[Patients with a wearable cardioverter-defibrillator (WCD) : Prescription, function and rehabilitation support]. / Patienten mit einer tragbaren Defibrillatorweste ("wearable cardioverter-defibrillator", WCD) : Verschreibung, Wirkweise und Nachsorge.

Assessment of a permanent risk of life-threatening ventricular arrhythmia in patients with severely reduced left ventricular ejection fraction (LVEF <35%), e. g. after myocarditis, dilated cardiomyopathy, acute myocardial infarction, in patients with postpartum cardiomyopathy or implantable cardioverter-defibrillator (ICD) and cardiac resynchronization treatment plus defibrillator (CRT-D) infection with temporary explantation of the system is a medical challenge. This is time-consuming and unsafe because life-threatening ventricular arrhythmias may occur during the time of risk assessment. During this phase of risk stratification, a wearable cardioverter-defibrillator (WCD) is indicated. The WCD, which is usually worn by the patient for several months, combines continuous retrievable electrocardiogram (ECG) recordings with a reliable defibrillation capability. The prescription of a WCD guarantees safe rehabilitation procedures for patients following acute inpatient treatment. Rehabilitation measures in patients with a WCD are indicated because of the underlying systolic cardiac insufficiency due to severe myocardial disease. In almost half of the patients, who are potentially threatened by ventricular tachyarrhythmias or sudden cardiac death (SCD), the LVEF and heart failure symptoms improve under controlled medication within a few months. Thus, the risk of SCD is lowered so that in many cases a first line ICD implantation is no longer necessary. The purpose of this article is to provide recommendations for rehabilitation procedures of patients with a WCD. A review of the currently available data on WCD publications was carried out with special emphasis on the current national and international guidelines.

Autophagy supports generation of cells with high CD44 expression via modulation of oxidative stress and Parkin-mediated mitochondrial clearance.

High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44Low-CD24High (CD44L) cells give rise to CD44High-CD24-/Low (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-ß. We couple patient samples and xenotransplantation studies with this tractable in vitro system of CD44L to CD44H cell conversion to investigate the functional role of autophagy in generation of cells with high CD44 expression. We report that high expression of the autophagy marker cleaved LC3 expression correlates with poor clinical outcome in ESCC. In ESCC xenograft tumours, pharmacological autophagy inhibition with chloroquine derivatives depletes cells with high CD44 expression while promoting oxidative stress. Autophagic flux impairment during EMT-mediated CD44L to CD44H cell conversion in vitro induces mitochondrial dysfunction, oxidative stress and cell death. During CD44H cell generation, transformed keratinocytes display evidence of mitophagy, including mitochondrial fragmentation, decreased mitochondrial content and mitochondrial translocation of Parkin, essential in mitophagy. RNA interference-mediated Parkin depletion attenuates CD44H cell generation. These data suggest that autophagy facilitates EMT-mediated CD44H generation via modulation of redox homeostasis and Parkin-dependent mitochondrial clearance. This is the first report to implicate mitophagy in regulation of tumour cells with high CD44 expression, representing a potential novel therapeutic avenue in cancers where EMT and CD44H cells have been implicated, including ESCC.

[Aftercare of patients after MitraClip® implantation]. / Die Nachsorge von Patienten nach MitraClip®-Implantation.

Many patients with moderate to severe mitral regurgitation cannot be subjected to surgical therapy due to their multimorbidity. For these patients, MitraClip® implantation is a therapeutic alternative.The aim of this article is to present recommendations for treatment after a MitraClip® procedure. For this purpose, a selective literature review has been carried out based on the current literature, notably on national and international guidelines.After a MitraClip® procedure, rehabilitation is indicated because of the underlying heart failure as well as the treatment of a heart valve. Here, optimization of drug therapy, implementation of standardized heart failure training, the initiation of strength and endurance training and psychosocial support are initiated. Patients will be briefed on endocarditis prophylaxis lasting for at least six months. Furthermore, according to current guidelines, treatment with ACE inhibitors, beta-blockers and aldosterone antagonists are optimized. A special feature is anticoagulation, which is currently empirically accounted for and performed in sinus rhythm typically for four weeks of dual antiplatelet therapy (aspirin and clopidogrel) followed by a monotherapy with aspirin. In atrial fibrillation, lifelong oral anticoagulation is indicated combined with a platelet aggregation inhibitor for four weeks.In particular, echocardiographic control in the rehabilitation clinic and by cardiologists has to be focused on a residual atrial septal defect, the transmitral gradient and a residual mitral regurgitation.

Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming.

Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of the electron transport chain component cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage-dependent growth and acquired invasive phenotypes. Disruption of the CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling includes activation of PI3-kinase, IGF1R and Akt, Ca2(+)-sensitive transcription factors and also TGFß1, MMP16 and periostin, which are involved in oncogenic progression. Whole-genome expression analysis showed the upregulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mitochondrial DNA depletion, although distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be the hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in the CcO complex can potentially induce tumor progression.

Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression.

Epithelial-mesenchymal transition (EMT) promotes cancer cell invasion, metastasis and treatment failure. EMT may be activated in cancer cells by reactive oxygen species (ROS). EMT may promote conversion of a subset of cancer cells from a CD44(low)-CD24(high) (CD44L) epithelial phenotype to a CD44(high)-CD24(-/low) (CD44H) mesenchymal phenotype, the latter associated with increased malignant properties of cancer cells. ROS are required for cells undergoing EMT, although excessive ROS may induce cell death or senescence; however, little is known as to how cellular antioxidant capabilities may be regulated during EMT. Mitochondrial superoxide dismutase 2 (SOD2) is frequently overexpressed in oral and esophageal cancers. Here, we investigate mechanisms of SOD2 transcriptional regulation in EMT, as well as the functional role of this antioxidant in EMT. Using well-characterized genetically engineered oral and esophageal human epithelial cell lines coupled with RNA interference and flow cytometric approaches, we find that transforming growth factor (TGF)-ß stimulates EMT, resulting in conversion of CD44L to CD44H cells, the latter of which display SOD2 upregulation. SOD2 induction in transformed keratinocytes was concurrent with suppression of TGF-ß-mediated induction of both ROS and senescence. SOD2 gene expression appeared to be transcriptionally regulated by NF-κB and ZEB2, but not ZEB1. Moreover, SOD2-mediated antioxidant activity may restrict conversion of CD44L cells to CD44H cells at the early stages of EMT. These data provide novel mechanistic insights into the dynamic expression of SOD2 during EMT. In addition, we delineate a functional role for SOD2 in EMT via the influence of this antioxidant upon distinct CD44L and CD44H subsets of cancer cells that have been implicated in oral and esophageal tumor biology.

Mitochondrial retrograde signaling induces epithelial-mesenchymal transition and generates breast cancer stem cells.

Metastatic breast tumors undergo epithelial-to-mesenchymal transition (EMT), which renders them resistant to therapies targeted to the primary cancers. The mechanistic link between mtDNA (mitochondrial DNA) reduction, often seen in breast cancer patients, and EMT is unknown. We demonstrate that reducing mtDNA content in human mammary epithelial cells (hMECs) activates Calcineurin (Cn)-dependent mitochondrial retrograde signaling pathway, which induces EMT-like reprogramming to fibroblastic morphology, loss of cell polarity, contact inhibition and acquired migratory and invasive phenotype. Notably, mtDNA reduction generates breast cancer stem cells. In addition to retrograde signaling markers, there is an induction of mesenchymal genes but loss of epithelial markers in these cells. The changes are reversed by either restoring the mtDNA content or knockdown of CnAα mRNA, indicating the causal role of retrograde signaling in EMT. Our results point to a new therapeutic strategy for metastatic breast cancers targeted to the mitochondrial retrograde signaling pathway for abrogating EMT and attenuating cancer stem cells, which evade conventional therapies. We report a novel regulatory mechanism by which low mtDNA content generates EMT and cancer stem cells in hMECs.

MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is activated in cancer cells by ZEB1, a member of the zinc finger/homeodomain family of transcriptional repressors. The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in human carcinoma cells. The present studies in breast cancer cells demonstrate that the oncogenic MUC1-C subunit induces expression of ZEB1 by a NF-κB (nuclear factor kappa B) p65-dependent mechanism. MUC1-C occupies the ZEB1 promoter with NF-κB p65 and thereby promotes ZEB1 transcription. In turn, ZEB1 associates with MUC1-C and the ZEB1/MUC1-C complex contributes to the transcriptional suppression of miR-200c, an inducer of epithelial differentiation. The co-ordinate upregulation of ZEB1 and suppression of miR-200c has been linked to the induction of EMT. In concert with the effects of MUC1-C on ZEB1 and miR-200c, we show that MUC1-C induces EMT and cellular invasion by a ZEB1-mediated mechanism. These findings indicate that (i) MUC1-C activates ZEB1 and suppresses miR-200c with the induction of EMT and (ii) targeting MUC1-C could be an effective approach for the treatment of breast and possibly other types of cancers that develop EMT properties.

Caspase 2-mediated tumor suppression involves survivin gene silencing.

