Non-Lung Solid Organ Transplantation From SARS-CoV-2-Positive Donors to Uninfected Recipients.

BACKGROUND: There is a paucity of evidence on the risk of donor-recipient transmission of the SARS-CoV-2 in solid organ transplant recipients. Initial impressions suggest non-lung solid organs may be safely transplanted from SARS-CoV-2-positive donors without risk of viral transmission. METHODS: We reviewed clinical results of transplants in which SARS-CoV-2-negative recipients received non-lung solid organs from SARS-CoV-2-positive donors at a single transplant center. No prisoners were used in this study, and participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Between June 2021 and January 2023, we transplanted 26 solid organs, including 13 kidneys, 8 livers, 3 hearts, and 1 simultaneous heart and kidney, from 23 SARS-CoV-2-positive donors into 25 SARS-CoV-2 negative recipients. Two of the recipients had a positive SARS-CoV-2 real-time polymerase chain reaction after transplantation, but otherwise, patients had no SARS-CoV-2-related complications, and all patients to date are alive with excellent allograft function. CONCLUSION: Transplantation of non-lung solid organs from SARS-CoV-2-positive donors into uninfected recipients can be safely performed without adverse effects from SARS-CoV-2.

A Compact MIMO Multiband Antenna for 5G/WLAN/WIFI-6 Devices.

This research work presents a compact design of a Multiple-Input Multiple-Output (MIMO) multiband antenna along with high-isolation characteristics. The presented antenna was designed for 3.50 GHz, 5.50 GHz, and 6.50 GHz frequencies for 5G cellular, 5G WiFi, and WiFi-6, respectively. The fabrication of the aforementioned design was undertaken using FR-4 (1.6 mm thickness) substrate material with a loss tangent and relative permittivity of about 0.025 and 4.30, respectively. The two-element MIMO multiband antenna was miniaturized to 16 × 28 × 1.6 mm3, making it desirable for devices operating in 5G bands. High isolation (>15 dB) was attained with thorough testing without employing a decoupling scheme in the design. Laboratory measurements resulted in a peak gain of 3.49 dBi and an efficiency of around 80% in the entire operating band. The evaluation of the presented MIMO multiband antenna was carried out in terms of the envelope correlation coefficient (ECC), diversity gain (DG), total active reflection coefficient (TARC), and Channel Capacity Loss (CCL). The measured ECC was less than 0.04, and the DG was well above 9.50. The observed TARC was also lower than -10 dB, and the CCL was below 0.4 bits/s/Hz in the entire operating band. The presented MIMO multiband antenna was analyzed and simulated using CST Studio Suite 2020.

Post Heart Transplantation Outcomes of Patients Supported on Biventricular Mechanical Support.

With the implementation of the new heart transplant (HT) allocation system, patients requiring biventricular support systems have the highest priority, a shorter waitlist time, and a higher frequency of HT. However, the short-term and long-term outcomes of such patients are often disputed. Hence, we examined the outcomes of these patients who underwent HT before change in allocation scheme. Additionally, we compared post-HT outcomes of extracorporeal membrane oxygenation (ECMO) with other nondischargeable biventricular (BiVAD) supported patients. We identified adult ECMO or BiVAD supported HT recipients between 2000 and 2018 in the Scientific Registry of Transplant Recipients database. We compared survival with the Kaplan-Meier method. Using overlap propensity score weighting, we constructed Cox proportional hazards regression models to determine the risk-adjusted influence of BiVAD versus ECMO on survival. Of the 730 patients HT recipients; 528 (72.3%) and 202 (27.7%) were bridged with BiVAD and ECMO, respectively. For BiVAD versus ECMO patients, the 30-day, 1-year, 3-year, and 5-year mortality rates were 8.0% versus 14.4%, 16.3% versus 21.3%, 22.4% versus 25.3%, and 26.3% versus 25.7%, respectively. Risk-adjusted post-HT survival of BiVAD and ECMO patients at 30-day (HR 1.24 [95% CI, 0.68-2.27]; P = 0.4863), 1-year (HR 1.29 [95% CI, 0.80-2.09]; P = 0.3009), 3-year (HR 1.27 [95% CI, 0.83-1.94]; P = 0.2801), and 5-year (HR 1.35, 95% CI, 0.90-2.05; P = 0.1501) were similar. Around three-fourth of the ECMO or BiVAD supported patients were alive at 5-years post-HT. The short-term and long-term post-HT survivals of groups were comparable.

