C. P. Kahler

The dose-related hyper-and-hypokalaemic effects of salbutamol and its arrhythmogenic potential

1 The hypokalaemic effect of salbutamol after more than 30 min of administration has been well described. A hyper‐and‐hypokalaemic effect for adrenaline has been reported, but no such hyperkalaemic effect for salbutamol. 2 The possible hyper‐and‐hypokalaemic effects of salbutamol with the concomitant potential for pro‐arrhythmia were assessed in the baboon (Papio ursinus). 3 Male and femal baboons were anaesthetized with ketamine (15 mg kg−1) and maintained with 6% pentobarbitone as spontaneously breathing animals. Six baboons in each group received either 10, 100 or 500 μg kg−1 salbutamol i.v. Lead II of the ECG and femoral i.a. blood pressure were recorded continuously for 10 min. Arterial blood samples were collected at 0 min and then after 3 and 10 min of salbutamol administration. 4 All the animals developed sinus tachycardia (above 200 beats min−1) within 30 s of each dose of salbutamol administration and the high heart rate persisted throughout the experiment. All the animals were hyperkalaemic after 3 min and hypokalaemic after 10 min for each dose of salbutamol. Left ventricular conduction defects were seen in 3 animals during the hyperkalaemic phase. No arrhythmia was seen during the hypokalaemic phase. 5 Salbutamol has a transient hyperkalaemic and a more prolonged hypokalaemic effect in the baboon. The hypokalaemia could not be associated with arrhythmia although conduction defects were associated with the hyperkalaemia. 6 Since salbutamol is used as a bronchodilator in asthmatic patients and to treat acute hyperkalaemia, it is suggested that caution should be exercised when using salbutamol in high doses to treat acute asthma especially during the first few minutes of administration. The finding of hyperkalaemia with salbutamol questions its use in the treatment of hyperkalaemia.

Effect of gammalinolenic acid, dihomogammalinolenic acid, ascorbyl-6-gammalinolenic acid and ascorbyl-6-dihomo gammalinolenic acid on histamine- and methacholine-induced contraction of the isolated guinea pig tracheal chain

The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA) were investigated and the role of the epithelial cells was determined. Salbutamol was used as control. The isolated tracheas of six to eight guinea pigs were used in each experiment and suspended in organ baths filled with Krebs-Henseleit solution and aerated with 95% O2 and 5% CO2. The relaxant effects produced for histamine-contracted preparations were as follows: AA=71.2+/-0.2%, GLA=55.2+/-4.2%, DGLA=69.8+/-3.9%, ascorbyl-6-GLA =26.2+/-5.1% and ascorbyl-6-DGLA=54.5+/-2.4%. For methacholine-contracted preparations: AA=46.6+/-3.2%, GLA=55.0+/-9.5%, DGLA=61.8+/-2.7%, ascorbyl-6-GLA=40.0+/-8.0% and ascorbyl-6-DGLA=88.0+/-15.3%. Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced contraction, which showed a significant increased relaxant effect. The removal of the epithelium showed decreased relaxant effects for the drugs except AA, which showed increased values after methacholine contraction. Histamine-contracted preparations showed varied results. Ascorbyl-6-GLA showed an increased relaxant effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6-DGLA showed decreased relaxant effects. In conclusion, it is clear that the contractant and the availability of epithelial cells could ultimately determine the results, though the mechanism remains very complex. The benefit of added ascorbate is still unclear and warrants more investigation.