Septal Muscle Research Articles

Functioning of unidirectional ventilation in flying hawkmoths evaluated by pressure and oxygen measurements and X-ray video and tomography.

Flying sphingids generate unidirectional ventilation with an inflow through the anterior thoracic spiracles and an outflow through the posterior thoracic spiracles. This phenomenon was documented by the CO2 emission and tracheal air pressure in split-chamber experiments in preceding studies. In the present study, we evaluated the function of the air pump mechanism by measuring the tracheal pressure and PO2in the air sacs and monitoring the wing beat using photocells. Microelectrodes recorded the abdomen flexing muscles and abdominal transverse muscle septum. The crucial structure was the vertical mesophragma, with longitudinal flight muscles attached anteriorly and large fused metathoracic air sacs posteriorly, continuous to the first abdominal segment. Longitudinal flight muscles and abdomen lifting muscles contracted synchronously, producing positive pressure pulses within the mesothoracic air sacs. In the scutellar air sacs, the PO2with starting full flight was elevated to 18-20 kPa, with a pressure increase of 35-50 Pa. In contrast, in the metathoracic air sacs, the O2 concentration during flight could rise to 10 kPa, then decline to 5±1 kPa. The metathoracic air sacs provided compliance for ventilation by the flight muscles. The initial rise and subsequent decrease of the PO2in these posterior metathoracic air sacs indicated the unidirectional flow path of the air used. Serial X-ray frames of flying Acherontia atropos visualised the cyclic phragma movement and volume changes in the metathoracic air sacs. The results showed that the contracting dorsolongitudinal flight muscles expanded the metathoracic air sacs, acting as a suction pump.

Efficacy and safety of a transaortic approach to midventricular and apical septal myectomy

ObjectiveThe study objective was to evaluate the safety and efficacy of a transaortic approach to midventricular and apical septal myectomy in patients with hypertrophic cardiomyopathy with left ventricular outflow tract or midventricular obstruction. MethodsFrom January 2018 to August 2023, 940 patients underwent transaortic septal myectomy at the Cleveland Clinic, of whom 682 (73%) had midventricular or apical resection. Patients who underwent isolated basal myectomies were excluded. Templated operative reports designated septal regions resected as basal (opposition to mitral valve up to the leaflet tips), midventricular (leaflet tips to just beyond the papillary muscle heads), and apical (apical third of the ventricle). Myocardial resection specimen weights, intraventricular gradients, and clinical outcomes were assessed. ResultsOf the 682 patients, 582 (85%) had basal plus midventricular resection and 78 (11%) had basal, midventricular, and apical resection. Mean preoperative intraventricular gradient was 102 ± 41 mm Hg. Median resection weight was 10 g (15th, 85th percentiles: 7, 15), and mean postoperative intraventricular gradient was 16 ± 10 mm Hg, with 625 (96%) patients achieving gradients 36 mm Hg or less. There were no iatrogenic mitral or aortic valve injuries. Permanent pacemaker placement was required in 38 patients (5.6%), of whom 8 (1.2%) had normal preoperative conduction. Operative mortality occurred in 1 patient (0.1%) after an intraoperative ventricular septal defect. ConclusionsMost patients undergoing septal myectomy for relief of obstruction required resection beyond the basal septum. With specialized instrumentation, detailed imaging and knowledge of variable septal anatomy, resecting midventricular and apical septal muscle can be safely and effectively achieved through a transaortic approach.

