Contraction Band Research Articles

Uncovering Diaphragm Cramp in SIDS and Other Sudden Unexpected Deaths.

The diaphragm is the primary muscle of respiration. Here, we disclose a fascinating patient's perspective that led, by clinical reasoning alone, to a novel mechanism of spontaneous respiratory arrests termed diaphragm cramp-contracture (DCC). Although the 7-year-old boy survived its paroxysmal nocturnal "bearhug pain apnea" episodes, essentially by breathing out to breathe in, DCC could cause sudden unexpected deaths in children, especially infants. Diaphragm fatigue is central to the DCC hypothesis in SIDS. Most, if not all, SIDS risk factors contribute to it, such as male sex, young infancy, rebreathing, nicotine, overheating and viral infections. A workload surge by a roll to prone position or REM-sleep inactivation of airway dilator or respiratory accessory muscles can trigger pathological diaphragm excitation (e.g., spasms, flutter, cramp). Electromyography studies in preterm infants already show that diaphragm fatigue and sudden temporary failure by transient spasms induce apneas, hypopneas and forced expirations, all leading to hypoxemic episodes. By extension, prolonged spasm as a diaphragm cramp would induce sustained apnea with severe hypoxemia and cardiac arrest if not quickly aborted. This would cause a sudden, rapid, silent death consistent with SIDS. Moreover, a unique airway obstruction could develop where the hypercontracted diaphragm resists terminal inspiratory efforts by the accessory muscles. It would disappear postmortem. SIDS autopsy evidence consistent with DCC includes disrupted myofibers and contraction band necrosis as well as signs of agonal breathing from obstruction. Screening for diaphragm injury from hypoxemia, hyperthermia, viral myositis and excitation include serum CK-MM and skeletal troponin-I. Active excitation could be visualized on ultrasound or fluoroscopy and monitored by respiratory inductive plethysmography or electromyography.

Ice-cold storage or controlled hypothermia to preserve marginal grafts in high-risk heart transplantation.

To evaluate the effectiveness of the Paragonix SherpaPak cardiac transport system (PSP) compared to the standard ice-cold storage (ICS) in extended-criteria donor grafts implanted in high-risk recipients. Data of all HTx at the University Centers of Udine and Bologna, between January 2020 and December 2023, employing extended-criteria donors in high-risk HTx conditions were retrospectively analyzed. Patient outcomes and complications after HTx were assessed. Endomyocardial biopsies were performed in donor hearts immediately after retrieval (T0), before implantation (T1) and at reperfusion (T2) to evaluate signs of myocardial damage. Overall, 90 patients who had heart transplantation (HTx) with a donor graft preserved with either ICS (n = 60) or PSP (n = 30) were included in the study. The 30-day mortality was 3% in both groups (p = 0.99), and 1-year survival 90% and 88% (p = 0.89) for recipients transplanted with PSP and ICS preserved grafts. Rates of moderate-to-severe graft dysfunction and bradi-arrhythmias for PSP and ICS groups were 7% versus 20% (p = 0.08), and 3% versus 15% (p = 0.09). Histologically, severe degrees of cellular and endothelial damage were absent in all PSP grafts while severe degree of contraction bands were higher in ICS hearts at T2. In high-risk donor-recipient matching, donor heart preservation with PSP seems to show a tendency toward better graft protection.

Local calcium chloride infusion after pulsed field ablation enhances acute efficacy of cardiac electroporation.

