Pancuronium effect on the neuromuscular function of hypoglycemic rats.

An expected response in a hypoglycemic patient to a muscle relaxant formed the basis for the research presented in this study. There was no information available in the accessible literature and references gave no data on this subject. But because perioperative hypoglycemia is not unusual, we scheduled this experimental work. Four groups of 6 white adult Wistar albino rats were used in the study. Group A was the normoglycemia control group, with blood glucose levels of 80-120 mg/dl. Groups B, C and D were made hypoglycemic by i.v. injection of insulin 1 IU/100 g b.w. Blood glucose levels were reduced to 50% of the control values in hypoglycemic animals, which were sacrificed 40 min later. Phrenic nerve-hemidiaphragm preparations were placed in a 100 ml bath containing Paradelis-Zaimis solution, 37 degrees C, pH 7.2, aerated with O2/CO2:95/5%. After stabilization and recording of neuromuscular activity, pancuronium bromide was administered in doses of 1.5 x 10(-9) M in groups A and B, 3 x 10(-9) M in group D. Statistical analysis between A-B, A-C, A-D groups was done with Student's paired t test. Results showed that under hypoglycemic conditions the amount of pancuronium bromide needed for complete neuromuscular blockade was 2.5-fold greater than that needed in normoglycemic conditions. These findings suggest that the integrity of the neuromuscular junction is altered during hypoglycemia.

The intra-nasal administration of insulin induces significant hypoglycaemia and classical counterregulatory hormonal responses in normal man.

The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon) diluted with a non ionic detergent (Laureth-9 0,25%) was administered intra-nasally in 8 overnight fasted healthy volunteers using a calibrated aerosol delivery device (90 microliters = 9 U of insulin/spray) up to a total insulin dose close to 1 U/kg body weight. After intra-nasal insulin administration, plasma insulin levels rose from 5 +/- 1 to 38 +/- 10 mU/l (2p less than 0.01) at min 15, blood glucose concentrations decreased from 4.4 +/- 0.2 to 3.2 +/- 0.3 mmol/l (2p less than 0.01) at min 45, plasma C-peptide levels diminished from 327 +/- 31 to 174 +/- 28 mumol/l (2p less than 0.01) at min 60 and plasma free fatty acids concentrations fell from 336 +/- 109 to 130 +/- 31 mumol/l (2p less than 0.05) at min 30. The fall in blood glucose resulted in a prompt increase in plasma glucagon levels (from 78 +/- 28 to 150 +/- 24 ng/l at min 45; 2p less than 0.05) and in later rises in plasma growth hormone and cortisol concentrations. There was a close relationship between the individual maximal decreases in blood glucose levels and the individual maximal increases in plasma insulin (r = 0.81), glucagon (r = 0.88), cortisol (r = 0.87) and growth hormone (r = 0.76) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of insulin concentration on bioavailability during nasal spray administration.

The bioavailability of rapid-acting insulin administered as a nasal spray was studied in 6 type 1 (insulin-dependent) diabetic patients. They received long-acting bovine insulin (Ultratardum 40 U/ml, Organon) as basal treatment at 8 a.m. Rapid-acting insulin was also administered at 8 a.m., then at noon and 6 p.m, subcutaneously on day 1 as a 100 U/ml solution and intranasally by aerosol spray as a 100 U/ml and 500 U/ml with 1% (w/v) 9 lauryl ether solution on day 2 and day 3 respectively. On days 2 and 3, the dose of insulin was at least nine times higher than the subcutaneous dose on day 1. Free and total plasma insulin concentrations were assayed after the noon insulin administration. The peaks of the free and total plasma insulin levels were reached earlier and the return to basal levels was obtained earlier after nasal insulin administration than after insulin injected subcutaneously. The bioavailability of nasal spray insulin versus subcutaneous insulin with a 100 U/ml insulin solution was similar to that with a 500 U/ml insulin solution: 5.14 +/- 0.38% (m +/- SEM) and 4.64 +/- 0.46% according to the total plasma insulin level. This study suggests that the bioavailability of nasal spray insulin is not increased by increasing insulin concentration in our experimental conditions.