative dromotropic activity of timolol (TML) and propranolol (PPL) was studied by means of His bundle electrograms in two groups of pentobarbital-anesthetized dogs: group I, 7 non-atropinized dogs; group II, 8 atropinized dogs. beta-Blocking agents were injected in 4 cumulative doses in each dog at 3 days' interval. The effects upon heart rate (HR), and A-V nodal (AH), His--Purkinje (HV) and intraventricular (QS) conduction times were measured. The dromotropic effects of PPL and TML during atrial electrical stimulation and their effects upon chronotropic and dromotropic isoprenaline-induced changes were compared. TML exerted a 9--10 times more potent negative chronotropic effect than PPL and a 4--5 times more potent negative dromotropic effect than PPL on AH conduction time. PPL and TML increased the duration of HV only in higher doses. This effect which was not modified by isoprenaline may be related to their membrane depressant effect. Neither TML, nor PPL nor isoprenaline modified QS duration. TML was 25 times more potent than PPL to antagonize the chronotropic action of isoprenaline and 11--8 times more potent than PPL to antagonize the dromotropic action of isoprenaline upon AH. Parasympathic blockade with atropine did not modify the negative dromotropic activity of PPL and TML but modified their chronotropic effects.

Animals↗
PubMed1976

[Comparative study, in the anesthetized dog, of the dromotropic effects of N-propyl ajmaline bitartrate, ajmaline hydrochloride and ajmaline monochloroacetate, by recording of His electrogram].

A-V and intraventricular conduction disturbances induced by 3 different salts of ajmaline: N-propyl ajmaline bitartrate (NPAB), hydrochloride (CHA) and mono chloro-acetate (MCAA), were studied by recording endocavitary His bundle activity in pentobarbital anesthetized dogs. Cumulative dose-response curves were obtained with 3 doses of each compound. The results demonstrate that: a) NPAB exerts a significant depressor effect (9 to 10 times more potent than CHA) on the following three conduction times: auriculo-Hisian, His-Pinkinje and Purkinje-ventricular; b) on His-Purkinje and intra ventricular conduction, MCAA exerts a weaker depressor effect than that of Nab. The lack of parallelism of dose-response curves prevents further comparative quantification; c) on atrio-hisian conduction, MCAA presents a delayed dose-related depressor effect suggesting the presence of an active metabolite. It is concluded that among ajmaline derivatives studied, Nab appears to be the most depressor on A-V and intraventricular conduction in the pentobarbital anesthetized dog.

Acetates↗
PubMed1975

[Study of changes in myocardial contraction and left ventricular diastolic regidity after aortocoronary bypass].

Eighteen patients with coronary insufficiency underwent a left ventricular cineangiography before and an average of four months after aorta-to-coronary bi-pass in order to assess the post-operative changes of myocardial contractility and diastolic rigidity. The contractility indices (VCF: mean speed, and VCF max: maximum shortening speed of the equatorial diameter of the left ventricle (% delta theta) were unmodified in the group (I) of fourteen patients with at least one pervious by-pass. On the contrary, a decreased % delta theta was observed in the group (II) of four patients in whom all the by-passes were occluded. The left ventricular end-diastolic pressure (LVEDP), the end-diastolic volume (LVEDV) and the "normalized" rigidity index (K) were unmodified in both groups after operation. The cardiac rate increased in the post-operative period in the group I (p less than 0.01) and the whole of the 18 patients (p less than 0.001); there was a positive correlation (p less than 0.02) between this variation and that of VCF, VCF max. and % delta theta, the significance of which is discussed. Besides there was a negative correlation between the variations of LVEDV and the VCF, and between the equatorial end diastolic diameter of the left ventricle and VCF, VCF max. and % delta theta, both in the pre-operative and the post-operative periods.

Adult↗