Pulsed field ablation (PFA) has emerged as an innovative therapy for cardiac arrhythmias. Drawing parallels with PFA's application in solid tumors, calcium chloride (CaCl2) as an adjuvant therapy, known as calcium electroporation, may amplify PFA's apoptotic effects. We propose that PFA in the atrium could enhance calcium uptake through PFA-created pores, thereby increasing ablation efficacy even at reduced power levels by exploiting PFA's permeabilization effects. We conducted in vivo ablations on the atria of seven pigs using low PFA power (250 V, 20 μs for 50 pulses at 200 ms intervals). Post-PFA, we randomly administered an infusion of either 200 mg/2 ml CaCl2 (calcium group) or saline (control) directly to the ablation site via the catheter tip. We evaluated reduction in electrogram voltage amplitude, electrocardiography (ECG) parameters, ablation lesion parameters, and histology after PFA. Nineteen lesions from control and calcium groups were examined. Control lesions showed no voltage decrease post-PFA, whereas calcium-treated lesions exhibited a significant voltage reduction. Gross pathology indicated marked differences in maximum lesion surface diameter, depth, and volume between the lesion groups. Histologically, calcium group lesions were characterized by a more severe acute PFA response with contraction band necrosis, myocytolysis and nuclear pyknosis in adjacent myocardium, in addition to microhemorrhages. Infusing calcium chloride locally after PFA markedly improves the immediate efficacy of electroporation in porcine atria. This study suggests that calcium electroporation could bolster PFA outcomes without higher energy levels, potentially diminishing associated risks. These preliminary findings warrant further research into the long-term efficacy and potential clinical application of calcium electroporation in PFA.

Cardiotoxic Effects of Lachesis acrochorda Snake Venom in Anesthetized Wistar Rats.

Ophidism is a public health problem in tropical countries, occurring predominantly in rural areas. In Colombia, among the species responsible for snakebite envenomation, inflicting high mortality, is the Chocoan bushmaster, Lachesis acrochorda, better known locally by the names "verrugosa (warty)" and "pudridora (rot-causing)". In this research, the cardiotoxic effect of the venom of L. acrochorda in male Wistar rats weighing 230 ± 20 g was evaluated. A statistical design of randomized blocks was implemented with three treated groups, injected with lyophilized venom (doses of 3.22 μg/g, 6.43 μg/g, 12.86 μg/g), and a control group injected with 0.9% saline solution. Electrocardiographic (ECG) recordings were taken from the anesthetized animals, revealing an increase in the amplitude of the P and T waves and an increase in the duration of the QT intervals in the electrocardiographic recordings. These increases were not observed in the control biomodels. In the analysis of the CK and CK-MB enzyme levels, increases were also observed in the levels of cardiac isoenzymes in the injected animals, but none in the control animals. The histopathological analyses carried out reveal that the injected animals showed effects such as interfibrillar and perivascular edema, cellular shortening of the cardiomyocytes, foci with tissue destructuring, and necrosis with contraction bands. In conclusion, the venom of the Lachesis acrochorda snake increases the P and T waves and the QT interval and increases the CK and CK-MB enzymes in the blood. Additionally, it causes interfibrillar and perivascular edema in the cardiac tissue, cardiocytolysis, and contraction bands.

Evaluation of Ablation Parameters to Predict Irreversible Lesion Size During Pulsed Field Ablation.

During pulsed field ablation (PFA), relationships between ablation parameters (contact force [CF], number of burst pulses, impedance decrease, and electrode temperature) and lesion size in beating hearts have not been well validated. A 7.5F-catheter with a 3.5-mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual-Energy, Biosense Webster, Inc, Irwindale, CA) was connected to a PFA system (TRUPULSE2, Biosense Webster, Inc). In 11 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and the skin patch at 219 sites in left ventricle and right ventricle using 12, 18, and 24 burst pulses with 4 different levels of CF: (1) low (n=57; CF, 4-15g; median, 10g); (2) moderate (n=60; CF, 16-30g; median, 22.5g); (3) high (n=68; CF, 32-65g; median, 40g); and (4) no electrode contact (n=34), 2 mm away from the endocardium. Swine were euthanized 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. All PFA lesions with electrode-myocardium contact were well demarcated with triphenyl tetrazolium chloride staining, demonstrating (1) pale central zone (contraction band necrosis with minimal coagulation necrosis), (2) dark brown zone (contraction band necrosis with hemorrhage), and (3) hyperstained red zone by triphenyl tetrazolium chloride (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). Lesion depth increased significantly with increasing CF and the number of PFA burst pulses. An exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlated lesion depth with high accuracy: R=0.809, P<0.0001, ±1.0-mm accuracy in 128 of 163 (79%) lesions, and ±1.5-mm accuracy in 153 of 163 (94%) lesions. Impedance decrease and electrode temperature were poor predictors of lesion size. There were no detectable lesions resulting from ablation without electrode contact. Acute PFA ventricular lesions demonstrate irreversible and reversible lesion boundaries. Electrode-tissue contact is required for effective lesion formation. Lesion depth increases significantly with increasing CF and PFA burst pulses. A new exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlates lesion depth with high accuracy.