Abstract 18703: No Time for Horseplay: A Case on a Traumatic Septal Defect

Background: A 74-year-old male with no past medical history presented to the clinic due to shortness of breath that had worsened over the past two weeks. He reports being “knocked over by a horse” about one month before and experienced chest pain immediately afterwards. A new holosystolic murmur was found prompting further evaluation. A walking test showed his oxygen saturation dropped from 98% to 81% on room air and was in respiratory distress. TTE revealed a large VSD of 1.5 cm with a left to right shunt, a dilated right ventricle measured at 4.9 cm, and severe pulmonary hypertension. Coronary angiography ruled out a prior myocardial infarction. RHC revealed an increase of oxygen saturation from the right atrium at 68.6% to 92% in the right ventricle. The patient was transferred to a facility where he underwent successful surgical VSD closure. He was discharged to rehab on post-operative day 8. He presented to the clinic one month later reporting resolution of his symptoms. Discussion: This patient with no past cardiac history presented with progressive dyspnea that was later identified to be caused by a trauma he experienced one month prior. The incidence of traumatic VSDs is quite low. Most VSDs are congenital in nature however few are reported to be trauma related. Trauma so intense that could cause a rupture in the septal muscle is quite intriguing. Prompt work up with imaging modalities such as TTE is the best next step for any trauma-related symptoms. Shared decision making with the patient and a multidisciplinary team will help to decide on a percutaneous or surgical repair of the defect. This case demonstrated a systematic approach to a unique presentation of a typically congenital condition.

Abstract 11477: Assessing New Onset of Atrial Arrhythmia in Patients Undergoing Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy

Introduction: Alcohol septal ablation (ASA) is an effective percutaneous procedure used to treat refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA relieves left ventricular outflow tract (LVOT) obstruction by creating a targeted infarction in the septal muscle. Diastolic dysfunction and mitral regurgitation are responsible for increased left atrial pressure which contributes to left atrial ectopy. We seek to assess the incidence of atrial arrhythmias post-ASA and identify predictors to risk stratify these patients. Methods: Using a patient database maintained internally, 144 consecutive patients who underwent ASA for HOCM between March 2017 and February of 2022 at MUSC were retrospectively reviewed. Patients were selected based on the need for cardiac event monitoring after ASA. Patients were retrospectively analyzed for a previous history of atrial fibrillation (AF) as well as a new onset of AF after ASA. SPSS statistics was used for statistical analysis. Results: A total of 31 patients met final inclusion criteria. During the monitored time, seven patients (22.58%) developed a new onset of AF after ASA. Patients who developed AF post-ASA were found to have a statistically higher left atrial end-systolic volume index (LAESVi, mL/m 2 ) and left ventricular end-diastolic pressure (LVEDP, mmHg) (59.96 ± 8.93, 34.33 ± 11.54) when compared to those who did not develop AF (41.13 ± 13.93, 23.33 ± 9.06 (p=0.0003, p=0.0331)). Conclusions: In this high-risk proportion of patients who required cardiac monitoring post-ASA, there is a higher-than-expected risk for new onset of AF. The left atrial size and left ventricular filling pressures before ablation were the only significant predictors for development of atrial arrhythmias after ASA. Longer-term evaluation will be able to address if the expected reduction in atrial size and LVOT gradient after ASA will reduce the overall long-term burden of atrial arrhythmias.

Perineal herniorrhaphy with pedunculated tunica vaginalis communis in dogs: Description of the technique and clinical case series.

BackgroundPerineal hernia (PH) in dogs is caused by the separation of the anal septal muscles and the displacement of pelvic/abdominal organs under the perineal skin. Reconstruction of the pelvic septum by surgical repositioning is the only curative treatment.ObjectivesTo describe the procedure and outcomes of surgical repair using the pedunculated tunica vaginalis communis (TVC) for PH in dogs.MethodsIntact male dogs diagnosed with PH were included in this study. For surgery, each dog was positioned in the Trendelenburg position. Castration was performed with the open technique, followed by colopexy and cystopexy via laparotomy. The remaining bilateral TVCs transposed to the opening of PH were used for the perineal herniorrhaphy. Intraoperative findings, complications, and outcomes were evaluated and recorded.ResultsEight dogs [median age 10.5 years (range, 9–13 years); median body weight 4.9 kg (range, 1.6–12.3 kg)] were treated using the TVC surgical technique. Perineal herniorrhaphy with the TVC was feasible in all dogs. The median operation time was 105.5 min (range, 46–149 min) in unilateral PH, and 92 and 122 min in two dogs with bilateral PH. Short-term postoperative complications during hospitalization did not occur in six dogs, whereas the residual two dogs had a temporary local infection as a minor complication. Postoperative recurrence occurred in one dog (13%) on postoperative day 136.ConclusionsOur study suggests that the herniorrhaphy technique using the pedunculated TVC is an alternative option for the repair of PH in dogs.

