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J Kaplanski

Publications and source records attributed to J Kaplanski.

At least 55 records · Page 3Linked to original sources
PubMed1983

Comparison of digoxin-induced cardiac toxicity in resistant and sensitive species.

We have examined the species-specific arrhythmogenic effects of digoxin in the rat (resistant species) and in the guinea-pig (sensitive species). 26 adult rats and 23 adult guinea-pigs were anaesthetized with pentobarbitone and injected subcutaneously with varying doses of digoxin. Electrocardiograms were monitored continuously for 4 1/2 h following digoxin administration. The arrhythmogenic dose (AD50) and lethal dose 50 under anaesthesia (LD50) were determined using the method of Litchfield & Wilcoxin. AD50 in rats was 13.0 +/- 1.0 mg kg-1 (mean +/- s.d.) compared with 0.60 +/- 0.04 (P less than 0.01) in the guinea-pig and LD50 was 30.0 +/- 1.9 mg kg-1 in the rat compared with 0.60 +/- 0.04 (P less than 0.01) in the guinea-pig. The onset of arrhythmias was not dose-dependent in the rat but was clearly so in the guinea-pig; for example 102 +/- 15 min (mean +/- s.e.m.) following 0.5 mg kg-1, and 43 +/- 2 min following 1 mg kg-1. In the rat the onset of arrhythmias was 54.0 +/- 11.5 min. Supraventricular arrhythmias (paroxysmal atrial tachycardia) appeared in 73% of rats compared with only 18% of guinea-pigs whereas ventricular arrhythmias (ventricular tachycardia), multiple premature ventricular contractions and or multifocal PVC's occurred in 100% of guinea-pigs compared with only 32% of rats. All guinea-pigs that developed arrhythmias died whereas several rats recovered from supraventricular tachycardias. In conclusion, the guinea-pig is much more sensitive to digoxin toxicity than the rat, develops arrhythmias at much lower doses and these arrhythmias are much more likely to be ventricular in origin and cause fatality.

Animals↗
PubMed1983

Effect of pinealectomy on heat-induced endocrine changes in female rats.

Exposure of pinealectomized rats to high ambient temperature (35 degrees C; PXH) brought about a diminution in pituitary weight and LH content when compared to their sham-operated peers (35 degrees C) or to pinealectomized controls (22 degrees C). Serum corticosterone level of PXH rats was significantly depressed while heat or pinealectomy alone had no effect. Mean oestrous cycle length was prolonged and blood serum progesterone was increased in the heat-exposed rats. However, the extended oestrous cycles and elevated serum progesterone levels of heat-exposed rats were depressed or abolished by pineal ablation. Thus, the pineal appears to exert a moderating effect on heat-induced endocrine changes in female rats. No changes were noticed in uterine and ovarian weights corrected for body weights either on the day of vaginal opening, at occurrence of the oestrous phase expressed as percentage of total oestrous cycle, or in N-acetyltransferase and hydroxyindole-O-methyltransferase activities.

Animals↗
PubMed1983

Verapamil and digoxin: interactions in the rat.

Verapamil and digoxin are often used in combination and clinical experience suggests that verapamil may increase digoxin toxicity. We have explored the effects of verapamil upon digoxin induced tachyarrhythmias and have undertaken a preliminary study of the influence of verapamil on digoxin pharmacokinetics in the rat. Anesthetized rats received 20 mg/kg of digoxin intraperitoneally followed by verapamil i.v., 0.3 mg/kg, in repeated doses either immediately after digoxin or only after the onset of digoxin induced arrhythmias. Digoxin alone produced prolonged paroxysmal atrial tachycardia in 88-100% of rats and verapamil converted 75% of rats to sinus rhythm and significantly reduced digoxin induced mortality. In a later study, rats were injected with 10 mg/kg verapamil i.p. twice a day for 7 days or only with saline. On the seventh day all the rats received 0.5 mg/kg of digoxin i.p. Eight hours later the animals were sacrificed and plasma, heart, brain, liver, kidney and muscle (diaphragm) digoxin concentration was measured by radioimmunoassay. Digoxin levels were twice as high in plasma, heart, liver and muscle of verapamil pretreated rats (p less than 0.01). Two types of verapamil - digoxin interactions are demonstrated in the above studies; one in which verapamil modifies digoxin induced arrhythmias and a second pharmacokinetic effect in which pretreatment with verapamil increases digoxin concentration in the plasma and in several tissues.

Animals↗
PubMed1983

Modification of digoxin induced arrhythmogenicity in adult rats following atropine administration.

Atropine alone in the two lower doses (20mg/kg and 40mg/kg) did not produce any arrhythmias while 80mg/kg of atropine produced arrhythmias in 33% of animals after 31.0 +/- 7.5 min. Only 11% of these rats developed paroxysmal atrial tachycardia. Atropine in lower doses (20,40mg/kg) with digoxin (40mg/kg) decreased the total percent of digoxin induced arrhythmias, delayed their onset, and changed the type of arrhythmias as compared with the digoxin group alone. Atropine given in higher dosage (80mg/kg) with digoxin (40mg/kg) produced arrhythmias in 100% of rats as did digoxin alone, but significantly shortened their onset and modified the types of arrhythmias seen. In conclusion, atropine in varying doses significantly modified digoxin toxicity.

Animals↗
PubMed1982

Quantitative electrocardiographic effects of digoxin in newborn and adult rats.

