Pulsed-field ablation: An alternative ablative method for gastric electrophysiological intervention.

Pulsed-field ablation (PFA) is an emerging ablative technology that has been used successfully to eliminate cardiac arrhythmias. As a non-thermal technique it has significant benefits over traditional radio-frequency ablation with improved target tissue specificity and reduced risk of adverse events during cardiac applications. We investigated whether PFA is safe for use in the stomach and whether it could modulate gastric slow waves. Female weaner pigs were fasted overnight before anesthesia was induced using tiletamine hydrochloride (50 mg mL-1) and zolazepam hydrochloride (50 mg mL-1) and maintained with propofol (Diprivan 2%, 0.2­0.4 mg kg­1 min­1). Pulsed-field ablation was performed on their gastric serosa in vivo. Adjacent point lesions (n=2-4) were used to create a linear injury using bipolar pulsed-field ablation consisting of 40 pulses (10 Hz frequency, 0.1 ms pulse width, 1000 V amplitude). High-resolution electrical mapping defined baseline and post-ablation gastric slow-wave patterns. A validated five-point scale was used to evaluate tissue damage in hematoxylin and eosin stained images. Results indicated that PFA successfully induced complete conduction blocks in all cases, with lesions through the entire thickness of the gastric muscle layers. Consistent post-ablation slow-wave patterns emerged immediately following ablation and persisted over the study period. Pulsed-field ablation induces rapid conduction blocks as a tool to modulate slow-wave patterns, indicating it may be suitable as an alternative to radio-frequency ablation.

Gastric slow-wave modulation via power-controlled, irrigated radio-frequency ablation.

BACKGROUND: Recently, radio-frequency ablation has been used to modulate slow-wave activity in the porcine stomach. Gastric ablation is, however, still in its infancy compared to its history in the cardiac field, and electrophysiological studies have been restricted to temperature-controlled, non-irrigated ablation. Power-controlled, irrigated ablation may improve lesion formation at lower catheter-tip temperatures that produce the desired localized conduction block. METHODS AND RESULTS: Power-controlled, irrigated radio-frequency ablation was performed on the gastric serosal surface of female weaner pigs (n = 5) in vivo. Three combinations of power (10-15 W) and irrigation settings (2-5 mL min-1) were investigated. A total of 12 linear lesions were created (n = 4 for each combination). Slow waves were recorded before and after ablation using high-resolution electrical mapping. KEY RESULTS: Irrigation maintained catheter-tip temperature below 50°C. Ablation induced a complete conduction block in 8/12 cases (4/4 for 10 W at 2 mL min-1, 1/4 for 10 W at 5 mL min-1, 3/4 for 15 W at 5 mL min-1). Blocks were characterized by a decrease in signal amplitude at the lesion site, along with changes in slow-wave propagation patterns, where slow waves terminated at and/or rotated around the edge of the lesion. CONCLUSIONS AND INFERENCES: Power-controlled, irrigated ablation can successfully modulate gastric slow-wave activity at a reduced catheter-tip temperature compared to temperature-controlled, non-irrigated ablation. Reducing the irrigation rate is more effective than increasing power for blocking slow-wave activity. These benefits suggest that irrigated ablation is a suitable option for further translation into a clinical intervention for gastric electrophysiology disorders.

Power-Controlled, Irrigated Radio-Frequency Ablation of Gastric Tissue: A Biophysical Analysis of Lesion Formation.