One of the pivotal functions of endogenous tumor suppression is to oppose aberrant cell survival, but the molecular requirements of this process are not completely understood. Here, we show that caspase 2, a death effector with largely unknown functions, represses transcription of the survivin gene, a general regulator of cell division and cytoprotection in tumors. This pathway involves caspase 2 proteolytic cleavage of the nuclear factor kappaB (NFkappaB) activator, RIP1. In turn, loss of RIP1 abolishes transcription of NFkappaB target genes, including survivin, resulting in deregulated mitotic transitions, enhanced apoptosis and suppression of tumorigenicity in vivo. Therefore, caspase 2 functions as an endogenous inhibitor of NFkappaB-dependent cell survival and this mechanism may contribute to tumor suppression in humans.

Physical properties of acetylated and enzyme-modified potato and sweet potato flours.

Textural profile, pasting behavior, gelatinization characteristics, sedimentation volume, and gel consistency of acetylated (Ac) and enzyme (glucoamylase)-modified (EM) potato and sweet potato flours have been investigated to determine their suitability in products such as baked goods, soup, and pudding. Dough hardness of Ac and EM samples was significantly higher than their native samples (P < 0.01). Dough cohesiveness of modified potato did not change, while it decreased in modified sweet potato. With increase in moisture, textural properties of modified samples, in general, showed reduced values. Rapid Visco Analyser showed least pasting viscosities of Ac flours due to restricted swelling of starch granules while EM flours exhibited high viscosities. Acetylated samples showed reduced gelatinization temperature (GT), and enthalpy (DeltaH) compared to native samples, whereas enzyme-treated samples showed no significant changes in GT, indicating their comparable crystallinity values with those of native samples. Modified flour samples had lower sediment volumes and gel consistency, and the gel consistency of EM flour correlated with its cold paste viscosity.

Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression.

Lipopolysaccharide (LPS) induces human monocytes to express many proinflammatory mediators, including the procoagulant molecule tissue factor (TF) and the cytokine tumor necrosis factor alpha (TNF-alpha). The TF and TNF-alpha genes are regulated by various transcription factors, including nuclear factor (NF)-kappaB/Rel proteins and Egr-1. In this study, the role of the MEK-ERK1/2 mitogen-activated protein kinase (MAPK) pathway in LPS induction of TF and TNF-alpha gene expression in human monocytic cells was investigated. The MAPK kinase (MEK)1 inhibitor PD98059 reduced LPS induction of TF and TNF-alpha expression in a dose-dependent manner. PD98059 did not affect LPS-induced nuclear translocation of NF-kappaB/Rel proteins and minimally affected LPS induction of kappaB-dependent transcription. In contrast, PD98059 and dominant-negative mutants of the Ras-Raf1-MEK-ERK (extacellular signal-regulated kinase) pathway strongly inhibited LPS induction of Egr-1 expression. In kinetic experiments LPS induction of Egr-1 expression preceded induction of TF expression. In addition, mutation of the Egr-1 sites in the TF and TNF-alpha promoters reduced expression of these proinflammatory genes. It was demonstrated that LPS induction of the Egr-1 promoter was mediated by 3 SRE sites, which bound an LPS-inducible complex containing serum response factor and Elk-1. LPS stimulation transiently induced phosphorylation of Elk-1 and increased the functional activity of a GAL4-Elk-1TA chimeric protein via the MEK-ERK1/2 pathway. The data indicate that LPS induction of Egr-1 gene expression is required for maximal induction of the TNF-alpha and TF genes in human monocytic cells.

LPS induction of gene expression in human monocytes.

Lipopolysaccharide (LPS [endotoxin]) is the principal component of the outer membrane of Gram-negative bacteria. Recent studies have elucidated how LPS is recognized by monocytes and macrophages of the innate immune system. Human monocytes are exquisitely sensitive to LPS and respond by expressing many inflammatory cytokines. LPS binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14. Next, LPS is transferred to the transmembrane signaling receptor toll-like receptor 4 (TLR4) and its accessory protein MD2. LPS stimulation of human monocytes activates several intracellular signaling pathways that include the IkappaB kinase (IKK)-NF-kappaB pathway and three mitogen-activated protein kinase (MAPK) pathways: extracellular signal-regulated kinases (ERK) 1 and 2, c-Jun N-terminal kinase (JNK) and p38. These signaling pathways in turn activate a variety of transcription factors that include NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun), which coordinate the induction of many genes encoding inflammatory mediators.

Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways.