Discussion

Discussion

Per‐oral endoscopic myotomy as treatment for Killian–Jamieson diverticulum

Killian–Jamieson diverticulum (KJD) is a rare type of esophageal diverticulum less commonly encountered compared with Zenker's diverticulum (ZD). Endoscopic approach for these diverticula has been rapidly evolving. Currently, a flexible endoscopic septum division is considered the first‐line treatment for symptomatic ZD patients, however reported recurrence rates are over 10% according to recent literature. With the advent of submucosal tunneling technique established by per‐oral endoscopic myotomy for achalasia, it has been applied to treat ZD named as Zenker's diverticulum per‐oral endoscopic myotomy (Z‐POEM) as a minimally invasive treatment. Although there are very few reports utilizing submucosal tunneling approach to KJD, we have opted to perform Z‐POEM in order to safely perform complete dissection of the muscle septum while maintaining mucosal integration. Due to the difficulty of anatomical location of KJD, we created mucosal incision and subsequent submucosal tunnel directly at the level of the septum as opposed to creating a submucosal tunnel few centimeters proximal to the septum as being previously proposed. We report a case in which this technique was successfully performed with complete resolution of dysphagia without any adverse event. This technique permits to perform complete myotomies without the fear of causing perforation. Although larger cohorts are required to assess its safety and efficacy, Z‐POEM to treat KJD seems to be promising.

A new technique for tricuspid valve repair addressing the subvalvular apparatus in functional tricuspid regurgitation.

Annular dilatation is the main mechanism for tricuspid regurgitation, but right ventricular dilatation often adds a restrictive mechanism, which may limit durability. We describe a subvalvular technique anchoring the chordal origins to the annuloplasty, with the aim to stabilize valve geometry and increase durability. A Goretex suture is attached to the anterior papillary muscle. One arm of the suture is stitched through the septal muscle and both arms are atrialized underneath the septal leaflet and tied to the annuloplasty band. In 12 patients (75 ± 6 years, EuroSCORE II 10 ± 9%), severe-torrential tricuspid regurgitation was successfully reduced to mild. Results were stable in all but one patient during follow-up (1-15 months). NYHA class and general health status was improved. This subvalvular technique is safe with the potential to generate a durable repair.

Videoscope-assisted transaortic myectomy in patients with hypertrophic cardiomyopathy with complex left ventricular anatomy.

The transaortic approach is the most common method of septal myectomy. However, difficulties arise due to a limited view of the surgical field. Here, we report our experience with videoscope-assisted transaortic myectomy. We reviewed myectomy operations that were performed between July 2015 and June 2019 at Chung-Ang University Hospital, Seoul, South Korea. Patients who previously had cardiac surgery, alcohol septal ablation, or concomitant disease which required combined surgery, were excluded. Among the 21 patients included, 10 patients underwent videoscope-assisted transaortic myectomy (VA group), and 11 patients underwent myectomy in a conventional manner (CO group). The preoperative data, echocardiographic images, operative records, and postoperative outcomes of these patients were reviewed. There were no differences in baseline characteristics between groups VA and CO. The main indications for videoscope-assisted transaortic myectomy in group VA were midventricular septal muscle resection (70%), abnormal papillary muscle resection (40%), and abnormal chordal connection resection (30%). Eight (80%) patients had multiple indications for videoscope-assisted transaortic myectomy. There was no surgical mortality in either group. Postoperative patients showed less than moderate mitral regurgitation and a New York Heart Association class either III or IV. There were no differences in hospital days (9.5 vs. 12.0 days; p = .383), nor postoperative pressure gradient (14 vs. 15 mmHg; p > .99). Videoscope-assisted transaortic myectomy is an effective surgical technique in selective hypertrophic cardiomyopathy patients with complex intraventricular anatomy, diffuse hypertrophy, and midventricular obstruction.