Effects of Contact Force on Lesion Size During Pulsed Field Catheter Ablation: Histochemical Characterization of Ventricular Lesion Boundaries.

Effects of contact force (CF) on lesion formation during pulsed field ablation (PFA) have not been well validated. The purpose of this study was to determine the relationship between average CF and lesion size during PFA using a swine-beating heart model. A 7F catheter with a 3.5-mm ablation electrode and CF sensor (TactiCath SE, Abbott) was connected to a PFA system (CENTAURI, Galvanize Therapeutics). In 5 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and a skin patch at 40 separate sites in right ventricle (28 Amp) and 55 separate sites in left ventricle (35 Amp) with 4 different levels of CF: (1) low (CF range of 4-13 g; median, 9.5 g); (2) moderate (15-30 g; median, 21.5 g); (3) high (34-55 g; median, 40 g); and (4) no electrode contact, 2 mm away from the endocardium. Swine were sacrificed at 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. In 1 additional swine, COX (cytochrome c oxidase) staining was performed to examine mitochondrial activity to delineate reversible and irreversible lesion boundaries. Histological examination was performed with hematoxylin and eosin and Masson trichrome staining. Ablation lesions were well demarcated with triphenyl tetrazolium chloride staining, showing (1) a dark central zone (contraction band necrosis and hemorrhage); (2) a pale zone (no mitochondrial activity and nuclear pyknosis, indicating apoptosis zone); and a hyperstained zone by triphenyl tetrazolium chloride and COX staining (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). At constant PFA current intensity, lesion depth increased significantly with increasing CF. There were no detectable lesions resulting from ablation without electrode contact. Acute PFA ventricular lesions show irreversible and reversible lesion boundaries by triphenyl tetrazolium chloride staining. Electrode-tissue contact is required for effective lesion formation during PFA. At the same PFA dose, lesion depth increases significantly with increasing CF.

The Effect of Nitroglycerine on Myocardial Injury Induced by Ischemia/Reperfusion in Adult Male Albino Rats

Abstract Background Despite, early reperfusion is the current optimal way to rescue the heart and salvage of greater amount myocardium, the process of reperfusion could induce myocardial injury and cardiomyocyte death, that result in heart failure and death. Several therapeutic medications such as nitroglycerine is currently under investigation for preventing myocardial reperfusion injury which has the potential to improve clinical outcomes in patients with acute myocardial infarction treated Aim of the Work To investigate the effect of nitroglycerin on myocardial ischemic reperfusion injury as regard histopathological changes. Materials and methods 30 Male adult albino rats were randomly divided into four groups (10 rats for each); Group I (2 subgroups: group 1A (control group) &amp; group 1B (sham group)). Group II (ischemia/reperfusion animal model). Group III (nitroglycerine 0.5 mg/kg BW 15 min before I/R). Tissue samples of heart ventricles of all animals were collected and processed for light microscopic examination. Results The ischemia /reperfusion group showed massive disruption of the normal histological cardiac muscle picture, interstitial hemorrhage, inflammatory cells infiltration, pyknotic changes in the nuclei and dark acidophilic contraction bands. Nitroglycerine treated group revealed disruption of cardiac muscle fibers and with minimal improvement in the histological appearance. Conclusion Nitroglycerine injection attributed to potential improvement for myocardial ischemia reperfusion injury which. Therefore, it might be assumed that nitroglycerine could be used as a safe drug before induction of reperfusion.

Increased Epicardial Adipose Tissue and Heart Characteristics Are Correlated with BMI and Predict Silent Myocardial Infarction in Sudden Cardiac Death Subjects: An Autopsy Study.

