Diverse Physiological Roles of Flavonoids in Plant Environmental Stress Responses and Tolerance.

Flavonoids are characterized as the low molecular weight polyphenolic compounds universally distributed in planta. They are a chemically varied group of secondary metabolites with a broad range of biological activity. The increasing amount of evidence has demonstrated the various physiological functions of flavonoids in stress response. In this paper, we provide a brief introduction to flavonoids' biochemistry and biosynthesis. Then, we review the recent findings on the alternation of flavonoid content under different stress conditions to come up with an overall picture of the mechanism of involvement of flavonoids in plants' response to various abiotic stresses. The participation of flavonoids in antioxidant systems, flavonoid-mediated response to different abiotic stresses, the involvement of flavonoids in stress signaling networks, and the physiological response of plants under stress conditions are discussed in this review. Moreover, molecular and genetic approaches to tailoring flavonoid biosynthesis and regulation under abiotic stress are addressed in this review.

Effect of Magnetopriming on Photosynthetic Performance of Plants.

Magnetopriming has emerged as a promising seed-priming method, improving seed vigor, plant performance and productivity under both normal and stressed conditions. Various recent reports have demonstrated that improved photosynthesis can lead to higher biomass accumulation and overall crop yield. The major focus of the present review is magnetopriming-based, improved growth parameters, which ultimately favor increased photosynthetic performance. The plants originating from magnetoprimed seeds showed increased plant height, leaf area, fresh weight, thick midrib and minor veins. Similarly, chlorophyll and carotenoid contents, efficiency of PSII, quantum yield of electron transport, stomatal conductance, and activities of carbonic anhydrase (CA), Rubisco and PEP-carboxylase enzymes are enhanced with magnetopriming of the seeds. In addition, a higher fluorescence yield at the J-I-P phase in polyphasic chlorophyll a fluorescence (OJIP) transient curves was observed in plants originating from magnetoprimed seeds. Here, we have presented an overview of available studies supporting the magnetopriming-based improvement of various parameters determining the photosynthetic performance of crop plants, which consequently increases crop yield. Additionally, we suggest the need for more in-depth molecular analysis in the future to shed light upon hidden regulatory mechanisms involved in magnetopriming-based, improved photosynthetic performance.

Effect of stent crimping on calcification of transcatheter aortic valves.

OBJECTIVES: Although many challenges related to the acute implantation of transcatheter aortic valves have been resolved, durability and early degeneration are currently the main concerns. Recent reports indicate the potential for early valve degeneration and calcification. However, only little is known about the underlying mechanisms behind the early degeneration of these valves. The goal of this study was to test whether stent crimping increases the risk for early calcification. METHODS: Stented valves that were crimped at 18-Fr and 14-Fr catheter and uncrimped controls were exposed to a standard calcifying solution for 50 million cycles in an accelerated wear test system. Subsequently, the leaflets of the valves were imaged by microcomputed tomography (micro-CT) followed by histochemical staining and microscopic analyses to quantify calcification and other changes in the leaflets' characteristics. RESULTS: Heavily calcified regions were found over the stent-crimped leaflets compared to uncrimped controls, particularly around the stent's struts. Micro-CT studies measured the total volume of calcification in the uncrimped valves as 77.31 ± 1.63 mm3 vs 95.32 ± 5.20 mm3 in 18-Fr and 110.01 ± 8.33 mm3 in 14-Fr stent-crimped valves, respectively. These results were congruent with the increase in leaflet thickness measured by CT scans (0.44 ± 0.07 mm in uncrimped valves vs 0.69 ± 0.15 mm and 0.75 ± 0.09 mm in 18-Fr and 14-Fr stent-crimped valves, respectively). Histological studies confirmed the micro-CT results, denoting that the percentage of calcification in uncrimped leaflets at the valve's posts was 5.34 ± 3.97 compared to 19.97 ± 6.18 and 27.64 ± 13.17 in the 18-Fr and 14-Fr stent-crimped leaflets, respectively. CONCLUSIONS: This study concludes that stent-crimping damage is associated with a higher level of passive leaflet calcification, which may contribute to early valve degeneration.

Transcatheter and Surgical Management of Mitral Paravalvular Leak: Long-Term Outcomes.