Age Wise Internal Morphometrical Studies on the Heart of Pre-natal Non-descript Sheep

Background: Heart is the central organ of circulatory system that pumps blood into the blood vessels and performs many vital functions. Its development before birth must be studied to safeguard the animal from the occurrence and consequences of various developmental anomalies. The detailed morphometry of different internal parameters of heart especially in pre-natal sheep has not yet been reported. Methods: The foeti of sheep were divided into two age groups viz. mid prenatal (51-100 days) and late prenatal (101 to 150 days) with fifteen animals in each age group. The various internal parameters were recorded by using digital weighing machine, graduated measuring cylinder, digital Vernier’s calliper, non-stretchable nylon thread and graduated scale. The data recorded was statistically analysed by independent t test with IBM SPSS 25.0 version software. Result: The average thickness of left ventricular wall of heart was measured as 2.85±0.15mm and 4.28±0.07mm in mid prenatal and late prenatal stages respectively with significant (p£0.01) differences between the ages. Similarly, the average diameter of left atrio-ventricular opening of heart was measured as 2.06±0.27mm and 6.08±0.36mm in mid prenatal and late prenatal stages respectively with significant (p£0.01) differences between the ages. The average length of septal papillary muscle in right ventricle was measured as 1.12±0.10mm and 3.29±0.21mm in mid prenatal and late prenatal stages respectively with significant (p£0.01) differences between the ages. Further, the average length of moderator band in heart was measured as 1.45±0.11mm and 4.34±0.23mm in mid prenatal and late prenatal stages respectively with significant (p£0.01) differences between the ages. Similarly, the average length of chordae tendinae in right ventricle of heart was measured as 0.97±0.09mm and 3.50±0.34mm in mid prenatal and late prenatal stages respectively with significant (p£0.01) differences between the ages.

Indocyanine green angiography technique assisted brachial artery perforator propeller flap to repair soft tissue defects of trunk and upper limb

To explore the feasibility of using indocyanine green (ICG) angiography to detect brachial artery perforators, and the clinical application of brachial artery perforator propeller (BAPP) flaps to repair soft tissue defects of the trunk and upper limbs. Between August 2016 and February 2019, ICG angiography was used to detect the perforating vessels of the brachial artery muscle septum, and the BAPP flaps were cut out with the detected perforating vessels as the pedicle to repair 19 cases of trunk and upper limb soft tissue defects. There were 12 males and 7 females, with an average age of 28.6 years (range, 5-66 years). Etiologies included the post-burn scar in 10 cases, soft-tissue sarcoma in 5 cases, congenital melanocytic nevi in 2 cases, chronic chest wall ulcer in 1 case, and malignant melanoma in 1 case. Defects located in axilla in 8 cases, chest wall in 4 cases, elbow in 5 cases, and shoulder in 2 cases. The area of the defect ranged from 15 cm×3 cm to 20 cm×8 cm. Pre-transfer tissue expansion was used in 11 patients. Thirteen flaps were pedicled with 1 perforator vessel, and 6 flaps were pedicled with 2 perforator vessels. The length of the vascular pedicle was 2.5-4.5 cm, with an average of 3.08 cm. The area of the skin flap ranged from 11 cm×5 cm to 22 cm×10 cm. The flap rotation angle was 110° in 1 case, 120° in 1 case, and 180° in 17 cases. Except for one donor site repaired by skin graft, the other donor sites were directly sutured. A total of 24 perforating vessels of the brachial artery muscle septum were detected by ICG angiography, 26 were identified during the operation, with an accuracy rate of 92.31%. Eighteen flaps survived without arteriovenous crisis. Venous congestion was observed in the distal 3-cm of one flap and the flap survived after conservative management. Intraoperative analysis showed that the blood perfusion of the distal 4-cm of one flap was poor, the relative value was less than 32%, the flap survived after removing the poor perfusion area. All the patients were followed up 3 to 23 months (mean, 8.6 months). The color and texture of the flap were similar to those of the recipient area. Flap debulking was not needed in all patients owing to the thinness of the flap. The contracture symptoms of patients with scar contracture on the medial of the elbow joint and axilla were significantly improved; a patient with malignant melanoma underwent tumor resection at 1 year and 5 months after operation due to tumor recurrence, and additional surgery was done to remove the recurrent tumor. No tumor recurrence was found in other patients. The ICG angiography technique can be used to explore the perforating vessels of the brachial artery muscle septum. The BAPP flap pedicled with the perforating vessels can be used for the repair of skin and soft tissue defects in the chest wall, axilla, shoulder, and elbow joint.

