The synthetic catecholamine isoprenaline (ISO) has been used as an inductor in the acute myocardial infarction model for more than a half century. Despite the fact that many articles were published on this topic, precise early haemodynamic pathology remains unknown. Acute haemodynamic changes were measured in rats; first, in preliminary experiments by the thermodilution method; and second, in main experiments continuously for 2 h using a Millar catheter. Animals received saline or ISO in the cardiotoxic dose (100 mg/kg, subcutaneously). Also, additional experiments were performed with salbutamol in order to evaluate the role of β(2)-receptors. ISO caused a rapid, within 1 min, approximately 40% decrease in arterial blood pressures, 30% increase in the heart rate, and 30% decrease in the stroke volume. Within the first 2 min, the changes were followed by decreases in afterload (-40%), preload (-10%), diastolic relaxation (-50%), diastolic filling (-40%), and a marked, but short-term, increase in the left ventricle contractility (+100%). Ejection fraction did not significantly change, suggesting diastolic dysfunction. Salbutamol, with the exception of diastolic pressure and afterload, did not substantially influence other parameters. In conclusion, this study demonstrated that diastolic dysfunction precedes systolic dysfunction and β(2)-receptor stimulation alone is not sufficient for an early induction of diastolic dysfunction.

Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského Hradec Králové Czech Republic

References provided by Crossref.org

Comprehensive review of cardiovascular toxicity of drugs and related agents

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