Clinical outcomes of older adults listed for heart transplantation in the United States.

OBJECTIVE: To examine if older age (>70 years) should be a relative contraindication for heart transplantation, we evaluated the characteristics and outcomes of patients with age ≥70 years listed for heart transplantation; and whether post-transplantation survival was inferior to younger counterparts. DESIGN: Retrospective cohort analysis. SETTING: The scientific registry of transplant recipients (SRTR). PARTICIPANTS: Adults (≥18 years) listed for heart transplantation in the SRTR between 2000 and 2018. INTERVENTIONS: Heart transplantation. MEASUREMENTS: Characteristics and outcomes were compared for adults ≥70 years and <70 years. We evaluated waitlist mortality and post-transplant 1-year and 5-year survivals. RESULTS: The study included 57,285 patients (age range 18-79 years) listed for heart transplantation; 1203 (2.1%) age ≥70 years. Of these, 37,135 patients underwent heart transplantation; 806 (2.2%) were age ≥70 years. Yearly listing of those age ≥70 years has consistently increased from 2.5% (n = 30) in 2000 to 11% (n = 132) in 2017 (p < 0.01). As compared with the age <70 years group, those ≥70 years had a similar risk of death while waiting (sub-hazard ratio [SHR] 0.86, 95% confidence interval [HR] 0.68-1.08; p = 0.19) but were more likely to be transplanted (SHR 1.36, 95% CI 1.26-1.48; p < 0.01). Among the older patients, the overall post-transplant 1- and 5-year mortality rate was 10.4% and 19.2%, respectively. Older recipients had lower unadjusted survival compared with younger recipients (log-rank p = 0.03). However, after adjustment for relevant covariates, there was no significant difference in 5-year mortality between both groups (HR 1.06, 95% CI 0.91-1.254; p = 0.43). CONCLUSIONS: Post-transplant survival up to 5 years among patients of age ≥70 years was similar to that of younger recipients. Older patients who received heart transplantation appear to have lower risk features but receive hearts from higher risk donors. Chronologic age alone should not constitute a contraindication for heart transplantation, although careful patient selection criteria should be applied.

A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors.

BACKGROUND: In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program. METHODS: This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival. RESULTS: During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30 days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84). CONCLUSIONS: DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation.

Evaluation of Case Volumes of a Heart Transplant Program and Short-term Outcomes After Changes in the United Network for Organ Sharing Donor Heart Allocation System.

Importance: Institution-level strategic changes may be associated with heart transplant volume and outcomes. Objective: To describe changes in practice that markedly increased heart transplant volume at a single center, as well as associated patient characteristics and outcomes. Design, Setting, and Participants: A pre-post cohort study was conducted of 107 patients who underwent heart transplant between September 1, 2014, and August 31, 2019, at Yale New Haven Hospital before (September 1, 2014, to August 31, 2018; prechange era) and after (September 1, 2018, to August 31, 2019; postchange era) a strategic change in patient selection by the heart transplant program. Exposure: Strategic change in donor and recipient selection at Yale New Haven Hospital that occurred in August 2018. Main Outcomes and Measures: Outcome measures were transplant case volume, donor and recipient characteristics, and 180-day survival. Results: A total of 49 patients (12.3 per year; 20 women [40.8%]; median age, 57 years [interquartile range {IQR}, 50-63 years]) received heart transplants in the 4 years of the prechange era and 58 patients (58 per year; 19 women [32.8%]; median age, 57 years [IQR, 52-64 years]) received heart transplants in the 1 year of the postchange era. Organ offers were more readily accepted in the postchange era, with an offer acceptance rate of 20.5% (58 of 283) compared with 6.4% (49 of 768) in the prechange era (P < .001). In the postchange era, donor hearts were accepted with a higher median number of prior refusals by other centers than in the prechange era (16.5 [IQR, 6-38] vs 3 [IQR, 1-6]; P < .001). Hearts accepted in the postchange era were from older donors than in the prechange era (median age, 40 years [IQR, 29-48 years] vs 30 years [IQR, 24-42 years]; P < .001). Recipients had a significantly shorter time on the waiting list in the postchange era compared with prechange era (median, 41 days [IQR, 12-289 days] vs 242 days [IQR, 135-428 days]; P < .001). More patients were supported on temporary circulatory assist devices preoperatively in the postchange era than the prechange era (14 [24.1%] vs 0; P < .001). Survival rates at 180 days were not significantly different (43 [87.8%] in the prechange era vs 52 [89.7%] in the postchange era). Mortality while on the waiting list was similar (2.8 deaths per year in the prechange era vs 3 deaths per year in the postchange era). During the comparable time period, 4 other regional centers had volume change ranging from -10% to 68%, while this center's volume increased by 374%. Conclusions and Relevance: This study suggests that strategic changes in donor heart and recipient selection may significantly increase the number of heart transplants while maintaining short-term outcomes comparable with more conservative patient selection. Such an approach may augment the allocation of currently unused donor hearts.

