Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 µM), ML-7 (0.5 µM), and L-NAME (2 µM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.

Bipolar endo-epicardial RF ablation: Animal feasibility study.

BACKGROUND: Bipolar radiofrequency ablation (B-RFA) is a method used to treat the arrhythmia substrate resistant to unipolar ablation. Few studies have addressed endo-epicardial B-RFA. OBJECTIVE: The aim of the study was to evaluate chronic lesions resulting from endo-epicardial B-RFA and to determine optimal settings for such procedures in an animal model. METHODS: In 7 pigs, up to 5 radiofrequency applications per animal were performed with 2 electrodes placed on both sides of the left ventricular free wall. Current was delivered for 60 seconds by a generator dedicated for B-RFA with power settings of 25, 30, 35, 40, and 50 W. RESULTS: At 12 weeks after ablation, 31 lesions were assessed. Their maximal cross-sectional area ranged from 7.2 to 68 mm2 and correlated with total power delivered (r = 0.53), with temperature increment at the endocardial catheter (r = 0.65), and inversely with temperature decrement at the epicardial catheter (r = 0.54). For power values between 30 and 40 W, the lesion area did not differ significantly (P = .92). Lesion depth ranged from 1.9 to 11 mm and correlated with impedance decrement (r = 0.5). Lesions were transmural in 8 cases. Lesion depth/wall thickness ratio was on average 0.6 ± 0.3, with the smallest value for 25 W (0.5 ± 0.3) and the largest for 50 W (0.8 ± 0.3). Steam pops occurred at a power range of 30-50 W, with an incidence of 1 in 5 applications, with 1 case of fatal tamponade at 40 W. Impedance decrement, endocardial catheter temperature increment, and endocardial electrogram amplitude decrement were greater during applications with steam pops. CONCLUSION: Chronic lesions resulting from endo-epicardial B-RFA appear smaller and less often transmural compared with acute lesions described in the literature. The incidence of steam pops during endo-epicardial B-RFA is relatively high even at low powers.

Punica granatum L. Extract Shows Cardioprotective Effects Measured by Oxidative Stress Markers and Biomarkers of Heart Failure in an Animal Model of Metabolic Syndrome.

Metabolic syndrome (MetS) significantly increases the risk of cardiovascular diseases (CVD), a leading cause of death globally. The presented study investigated the cardioprotective role of dietary polyphenols found in pomegranate peels in an animal model of metabolic syndrome. Zucker diabetic fatty rats (ZDF, MetS rats, fa/fa) were supplemented with polyphenol-rich pomegranate peel extract (EPP) at two dosages: 100 mg/kg BW and 200 mg/kg BW. The extract was administered for 8 weeks. The effect of ethanolic peel extract on the concentration of oxidative stress markers (CAT, SOD, MnSOD, GR, GST, GPx, TOS, SH, and MDA), biomarkers of heart failure (cTnI, GAL-3), and alternations in tissue architecture was assessed. The results showed a significant increase in SH concentration mediated via EPP supplementation (p < 0.001). Treatment with a 100 mg/kg BW dosage reduced the TOS level more efficiently than the higher dose. Interestingly, the CAT and GST activities were relevantly higher in the MetS 100 group (p < 0.001) compared to the MetS control. The rats administered EPP at a dose of 200 mg/kg BW did not follow a similar trend. No differences in the GR (p = 0.063), SOD (p = 0.455), MnSOD (p = 0.155), and MDA (p = 0.790) concentration were observed after exposure to the pomegranate peel extract. The administration of EPP did not influence the cTnI and GAL-3 levels. Histology analysis of the heart and aorta sections revealed no toxic changes in phenolic-treated rats. The findings of this study prove that the extract from pomegranate peels possesses free radical scavenging properties in the myocardium. The effect on alleviating ventricular remodeling and cardiomyocyte necrosis was not confirmed and requires further investigation.

The Impact of a Modified Anaesthetic Protocol on Animal Survival and the Characteristics of Ventricular Arrhythmias in the Course of Acute Myocardial Infarction in a Domestic Pig Model.

Introduction: Acute myocardial infarction (MI) is one of the most common causes of death in humans in highly developed countries. Among its most frequent complications affecting the patient's prognosis are cardiac arrhythmias: ventricular tachycardia (VT) and ventricular fibrillation (VF). Material and Methods: The study aimed to characterise arrhythmias in 19 pigs subjected to experimentally induced MI obtained by occlusion of the proximal left anterior descending (LAD) coronary artery using an angioplasty balloon. The anaesthetic protocol was modified to reduce mortality by including procedures stabilising haemodynamic disorders which develop during episodes of ischaemia and arrhythmia. During 30 min of experimentally induced ischaemia, the heart rhythm was recorded using a 12-lead ECG. The time, frequency, and type of arrhythmias were analysed. Results: Ventricular arrhythmias were found in 94.74% of the treated pigs. The most common were ventricular premature complexes, reported in 88.89% of pigs with arrhythmia. Ventricular tachycardia was recorded in 66.67% and ventricular fibrillation in 50% of pigs with arrhythmias. Conclusion: Myocardial infarction due to proximal LAD occlusion is characterised by a high incidence of ventricular arrhythmias, especially VT and VF. Because of the high survival rate, this MI porcine model may serve as a model for research on acute ischaemic ventricular arrhythmias in humans. Additionally, it reduces the total number of animals required for testing while yielding meaningful results, which is in line with the 3R principle.

Comparative analysis of ECG records depending on body position in domestic swine (Sus scrofa domestica).