OBJECTIVES: The aim of this study was to report the use trends and immediate and long-term outcomes of a large cohort of patients who underwent redo surgery or transcatheter repair of paravalvular leaks (PVLs) at a tertiary referral center. BACKGROUND: Percutaneous treatment of mitral PVL has emerged as an alternative to surgical treatment in high-risk surgical candidates. There are limited data on the utilization trends, safety, and efficacy of both procedures in the management of mitral PVL. METHODS: Patients who underwent treatment of mitral PVL at the Mayo Clinic between January 1995 and December 2015 were enrolled. Utilization trends, procedural details, technical success, and in-hospital and long-term outcomes were assessed. RESULTS: Three hundred eighty-one patients underwent percutaneous (n = 195) or surgical (n = 186) treatment of mitral PVLs. The mean age was 66 ± 12 years, and 37% of patients had bioprosthetic valves. Technical success was higher in the surgical group (95.5% vs. 70.1%; p < 0.001). In-hospital major adverse events were more common after surgery (22.5% vs. 7.7%; p < 0.001). In-hospital death occurred in 3.1% and 8.6% of patients undergoing percutaneous and surgical treatment, respectively (p = 0.027). However, in a multivariate logistic regression analysis, only active endocarditis, chronic renal failure, and severe mitral annular calcifications were significant predictors of in-hospital mortality. Reintervention rates were similar (11.3% vs. 17.2% in the percutaneous and surgical groups, respectively; p = 0.10), with the majority of reinterventions in the percutaneous group occurring early because of residual leak or persistent hemolysis. After risk adjustment, there was no significant difference in long-term survival between patients who underwent surgical versus transcatheter treatment of PVLs. CONCLUSIONS: In contemporary practice, patients with symptomatic mitral PVLs are best treated with an integrated team approach incorporating both surgical and percutaneous techniques. Patient selection and timing of intervention are critical to achieve optimal results.

Characteristics and outcomes of re-do percutaneous paravalvular leak closure.

BACKGROUND: Percutaneous paravalvular leak (PVL) closure is an alternative treatment option for severely symptomatic, high-surgical risk patients with PVL. Some patients require multiple percutaneous PVL closure procedures. However, the procedural characteristics and success rate of re-do PVL closure have not been well studied. AIMS: The aim of this study is to investigate the indications, procedural characteristics, technical success rate, and 30-day major adverse cardiovascular events (MACE) in patients who underwent re-do PVL closure. METHODS: Consecutive patients who underwent percutaneous paramitral or paraaortic leak closure at Mayo Clinic, Rochester, Minnesota from 2004 through 2015 were studied. Clinical and procedural characteristics of patients who underwent re-do PVL closure were compared to age- and sex-matched patients who underwent their first percutaneous PVL closure. Procedure success and 30-day MACE were compared in both the groups. RESULTS: Among 223 identified percutaneous PVL closures, 16 (7%) were re-do procedures. Patients who underwent re-do PVL closure were predominantly men (87.5%) with a mean age of 68 ± 15 years and an estimated mean Society of Thoracic Surgery (STS) 30-day mortality of 4.6 ± 2.8. Half of the re-do PVL closures were performed on mechanical valves and 62.5% were performed on paramitral defects. Indications for re-do PVL closure were: (1) emergence of new significant paravalvular defects in 50%, (2) incomplete index defect closure in 43.75%, and (3) index procedural complication in 6.25% of the cases. Procedural success was 75% in re-do procedures vs. 85.4% in age- and sex-matched control group (P = 0.45). Thirty-day MACE was 12.5% in the re-do group compared to 4.2% in the age- and-sex matched patients who underwent PVL closure for the first time (P = 0.35). CONCLUSION: Re-do percutaneous PVL closure is feasible with favorable procedural success rate and low 30-day MACE. Development of new paravalvular defects is the most common indication for re-do PVL closure, highlighting the importance of careful longitudinal monitoring and follow-up. © 2017 Wiley Periodicals, Inc.

Techniques and Outcomes of Percutaneous Aortic Paravalvular Leak Closure.