Mulibrey Nanism Syndrome: A Case for Heart Transplantation.

Mulibrey nanism syndrome is a rare genetic disorder affecting multiple organ systems. The cardiovascular system is one of the most significantly affected, with simultaneous myocardial and pericardial disease. These patients are usually managed by pericardiectomy to resolve the milieu of hemodynamic problems ensuing due to concurrent constrictive and restrictive pathologies. We highlight the use of cardiac transplantation as a definitive management for a hemodynamically decompensated patient with Mulibrey nanism syndrome.

Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices.

Importance: Left ventricular assist devices (LVADs) improve outcomes in patients with advanced heart failure, but little is known about the role of neurohormonal blockade (NHB) in treating these patients. Objective: To analyze the association between NHB blockade and outcomes in patients with LVADs. Design, Setting, and Participants: This retrospective cohort analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) included patients from more than 170 centers across the United States and Canada with continuous flow LVADs from 2008 to 2016 who were alive with the device in place at 6 months after implant. The data were analyzed between February and November 2019. Exposures: Patients were stratified based on exposure to NHB and represented all permutations of the following drug classes: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ß-blockers, and mineralocorticoid antagonists. Main Outcomes and Measures: The outcomes of interest were survival at 4 years and quality of life at 2 years based on Kansas City Cardiomyopathy Questionnaire scores and a 6-minute walk test. Results: A total of 12 144 patients in INTERMACS met inclusion criteria, of whom 2526 (20.8% ) were women, 8088 (66.6%) were white, 3024 (24.9%) were African American, and 753 (6.2%) were Hispanic; the mean (SD) age was 56.8 (12.9) years. Of these, 10 419 (85.8%) were receiving NHB. Those receiving any NHB medication at 6 months had a better survival rate at 4 years compared with patients not receiving NHB (56.0%; 95% CI, 54.5%-57.5% vs 43.9%; 95% CI, 40.5%-47.7%). After sensitivity analyses with an adjusted model, this trend persisted with patients receiving triple therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ß-blocker, and mineralocorticoid antagonist having the lowest hazard of death compared with patients in the other groups (hazard ratio, 0.34; 95% CI, 0.28-0.41). Compared with patients not receiving NHB, use of NHB was associated with a higher Kansas City Cardiomyopathy Questionnaire score (66.6; bootstrapped 95% CI, 65.8-67.3 vs 63.0; bootstrapped 95% CI, 60.1-65.8; P = .02) and a 6-minute walk test (1103 ft; bootstrapped 95% CI, 1084-1123 ft vs 987 ft; bootstrapped 95% CI, 913-1060 ft; P < .001). Conclusions and Relevance: Among patients with LVADs who tolerated NHB therapy, continued treatment was associated with improved survival and quality of life. The optimal heart failure regimen for patients after LVAD implant may be the initiation and continuation of guideline-directed medical therapy.

Clinical Implications of Respiratory Failure in Patients Receiving Durable Left Ventricular Assist Devices for End-Stage Heart Failure.