BACKGROUND: Electrocardiography is a method widely applied in diagnosing abnormalities in the functioning of the heart muscle in veterinary medicine. It is a non-invasive and easy to perform test helpful in the general examination and a widely used patient monitoring method during anesthesia. Since the 1980s, pigs have become more and more popular companion animals. Moreover, the pig is a widely used model animal in biomedical research. Therefore, there is need to provide them with higher-quality veterinary services, also in emergency situations. It creates new challenges for veterinarians and the need to expand their knowledge of pigs' treatment as pets. The aim of the planned experiment was to compare the ECG recordings made with two different body positions and determine if any differences occurred. Standard ECG in swine is performed under general anesthesia in the lying position on the left side, for this position of the body have been developed and reported standards in the literature. However, some procedures performed on swine require a different body position, for which there is less data in the literature. METHODS: The study was carried out on 29 Polish landrace pigs weighing in the range of 33-44 kg. The tests were performed under general anesthesia with the same protocol for each animal, placing the animals first lying down on their right side, and then on their backs. The anesthesia protocol included medetomidine, midazolam, ketamine, and propofol. During the examination, ECG records were performed and analyzed in a 12-lead system with software support. RESULTS: The results show significant differences in electrocardiogram recordings depending on the animal's body position. Those differences mainly concern the amplitude of the P wave and R wave in the recordings and are even more visible comparing the electrocardiograms of the same specimen. There are also some significant differences in the duration of intervals. Based on the obtained results, reference ranges for the right lateral and dorsal positions were developed. CONCLUSION: In conclusion, the body position has a significant impact on the ECG recording in swine, therefore performing this examination, chosen normative value tables should be compatible with the position of the examined animal.

Cardioprotective Effect of Acetylsalicylic Acid in the Myocardial Ischemia-Reperfusion Model on Oxidative Stress Markers Levels in Heart Muscle and Serum.

Heart failure occurs in increased oxidative stress conditions, which contribute to the progression of pathological changes. Orally or intravenously administered acetylsalicylic acid (ASA, aspirin) is typically used in human patients with acute myocardial ischemia. The study used an experimental porcine ischemia-reperfusion model to evaluate the potential cardioprotective effect of intracoronary administered ASA on myocardial ischemia-reperfusion injury. The cardioprotective effect of ASA was evaluated by measuring selected oxidative stress markers levels in infarcted and non-infarcted myocardium 14 days after the procedure, and three times in serum, before the procedure, during the reperfusion process, and after 14-day recovery. The results showed that intracoronary administrated ASA reduced the oxidative stress. The level of oxidative stress, measured with the non-enzymatic markers total antioxidant capacity (TAC), total oxidative status (TOS), and malondialdehyde (MDA), and the enzymatic markers glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), in heart tissue was significantly higher in a control group injected with saline. The level of oxidative stress in serum, measured with TAC, TOS, oxidative stress index (OSI), and lipofuscin (LF), was also higher in the control group than in animals injected with ASA. The confirmed cardioprotective effect of intracoronary administered ASA provides the foundation for further studies on ASA intracoronary application, which may lead to the development of a new therapy for the treatment of ischemia-reperfusion complications in humans.

Large animals as models of atrial fibrillation.

In clinical practice, atrial fibrillation (AF) is the most common cardiac arrhythmia in humans and it may lead to numerous complications, including central nervous system embolism. The electrical activity of the heart in AF is rapid and chaotic, while the atrioventricular conduction leads to irregular ventricular contraction. Consequently, the stroke volume is reduced, which may lead to symptoms of heart failure. Heart failure is one of the causes of AF as well. Numerous in vivo and in vitro models are used to study the pathophysiology of AF. Animal models play a key role in understanding the mechanisms of arrhythmias as well as in developing treatment regimens. The models of AF include large animals (goats, sheep, pigs, dogs) as well as small laboratory animals. This study reviews the large animal models of AF, which enhance our understanding of numerous mechanisms responsible for the development of AF, but we must be aware that the pathomechanism of AF in humans is complex and is affected by numerous factors, including environmental and congenital ones.

Use of aVR and Jastrzebski Algorithms in the Classification of Wide Complex Tachycardia in Dogs - A Preliminary Study.

INTRODUCTION: Ventricular rhythm disturbances are a common pathology in human and veterinary medicine. In humans, the algorithmic approach is used to differentiate wide QRS complex tachycardia. The most commonly used are the aVR and Brugada algorithms as well as the ventricular tachycardia (VT) score developed by Jastrzebski and coworkers. In veterinary medicine, no such algorithms are available and the only parameter used to describe VT abnormalities is the duration of the QRS complexes. The aim of this analysis was determining whether human medicine algorithms for VT are applicable in veterinary medicine to differentiate wide QRS complex tachycardia in dogs. MATERIAL AND METHODS: A retrospective analysis was performed on 11 dogs of both sexes and various breeds and age diagnosed with VT. The diagnosis was based on ambulatory ECG, further established based on the reaction to lidocaine or adenosine or an invasive electrophysiological study. RESULTS: Of the 11 tracings passed through the aVR algorithm, 10 met the VT criteria. The most common criterion was the Vi/Vt ratio (8 out of 11 tracings). Based on the VT score, seven out of eight dogs had a high probability of VT. CONCLUSION: Retrospective analysis of ECGs by aVR and VT score indicates that the applied algorithms may be useful in differentiating wide QRS complex tachycardia as a quick, easy, and non-invasive alternative to cardiac electrophysiology.