OBJECTIVES: The aim of this study is to provide a summary of the currently applied aortic paravalvular leak (PVL) closure techniques and describe the procedural and long-term outcomes in a large consecutive cohort of patients. BACKGROUND: Percutaneous repair has emerged as an effective therapy for patients with PVL. To date, clinical outcome data on percutaneous closure of aortic PVL are limited. METHODS: All patients who underwent catheter-based treatment of aortic PVL between 2006 and 2015 were identified. Procedural and short-term results were assessed. Patients were contacted for clinical events and symptoms. RESULTS: Eighty-six procedures were performed in 80 patients. The mean age was 68 ± 15 years, and 70% were men. The primary indications for PVL closure were symptoms of heart failure, hemolysis, and both in 83%, 5%, and 12%, respectively. Successful device deployment was accomplished in 94 defects (90%). Reduction in PVL to mild or less was achieved in 62% of patients. In-hospital major adverse events occurred in 8% of procedures. Symptomatic improvement at 30 days was achieved in 64% of patients. Patients who had reduction in the PVL grade to mild or less experienced more improvement in New York Heart Association functional class (from 2.93 ± 0.62 to 1.72 ± 0.73) compared with those with mild or greater residual leak (from 3.03 ± 0.57 to 2.52 ± 0.74) (p < 0.001). In patients with severe hemolysis (n = 8), transfusion requirements were eliminated in 7 (88%) after PVL closure. Kaplan-Meier survival analysis showed that the cumulative probability of freedom from repeat surgery at 2 years was 98 ± 2% in patients who had mild or less residual leak compared with 68 ± 10% in patients with higher grades of residual PVL (log-rank p = 0.004). CONCLUSIONS: Percutaneous reduction of aortic PVL is associated with durable symptom relief and lower rates of repeat cardiac surgery. The magnitude of benefit is greatest with PVL reduction to a grade of mild or less. Therefore, attempts should be made to reduce PVL as much as possible.

Percutaneous intervention for mitral regurgitation.

Percutaneous treatment of mitral regurgitation (MR) is a promising alternative for patients with functional MR (FMR) who are not appropriate for surgery and are not responding to optimal medical therapy and cardiac resynchronization therapy. Unlike degenerative MR, where repair therapy is clearly preferred, the optimal approach for FMR has not been defined. Challenges for novel mitral repair devices are to demonstrate safety and superior efficacy to medical management in higher risk patients. Transcatheter mitral valve replacement is emerging as a feasible therapy, but requires significant additional clinical trials to define its place in treating heart failure related to MR.

Safety and efficacy of the MitraClip® system for severe mitral regurgitation: a systematic review.

BACKGROUND: The MitraClip® system is a newer percutaneous device that has shown promising results but data on its safety and efficacy in low- and high-surgical risk populations continues to evolve. We performed a systematic review of the published studies reporting the safety and efficacy of MitraClip® implantation for treatment of moderate to severe and severe mitral regurgitation (MR). METHODS: Reviewers independently searched for relevant articles in Medline and abstracted clinical information based on pre-defined criteria and end-points. Patients were classified as low- or high-surgical risk for conventional mitral valve (MV) surgery based on Society of Thoracic Surgeons score, EuroSCORE, or surgeon discretion. Primary safety outcome was 30-day mortality and primary efficacy outcomes were freedom from death, ≥3+ MR, and requirement for MV surgery during follow-up. RESULTS: Immediate and long-term outcomes of 16 studies, including 2980 patients (age 73.7 ± 0.6 years; 63.3% males) receiving the MitraClip®, were analyzed. Acute procedural success rate was 91.4% with a procedural mortality of 0.1%. Mortality at 30 days and long-term (310 days) follow-up was 4.2 and 15.8%, respectively and was significantly higher in the high-risk group (P = 0.003 and 0.019, respectively). Incidence of major procedural adverse outcomes was relatively low with blood transfusion accounting for most events. At follow-up, the number of patients with ≥3+ MR reduced from 96.3% to 14.7% (P < 0.001), and those with NYHA class III/IV reduced from 83.2% to 23.4% (P < 0.001). CONCLUSION: MitraClip® implantation for moderate to severe or severe MR appears to be safe with a very low procedural mortality. There is significant improvement in functional outcomes although long-term mortality is high, especially in high surgical risk patients.

Ischemic post-conditioning and vasodilator therapy during standard cardiopulmonary resuscitation to reduce cardiac and brain injury after prolonged untreated ventricular fibrillation.

