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.

Characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys

“…These results suggested that in the cynomolgus monkey, TnT and TnI distribution was from humans, mice, and rats as reported by Wallace et al (2004). Pinelli et al (2004) reported that myocardial injury in rabbits induced by administration of ISO + VASO (3 + 0.3 mg/kg) was characterized by necrosis of cardiac muscle, -dial infarction in humans. It has been reported that ISO, -traction and induces tachycardia, and that VASO, an anti- T max and C max were calculated for ASAT, ALAT, LDH, CPK, and ALD for each animal, and the mean level ± S.D.…”

“…34 No. 6 diuretic hormone, increases blood pressure by increasconsidered to induce ischemic myocardial injury by heart overload from increases in myocardial contraction and blood pressure (Pinelli et al, 2004). We administered ISO + VASO to cynomolgus monkeys, and investigated chronological changes in biomarkers, the relationship between those biomarkers and the severity of morphological myocardial injury.…”

“…Myocardial injury was induced by concomitant administration of isoproterenol (ISO) and vasopressin (VASO), which has been reported to induce severe myocardial injury than administration of ISO alone (Pinelli et al, 2004). Twelve naive cynomolgus monkeys were divided into four groups (one control group and three ISO + VASO groups).…”

Exploration of pharmacological interventions to prevent isoproterenol-induced myocardial infarction in experimental models

“…Moreover, verapamil exerts protection against myocardial lesions, electrocardiographic alterations, high plasma cardiac necrosis marker c-troponin I levels, and prevents the hemodynamic and procoagulation changes. Therefore verapamil seems to be suitable for preventing myocardial ischaemic lesions induced by ISO and vasopressin [Pinelli et al 2004]. Nimodipine is used in the management of patients with stroke or subarachnoid haemorrhage [Towart and Kazda, 1979].…”

Ca2+-Sensitisers—A Promising Option to Treat Heart Failure?

“…Positive inotropic agents which enhance cardiac force via increasing the intracellular Ca 2+ -concentration are disadvantageous because they may induce a Ca 2+ -overload of the cells, possibly followed by apoptosis (i.e. a programmed cell cycle which ends in the death of the cells [1], necrosis [2] and/or the development of tachycardia and arrhythmia [3]). In addition, the Ca 2+ -dependent increase in contractility is linked to increased cardiac energy/ATP and O 2 -consumption, which may be detrimental in situations where the oxygen supply of the heart is already limited.…”