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A cardiovascular response to injected propylene glycol
Pharmacology, Pathology--fd
450
In a similar experiment designed to assess the of effects of diet restriction on the survival monocrotaline-treated rats, 36 rats were injected SC with 60 mg monocrotaline/kg. Twelve of the rats were given food and water ad lib. and consumed 17.8 k 1.7 g feed/rat/day. A second group was given only 8 g feed/rat/day and the remaining 12 rats were given 8 g feed/rat/day for 30 days after injection and were then given food ad lib. All surviving rats were killed 90 days after injection. The group fed ad lib. showed laboured breathing from about 20 days after injection, and 11 of these rats died between days 22 and 40. The diet-reduced group survived the 90 days with no sign of respiratory distress: throughout the
Costner. Tori&.
Vol. 18. no. 4
experiment their growth was almost completely suppressed. The growth of the animals in the third group was also suppressed for the 30 days when food intake was limited and during this time there was no respiratory dysfunction. However once ad lib. feeding was resumed these animals began to show laboured breathing and seven of them died between days 45 and 84. It therefore seems that restriction of food intake can inhibit the toxic effects of monocrotaline in rats, although whether these inhibitory effects are related to the reduced food intake or to the suppression of their growth remains to be determined.
PHARMACOLOGY
A cardiovascular
response
to injected
propylene
glycol
Gross, D. R., Kitzman, J. V. & Adams, H. R. (1979). Cardiovascular effects of intravenous administration of propylene glycol and of oxytetracycline in propylene glycol in calves. Am. J. wt. Rex 40. 783. Propylene glycol (PG) has been found to be capable of inducing primary irritation and dermatitis (Cited in F.C.T. 1975. 13. 403: ibid 1977, 15. 84). The pharmacological effects of PG are generally slight, and despite mild irritancy and its possible effects on some liver microsomal-enzyme systems (ibid 1975, 13, 582). it has been widely used as a solvent for drugs to be injected. Its implication in the aetiology of a cardiovascular-collapse syndrome associated with injections of normally-well-tolerated doses of tetracycline and related antibiotics has now been reported. This reaction has been encountered in a variety of experimental situations and in cattle undergoing tetracycline therapy, although signs of overt cardiovascular depression following the clinical use of tetracycline antibiotics are relatively rare. Intravenous injections of aqueous solutions of oxytetracycline into calves failed to induce any alteration in heart rate, or in pulmonary and renal arterial re-
sistance, measured by means of indwelling catheters and electromagnetic flowmeter transducers, although the doses used (11.2-56 mg/kg) were the same as those that had been shown to induce a transient (14 min) reaction in the same calves when given in 79.2”” PG. This cardiovascular reaction was characterized by periods of asystole, lasting for 5-1Osec and followed by atrioventricular nodal blockade, together with an increase in pressure and decrease in flow in both pulmonary and renal arteries. Haemolysis and haemoglobinuria occurred in all the calves after the oxytetracycline in PG injection and persisted for up to 36 hr. The same reactions occurred in all the calves after injection of an equivalent volume of 79.29; PG alone, the degree of response in comparison with the baseline data being very similar following the two treatments. Subsequently, on different days, the same dose of oxytetracycline in PG or PG alone was injected following administration of one of three autonomic blocking agents (phentolamine. propanolol and atropine) or combinations of the first two or of all three of these. All of the blocking agents altered the responses to PG alone and to oxytetracycline in PG and this aspect of the study has provided some basis for speculation on the possible mechanisms involved in this reaction to PG.
PATHOLOGY
Trimethyltin
levels
and
brain
lesions
Brown, A. W., Aldridge, W. N., Street, B. W. & Verschoyle, R. D. (1979). The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat. Am. J. Path. 97, 59. Trimethyltin chloride (TMC) affects the central nervous system. In man, it is alleged to produce memory defects, hyperactivity, insomnia and disorientation, followed by mental confusion and convulsions. In the rat, tremors and convulsions have been reported.
