Isoproterenol-induced myocardial infarction in rabbits. Protection by propranolol or labetalol: a proposed non-invasive procedure.
Myocardial infarction is usually induced in small animals by means of invasive techniques based on mechanical coronary obstruction. As it has been reported that isoproterenol can cause ischemic myocardial alterations, lipid peroxide generation and procoagulant activity, we administered it to rabbits in order to induce a non-invasive myocardial infarction associated with above mentioned cardiovascular risk factors. Considerable ischemic alterations were observed in the animals treated with isoproterenol, including areas of myocardial necrosis, contraction band necrosis, increased plasma levels of cardiac necrosis markers (c-troponin I and myoglobin), and electrocardiographic modifications (ST segment changes and T wave inversion). The myocardial infarction was attributed to the inotropic activity of isoproterenol leading to intracellular calcium overload. The cardiac necrosis phenomena appear to be associated with isoproterenol-induced lipid peroxide generation (as shown by the decrease in plasma Vitamin E levels) and increased procoagulant activity (a shortened PTT). As this model of myocardial damage is based on the use of beta-stimulatory isoproterenol, the beta-blockers propranolol and labetalol were administered to isoproterenol-treated animals. Pretreatment with propranolol or labetalol counteracted the appearance of the myocardial histological alterations and the associated ECG and biochemical lesions. This protective activity was attributed to the beta-blockade. The results of this study demonstrate that myocardial infarction can be induced chemically and non-invasively in small laboratory animals. The procedure is proposed for the study of early ischemic myocardial lesions and the screening of drugs (such as beta-blockers) that can prevent myocardial necrosis damage and the associated risk factors.
Department of Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. arnaldo.pinelli@unimi.it
Arnaldo
A
Pinelli
Silvio
S
Trivulzio
Livio
L
Tomasoni
Sergio
S
Brenna
Edgardo
E
Bonacina
Roberto
R
Accinni
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D004562:Electrocardiography; D007545:Isoproterenol; D007741:Labetalol / Q000627:therapeutic use*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D010314:Partial Thromboplastin Time; D011433:Propranolol / Q000627:therapeutic use*; D011817:Rabbits; D014810:Vitamin E / Q000097:blood
D000319:Adrenergic beta-Antagonists; D008054:Lipid Peroxides; D014810:Vitamin E; D011433:Propranolol; D007545:Isoproterenol; D007741:Labetalol