We investigated the age and dose-specific quantitative electrocardiographic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. PR, QT, and RR intervals, QRS duration (msec), and T amplitude (mm) were measured every 15 minutes in all animals. QTc and PTQ index using the method of Joubert were calculated. Newborns demonstrated significant prolongation of the PR, QT, and RR intervals, an increase in the PTQ index, and a decrease in QTc when compared to adults (receiving the same dosage of digoxin) (P less than or equal to 0.05). In addition they developed toxic changes at much lower doses. Adults developed various tachycardias (tachyarrhythmias) compared to severe sinus bradycardias in the newborns. In conclusion, the newborn rat is much more sensitive to digoxin toxicity than the adult as demonstrated by ECG criteria. The newborns seem to be primarily "parasympathetic" responders as compared to adults who seem to be mainly "sympathetic" responders.

Age Factors↗
PubMed1981

Role of the pineal gland in male rats chronically exposed to increased temperature.

The effects of the pineal gland on endocrine function (especially those of the gonads) were investigated in male rats chronically exposed to increased temperature. Weanling male rats were either pinealectomized (Px) or sham-operated (Sh). Following one week of recovery, animals were assigned to either control temperature of 21 +/- 1 degree C (PxC and ShC) or a temperature of 35 +/- 1 degrees C (PxH and ShH). The animals were kept at their respective temperature for at least 30 days. In both groups (PxH and ShH) exposure to increased temperature resulted in a significant reduction in body and hypophysial weights, and in serum LH and testosterone levels as compared with the respective controls (PxC and ShC). Rectal temperature and serum corticosterone were also significantly increased. No changes were found in pineal hydroxyindole-O-methyltransferase activity of sham-operated rats kept in increased temperature (ShH vs. ShC). Pinealectomy alone (PxC vs. ShC) did not alter any of the measured parameters, except for increased pituitary LH content. Increased temperature plus pinealectomy (PxH vs. PxC; and PxH vs. ShH) caused a significant reduction in pituitary LH content and further accentuated (PxH vs. ShH) the diminished serum LH and testosterone levels evoked by exposure to high temperature. The results suggest that in male rats the pineal gland may play a role in moderating the changes in the reproductive processes that are induced by increased temperature.

Animals↗
PubMed1980

Cardiac toxicity of digoxin in newborn and adult rats.

We investigated the age-specific arrhythmogenic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. The arrhythmogenic dose 50 (AD50) and lethal dose 50 under anesthesia (LD50) were determined using the method of Litchfield and Wilcoxon. AD50 in adults was 13.0 +/- 1.0 mg/kg (X +/- SD) compared with 2.9 +/- 0.3 mg/kg in the newborns (P less than 0.01), and LD50 in adults was 30.0 +/- 1.9 mg/kg compared with 5.0 +/- 0.2 mg/kg in the newborns (P less than 0.01). Arrhythmias appeared earlier in adults (54 +/- 11.5 minutes after digoxin, X +/- SEM) than in newborns (132.2 +/- 11.0 minutes, P less than 0.01). Paroxysmal atrial tachycardia was the predominant arrhythmia in adults (73%), while transient sinus bradycardia appeared in only 9%. In contrast, all newborns with arrhythmias had severe sinus bradycardia and 69% had profound first degree heart block as well. In conclusion, the newborn rat is more sensitive to digoxin toxicity and develops lethal arrhythmias much more readily than the adult.

Aging↗
PubMed1979

Toxicity of digoxin in acutely and chronically heat-exposed rats.

Rats exposed acutely or chronically to high ambient temperatures (35 degrees C) were much more susceptible to digoxin toxicity than rats kept at 22 degrees C. LD 50 values were 8.8 +/- 1.8 mg/kg in the acute group and 10 +/- 5 2.5 mg/kg in the chronic group, which contrasted with 32.0 +/- 4.4 mg/kg in the control group. Toxic doses of digoxin cause marked hyperthermia in both the acute and chronic groups. Transferring the rats to 22 degrees C not only prevented the extreme hyperthermia, but also prevented death in the acute group (from the expected 100% to 0% mortality) and lowered the incidence of death in the chronic group (from the expected 78.5% to 30.7%). The suggestion is made that death may result from hyperthermia in the heat-exposed rats.

Acclimatization↗
PubMed1978

Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats.

The toxicity of aminophylline and caffeine was studied in adult and 2-day-old rats following a single subcutaneous injection of the respective drug. Following the injection of high doses of either methylxanthine, adult rats developed convulsions, tremors, lethargy and licking of lips. In adult rats, the LD50 of caffeine and aminophylline was the same after 24 h and after 1 week of observation: caffeine 265 mg/kg, and aminophylline 202 mg/kg (theophylline base 172 mg/kg). In young rats, the LD50 was greater when the observation was carried out for 1 week than at 24 h after the injection; at 24 h: caffeine 220 mg/kg, and aminophylline 169 mg/kg (theophylline base 144 mg/kg); at 1 week: caffeine 155 mg/kg, and aminophylline 140 mg/kg (theophylline base 119 mg/kg). Young rats failed to gain weight at a normal rate after administration of either methylxanthine. The greater toxicity of both methylxanthines in newborn animals may be at least partly due to the extremely slow elimination of theophylline and caffeine in the neonate.

Age Factors↗
PubMed1975

Reserpine and calcium: interaction at the injection site.

The subcutaneous administration of calcium prior to reserpine prevented the development of the well-known reserpine effects. Pretreatment with other bivalent cations induced a similar effect. The inhibitory effect of reserpine on the in vitro uptake of labelled catecholamines in brain homogenates was also prevented in rats pretreated with bivalent cations. On the other hand when calcium was injected at a site other than that of reserpine, there was no antagonistic effect. The latter results suggest an interaction between bivalent cations and reserpine at the injection site that prevents the systemic absorption of reserpine.

Animals↗