Hypotension may cause cardiac damage in critically ill patients with acute non-cardiac diseases as shown by abnormal levels of cTnI. It is likely that a high number of these myocardial necroses may go unnoticed on the ECG.

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.

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.

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