Increased oxidative stress has been reported in vivo in the diabetic state via the production of reactive oxygen species (ROS). Such stress is bound to play a key role on activation of circulating monocytes, leading to the accelerated atherosclerosis observed in diabetics. However the exact molecular mechanisms of monocyte activation by high glucose is currently unclear. Here, we demonstrate that chronic high glucose (CHG) causes a dramatic increase in the release of the inflammatory cytokine tumor necrosis factor alpha (TNFalpha), at least in part through enhanced TNFalpha mRNA transcription, mediated by ROS via activation of transcription factors nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1). TNFalpha accumulation in the conditioned media was increased 10-fold and mRNA levels were increased 11.5-fold by CHG. The following observations supported that both NF-kappaB and AP-1 mediated enhanced TNFalpha transcription by CHG: 1) A 295-base pair fragment of the proximal TNFalpha promoter containing NF-kappaB and AP-1 sites reproduced the effects of CHG on TNFalpha transcription in a luciferase reporter assay, 2) mutational analyses of both NF-kappaB and the AP-1 sites abrogated 90% of the luciferase activity, 3) gel-shift analysis using the binding sites showed activation of NF-kappaB and AP-1 in CHG nuclear extracts, and 4) Western blot analyses demonstrated elevated nuclear levels of p65 and p50 and decreased cytosolic levels of IkappaBalpha in CHG-treated monocytes. That ROS acted as a key intermediate in the CHG pathway was supported by the following evidence: 1) increased superoxide levels similar to those observed with PMA or TNFalpha, 2) increased phosphorylation of stress-responsive mitogen-activated protein kinases p38 and JNK-1, 3) counteraction of the effects of CHG on TNFalpha production, the 295TNFluc reporter activity, activation of NF-kappaB, and repression of IkappaBalpha by antioxidants and p38 mitogen-activated protein kinase inhibitors. The study suggests that ROS function as key components in the regulatory pathway progressing from elevated glucose to monocyte activation.

Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.

Mammalian Toll-like receptors (TLRs) are expressed on innate immune cells and respond to the membrane components of Gram-positive or Gram-negative bacteria. When activated, they convey signals to transcription factors that orchestrate the inflammatory response. However, the intracellular signaling events following TLR activation are largely unknown. Here we show that TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2. Dominant-negative Rac1N17, but not dominant-negative Cdc42N17, block nuclear factor-kappa B (NF-kappa B) transactivation. S. aureus stimulation causes the recruitment of active Rac1 and phosphatidylinositol-3 kinase (PI3K) to the TLR2 cytosolic domain. Tyrosine phosphorylation of TLR2 is required for assembly of a multiprotein complex that is necessary for subsequent NF-kappa B transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of I kappa B alpha degradation. Thus Rac1 controls a second, I kappa B-independent, pathway to NF-kappa B activation and is essential in innate immune cell signaling via TLR2.

Transduction of primitive human marrow and cord blood-derived hematopoietic progenitor cells with adeno-associated virus vectors.

We evaluated the capacity of adeno-associated virus (AAV) vectors to transduce primitive human myeloid progenitor cells derived from marrow and cord blood in long-term cultures and long-term culture-initiating cell (LTC-IC) assays. Single-colony analyses showed that AAV vectors transduced CD34(+) and CD34(+)38(-) clonogenic cells in long-term culture. Gene transfer was readily observed in LTC-ICs derived from 5-, 8-, and 10-week cultures. Recombinant AAV (rAAV) transduction was observed in every donor analyzed, although a wide range of gene transfer frequencies (5% to 100%) was noted. AAV transduction of LTC-ICs was stable, with week-8 and -10 LTC-ICs showing comparable or better transduction relative to week-5 LTC-ICs. Fluorescence in situ hybridization (FISH) analyses performed to determine the fate of AAV vectors in transduced cells showed that 9% to 28% of CD34(+) and CD34(+)38(-) cells showed stable vector integration as evidenced by chromosome-associated signals in metaphase spreads. Comparisons of interphase and metaphase FISH suggested that a fraction of cells also contained episomal vector at early time points after transduction. Despite the apparent loss of the episomal forms with continued culture, the number of metaphases containing integrated vector genomes remained stable long term. Transgene transcription and placental alkaline phosphatase (PLAP) expression was observed in CD34(+), CD34(+)38(-) LTC-ICs in the absence of selective pressure. These results suggest that primitive myeloid progenitors are amenable to genetic modification with AAV vectors.

The experience of hospitalization and restraint of women who have a history of childhood sexual abuse.

