Effects of rhIGF-I and insulin-induced hypoglycaemia on cardiovascular parameters recorded with telemetry in the conscious dog.
Using telemetry, the effects on cardiovascular parameters after single intravenous administration (0.5 mg/kg) of recombinant human insulin-like growth factor-I (rhIGF-I) were studied in conscious and unrestrained dogs. Insulin (1.1 IU/kg) was used as a reference compound. Telemetry transmitters were implanted subcutaneously with a pressure catheter in the femoral artery and electrodes for ECG subcutaneously. Cardiovascular effects and changes in blood glucose levels induced with rhlGF-I were similar to those induced with insulin. Heart rate increased continuously for about 90 min. after treatment, regardless of compound. Thereafter, heart rate slowly decreased but did not fully reach predose values 4 hr after treatment. Both systolic and diastolic blood pressure decreased continuously for about 90 min. and remained low for up to 4 hr after treatment. Treatment with rhIGF-I or insulin did not influence dp/dt values. Treatment with glucose intravenously to abolish the rhIGF-I-induced hypoglycaemia reduced the heart rate, but caused a substantial increase in dp/dt and a slight increase in blood pressure. RhIGF-I and insulin induced an almost identical onset and degree of hypoglycaemia. Blood glucose reached a minimum level 1 hr after treatment and was almost returned to normal 4 hr after treatment. There was an increase in the amplitude of the T-waves, though this effect occurred earlier and was longer lasting with insulin than with rhIGF-I. After 4 hr, the T-wave amplitude was normal with rhIGF-I but remained high with insulin. These T-wave effects were probably due to an increase in the transport of potassium or calcium since they decreased in plasma. This suggests that the effects of rhIGF-I and insulin are highly comparable and that the cardiovascular changes induced by rhIGF-I are likely caused by its insulin-like activity. As shown by the recorded cardiovascular responses induced by rhIGF-1 and insulin, the telemetric recording system makes it possible to evaluate the effects of different drugs in a continuous way that is not possible with conventional techniques. This new telemetric technique can be of significant importance in the process of future drug development.
Ilbäck
Nils-Gunnar
NG
Toxicology Division, National Food Adminstration, Uppsala, Sweden. ngil@slv.se
Gunnarsson
Kjell
K
Stålhandske
Torbjörn
T
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013686:Telemetry
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I