Left Ventricular Papillary Muscle: Anatomy, Pathophysiology, and Multimodal Evaluation.

As an integral part of the mitral valve apparatus, the left ventricle papillary muscle (PM) controls mitral valve closure during systole and participates in the ejection process during left ventricular systole. Mitral regurgitation (MR) is the most immediate and predominant result when the PM is structurally or functionally abnormal. However, dysfunction of the PM is easily underestimated or overlooked in clinical interventions for MR-related diseases. Therefore, adequate recognition of PM dysfunction and PM-derived MR is critical. In this review, we systematically describe the normal anatomical variations in the PM and the pathophysiology of PM dysfunction-related diseases and summarize the commonly used parameters and the advantages and disadvantages of various noninvasive imaging modalities for the structural and functional assessment of the PM.

Echocardiographic diagnosis of rupture of mitral valve papillary muscle.

OBJECTIVE: To explore the value of echocardiography in diagnosing papillary muscle rupture (PMR) of the mitral valve, and summarize the characteristic echocardiographic features of different types. METHODS: Echocardiograms of 13 PMR patients confirmed by surgery in Wuhan Union Hospital between January 2009 and December 2022 were retrospectively analyzed and their preoperative transthoracic echocardiography (TTE) was compared with surgical findings. RESULTS: A total of 9020 patients underwent mitral valve repair or replacement surgery during the study period including 13 (0.14%) for PMR. Of the 13 PMRs, 8 cases were partial PMR(P-PMR), 5 cases were complete PMR(C-PMR); 3 cases were anterolateral PMR, and 10 were posteromedial PMR. The diagnostic accuracy, sensitivity, and specificity of the preoperative TTE were 99.9%, 53.8% and 99.9% respectively. Echocardiographic features of 10 patients (5-C-PMR and 5 P-PMR) with detailed TTE and intraoperative transesophageal echocardiography (TEE) data included: both anterior and posterior leaflets prolapse (C-PMR 60% vs P-PMR 60%); flail leaflet (C-PMR100% vs P-PMR 40%); All C-PMRs and P-PMRs have severe, eccentric and lateral regurgitation; flail attachment (chordae tendinae and ruptured PM) at the tip of prolapsed leaflet (C-PMR100% vs P-PMR 60%); high-echo masses resembled "champagne glasses" in 100% of the C-PMR; high-echo masses resembled "lotus-seedpod" in 60% and "dumbbell-shaped" torn PM in remaining 40% of the P-PMR. CONCLUSIONS: Different PMR subtypes have different echocardiographic characteristics. Combining TTE and TEE can accurately identify the typical features of PMR such as ipsilateral hemipetal leaflet prolapse, high-echoic mass at the tip of the leaflet, massive eccentricity and lateral regurgitation.

Electrospun polymer fibers modified with FK506 for the long-term treatment of acute cardiac allograft rejection in a heart transplantation model.

FK506, a first-line immunosuppressant, is routinely administered orally and intravenously following heart transplantation. However, frequent administration can result in a substantial psychological burden to patients, resulting in non-adherence to medication. The purpose of our study is to overcome the disadvantages of systemic drug administration by developing a polymer-based delivery system that is tunable and biodegradable and that can release highly hydrophobic FK506 over extended periods to treat or prevent acute cardiac allograft rejection. Using an electrospinning method, long-acting microfibers were prepared, and FK506 appeared to be continuously released for up to 14 days based on the in vitro release profiles. After implanting the microfiber subcutaneously into the abdominals of transplanted rats, it was found that the infiltration of T cells and macrophages and the secretion of interleukin-2 (IL-2) and IL-1ß were significantly reduced compared with those of the free FK506 groups. More importantly, the mean survival time (MST) of the PCL-FK506 group was significantly extended in comparison with that of untreated control recipients and free FK506 (MST of untreated control recipients, free FK506, and PCL-FK506 was 8, 26.1, and 37, respectively). In conclusion, we propose that this drug delivery approach would be suitable for developing long-lasting immunomodulatory agents that prolong cardiac graft survival safely and effectively.

Amplification of Plasma MicroRNAs for Non-invasive Early Detection of Acute Rejection after Heart Transplantation With Ultrasound-Targeted Microbubble Destruction.

OBJECTIVE: Acute rejection (AR) screening has always been the focus of patient management in the first several years after heart transplantation (HT). As potential biomarkers for the non-invasive diagnosis of AR, microRNAs (miRNAs) are limited by their low abundance and complex origin. Ultrasound-targeted microbubble destruction (UTMD) technique could temporarily alter vascular permeability through cavitation. We hypothesized that increasing the permeability of myocardial vessels might enhance the abundance of circulating AR-related miRNAs, thus enabling the non-invasive monitoring of AR. METHODS: The Evans blue assay was applied to determine efficient UTMD parameters. Blood biochemistry and echocardiographic indicators were used to ensure the safety of the UTMD. AR of the HT model was constructed using Brown-Norway and Lewis rats. Grafted hearts were sonicated with UTMD on postoperative day (POD) 3. The polymerase chain reaction was used to identify upregulated miRNA biomarkers in graft tissues and their relative amounts in the blood. RESULTS: Amounts of six kinds of plasma miRNA, including miR-142-3p, miR-181a-5p, miR-326-3p, miR-182, miR-155-5p and miR-223-3p, were 10.89 ± 1.36, 13.54 ± 2.15, 9.84 ± 0.70, 8.55 ± 2.00, 12.50 ± 3.96 and 11.02 ± 3.47 times higher in the UTMD group than those in the control group on POD 3. Plasma miRNA abundance in the allograft group without UTMD did not differ from that in the isograft group on POD 3. After FK506 treatment, no miRNAs increased in the plasma after UTMD. CONCLUSION: UTMD can promote the transfer of AR-related miRNAs from grafted heart tissue to the blood, allowing non-invasive early detection of AR.