BACKGROUND: Radio-frequency ablation of gastric tissue is in its infancy compared to its extensive history and use in the cardiac field. AIMS: We employed power-controlled, irrigated radio-frequency ablation to create lesions on the serosal surface of the stomach to examine the impact of ablation power, irrigation, temperature, and impedance on lesion formation and tissue damage. METHODS: A total of 160 lesions were created in vivo in female weaner pigs (n = 5) using a combination of four power levels (10, 15, 20, 30 W) at two irrigation rates (2, 5 mL min-1) and with one temperature-controlled (65 °C) reference setting previously validated for electrophysiological intervention in the stomach. RESULTS: Power and irrigation rate combinations above 15 W resulted in lesions with significantly higher surface area and depth than the temperature-controlled setting. Irrigation resulted in significantly lower temperature (p < 0.001) and impedance (p < 0.001) compared to the temperature-controlled setting. No instances of perforation or tissue pop were recorded for any ablation sequence. CONCLUSION: Power-controlled, irrigated radio-frequency ablation of gastric tissue is effective in creating larger and deeper lesions at reduced temperatures than previously investigated temperature-controlled radio-frequency ablation, highlighting a substantial improvement. These data define the biophysical impact of ablation parameters in gastric tissue, and they will guide future translation toward clinical application and in silico gastric ablation modeling. Combination of ablation settings (10-30 W power, 2-5 mL min-1 irrigation) were used to create serosal spot lesions. Histological analysis of lesions quantified localized tissue damage.

Anaesthesia by intravenous propofol reduces the incidence of intra-operative gastric electrical slow-wave dysrhythmias compared to isoflurane.

Gastric motility is coordinated by bioelectrical slow-wave activity, and abnormal electrical dysrhythmias have been associated with nausea and vomiting. Studies have often been conducted under general anaesthesia, while the impact of general anaesthesia on slow-wave activity has not been studied. Clinical studies have shown that propofol anaesthesia reduces postoperative nausea and vomiting (PONV) compared with isoflurane, while the underlying mechanisms remain unclear. In this study, we investigated the effects of two anaesthetic drugs, intravenous (IV) propofol and volatile isoflurane, on slow-wave activity. In vivo experiments were performed in female weaner pigs (n = 24). Zolazepam and tiletamine were used to induce general anaesthesia, which was maintained using either IV propofol (n = 12) or isoflurane (n = 12). High-resolution electrical mapping of slow-wave activity was performed. Slow-wave dysrhythmias occurred less often in the propofol group, both in the duration of the recorded period that was dysrhythmic (propofol 14 ± 26%, isoflurane 43 ± 39%, P = 0.043 (Mann-Whitney U test)), and in a case-by-case basis (propofol 3/12, isoflurane 8/12, P = 0.015 (Chi-squared test)). Slow-wave amplitude was similar, while velocity and frequency were higher in the propofol group than the isoflurane group (P < 0.001 (Student's t-test)). This study presents a potential physiological biomarker linked to recent observations of reduced PONV with IV propofol. The results suggest that propofol is a more suitable anaesthetic for studying slow-wave patterns in vivo.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

Gastric pacing response evaluated with simultaneous electrical and optical mapping.

Gastric pacing is an attractive therapeutic approach for correcting abnormal bioelectrical activity. While high-resolution (HR) electrical mapping techniques have largely contributed to the current understanding of the effect of pacing on the electrophysiological function, these mapping techniques are restricted to surface contact electrodes and the signal quality can be corrupted by pacing artifacts. Optical mapping of voltage sensitive dyes is an alternative approach used in cardiac research, and the signal quality is not affected by pacing artifacts. In this study, we simultaneously applied HR optical and electrical mapping techniques to evaluate the bioelectrical slow wave response to gastric pacing. The studies were conducted in vivo on porcine stomachs ( n=3) where the gastric electrical activity was entrained using high-energy pacing. The pacing response was optically tracked using voltage-sensitive fluorescent dyes and electrically tracked using surface contact electrodes positioned on adjacent regions. Slow waves were captured optically and electrically and were concordant in time and direction of propagation with comparable mean velocities ([Formula: see text]) and periods ([Formula: see text]). Importantly, the optical signals were free from pacing artifacts otherwise induced in electrical recordings highlighting an advantage of optical mapping. Clinical Relevance- Entrainment mapping of gastric pacing using optical techniques is a major advance for improving the preclinical understanding of the therapy. The findings can thereby inform the efficacy of gastric pacing in treating functional motility disorders.

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

KEY POINTS: Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. ABSTRACT: Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca2+ cycling.

Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure.

Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV) atrophies. Multiple lines of clinical and experimental evidence lead us to hypothesize that the impaired stroke volume and systolic pressure of the LV are a direct consequence of the effect of pressure overload in the RV, and that atrophy in the LV plays only a minor role. In this study, we tested this hypothesis by examining the mechanoenergetic response of the atrophied LV to RV hypertrophy in rats treated with monocrotaline. Experiments were performed across multiple-scales: the whole-heart in vivo and ex vivo, and its trabeculae in vitro. Under the in vivo state where the RV was pressure-overloaded, we measured reduced systemic blood pressure and LV ventricular pressure. In contrast, under both ex vivo and in vitro conditions, where the effect of RV pressure overload was circumvented, we found that LV was capable of developing normal systolic pressure and stress. Nevertheless, LV atrophy played a minor role in that LV stroke volume remained lower, thereby contributing to lower LV mechanical work output. Concomitantly lower oxygen consumption and change of enthalpy were observed, and hence LV energy efficiency was unchanged. Our internally consistent findings between working-heart and trabecula experiments explain the rapid improvement of LV systolic function observed in patients with chronic pulmonary hypertension following surgical relief of RV pressure overload.

Dietary supplementation with either saturated or unsaturated fatty acids does not affect the mechanoenergetics of the isolated rat heart.

Abstract It is generally recognized that increased consumption of polyunsaturated fatty acids, fish oil (FO) in particular, is beneficial to cardiac and cardiovascular health, whereas equivalent consumption of saturated fats is deleterious. In this study, we explore this divergence, adopting a limited purview: The effect of dietary fatty acids on the mechanoenergetics of the isolated heart per se. Mechanical indices of interest include left-ventricular (LV) developed pressure, stroke work, cardiac output, coronary perfusion, and LV power. The principal energetic index is whole-heart oxygen consumption, which we subdivide into its active and basal moieties. The primary mechanoenergetic index of interest is cardiac efficiency, the ratio of work performance to metabolic energy expenditure. Wistar rats were divided into three Diet groups and fed, ad libitum, reference (REF), fish oil-supplemented (FO), or saturated fatty acid-supplemented (SFA) food for 6 weeks. At the end of the dietary period, hearts were excised, mounted in a working-heart rig, and their mechanoenergetic performance quantified over a range of preloads and afterloads. Analyses of Variance revealed no difference in any of the individual mechanoenergetic indices among the three Diet groups. In particular, we found no effect of prior dietary supplementation with either saturated or unsaturated fatty acids on the global efficiency of the heart.

Dietary pre-exposure of rats to fish oil does not enhance myocardial efficiency of isolated working hearts or their left ventricular trabeculae.

Numerous epidemiological studies, supported by clinical and experimental findings, have suggested beneficial effects of dietary fish or fish oil supplementation on cardiovascular health. One such experimental study showed a profound (100%) increase in myocardial efficiency (i.e. the ratio of work output to metabolic energy input) of the isolated whole heart, achieved by a corresponding decrease in the rate of myocardial oxygen consumption. However, a number of other investigations have returned null results on the latter energetic index. Such conflicting findings have motivated us to undertake a re-examination. To that effect, we investigated the effects of dietary fatty acid supplementation on myocardial mechano-energetics, with our primary focus on cardiac efficiency. We used both isolated hearts and isolated left ventricular trabeculae of rats fed with one of three distinct diets: reference (REF), fish oil-supplemented (FO) or saturated fat-supplemented (SFA). For all three groups, and at both spatial levels, we supplied 10 mm glucose as the exogenous metabolic substrate. In the working heart experiments, we found no difference in the average mechanical efficiency among the three dietary groups: 14.8 ± 1.1% (REF), 13.9 ± 0.6% (FO) and 13.6 ± 0.7% (SFA). Likewise, we observed no difference in peak mechanical efficiency of left ventricular trabeculae among the REF, FO and SFA groups: 13.3 ± 1.4, 11.2 ± 2.2 and 12.5 ± 1.5%, respectively. We conclude that there is no effect of a period of pre-exposure to a diet supplemented with either fish oil or saturated fatty acids on the efficiency of the myocardium at either spatial level: tissue or whole heart.