The phosphodiesterase-4 and glycine transporter-1 inhibitors enhance in vivo hippocampal theta network connectivity and synaptic plasticity, whereas D-serine does not.

Dysfunctional N-methyl-D-aspartate receptors (NMDARs) and cyclic adenosine monophosphate (cAMP) have been associated with deficits in synaptic plasticity and cognition found in neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia. Therapeutic approaches that indirectly enhance NMDAR function through increases in glycine and/or D-serine levels as well as inhibition of phosphodiesterases that reduces degradation of cAMP, are expected to enhance synaptic strength, connectivity and to potentially impact cognition processes. The present in vivo study investigated effects of subcutaneous administration of D-serine, the glycine transporter 1 (GlyT1) inhibitor SSR504734 and the PDE4 inhibitor rolipram, on network oscillations, connectivity and long-term potentiation (LTP) at the hippocampi circuits in Sprague-Dawley rats. In conscious animals, multichannel EEG recordings assessed network oscillations and connectivity at frontal and hippocampal CA1-CA3 circuits. Under urethane anaesthesia, field excitatory postsynaptic potentials (fEPSPs) were measured in the CA1 subfield of the hippocampus after high-frequency stimulation (HFS) of the Schaffer collateral-CA1 (SC) pathway. SSR504734 and rolipram significantly increased slow theta oscillations (4-6.5 Hz) at the CA1-CA3, slow gamma oscillations (30-50 Hz) in the frontal areas and enhanced coherence in the CA1-CA3 network, which were dissociated from motor behaviour. SSR504734 enhanced short-term potentiation (STP) and fEPSP responses were extended into LTP response, whereas the potentiation of EPSP slope was short-lived to STP with rolipram. Unlike glycine, increased levels of D-serine had no effect on network oscillations and limits the LTP induction and expression. The present data support a facilitating role of glycine and cAMP on network oscillations and synaptic efficacy at the CA3-CA1 circuit in rats, whereas raising endogenous D-serine levels had no such beneficial effects.

Cortical high gamma network oscillations and connectivity: a translational index for antipsychotics to normalize aberrant neurophysiological activity.

Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801). Subsequently, the efficacies of marketed atypical antipsychotics (olanzapine, risperidone, and clozapine) to normalize dysfunctional oscillations and network connectivity were examined. Acute NMDA antagonists elicited aberrant synchrony in the gamma frequency oscillations. In addition, coherent slow alpha network activity was observed with MK801 and amphetamine, both of whose oscillatory rhythms were correlated with pronounced locomotor activity. All antipsychotics commonly decreased slow alpha and high gamma network oscillations in different cortical regions as well as motion behavior. In the combined treatments, antipsychotics attenuated NMDA antagonist-induced abnormalities in functional network oscillations and connectivity, whose effects on motor behavior is mechanistically related. These results suggest that pharmacologically induced disruption of cortical gamma oscillations and network connectivity in rats is a candidate model to study dysfunctional oscillatory patterns described in positive and negative symptoms of schizophrenia. The efficacy of antipsychotics to rescue cortical network oscillatory patterns is in line with the idea that glutamatergic and dopaminergic systems play a role in maintaining the integrity of cortical circuits. Thus, gamma oscillations could provide a powerful translational index to assess the integrity of neural networks and to evaluate the efficacy of drugs with potential antipsychotic properties.

Ketamine: differential neurophysiological dynamics in functional networks in the rat brain.

Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2.5, 5 and 10 mg kg-1) on sleep-wake cycle, multichannels network interactions assessed by coherence and phase-amplitude cross-frequency coupling, locomotor activity (LMA), cognitive information processing as reflected by the mismatch negativity-like (MMN) component of event-related brain potentials (ERPs). Acute ketamine elicited a short, lasting inhibition of rapid eye movement (REM) sleep, increased coherence in higher gamma frequency oscillations independent of LMA, altered theta-gamma phase-amplitude coupling, increased MMN peak-amplitude response and evoked higher gamma oscillations. In contrast, chronic ketamine reduced large-scale communication among cortical regions by decreasing oscillations and coherent activity in the gamma frequency range, shifted networks activity towards slow alpha rhythm, decreased MMN peak response and enhanced aberrant higher gamma neuronal network oscillations. Altogether, our data show that acute and chronic ketamine elicited differential changes in network connectivity, ERPs and event-related oscillations (EROs), supporting possible underlying alterations in NMDAR-GABAergic signaling. The findings underscore the relevance of intermittent dosing of ketamine to accurately maintain the functional integrity of neuronal networks for long-term plastic changes and therapeutic effect.

[Who may place the first donor heart? Conflict surrounding the first heart transplant in the Netherlands]. / De strijd rond het primaat van de eerste harttransplantatie in Nederland.

On Friday 22 June 1984 a patient was waiting in Rotterdam to be moved to Brussels for a heart transplant. The Dutch heart surgery centres tried to mutually agree on the place where the first heart transplant should be performed. When this proved impossible, the decision was made by the cardiac surgeons from Rotterdam and Leiden. In this article we will reconstruct the events that took place at that time, partly on the basis of a recent 'witness seminar'.

Off-target potential of AMN082 on sleep EEG and related physiological variables: Evidence from mGluR7 (-/-) mice.