Sudden cardiac death (SCD) is a significant global public health issue and the leading cause of death worldwide. Its etiopathogenesis is complex and multilayered, involving dynamic factors interacting with a preexistent cardiovascular pathology, frequently unknown, and resulting in cardiac rhythm disorders and cardiac arrest; Methods: This study conducted a retrospective descriptive analysis over a one-year period, identifying 321 autopsy cases of sudden deaths from the Institute of Legal Medicine in Mures County, Romania, in 2019. From the 321 sudden death cases, 189 autopsy reports were selected for analysis based on inclusion and exclusion; Results: The autopsies had a mean age of 61.16 years and included 140 males and 49 females. No significant differences were found between the silent myocardial infarction (SMI) and no-SMI groups regarding demographic data. The SMI group exhibited higher thickness of LV (left ventricle), IV (interventricular septum), EAT LCx (epicardial adipose tissue at left circumflex artery), EAT LAD (epicardial adipose tissue at left anterior descending artery), heart weight, and BMI (body mass index). The left coronary artery showed a higher incidence of type V plaques, while the right coronary artery showed higher incidences of type V and type VI plaque. The SMI group also exhibited a higher incidence of moderate and severe valvular atherosclerosis, severe left ventricle dilatation, and a lower incidence of mild left ventricle dilatation. In addition, the SMI group showed a higher presence of contraction band necrosis on histological examination. Multivariate analysis revealed that type V and type VI plaques for the right and left coronary arteries, moderate and severe valvular atherosclerosis, severe left ventricle dilatation, heart weight, EAT LCx, EAT LAD, LV thickness, IV thickness, BMI, and the presence of contraction band necrosis are all independent predictors of SMI; Conclusions: The findings suggest that SCD is a complex condition, and its etiopathogenesis involves dynamic factors interacting with pre-existing cardiovascular pathology. The risk factors of SCD are similar to those of ischemic heart disease. The findings of this study could guide clinicians in identifying patients at risk of SCD and implementing preventive measures.

Pathological Aspects and Immunohistochemical Evaluation of Troponin C in the Cardiovascular System of Dogs With Pheochromocytoma

Functional pheochromocytomas secrete catecholamines and have been associated with cardiovascular lesions in dogs. This study aimed to describe the postmortem pathological findings in the cardiovascular system of dogs with pheochromocytoma and to evaluate the expression of cardiac troponin C in these dogs using immunohistochemical analysis. Twelve cases were identified, with a mean age of 10.6 years. The heart of all dogs was enlarged and with concentric hypertrophy of the left ventricular myocardium. Histological analysis showed cardiomyocyte necrosis and degeneration in the myocardium, with frequent bands of contraction, fibrosis, inflammation, and thickening of the medium-caliber arteries in the myocardium. There was a marked decrease or absence of immunolabeling in necrotic cardiomyocytes. We conclude that IHC for troponin C can be a useful tool for detecting myocardial necrosis in dogs with pheochromocytomas, including early cases of necrosis with only incipient cardiac changes where overt histologic abnormalities are not immediately apparent in the cardiomyocytes.

Development and prevention of ischemic contracture ("stone heart") in the pig heart.

Stone heart (ischemic contracture) is a rare and serious condition observed in the heart after periods of warm ischemia. The underlying mechanisms are largely unknown and treatment options are lacking. In view of the possibilities for cardiac donation after circulatory death (DCD), introducing risks for ischemic damage, we have investigated stone heart in pigs. Following cessation of ventilation, circulatory death (systolic pressure <8 mmHg) occurred within 13.1 ± 1.2 min; and a stone heart, manifested with asystole, increased left ventricular wall thickness and stiffness, established after a further 17 ± 6 min. Adenosine triphosphate and phosphocreatine levels decreased by about 50% in the stone heart. Electron microscopy showed deteriorated structure with contraction bands, Z-line streaming and swollen mitochondria. Synchrotron based small angle X-ray scattering of trabecular samples from stone hearts revealed attachment of myosin to actin, without volume changes in the sarcomeres. Ca2+ sensitivity, determined in permeabilized muscle, was increased in stone heart samples. An in vitro model for stone heart, using isolated trabecular muscle exposed to hypoxia/zero glucose, exhibited the main characteristics of stone heart in whole animals, with a fall in high-energy phosphates and development of muscle contracture. The stone heart condition in vitro was significantly attenuated by the myosin inhibitor MYK-461 (Mavacamten). In conclusion, the stone heart is a hypercontracted state associated with myosin binding to actin and increased Ca2+ sensitivity. The hypercontractile state, once developed, is poorly reversible. The myosin inhibitor MYK-461, which is clinically approved for other indications, could be a promising venue for prevention.