BACKGROUND: The impact of respiratory failure on patients undergoing left ventricular assist device (LVAD) implantation is not well understood, especially since these patients were excluded from landmark clinical trials. We sought to evaluate the associations between immediate preimplant and postimplant respiratory failure on outcomes in advanced heart failure patients undergoing LVAD implantation. METHODS AND RESULTS: We included all patients in the Interagency Registry for Mechanically Assisted Circulatory Support who were implanted with continuous-flow LVADs from 2008 to 2016. Of the 16 362 patients who underwent continuous-flow LVAD placement, 906 (5.5%) required preimplant intubation within 48 hours before implantation, and 1001 (6.1%) patients developed respiratory failure within 1 week after implantation. A higher proportion of patients requiring preimplant intubation were Interagency Registry for Mechanically Assisted Circulatory Support profile 1, required mechanical circulatory support, and presented with cardiac arrest or myocardial infarction (P<0.001, all). At 1 year, 54.3% of patients intubated preimplant were alive without transplant, 20.1% had been transplanted, and 24.2% died before transplant. Patients requiring preimplant intubation had higher rates of postimplant complications, including bleeding, stroke, and right ventricular assist device implantation (P<0.01 for all). Among Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients, preimplant intubation incurred additional risk of death at 1 year compared with Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients not intubated (hazard ratio, 1.37 [95% CI, 1.13-1.65]; P=0.001). After multivariable analysis, both preimplant intubation (hazard ratio, 1.20 [95% CI, 1.03-1.41]; P=0.021) and respiratory failure within 1 week (hazard ratio, 2.54 [95% CI, 2.26-2.85]; P<0.001) were associated with higher all-cause 1-year mortality. CONCLUSIONS: Respiratory failure both before and after LVAD implantation identifies an advanced heart failure population with significantly worse 1-year mortality. This data might be helpful in counseling patients and their families about expectations about life with an LVAD.

Clinical Outcomes After Left Ventricular Assist Device Implantation in Older Adults: An INTERMACS Analysis.

OBJECTIVES: The purpose of this study was to examine outcomes after left ventricular assist device (LVAD) implantation in older adults (>75 years of age). BACKGROUND: An aging heart failure population together with improvements in mechanical circulatory support (MCS) technology have led to increasing LVAD implantations in older adults. However, data presenting age-specific outcomes are limited. METHODS: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who required durable MCS between 2008 and 2017 were included. Patients were stratified by 4 age groups: <55 years of age, 55 to 64 years of age, and >75 years of age. Kaplan-Meier survival estimates were used to assess post-LVAD outcomes, with log-rank testing used to compare groups. Univariate and multivariate cox proportional hazard regression models were used to determine predictors of survival and complications. RESULTS: A total of 20,939 individuals received an LVAD during the study period: 7,743 (37.0%) were <55 years of age, 6,755 (32.3%) were 55 to 64 years of age, 5,418 (25.9%) were 65 to 74 years of age, and 1,023 (4.9%) were ≥75 years of age or older. After multivariate adjustment, adults ≥75 years of age had increased mortality post-LVAD implantation. Elderly patients with LVADs had a higher incidence of gastrointestinal bleeding but lower rates of device thrombosis. Compared to 84.5% of patients <55 years of age who were discharged home, only 46.8% of adults ≥75 years of age were discharged home following implantation (p < 0.001). Use of a RVAD, serum albumin level, and 6-min walk test distances were identified as predictors of outcomes in the oldest cohort. CONCLUSIONS: Despite careful selection of older adults for LVAD implantation, age remains a significant predictor of mortality. Higher bleeding and lower clotting risk in elderly patients with LVADs support the use of a less intense antithrombotic regimen in this unique population.

Early Outcomes After Mitral Valve Repair versus Replacement in the Elderly: A Propensity Matched Analysis.

BACKGROUND: To compare early outcomes of mitral valve repair versus replacement in elderly patients with degenerative mitral valve disease. METHODS: A retrospective review of prospectively collected clinical data of patients over 75 years of age, who underwent mitral valve surgery for degenerative disease, between 2010 and 2013, was carried out. Those undergoing mitral valve repair and replacement were propensity matched to adjust for baseline clinical differences. RESULTS: A total 260 patients were identified: mitral valve repair was undertaken in 145 and replacement in 115 patients. After propensity matching, 78 patients were included in each group. In the entire, unmatched population, in-hospital mortality was significantly higher in those undergoing replacement compared with those undergoing repair (9.6% vs 1.4%, p=0.003). In-hospital death occurred in six (7.7%) of the propensity matched replacement group and none in the repair group (p=0.012). Amongst the propensity matched groups, probability of survival at 1, 2 and 3 years were 0.94, 0.90 and 0.86 respectively for the repair group and 0.85, 0.77 and 0.69 for the replacement group: the HR for death between replacement and repair is 2.5 (1.2-5.4), p=0.012. CONCLUSIONS: Within the limitations imposed by retrospective analyses, our study demonstrates that, in elderly patients with degenerative disease of the mitral valve, repair is associated with improved short-term and mid-term outcomes compared with mitral valve replacement.

