Prophylactic amiodarone and lidocaine improve survival in an ovine model of large size myocardial infarction

Abstract

Background Large animal models serve as a critical link in the translation of basic science to clinical practice. However, large animal models of MI, especially a large size MI, are associated with high mortality due to arrhythmia. The prophylactic effect of amiodarone and lidocaine were retrospectively reviewed in our ovine MI model. Methods One hundred-fourteen Dorset hybrid sheep with 25–30% MI were included in this study. Animals were prophylacticly treated with amiodarone plus lidocaine before ligation of the 4–6 coronary artery branches supplying the apex of the heart (arrhythmia-prevention group, AP group, n=45) and with epinephrine (shock-prevention group, SP group, n=49), respectively. Animals without prophylactic treatment (no-prevention group, NP group, n=20) were used as the control group. The incidence of arrhythmia requiring treatment, mortality due to arrhythmias, hemodynamics and arterial blood gas values during the surgery were analyzed in these three groups. Results There was no significant difference in infarct size among the three groups. The incidence of arrhythmia requiring treatment was significantly decreased in the AP group compared to the NP or SP groups 4.4% (AP) vs. 35% (SP) or 45% (NP) p<0.05). The mortality due to lethal arrhythmia was 2.2% in the AP group, significantly lower than in the NP group (15%) or the SP group (18.4%). Besides heart rate (HR), hemodynamic data there were no significant differences between the AP and NP group. Metabolic acidosis was not observed in any group as indicated by pH and lactate values. Conclusions Prophylactic amiodarone plus lidocaine decreased the mortality due to lethal arrhythmia after acute myocardial infarction in our sheep model without significant negative effect on hemodynamics. However, epinephrine improved hemodynamics but also increased mortality due to lethal arrhythmia. Thus, prophylactic amiodarone plus lidocaine is recommended to improve the stability in a large MI animal model.

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload

“…On the morning of stem cell injection, MSCs at passage 3 were harvested with TrypLE Express (Gibco, Life Technologies, Grand Island, NY) and resuspended in PBS. Prior to injection, swines were treated with amiodarone (2 mg/kg iv bolus followed by 0.5 mg·kg Ϫ1 ·h Ϫ1 infusion) (25). After 30 min postbanding, swines underwent stem cell (n ϭ 5, 1 ϫ 10 6 MSCs) or placebo (n ϭ 5, PBS) injection to the RV myocardium via six separate 200-l aliquots (total volume of 1.2 ml) with a 29-gauge needle at a 30-degree angle to the epicardium.…”

Ventricular Arrhythmias in First Acute Myocardial Infarction: Epidemiology, Mechanisms, and Interventions in Large Animal Models

“…Treatment with amiodarone has been tested in a variety of animal models before and after AMI, as well as during VF. Overall, animal models showed reduced ventricular arrhythmia (100–102), decreased dispersion (103) and improved defibrillation success rate (99). We showed reduced VF incidence rates with amiodarone when given 10 min after AMI onset (64).…”

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

“…Comparatively, we used a total ischemic time slightly less than the reported median [ 5 ], but certainly still within the clinically relevant range. Sheep are commonly used as reliable and reproducible preclinical models of chronic heart failure and myocardial infarction, despite an accepted 30% mortality rate, predominantly due to malignant arrhythmias [ 56 – 58 ]. Sheep and humans have similarities in cardiac myocyte, electrophysiological, contractile and metabolic properties [ 56 , 59 ].…”