In vivo pulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization.

Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

Generation of myocyte agonal Ca2+ waves and contraction bands in perfused rat hearts following irreversible membrane permeabilisation

Although irreversible cardiomyocyte injury provokes intracellular Ca2+ ([Ca2+]i) overload, the underlying dynamics of this response and its effects on cellular morphology remain unknown. We therefore visualised rapid-scanning confocal fluo4-[Ca2+]i dynamics and morphology of cardiomyocytes in Langendorff-perfused rat hearts following saponin-membrane permeabilisation. Our data demonstrate that 0.4% saponin-treated myocytes immediately exhibited high-frequency Ca2+ waves (131.3 waves/min/cell) with asynchronous, oscillatory contractions having a mean propagation velocity of 117.8 μm/s. These waves slowly decreased in frequency, developed a prolonged decay phase, and disappeared in 10 min resulting in high-static, fluo4-fluorescence intensity. The myocytes showing these waves displayed contraction bands, i.e., band-like actin-fibre aggregates with disruption of sarcomeric α-actinin. The contraction bands were not attenuated by the abolition of Ca2+ waves under pretreatment with ryanodine plus thapsigargin, but were partially attenuated by the calpain inhibitor MDL28170, while mechanical arrest of the myocytes by 2,3-butanedione monoxime completely attenuated contraction-band formation. The depletion of adenosine 5′-triphosphate by the mitochondrial electron uncoupler carbonyl cyanide 4-trifluoromethoxy phenylhydrazone also attenuated Ca2+ waves and contraction bands. Overall, saponin-induced myocyte [Ca2+]i overload provokes agonal Ca2+ waves and contraction bands. Contraction bands are not the direct consequence of the waves but are caused by cross-bridge interactions of the myocytes under calpain-mediated proteolysis.

L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenolinduced cardiac hypertrophy

Objective: To explore the therapeutic efficacy of L-carvone from Mentha spicataL. leaf extracts against isoproterenol-induced cardiac hypertrophy in rats. Methods: Isoproterenol (5 mg/kg) was injected intraperitoneally into rats for one month to induce cardiac hypertrophy. L-carvone (25 and 100 mg/kg) was administered orally to treat cardiac hypertrophy. The cardioprotective activity of L-carvone was evaluated by electrocardiogram, histopathological analysis as well as determination of biochemical parameters and enzymatic markers. Results: L-carvone from Mentha spicata L. at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy, as evidenced by reduced QRS interval on electrocardiogram, and decreased heart weight and heart index. In addition, both doses of L-carvone markedly lowered the levels of glucose, total protein, low-density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase MB, troponin-I, N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level (P&lt;0.05). Moreover, L-carvone alleviated contraction band necrosis, and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy. Conclusions: L-carvone from Mentha spicata L. leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.

The Clinical Significance of iNOS/NO Signaling Pathway in Traumatic Shock and the Mechanism under the Promotion on the Development of Traumatic Shock via Endoplasmic Reticulum Stress.

