title: Myocardial infarction non-invasively induced in rabbits by administering isoproterenol and vasopressin: protective effects exerted by verapamil.
abstract: Myocardial infarction is usually induced in small animals by means of invasive procedures: the aim of this study was to cause heart necrosis lesions by non-invasive means. We injected rabbits with isoproterenol (3 mg/kg, i.p.) and vasopressin (0.3 mg/kg/5 min, i.v.) alone and in combination, and studied their effects on myocardial histology, electrocardiographic profiles, the appearance of the plasma cardiac necrosis marker c-troponin I (c-TPN I), hemodynamic parameters (blood pressure, heart rate), the coagulative process partial throboplastine time (PTT), and plasma nitric oxide (NO) levels. In the rabbits treated with vasopressin alone, the ischemic damage was associated with a decrease in NO values, and the appearance of electrocardiographic T-wave inversion and low plasma c-TPN I levels, whereas the animals treated with isoproterenol alone had necrotic bands in the myocardium, plasma c-TPN I, and electrocardiographic modifications (ST-segment changes and T-wave inversion). Combined treatment increased myocardial alterations such as contraction band necrosis, induced the appearance of specific hypoxic lesions such as areas of coagulative necrosis and leukocyte infiltration, and led to higher plasma c-TPN I levels and altered ECG profiles. Both drugs favored a decrease in plasma NO values and further alterations in hemodynamic parameters, such as higher blood pressure and greater procoagulant activity. The myocardial necrosis and modified cardiovascular parameters were attributed to calcium activated processes and the decrease in NO levels. As this model of myocardial damage involves the use of drugs that facilitate the opening of L-calcium channels, we also investigated their effects on cardiovascular parameters and heart histology after pretreatment with the calcium antagonist verapamil; this drug protected against the appearance of histological myocardial lesions, electrocardiographic alterations and high plasma c-TPN I levels, and prevented the hemodynamic and procoagulation changes, but did not affect the decrease in plasma NO values. The protective effects were attributed to the drug's calcium antagonist activity. In conclusion, the injection of isoproterenol and vasopressin induces a myocardial infarction non-invasively and seems to be suitable for studying early myocardial ischemic lesions and the effects of drugs interfering with myocardial damage and its related phenomena.
authors.affiliation: Department of Pharmacology, Via Vanvitelli 32, 20129 Milano, Italy. arnaldo.pinelli@unimi.it
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Pinelli
authors.forename: Silvio
authors.initials: S
authors.lastname: Trivulzio
authors.forename: Livio
authors.initials: L
authors.lastname: Tomasoni
authors.forename: Boris
authors.initials: B
authors.lastname: Bertolini
authors.forename: Sergio
authors.initials: S
authors.lastname: Brenna
authors.forename: Edgardo
authors.initials: E
authors.lastname: Bonacina
authors.forename: Silvano
authors.initials: S
authors.lastname: Vignati
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood; D010314:Partial Thromboplastin Time; D011817:Rabbits; D013566:Sympathomimetics; D019210:Troponin I / Q000097:blood; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects; D014667:Vasopressins; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D002121:Calcium Channel Blockers; D013566:Sympathomimetics; D019210:Troponin I; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009569:Nitric Oxide; D014700:Verapamil; D007545:Isoproterenol