Glucagon's Cardiovascular Effects With and Without Beta-blocker-induced Cardioinhibition (GLUCAGON)
Drug Overdose, Overdose of Beta-adrenergic Blocking Drug
About this trial
This is an interventional basic science trial for Drug Overdose focused on measuring Glucagon, Beta-adrenergic antagonist, poisoning
Eligibility Criteria
Inclusion Criteria:
- Healthy male determined by investigator, based upon physical examination, medical history, ECG, vital signs and laboratory results
- Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2 and body weight between 50 and 100 kg, inclusive, at screening visit.
Exclusion Criteria:
- Abnormal blood levels of sodium, potassium, creatinine, alanine transaminase (ALT), alkaline phosphatase, albumin, bilirubin, hemoglobin, HbA1c, cholesterol fractions.
- Bradycardia (<45 beats per minute)
- Hypotension (systolic blood pressure < 100 mmHg)
- Second or third degree atrioventricular conduction delay
- Sick sinus syndrome
- Any heart disease or hypertension
- Pheochromocytoma
- Allergy to any active or inactive ingredient contained in investigatory medicines or tools.
- Raynaud's syndrome
- Prinzmetal's angina
- Diabetes
- Pulmonary disease
- Pheochromocytoma
- Any contraindication against investigatory medicines or tools.
Sites / Locations
- University Hospital Bispebjerg
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Esmolol-placebo+glucagon 1 placebo (A)
Esmolol+glucagon 1 placebo (B)
Esmolol+glucagon 1 (C)
Esmolol-placebo+glucagon 2 (D)
Esmolol-placebo+glucagon 1 (E)
Physiologic saline - esmolol dummy (10 mg esmolol/ml) is administered as a loading dose at baseline (time= -15 minutes) (corresponding to 0.125 ml/kg/min of saline). Continuous infusion (0.05-0.075 ml/kg/min) of saline is then administered until T=30 minutes. + Physiologic saline - glucagon dummy bolus 50 ml at time=0.
Esmolol intravenous solution (10 mg/ml esmolol hydrochloride) is administered as a loading dose (1.25 mg/kg/min esmolol) at baseline (time= -15 minutes). Continuous infusion (500-750 micrograms/kg/min) of esmolol/placebo is then administered until T=30 minutes. + Physiologic saline - glucagon dummy bolus (50 ml) at time=0.
Esmolol intravenous solution (10 mg/ml esmolol hydrochloride) is administered as a loading dose (1.25 mg/kg/min esmolol) at baseline (time= -15 minutes). Continuous infusion (500-750 micrograms/kg/min) of esmolol/placebo is then administered until T=30 minutes. +Glukagon 1 (50 μg/kg bolus - over 1-3 min from time=0 min in 50 ml isotonic fluid)
Physiologic saline - esmolol dummy (10 mg esmolol/ml) is administered as a loading dose at baseline (time= -15 minutes) (corresponding to 0.125 ml/kg/min of saline). Continuous infusion (0.05-0.075 ml/kg/min) of saline is then administered until T=30 minutes. +Glukagon 2 (50 μg/kg bolus - over 30 min in 50 ml isotonic fluid from time=0 min)
Physiologic saline - esmolol dummy (10 mg esmolol/ml) is administered as a loading dose at baseline (time= -15 minutes) (corresponding to 0.125 ml/kg/min of saline). Continuous infusion (0.05-0.075 ml/kg/min) of saline is then administered until T=30 minutes. + Glukagon 1 (50 μg/kg bolus - over 1-3 min from time=0 min in 50 ml isotonic fluid)