This study aims to clarify the clinical significance of the inducible nitric oxide synthase (iNOs)/nitric oxide (NO) signaling pathway and endoplasmic reticulum stress (ERS) in traumatic shock (TS) and the mechanism of action, so as to offer a novel direction for the emergency treatment of TS in the future. The clinical data of 90 patients with TS treated in our hospital between June 2019 and January 2021 were retrospectively analyzed. Patients were divided into mild (n = 30), moderate (n = 30), and severe group (n = 30) based on their disease severity. Furthermore, patients were assigned into Groups A and B for fluid resuscitation based on a pulse index continuous cardiac output (PICCO) monitor and fluid resuscitation based on monitoring results of central venous pressure (CVP) and mean arterial pressure (MAP), respectively. Additionally, the 18 purchased Sprague Dawley (SD) rats were randomized into model (TS model), control (normal rats) and intervention (TS model injected with iNOS inhibitor) groups, with 6 rats each. iNOs and NO levels were measured by colorimetry, and the concentrations of inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs). Polymerase chain reaction (PCR) and western blot were adopted for the quantification of ERS markers (glucose-related protein 78 (GRP78), GRP94 and C/EBP homologous protein (CHOP)), and hematoxylin-eosin (HE) staining of rat cardiac tissue was carried out to observe the pathological state of myocardial tissue. The moderate group showed higher levels of iNOS, NO, GRP78, GRP94 and CHOP than the mild group and lower levels of them than the severe group (all p < 0.05). MAP, extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and locus control region (LCR) increased in both Groups A and B after resuscitation, with more significant increases of these parameters in Group A. The application of PICCO technique lowered the levels of iNOS, NO, inflammatory factors, GRP78, GRP94 and CHOP in TS patients. In addition, the intervention group had lower levels of iNOS, NO, inflammatory factors, GRP78, GRP94, and CHOP than the model group and higher levels of them than the control group. According to the results of HE staining of myocardial tissue, the intervention group had significantly alleviated myocardial necrosis than the model group, with slightly stained cytoplasm, visible contraction bands in most myocardium, and significantly reduced neutrophil infiltration. iNOS/NO and ERS increase with the severity of TS, and PICCO can effectively lower their levels. The results of animal experiments suggest that the inhibition of iNOS/NO can relieve inflammation and ERS intensification, thus alleviating the progression of TS.

Characteristics of pulsed electric field cardiac ablation porcine treatment zones with a focal catheter.

Pulsed electric field (PEF) therapies employ punctuated energy delivery to kill cells in a volume of tissue through mechanisms that are not dependent on thermal processes. A key component to successful cardiac ablation procedures is ensuring the generation of transmural, contiguous ablation zones, which requires in-depth knowledge regarding treatment sizes for a given therapeutic application. In this study, a series of acute treatments were delivered to porcine ventricles, where triphenyl tetrazolium chloride (TTC) vitality stain was used to identify treatment effect sizes for the three focal monopolar CENTAURI PEF cardiac ablation energy settings. Treatment depths were 5.7, 7.2, and 8.2 mm for the 19, 22, and 25 A energy settings, respectively. Gross pathology indicated umbral zones of hemorrhage surrounded by pale avital TTC-negative-negative tissue, which contrasted significantly from radiofrequency ablation (RF) controls. Histologically, treatment zones are identified by regions of contraction band necrosis and cardiomyocytolysis, which contrasted with RF control lesions composed primarily of coagulation necrosis. Together, these data indicate the ability for focal monopolar PEF treatments to generate deep treatment zones in cardiac ablation without incurring the gross or histological coagulative characteristics of RF thermal lesions.

Abstract 11573: Refractory Ventricular Tachyardia Storm: Treatment With Sympathetic Denervation in Patient With Non-Ischemic Cardiomyopathy

