Effects of rhIGF‐I and Insulin‐Induced Hypoglycaemia on Cardiovascular Parameters Recorded with Telemetry in the Conscious Dog

Abstract

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.

Growth hormone decreases phase II ventricular tachyarrhythmias during acute myocardial infarction in rats

“…Nonetheless, a direct electrophysiological action of GH on ventricular myocytes cannot be excluded, and this view is supported by reports of a significant effect of GH/IGF-1 on calcium channels in atrial myocytes [26] and rapid delayed rectifier K + current in neonatal ventricular myocytes [27]. Furthermore, GH/IGF-1 may lead to an 'insulin-like' stimulation of Na + /K + pump activity [28], resulting in T-wave alterations [29].…”

Cardiovascular effects of xylazine recorded with telemetry in the dog

“…The experiment was approved by the Research Ethics Committee at the University of Lund (Lund, Sweden). These dogs participated in a more extensive safety pharmacology study of insulin and IGF‐1 (Ilbäck et al., 2002a). In that study xylazine treatment was given before and after drug treatment to validate the stability of obtained telemetry data.…”

“…The system allows free movement of the animal and eliminates stress associated with handling and restraint, anaesthesia artefacts, exit site infections and movement artefacts (Eisermann, 1988; Lange et al., 1991). Pharmacological and toxicological evaluations of drugs benefit from the ability to monitor blood pressure, ECG, heart rate and temperature continuously in conscious animals that are freely mobile and completely naive to drugs (Ilbäck et al., 2002a,b). In contrast to telemetry, comparable and reliable data cannot be obtained by conventional data acquisition techniques.…”

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

“…Direct inotropic effects of IGF-1 have been described in neonatal rat cardiomyocytes in vitro, demonstrating the sensitivity of the neonatal heart to IGF-1 [56]. In dogs followed by telemetry, heart rate continuously increased for approximately 90 min after treatment, whilst both systolic and diastolic blood pressures decreased [57].…”