Lung donation after circulatory determined death: a single-centre experience.

OBJECTIVES: Donor organ utilization and shortage remain the major limitations to the opportunity of a lung transplantation (LTx). Donation after circulatory determined death (DCD) has been adopted as a source of additional organs worldwide. However, concerns about organ quality and ischaemia-reperfusion injury have limited its application. The aim of this study was to retrospectively analyse a single-centre experience in the DCD LTx and compare early and mid-term outcomes with those from a standard donation after brain death (DBD). METHODS: During the 6-year study period, 186 LTxs were performed: 147 bilateral LTxs (79%) and 39 single LTxs (21%). Of these, 23 recipients received organs retrieved from DCD donors (12.4%). RESULTS: No differences were found between the 2 groups of recipients except for age and cystic fibrosis as an underlying disease. No differences in terms of duration of mechanical ventilation, incidence of postoperative extracorporeal membrane oxygenation support, intensive care unit stay, hospital length of stay, airway anastomotic complications, incidence and grade of rejection and freedom from bronchiolitis obliterans syndrome were demonstrated. There was a non-statistically significant trend towards older age in the DCD group. Actuarial survival in the subgroup of bilateral LTx at 1 year and 5 years was 75% and 51% for the DCD group and 82% and 61% for the DBD group, respectively (P = 0.12). CONCLUSIONS: Short- and medium-term outcomes after the DCD LTx are comparable with those achieved after transplantation from the DBD donors, despite a tendency to use DCD lungs for older recipients. Therefore, the DCD LTx is a clinical option that can be used with favourable results to expand the lung donor pool.

Outcome after heart transplantation from donation after circulatory-determined death donors.

BACKGROUND: The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants. METHODS: DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation, whereas DPP hearts were removed directly. All hearts were maintained on machine perfusion during transportation. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics, was used as a comparison group. The primary outcome measure of this study (set by the United Kingdom regulatory body) was 90-day survival. RESULTS: There were 28 DCD heart transplants performed during the 25-month study period. Survival at 90 days was not significantly different between DCD and matched DBD transplant recipients (DCD, 92%; DBD, 96%; p = 1.0). Hospital length of stay, treated rejection episodes, allograft function, and 1-year survival (DCD, 86%; DBD, 88%; p = 0.98) were comparable between groups. The method of retrieval (NRP or DPP) was not associated with a difference in outcome. CONCLUSIONS: These results suggest that heart transplantation from DCD heart donation provides comparable short-term outcomes to traditional DBD heart transplants and can serve to increase heart transplant activity in well-selected patients.

Functional assessment and transplantation of the donor heart after circulatory death.

BACKGROUND: After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program. METHODS: Normothermic regional perfusion (NRP) was used to restore function to the arrested DCD heart within the donor after exclusion of the cerebral circulation. After weaning from support, DCD hearts underwent functional assessment with cardiac-output studies, echocardiography, and pressure-volume loops. In the feasibility phase, hearts were transported perfused before evaluation of function in modified working mode extracorporeally. After the establishment of a reliable assessment technique, hearts with demonstrable good function were then selected for clinical transplantation. RESULTS: NRP was instituted in 13 adult DCD donors, median age of 33 years (interquartile range [IQR], 28-38 years), after a median ischemic time from withdrawal to perfusion of 24 minutes (IQR, 21-29; range, 17-146 minutes). Two of 4 hearts in the feasibility phase were unsuitable for transplantation after functional assessment. Nine DCD hearts were transplanted in the clinical phase, with 100% survival. The median intensive care duration was 5 days (IQR, 4-5 days), with 2 patients requiring mechanical support. There were no episodes of rejection (total, 1,436 patient-days; range, 48-297). During the same period, we performed 20 standard heart transplants using brain-dead donors. CONCLUSIONS: NRP allows rapid reperfusion and functional assessment of the DCD donor heart, ensuring only viable hearts are selected for transplantation. This technique minimizes the risk of primary graft dysfunction and maximizes confidence in DCD heart transplantation, realizing a 45% increase in our heart transplant activity.