Introduction: Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia commonly present in cardiomyopathy. Implantable cardioverter-defibrillator (ICD) placement can decrease mortality in patients with VT. However, when an ICD shocks it can cause direct myocardial injury, contraction band necrosis, fibrosis, and significant morbidity. Antiarrhythmic medications and catheter ablation can decrease arrhythmia burden and ICD shocks. Cardiac sympathetic denervation has been effective in a few refractory cases, but prospective data is scarce, especially in non-ischemic cardiomyopathy. Case description We present the case of a 59-year-old gentleman with a past medical history of hypertension, diabetes, hypothyroidism, atrial fibrillation, and non-ischemic cardiomyopathy, who presented to the hospital with recurrent ICD shocks. The patient had an ICD placed due to an episode of non-sustained VT resulting in presyncope. The patient had an arrhythmia-free period of 10 years followed by frequent VT. He was managed in the outpatient setting with amiodarone, dofetilide, and mexiletine which did not suppress his arrhythmia burden. Cardiac MRI showed multi-segment transmural late gadolinium enhancement consistent with a non-ischemic pattern. He underwent three endocardial and epicardial ablations over eight months before this admission. He was started on amiodarone and lidocaine infusions. With his history of recurrent VT despite multiple ablations, the patient underwent bilateral thoracoscopic sympathetic denervation. He was discharged from the hospital six days post-op without any episodes of VT. His latest ICD check which was ten months post-operatively did not show any VT or VT-induced ICD shock. Conclusion VT storm may be associated with a catecholaminergic surge and be refractory to traditional therapy. Due to this, sympathetic denervation is a viable option to prevent morbidity of frequent defibrillator therapy. This case highlights the utility of sympathetic denervation as a treatment of refractory ventricular arrhythmias in non-ischemic cardiomyopathy.

The Value of Myocardium and Kidney Histopathological and Immunohistochemical Findings in Accidental Hypothermia-Related Fatalities.

Background and Objectives: The post-mortem diagnosis of hypothermia is challenging in forensics. The aim of our study was to detect the kidney and heart histopathological changes that occurred in a group of hypothermia-related fatalities. Materials and Methods: The cohort included 107 cases identified in the database of our department between 2007 and 2021, which have been associated with extreme cold stress. Demographic and clinicopathological data were collected from the medico-legal reports. Archived tissue samples were evaluated to identify the histopathological features, in routine haematoxylin-eosin (H&E), Periodic acid-Schiff (PAS), and Masson's trichrome stainings, while cardiac sirtuin1 (SIRT1) and renal ubiquitin (Ub) immunostaining have been performed. Results: The majority of cases exposed to low temperatures were males (76%) from rural regions (68.2%) during the cold season. Paradoxical undressing was documented in 9.3% of cases. The common comorbidities included alcoholism (50.5%), neuropsychiatric diseases (10.3%), diabetes mellitus (3.7%), and lung tuberculosis (4.7%). The microscopic heart exam revealed areas of myocardial degeneration (100%), contraction bands (95.3%), fatty change (13.1%) and focal wavy contractile myocardial cells. Basal vacuolisation of renal tubular epithelial cells (Armanni-Ebstein lesions) (21.5%), focal tubular necrosis (7.5%), tubular renal cysts (7.5%), interstitial haemorrhages (5.6%), diabetic kidney disease (3.7%), background benign nephroangiosclerosis (42.1%), variable thickening of tubules and corpuscles basement membranes, capsular space amorphous material, and intratubular casts were identified in kidney tissue samples. Myocardial cells displayed SIRT1 weak expression, with a loss of immunopositivity correlated with areas with contraction bands, while a variable Ub expression was observed in renal corpuscles capsules, proximal, distal, and collecting renal tubules, Henle's loops, urothelium, and intratubular casts. Conclusions: In the context of the current concept that death associated with hypothermia is still a diagnosis of exclusion, our findings suggest that the microscopic exam provides relevant data that support the diagnosis of hypothermia-related fatalities in appropriate circumstances of death. A deeper insight into the histopathologic findings in hypothermic patients may lead to new therapeutic approaches in these cases.

Contraction Band Necrosis with Dephosphorylated Connexin 43 in Rat Myocardium after Daily Cocaine Administration.