Adult Monozygotic Twins With Hypertrophic Cardiomyopathy and Identical Disease Expression and Clinical Course

A unique clinical circumstance involving middle-aged male identical twins with obstructive hypertrophic cardiomyopathy (HC) is reported. The concordance of morphologic (i.e., phenotype) findings and clinical course between the 2 patients is remarkable, including timing of the onset and progression of heart failure due to left ventricular outflow tract obstruction, frequency of paroxysmal atrial fibrillation and beneficial response to surgical myectomy and Cox-Maze IV procedure (performed 14 days apart). Histopathology of resected ventricular septal muscle showed identical hallmarks of HC including myocyte disorganization, small vessel disease, and myocardial fibrosis. A missense variant of the CRYAB gene was identified as potentially relevant to the pathogenesis of HC in the twins. Taken together, these observations support a powerful genetic determinant for the morphologic and clinical expression of HC, with little or no environmental influence.

Pressure Overload Is Associated With Low Levels of Troponin I and Myosin Binding Protein C Phosphorylation in the Hearts of Patients With Aortic Stenosis.

In previous studies of septal heart muscle from HCM patients with hypertrophic obstructive cardiomyopathy (HOCM, LVOT gradient 50–120 mmHg) we found that the level of phosphorylation of troponin I (TnI) and myosin binding protein C (MyBP-C) was extremely low yet samples from hearts with HCM or DCM mutations that did not have pressure overload were similar to donor heart controls. We therefore investigated heart muscle samples taken from patients undergoing valve replacement for aortic stenosis, since they have pressure overload that is unrelated to inherited cardiomyopathy. Thirteen muscle samples from septum and from free wall were analyzed (LVOT gradients 30–100 mmHg) The levels of TnI and MyBP-C phosphorylation were determined in muscle myofibrils by separating phosphospecies using phosphate affinity SDS-PAGE and detecting with TnI and MyBP-C specific antibodies. TnI was predominantly monophosphorylated and total phosphorylation was 0.85 ± 0.03 molsPi/mol TnI. This phosphorylation level was significantly different (p < 0.0001) from both donor heart TnI (1.6 ± 0.06 molsPi/mol TnI) and HOCM heart TnI (0.19 ± 0.04 molsPi/mol TnI). MyBP-C is phosphorylated at up to four sites. In donor heart the 4P and 3P species predominate but in the pressure overload samples the 4P species was much reduced and 3P and 1P species predominated. Total phosphorylation was 2.0 ± 0.2 molsPi/mol MyBP-C (n = 8) compared with 3.4 ± 0.07 (n = 21) in donor heart and 1.1 ± 0.1 (n = 10) in HOCM heart. We conclude that pressure overload may be associated with substantial dephosphorylation of troponin I and MyBP-C.

Dual-layer detector spectral CT versus magnetic resonance imaging for the assessment of iron overload in myelodysplastic syndromes and aplastic anemia.