A detailed study of the neurotoxicity of TMC in rats has shown that after a single dose of 15.8, 25 or 40mg TMC kg, given in arachis oil by gavage. tremors and prostration developed within 48 hr and deaths were recorded between 48 and I20 hr after treatment. The earlier deaths occurred in the rats given the larger doses. Rats receiving a single dose of IO mg/kg became extremely aggressive and at 72 hr had to be caged individually. No deaths occurred after this dose, and 7 days after treatment the signs of aggression had abated. The pathological lesion in the brain was studied in
450
In a similar experiment designed to assess the of effects of diet restriction on the survival monocrotaline-treated rats, 36 rats were injected SC with 60 mg monocrotaline/kg. Twelve of the rats were given food and water ad lib. and consumed 17.8 k 1.7 g feed/rat/day. A second group was given only 8 g feed/rat/day and the remaining 12 rats were given 8 g feed/rat/day for 30 days after injection and were then given food ad lib. All surviving rats were killed 90 days after injection. The group fed ad lib. showed laboured breathing from about 20 days after injection, and 11 of these rats died between days 22 and 40. The diet-reduced group survived the 90 days with no sign of respiratory distress: throughout the
Costner. Tori&.
Vol. 18. no. 4
experiment their growth was almost completely suppressed. The growth of the animals in the third group was also suppressed for the 30 days when food intake was limited and during this time there was no respiratory dysfunction. However once ad lib. feeding was resumed these animals began to show laboured breathing and seven of them died between days 45 and 84. It therefore seems that restriction of food intake can inhibit the toxic effects of monocrotaline in rats, although whether these inhibitory effects are related to the reduced food intake or to the suppression of their growth remains to be determined.
PHARMACOLOGY
A cardiovascular
response
to injected
propylene
glycol
Gross, D. R., Kitzman, J. V. & Adams, H. R. (1979). Cardiovascular effects of intravenous administration of propylene glycol and of oxytetracycline in propylene glycol in calves. Am. J. wt. Rex 40. 783. Propylene glycol (PG) has been found to be capable of inducing primary irritation and dermatitis (Cited in F.C.T. 1975. 13. 403: ibid 1977, 15. 84). The pharmacological effects of PG are generally slight, and despite mild irritancy and its possible effects on some liver microsomal-enzyme systems (ibid 1975, 13, 582). it has been widely used as a solvent for drugs to be injected. Its implication in the aetiology of a cardiovascular-collapse syndrome associated with injections of normally-well-tolerated doses of tetracycline and related antibiotics has now been reported. This reaction has been encountered in a variety of experimental situations and in cattle undergoing tetracycline therapy, although signs of overt cardiovascular depression following the clinical use of tetracycline antibiotics are relatively rare. Intravenous injections of aqueous solutions of oxytetracycline into calves failed to induce any alteration in heart rate, or in pulmonary and renal arterial re-
sistance, measured by means of indwelling catheters and electromagnetic flowmeter transducers, although the doses used (11.2-56 mg/kg) were the same as those that had been shown to induce a transient (14 min) reaction in the same calves when given in 79.2”” PG. This cardiovascular reaction was characterized by periods of asystole, lasting for 5-1Osec and followed by atrioventricular nodal blockade, together with an increase in pressure and decrease in flow in both pulmonary and renal arteries. Haemolysis and haemoglobinuria occurred in all the calves after the oxytetracycline in PG injection and persisted for up to 36 hr. The same reactions occurred in all the calves after injection of an equivalent volume of 79.29; PG alone, the degree of response in comparison with the baseline data being very similar following the two treatments. Subsequently, on different days, the same dose of oxytetracycline in PG or PG alone was injected following administration of one of three autonomic blocking agents (phentolamine. propanolol and atropine) or combinations of the first two or of all three of these. All of the blocking agents altered the responses to PG alone and to oxytetracycline in PG and this aspect of the study has provided some basis for speculation on the possible mechanisms involved in this reaction to PG.
PATHOLOGY
Trimethyltin
levels
and
brain
lesions
Brown, A. W., Aldridge, W. N., Street, B. W. & Verschoyle, R. D. (1979). The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat. Am. J. Path. 97, 59. Trimethyltin chloride (TMC) affects the central nervous system. In man, it is alleged to produce memory defects, hyperactivity, insomnia and disorientation, followed by mental confusion and convulsions. In the rat, tremors and convulsions have been reported.
A detailed study of the neurotoxicity of TMC in rats has shown that after a single dose of 15.8, 25 or 40mg TMC kg, given in arachis oil by gavage. tremors and prostration developed within 48 hr and deaths were recorded between 48 and I20 hr after treatment. The earlier deaths occurred in the rats given the larger doses. Rats receiving a single dose of IO mg/kg became extremely aggressive and at 72 hr had to be caged individually. No deaths occurred after this dose, and 7 days after treatment the signs of aggression had abated. The pathological lesion in the brain was studied in