Contraction band necrosis (CBN) is a common abnormality found in the myocardium of cocaine abusers, but is rarely reported in experimental models of cocaine abuse. Connexin 43 (Cx43) is essential for cardiac intercellular communication and the propagation of CBN. Under stress or injury, cardiac Cx43 is dephosphorylated, which is related to cardiomyocyte dysfunction and pathogenesis, whereas adiponectin exerts beneficial effects in the myocardium. In this study, we explore the effects of cocaine on cardiac Cx43 in vivo. Rats were administered cocaine via the tail vein at 20 mg/kg/day for 14 days, and showed widespread CBN, microfocal myocarditis and myocardial fibrosis, corresponding to a dysfunction of cardiac mitochondria under increased oxidative stress. The increase in dephosphorylated cardiac Cx43 and its negative correlation with the myocardial distribution of CBN after cocaine administration were determined. In addition, apoptosis and necroptosis, as well as increased adiponectin levels, were observed in the myocardium after cocaine exposure. Accordingly, we found altered profiles of cardiac Cx43, CBN and its negative correlation with dephosphorylated cardiac Cx43, and the possible involvement of adiponectin in the myocardium after 14 days of cocaine administration. The latter might play a protective role in the cardiotoxicity of cocaine. The current findings would be beneficial for establishing novel therapeutic strategies in cocaine-induced cardiac consequences.

Effect of Pulsed-Field and Radiofrequency Ablation on Heterogeneous Ventricular Scar in a Swine Model of Healed Myocardial Infarction.

Pulsed-field ablation (PFA) is a nonthermal energy with higher selectivity to myocardial tissue in comparison to radiofrequency ablation (RFA). We compared the effects of PFA and RFA on heterogeneous ventricular scar in a swine model of healed infarction. In 9 swine, myocardial infarction was created by balloon occlusion of the left anterior descending artery. After a survival period of 8 to 10 weeks, ablation with PFA or RFA was performed at infarct border zones identified by abnormal electrograms. In the PFA group (4 swine), ablation was performed with a lattice catheter (Sphere-9, Affera, Inc). In the RFA group (5 swine), ablation was performed using a 3.5-mm tip catheter (Thermocool ST-SF; Biosense Webster). To further investigate the effect of RFA on temperature development in scar tissue, intramyocardial temperature was measured in healthy and infarcted myocardium using an ex vivo bath model. A total of 11 PFA and 15 RFA lesions were created at infarct border zones with heterogeneous scar. PFA produced uniform and well-demarcated lesions exhibiting irreversible injury characterized by cardiomyocyte death, contraction bands, and lymphocytic infiltration. This effect of PFA extended from the subendocardium through collagen and fat to the epicardial layers. In contrast, the effect of RFA is less uniform and largely limited to the subendocardium with minimal effect on viable myocardium deeper to separating layers of collagen and fat. PFA produced deeper and more transmural lesions (6.4 [interquartile range, 5.5-7.5) versus 5.4 [interquartile range, 4.8-5.9]), 72% versus 30%, respectively; P≤0.02 for each comparison). The limited effect of RFA on viable myocardium at deeper infarct layers was related to a lower intramyocardial maximal temperature compared with healthy myocardium (P=0.01). PFA may be advantageous for ablation in ventricular scar, producing lesions that unlike RFA are not limited to the subendocardium, but also eliminate viable myocardium separated from the catheter by collagen and fat.

Microscopic Findings in the Cardiac Muscle of Stranded Extreme Deep-Diving Cuvier's Beaked Whales (Ziphius cavirostris).

Considerable information has been gained over the last few decades on several disease processes afflicting free-ranging cetaceans from a pathologist's point of view. Nonetheless, there is still a dearth of studies on the hearts of these species. For this reason, we aimed to improve our understanding of cardiac histological lesions occurring in free-ranging stranded cetaceans and, more specifically, in deep-diving Cuvier's beaked whales. The primary cardiac lesions that have been described include vascular changes, such as congestion, edema, hemorrhage, leukocytosis, and intravascular coagulation; acute degenerative changes, which consist of contraction band necrosis, wavy fibers, cytoplasmic hypereosinophilia, and perinuclear vacuolization; infiltration of inflammatory cells; and finally, the presence and/or deposition of different substances, such as interstitial myoglobin globules, lipofuscin pigment, polysaccharide complexes, and intra- and/or extravascular gas emboli and vessel dilation. This study advances our current knowledge about the histopathological findings in the cardiac muscle of cetaceans, and more specifically, of Cuvier's beaked whales.