Within psychiatric settings, many female clients report experiences of childhood sexual abuse (CSA). In this paper we explore the experience of 10 women who were hospitalized in psychiatric settings, restrained, and given forced medication (FM). All the women have histories that included CSA. Some authors have suggested that the experience of psychiatric hospitalization may represent an event that reenacts the experience of trauma. The results suggest that from the perspective of these women, the experience of restraint engendered traumatic emotional reactions such as fear, anxiety, and rage, and in no way was viewed as therapeutic even years later. Women felt powerless and unheard. The women wanted nurses who were empathic and responsive to their human needs as clients, but they felt nurses did not want to hear about the abuse or their internal distress. We hope that the perspective of these women will help in the consideration of alternatives and modifications to the use of restraint in psychiatric settings.

The experience of thought-disordered individuals preceding an aggressive incident.

The purpose of this qualitative study was to increase the understanding of the experiences of individuals with thought disorders, which precede incidents of aggression. Twelve individuals, from two hospitals, who had a nursing diagnosis of thought disorder and a history of aggression were interviewed, between one and four times, to collect baseline information and information about particular aggressive incidents. The participants described in their own words their thoughts, feelings and experiences preceding the aggressive incidents. Three themes emerged. First, participants perceived themselves to be strongly affected by the external environment; their responses to aspects of the environment were influential in precipitating the aggressive incident. Second, participants perceived themselves, paradoxically, to be both powerful and powerless; the act of aggression becomes an incident of brief self-empowerment. Third, the aggressive incident occurred in spite of the participants' acknowledgement and previous use of anger-controlling strategies; the participants' perceptions of themselves as powerless in an oppressive environment may have mitigated against the success of these strategies. Nurses need to know what triggers aggressiveness in psychiatric patients, in order to intervene effectively. Mental health professionals must also reexamine the psychiatric hospital environment, to make sure they are not needlessly exacerbating their patients' powerlessness with policies that are unjustifiably controlling.

Time course of lung function and exercise performance after heart transplantation.

To study the time course of exercise performance and the diffusion capacity after heart transplantation, we submitted two groups of patients to graded symptom-limited supine exercise. Patients in group 1 (n = 11) underwent operation 12.9 +/- 7.0 months before the study; those in group 2 (n = 10) underwent operation 53.9 +/- 14.8 months before the study. Respiratory and cardiovascular parameters were evaluated noninvasively at rest, at individual peak exercise, and 10 minutes later with a commercially available Sensormedics MMC 4400 metabolic measurement chart. Short-term survivors exhibited a lower maximum work capacity compared with that of long-term survivors (63.6 +/- 25.9 versus 100 +/- 50 W, p < 0.05), with a concomitant lower terminal heart rate (123 +/- 19 versus 137 +/- 17 beats/min, p < 0.05) that accounts for the lower cardiac output in this group, but statistical significance was not achieved (13.0 +/- 4.6 versus 17.5 +/- 6.3 L/min, not significant). Interestingly, significant differences were also observed for diffusion capacity before exercise (11.9 +/- 4.8 versus 19.3 +/- 7.3 ml/min/mm Hg, p < 0.05). The improvement of the diffusion capacity may be associated with a time-dependent change in the diffusion characteristics of the alveolocapillary membrane.

Time course of dimension and function of the autologous pulmonary root in the aortic position.

Although the autologous, fully vital, and compatible pulmonary root theoretically offers the prospect of an ideal aortic valve substitute, this type of replacement is performed in only a few centers. Major concern relates to the fate of root dimension and function in the systemic circulation and is largely unknown. To investigate the fate of the aortic root, we conducted echocardiographic examinations of eight freestanding pulmonary roots used for aortic valve replacement in adults. The studies were performed at discharge from the hospital and up to 21 months (mean 12.5 +/- 6.6 months) after the operation, as well as in 26 matched control subjects. There were no significant differences between the first and second postoperative studies regarding the root diameter (mean 26.6 +/- 2.1 mm and 27.6 +/- 2.6 mm, respectively), which was within control limits, the maximum transvalvular pressure gradient (mean 4.6 +/- 1.2 mm Hg and 6.6 +/- 2.1 mm Hg, respectively), the maximum leaflet separation (mean 22.1 +/- 1.4 mm and 22.1 +/- 1.8 mm, respectively), and the degree of insufficiency. At the first study, grade I aortic regurgitation was found in four patients and grade I-II in one patient. Regurgitation increased slightly in one patient with an abnormal leaflet. In three patients primary grade I regurgitation disappeared. These data suggest that the pulmonary root in the aortic position can withstand systemic circulation without changes in dimension and function for up to 21 months. Furthermore, some evidence is provided to indicate that in certain cases the viable autograft may adapt to systemic pressure, as indicated by the disappearance of primary regurgitation.