In Vivo Post-Cardiac Arrest Myocardial Dysfunction Is Supported by Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2.

BACKGROUND: Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. METHODS: We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement. In postarrest isolated cardiomyocytes, we assessed mechanical load and Ca(2) (+)-induced Ca(2+) release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel fiberoptic catheter imaging system and a genetically encoded calcium sensor, GCaMP6f, to image CICR in vivo. RESULTS: We found potentiation of CICR in isolated cells from this extracorporeal membrane oxygenation model and in cells isolated from an ischemia/reperfusion Langendorff model perfused with oxygenated blood from an arrested animal but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed after arrest was mediated by the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban, and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca(2+) potentiation but was associated with lesser CaMKII activation. Because oxidative stress and aldehydic adduct formation were high after arrest, we tested a small-molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and postarrest outcome in vivo. CONCLUSIONS: Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation, which support cardiomyocyte contractility in the face of impaired postarrest myofilament calcium sensitivity. Alda-1 mitigates these effects, normalizes calcium cycling, and improves outcome.

An efficient technique for higher order fractional differential equation.

In this study, we establish exact solutions of fractional Kawahara equation by using the idea of [Formula: see text]-expansion method. The results of different studies show that the method is very effective and can be used as an alternative for finding exact solutions of nonlinear evolution equations (NLEEs) in mathematical physics. The solitary wave solutions are expressed by the hyperbolic, trigonometric, exponential and rational functions. Graphical representations along with the numerical data reinforce the efficacy of the used procedure. The specified idea is very effective, expedient for fractional PDEs, and could be extended to other physical problems.

An isolated working heart system for large animal models.

Since its introduction in the late 19(th) century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease(1-15). Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals(1,3,11). One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes - a key component of any experiment utilizing this device(1,11). By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user's preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.

Impact of major bleeding on long-term mortality in anemic versus nonanemic patients undergoing percutaneous coronary intervention using bivalirudin.

Bleeding complications after percutaneous coronary intervention (PCI) have been associated with higher short and long-term mortality. Bivalirudin has been shown to reduce bleeding complications in patients who underwent PCI; however, the impact of anemia on bleeding complications and long-term mortality has not been studied. A total of 11,991 patients who underwent PCI over a period of 8 years with bivalirudin as the primary antithrombotic agent were included. Anemia was defined according to the World Health Organization definition. Bleeding complications were prospectively collected. Survival analysis was performed using multivariable Cox proportional hazards models. Of the 11,991 patients, 4,815 patients (40%) had baseline anemia. Major bleeding occurred in 3.3% of patients with anemia compared with 0.7% of patients without anemia (p <0.001) driven largely by transfusion events. In the overall study population, major bleeding was a significant predictor of mortality (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.04 to 1.8, p = 0.027) at a mean follow-up of 2.6 years (interquartile range 1.4 to 3.5). In patients with anemia, major bleeding remained an independent predictor of mortality (HR 1.5, 95% CI 1.1 to 2.0, p = 0.008); however, in patients without anemia, it did not (HR 1.25, 95% CI 0.52 to 3.03, p = 0.62). In patients who underwent PCI with bivalirudin therapy, major bleeding is associated with early and long-term mortality, which is more pronounced in patients with baseline anemia.

Rat model of veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: We aim to develop a rat model of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: VA-ECMO was established in twelve Male Sprague-Dawley rats (250-350 g) through cannulation of the right jugular vein for venous drainage and the right femoral artery for arterial reinfusion. Arterial blood pressure was measured using a conductance catheter through cannulation of the left carotid artery. Heart rate was monitored by electrocardiography and arterial blood gas parameters with a blood gas analyzer. The VA-ECMO circuit was tested by subjecting the rats to hypoxic cardiac arrest with resuscitation using VA-ECMO. Both load-dependent and load-independent measures of myocardial contractility were measured using pressure-volume loop analysis to confirm restoration of myocardial function post-resuscitation. RESULTS: Following hypoxic cardiac arrest VA-ECMO provided sufficient oxygenation to support the circulation. The haemodynamic and blood gas parameters were maintained at transition and during ECMO. All animals were resuscitated, regained cardiac function and were able to be weaned off ECMO post-resuscitation. CONCLUSION: We have established a safe, high-throughput, economical, functioning rat model of VA-ECMO.