The purpose of this study is to investigate the performance of dual-layer detector spectral CT for iron deposition compared to magnetic resonance imaging (MRI) T2* imaging. Thirty-one patients with a clinical history of myelodysplastic syndromes and aplastic anemia underwent liver and cardiac T2*-weighted unenhanced MRI on a three-tesla MRI scanner, and underwent unenhanced CT scan laterally on a 128-row spectral detector CT. R2* values of the liver, septal muscle, and paraspinal muscle were calculated. Attenuation differences (ΔH) in the liver and myocardium were calculated between the lower (50keV) and higher (120keV) energy levels. The liver and cardiac T2* values were 9.54 ± 5.63ms and 21.41 ± 2.44ms, respectively. The liver-to-muscle and myocardium-to-muscle T2* value ratios were 0.37 ± 0.23 and 0.79 ± 0.19, respectively. The liver and cardiac ΔH were -1.13 ± 4.24HU and 2.22 ± 4.41HU, respectively. There was a strong linear correlation between the liver R2* and ΔH (r = -0.832, P < 0.001), but weak correlation existed between the cardiac R2* and ΔH (P = 0.041). Dual-layer detector spectral unenhanced CT seemed to be equally valuable to MRI T2* imaging for evaluating liver iron overload.

Attention PCP&amp;apos;s: The Prior Inpatient Post-MI Complications Are Now More Likely to Present to Your Outpatient Clinic

Cardiovascular disease is one of the leading causes of hospitalization and death in the United States. Every 40 seconds an acute myocardial infarction occurs. Most of the mortality occurs before the patient can reach medical care. Those that do reach medical care have seen a dramatic improvement in survival. The American Heart Association 2019 heart disease and stroke statistics from 2006 to 2016 show that the death rate has decreased by 31.8%. This decrease in mortality is multifactorial starting with enhanced public awareness of the early signs of myocardial infarction with mobilization of first responders, rapid reperfusion therapy and improved medical care. These improvements have resulted in a decrease in the mechanical complications of left ventricular rupture, acquired ventricular septal defect and papillary muscle rupture. However, these have not been eliminated and due to the shorter hospital stay after an MI with their peak incidence occurring more than 3 days post infarction has resulted in a change in the presentation of these complications. It was not that long ago that the usual length of stay for what was called a transmural MI or Q –wave MI was 21 days and a sub-endocardial or non-Q wave 10 days. This duration of observation made the presentation of post myocardial mechanical complications an in-hospital diagnosis. However, now in the era of reperfusion for both STEMI and NSTEMI, it is uncommon to see a length of stay longer than 3 days. While this early discharge practice has been shown to be safe, it shifts the diagnosis and treatment of post MI complications to the outpatient clinic where the Primary Care Provider (PCP) may be the first to see the patient post discharge. This paper will review the three most common mechanical complications that occur post MI and provide keys to their diagnosis and triage.

Musculature development in planuloids of Cassiopeia xamachana (Cnidaria: Scyphozoa)

Polyps of the family Cassiopeidae (Cnidaria: Scyphozoa) can reproduce asexually by forming a ciliated swimming stage, the planuloid. It is externally similar to the planula larva and has traditionally been referred to as the planuloid bud. Using phalloidin labeling, we described the development of the muscular system in planuloids of Cassiopeia xamachana during growth and metamorphosis into the polyp. Early growth stages of the planuloid involve septal muscle bands of the polyp but after separation from the mother organism it forms its own musculature de novo. Muscular elements of the newly separated planuloid are represented by short disordered fibers and four main groups of longitudinal muscles. These elements are the primary musculature of the future polyp. During further development the planuloid grows, changes in shape from elongated to triangular and starts to form the musculature of the hypostome and the tentacles anlages. By the time of settlement the muscular groups form four bands. Process of musculature formation in planuloids differs from that in scyphozoan planulae, which lack well-developed muscular elements. The formation of planuloids might be a modification of lateral budding, with the development of the daughter polyp occurring distantly from the mother organism. These stages could not be called true buds because of their independent growth, and so the term “planuloid bud” is misleading. We argue that the planuloid is the best name for this stage since it reflects its biology and at the same time emphasizes its similarity to the planula larva.