AIM OF THE STUDY: We investigated the effects of ischemic postconditioning (IPC) with and without cardioprotective vasodilatory therapy (CVT) at the initiation of cardiopulmonary resuscitation (CPR) on cardio-cerebral function and 48-h survival. METHODS: Prospective randomized animal study. Following 15 min of ventricular fibrillation, 42 Yorkshire farm pigs weighing an average of 34 ± 2 kg were randomized to receive standard CPR (SCPR, n=12), SCPR+IPC (n=10), SCPR+IPC+CVT (n=10), or SCPR+CVT (n=10). IPC was delivered during the first 3 min of CPR with 4 cycles of 20s of chest compressions followed by 20-s pauses. CVT consisted of intravenous sodium nitroprusside (2mg) and adenosine (24 mg) during the first minute of CPR. Epinephrine was given in all groups per standard protocol. A transthoracic echocardiogram was obtained on all survivors 1 and 4h post-ROSC. The brains were extracted after euthanasia at least 24h later to assess ischemic injury in 7 regions. Ischemic injury was graded on a 0-4 scale with (0=no injury to 4 ≥ 50% neural injury). The sum of the regional scores was reported as cerebral histological score (CHS). 48 h survival was reported. RESULTS: Post-resuscitation left ventricular ejection (LVEF) fraction improved in SCPR+CVT, SCPR+IPC+CVT and SCPR+IPC groups compared to SCPR (59% ± 9%, 52% ± 14%, 52% ± 14% vs. 35% ± 11%, respectively, p<0.05). Only SCPR+IPC and SCPR+IPC+CVT, but not SCPR+CVT, had lower mean CHS compared to SCPR (5.8 ± 2.6, 2.8 ± 1.8 vs. 10 ± 2.1, respectively, p<0.01). The 48-h survival among SCPR+IPC, SCPR+CVT, SCPR+IPC+CVT and SCPR was 6/10, 3/10, 5/10 and 1/12, respectively (Cox regression p<0.01). CONCLUSIONS: IPC and CVT during standard CPR improved post-resuscitation LVEF but only IPC was independently neuroprotective and improved 48-h survival after 15 min of untreated cardiac arrest in pigs.

Impaired contractile recovery after low-flow myocardial ischemia in a porcine model of metabolic syndrome.

Clinical metabolic syndrome conveys a poor prognosis in patients with acute coronary syndrome, not fully accounted for by the extent of coronary atherosclerosis. To explain this observation, we determined whether postischemic myocardial contractile and metabolic function are impaired in a porcine dietary model of metabolic syndrome without atherosclerosis. Micropigs (n = 28) were assigned to a control diet (low fat, no added sugars) or an intervention diet (high saturated fat and simple sugars, no added cholesterol) for 7 mo. The intervention diet produced obesity, hypertension, dyslipidemia, and impaired glucose tolerance, but not atherosclerosis. Under open-chest, anesthetized conditions, pigs underwent 45 min of low-flow myocardial ischemia and 120 min of reperfusion. In both diet groups, contractile function was similar at baseline and declined similarly during ischemia. However, after 120 min of reperfusion, regional work recovered to 21 ± 12% of baseline in metabolic syndrome pigs compared with 61 ± 13% in control pigs (P = 0.01). Ischemia-reperfusion caused a progressive decline in mechanical/metabolic efficiency (regional work/O2 consumption) in metabolic syndrome hearts, but not in control hearts. Metabolic syndrome hearts demonstrated altered fatty acyl composition of cardiolipin and increased Akt phosphorylation in both ischemic and nonischemic regions, suggesting tonic activation. Metabolic syndrome hearts used more fatty acid than control hearts (P = 0.03). When fatty acid availability was restricted by prior insulin exposure, differences between groups in postischemic contractile recovery and mechanical/metabolic efficiency were eliminated. In conclusion, pigs with characteristics of metabolic syndrome demonstrate impaired contractile and metabolic recovery after low-flow myocardial ischemia. Contributory mechanisms may include remodeling of cardiolipin, abnormal activation of Akt, and excessive utilization of fatty acid substrates.

Cardiorenal syndrome in acute heart failure syndromes.

Impaired cardiac function leads to activation of the neurohumoral axis, sodium and water retention, congestion and ultimately impaired kidney function. This sequence of events has been termed the Cardiorenal Syndrome. This is different from the increase in cardiovascular complications which occur with primary kidney disease, that is, the so-called Renocardiac Syndrome. The present review discusses the pathogenesis of the Cardiorenal Syndrome followed by the benefits and potential deleterious effects of pharmacological agents that have been used in this setting. The agents discussed are diuretics, aquaretics, natriuretic peptides, vasodilators, inotropes and adenosine α1 receptor antagonists. The potential role of ultrafiltration is also briefly discussed.

A case of tuberous sclerosis complex that progressed to end-stage renal disease.

BACKGROUND: A 31-year-old woman with tuberous sclerosis complex presented with a 1 week history of subjective fever, chills, rigors, poor appetite and dizziness. INVESTIGATIONS: Physical examination, urine and blood analysis, CT of the abdomen, chest and brain, and chest X-ray. DIAGNOSIS: End-stage renal disease, septic shock and urinary tract infection secondary to huge bilateral angiomyolipomas of the kidney associated with tuberous sclerosis complex. MANAGEMENT: Antibiotic therapy, vasopressor treatment and bilateral nephrectomy, followed by hemodialysis while awaiting renal transplantation.