Establishment and evaluation of a prediction model for acute gastrointestinal injury in patients with prolonged disorder of consciousness.

OBJECTIVE: To establish a prediction model for acute gastrointestinal injury (AGI) in patients with prolonged disorder of consciousness (pDOC) and to evaluate and apply the prediction model.  METHODS: The clinical data of 165 patients with pDOC admitted to the hyperbaric oxygen department from January 2021 to December 2021 were retrospectively reviewed, and the patients were divided into an AGI group (n = 91) and an N-AGI group (n = 74) according to whether AGI occurred. A prediction model was built by fitting multiple independent influencing factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model, the Hosmer-Lemeshow (H-L) test was used to evaluate the goodness-of-fit of the model, and the ROC curve and calibration curve were drawn to evaluate the predictive performance. A nomogram was plotted to visualize the prediction model. RESULTS: According to the multivariate logistic regression analysis results, the prediction model was finally constructed with the CRS-R score, DAO, PCT, ALB, and I-FABP, and a nomogram was generated. The area under the ROC curve (AUC) of the prediction model was 0.931, the sensitivity was 83.5%, and the specificity was 93.2%. The data were divided into 5 groups for the H-L test (χ2 = 2.54, P = 0.468 > 0.05) and into 10 groups for the H-L test (χ2 = 9.98, P = 0.267 > 0.05). A calibration curve was drawn based on the test results, indicating that the prediction model has a good goodness-of-fit and good prediction stability. CONCLUSION: The prediction model for AGI in pDOC patients constructed in this study can be used in clinical practice and is helpful to predict the occurrence of AGI in pDOC patients.

Immunosuppressive effect of PLGA-FK506-NPs in treatment of acute cardiac rejection via topical subcutaneous injection.

FK506, a first-line immunosuppressant, is routinely administered orally and intravenously to inhibit activation and proliferation of T cells after heart transplantation (HT). Current administration route is not conducive enough to exert its efficacy in lymphatic system. Herein, we proposed that subcutaneous (SC) administration of FK506-loaded nanoparticles (PLGA-FK506-NPs) would be valuable for treating acute rejection after HT. The biodistribution and pharmacokinetic study revealed that it could effectively deliver FK506 to the lymph nodes (LNs) due to their suitable particle size, especially in inguinal LNs. Subsequently, the therapeutic efficacy of PLGA-FK506-NPs on the HT model was evaluated using intravenous (IV), intragastric (IG), or SC injection. Histopathological analysis revealed that 80% of allografts exhibited only grade 1R rejection with negligible lymphocyte infiltration in the SC group. The IV group exhibited 40% 1R rejection with mild lymphocyte infiltration and 20% grade 3R that require further intervention, and the IG group exhibited grades 40% 3R rejection with more lymphocyte infiltration. Moreover, the infiltration of T cells and the secretion of IL-2 and IFN-γ were significantly reduced in the SC group compared with the IG or IV group. The mean survival time (MST) further revealed that 50% of grafts treated with PLGA-FK506-NPs via SC injection survived longer than IG and IV groups. Moreover, the MST of single-dose SC injection of PLGA-FK506-NPs demonstrated that it would effectively reduce the required dose for a similar therapeutic effect. Overall, these results indicate that SC administration of PLGA-FK506-NPs is a more effective route for chronic FK506 treatment.

Biomimetic PLGA Microbubbles Coated with Platelet Membranes for Early Detection of Myocardial Ischaemia-Reperfusion Injury.

Early diagnosis of myocardial ischaemia-reperfusion (MI/R) injury is important for protecting the myocardium and improving patient prognoses. Fortunately, the platelet membrane possesses the ability to target the region of MI/R injury. Therefore, we hypothesized that platelet membrane-coated particles (PMPs) could be used to detect early MI/R injury by ultrasound imaging. We designed PMPs with a porous polylactic-co-glycolic acid (PLGA) core coated with a platelet membrane shell. Red blood cell membrane-coated particles (RMPs) were fabricated as controls. Transmission electron microscopy (TEM) and fluorescence microscopy were applied to confirm the membrane coatings of the PMPs and RMPs. In vitro imaging of the PMPs and RMPs was verified. Moreover, binding experiments were designed to examine the targeting ability of the PMPs. Finally, we assessed the signal intensity of the adherent PMPs in the risk area and remote area by ultrasound imaging based on an MI/R rat model. The platelet membrane equipped the PMPs with an accurate targeting ability. Compared with RMPs, PMPs showed significantly more adhesion to human umbilical vein endothelial cells and collagen IV in vitro. Both PMPs and RMPs exhibited good enhancement ability in vitro and in vivo. Furthermore, the signal intensity of PMPs in the risk area was significantly higher than that in remote areas. These results were further validated by an immunofluorescence assay and ex vivo fluorescence imaging. In summary, ultrasound imaging with PMPs can detect early MI/R injury in a noninvasive manner.