Role of Preoperative Cardiovascular Magnetic Resonance in Planning Ventricular Septal Myectomy in Patients With Obstructive Hypertrophic Cardiomyopathy

In obstructive hypertrophic cardiomyopathy (HC), extreme heterogeneity of septal morphology makes septal myectomy particularly challenging. Although cardiovascular magnetic resonance (CMR) reconstructs ventricular anatomy with high spatial resolution, CMR is not used systematically to plan preoperatively septal myectomy. In this study, we report our results with using CMR to plan the extent of septal excision in 112 consecutive HC patients who subsequently underwent myectomy. Depth and length of the myectomy planned at CMR were compared with those of the septal muscle excised in a single piece in all patients. Anterior septum maximal thickness at CMR was 22 ± 5 mm and excised muscle thickness 9 ± 3 mm. Planned myectomy length was 35 ± 11 mm (range 17 to 65) and excised muscle length 38 ± 10 mm (range 10 to 70), indicating extension of septal resection to mid-cavity. Thickness and length of the planned myectomy showed a significant correlation with the excised muscle (R2 = 0.345; p <0.001; and R2 = 0.358; p <0.001, respectively). Deep septal crypts were identified at CMR in 12(11%) patients, preventing muscle excision from areas at increased risk of iatrogenic septal defect. Large aberrant muscle bundles that could decrease mid-cavity dimension were identified at CMR and excised in 26(23%) patients. In the 55 patients with postoperative CMR, qualitative comparison of pre and postoperative ventricular morphology showed a smooth and apically extended myectomy. In conclusion, CMR planning of septal myectomy provided high resolution images of septal morphology and allowed us to perform a standardized and apically extended septal excision that was associated with favorable outcome. Our novel approach could make myectomy more accessible to cardiovascular surgeons.

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats.

Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg.

Clinical Spectrum and Management Implications of Left Ventricular Outflow Obstruction With Mild Ventricular Septal Thickness in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) has historically been characterized as a disease of substantial left ventricular hypertrophy, often associated with dynamic left ventricular outflow tract obstruction. However, we have recently encountered patients with subaortic obstruction and only minimal basal septal thickness, raising important management implications. Thereby, we sought to characterize the natural history and treatment strategies for this under-recognized subgroup of HC patients with dynamic obstruction. Of 1,591 consecutive patients with a HC diagnosis, 113 (7%) were identified with outflow obstruction due to elongated mitral valve leaflets producing systolic anterior motion and septal contact typical of HC (gradient, 84 ± 29 mm Hg at rest or with exercise), with maximal ventricular septal thickness ≤15 mm, including 14 patients with only 10 to 12 mm. In addition to the mechanism of outflow obstruction, other evidence supporting a HC diagnosis prominently included: positive HC family history and/or pathogenic sarcomere mutation, arrhythmic sudden death event, typical histopathology of septal muscle, and characteristic mitral valve and papillary muscle anomalies. Over 3.8 ± 3.5 years, 41 patients (36%) developed severe heart failure including 36 who have undergone myectomy associated with reconstruction of the outflow tract and mitral valve apparatus, resulting in relief of gradient without iatrogenic ventricular septal defect or mitral valve replacement. Postoperatively, all 36 patients have survived with symptom relief to New York Heart Association classes I/II. In conclusion, these observations expand the HC clinical profile and phenotype to include an under-appreciated subgroup in which disease expression includes outflow obstruction due primarily to an elongated mitral valve, associated with only minimal (or normal) ventricular septal thickness. Such HC patients can develop marked functional limitation amenable to an operative strategy that effectively relieved symptoms due to outflow obstruction, but without mitral valve replacement.

Tips for Successful Septal Myectomy in Patients with Hypertrophic Cardiomyopathy.

Septal myectomy is the gold-standard treatment of hypertrophic cardiomyopathy. However, it involves the risk of incomplete resection of septal muscles or iatrogenic septal perforation depending on the surgeon’s practice. Herein, we suggest a few tips for successful septal myectomy and present a relevant case.