The metabotropic glutamate receptor type 7 (mGluR7), a most abundant presynaptic G protein-coupled receptor in the brain provides an attractive mechanism to fast fine-tune abnormal excitatory neurotransmission and synaptic plasticity associated with emotional and cognitive impairments in neuropsychiatric and neurodegenerative disorders. Preclinical studies using AMN082, the mGluR7 allosteric agonist, produced conflicting results, so that results of further in-vivo studies are needed. Here, we investigated effects of subcutaneous administration at the lights onset of AMN082 on sleep-wake architecture and spectral contents in rats. In an attempt to solve the reported mixed results, we estimated the specific functional effects in mGluR7 (-/-) mice and their wild type (WT) littermates. In rats, AMN082 (2.5mg/kg) elicited a primary waking effect over the first 2h post-administration by consistent increases in the number of waking bouts and transitions from sleep states towards wakefulness. In mice, baseline recordings over 72h showed comparable spontaneous sleep-wake cycle in mGluR7 (-/-) mice and their WT littermates, suggesting that mGluR7 is not involved in the regulation of vigilance states. Remarkably, cortical arousal properties of AMN082 were confirmed in WT mice, and occurred concomitantly with a marked decrease in body temperature, likely dissociated from locomotor activity. Surprisingly, the wake arousal and hypothermia effects of AMN082 were also observed in mGluR7 (-/-) mice. AMN082 significantly attenuated the slow wave activity during sleep and had no effect on waking EEG power in the 4-50Hz range. The present findings in rats do not lend support to proposed somnogenic effects of AMN082, while comparable responses in WT and mGluR7 (-/-) mice provide further evidence of an off-target action of AMN082 that contributes to its waking properties.

Translational neurophysiological markers for activity of the metabotropic glutamate receptor (mGluR2) modulator JNJ-40411813: Sleep EEG correlates in rodents and healthy men.

Alterations in rapid eye movement sleep (REM) have been suggested as valid translational efficacy markers: activation of the metabotropic glutamate receptor 2 (mGluR2) was shown to increase REM latency and to decrease REM duration. The present paper addresses the effects on vigilance states of the mGluR2 positive allosteric modulator (PAM) JNJ-40411813 at different circadian times in rats and after afternoon dosing in humans. Due to its dual mGluR2 PAM/serotonin 2A (5-HT2A) receptor antagonism in rodents, mGlu2R specificity of effects was studied in wild-type (WT) and mGluR2 (-/-) mice. 5-HT2A receptor occupancy was determined in humans using positron emission tomography (PET). Tolerance development was examined in rats after chronic dosing. EEG oscillations and network connectivity were assessed using multi-channel EEG. In rats, JNJ-40411813 increased deep sleep time and latency of REM onset but reduced REM time when administered 2 h after 'lights on' (CT2): this was sustained after chronic dosing. At CT5 similar effects were elicited, at CT10 only deep sleep was enhanced. Withdrawal resulted in baseline values, while re-administration reinstated drug effects. Parieto-occipital cortical slow theta and gamma oscillations were correlated with low locomotion. The specificity of functional response was confirmed in WT but not mGluR2 (-/-) mice. A double-blind, placebo-controlled polysomnographic study in healthy, elderly subjects showed that 500 mg of JNJ-40411813 consistently increased deep sleep time, but had no effect on REM parameters. This deep sleep effect was not explained by 5-HT2A receptor binding, as in the PET study even 700 mg only marginally displaced the tracer. JNJ-40411813 elicited comparable functional responses in rodents and men if circadian time of dosing was taken into account. These findings underscore the translational potential of sleep mechanisms in evaluating mGluR2 therapeutics when administered at the appropriate circadian time.

Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential.

Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations. Cognition enhancers elicited systematic ("fingerprint") enhancement of cortical slow theta (4.5-6 Hz) and gamma (30.5-50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to assess efficacy of novel therapeutic drugs with cognition enhancing potential.

Contribution of melanin-concentrating hormone (MCH1) receptor to thermoregulation and sleep stabilization: evidence from MCH1 (-/-) mice.

Recent studies have explored the implication of melanin-concentrating hormone (MCH) in the process of vigilance states. The current experiments were carried out in mice lacking the MCH(1) receptor (-/-) and wild-type (WT) littermates, to assess the role of MCH(1) receptor in the regulation of sleep architecture, body temperature (BT) and locomotor activity (LMA) under normal condition and following a 1h restraint stress at lights onset. Under baseline conditions, MCH(1) (-/-) mice exhibited consistent changes in waking and sleeping time across the 24-h recording period. We found an increase in the amount of wakefulness (MCH(1) (-/-) 680.1 ± 15.3 min vs. WT, 601.9 ± 18.1, p<0.05) at the expense of total duration of non rapid eye movement (NREM) sleep (MCH(1) (-/-) 664.1 ± 13.9 min vs. WT 750.1 ± 18.5, p<0.05). Additionally, MCH(1) (-/-) mice had a higher mean basal body temperature (MCH(1) (-/-), 36.6 ± 0.1°C vs. WT, 36.0 ± 0.1°C, p<0.05), particularly during the light-resting period. Restraint stress resulted in an immediate increase in wakefulness with a concomitant reduction in NREM sleep and REM sleep in both genotypes, followed by a homeostatic rebound sleep. A concomitant long lasting increase in BT, independently of the behavioural state accompanied those changes in both genotypes. The elevated basal body temperature and reduction in NREM sleep time resulting from shorter NREM episode durations observed in MCH(1) (-/-) suggests that central MCH(1) receptor has a role in thermoregulation and presumably stabilization of NREM sleep.

Prime solutions for cardiopulmonary bypass in neonates: antioxidant capacity of prime based on albumin or fresh frozen plasma.

OBJECTIVE: Oxidative damage and inflammation are believed to play an important role in postoperative complications after cardiopulmonary bypass. During bypass, a prime solution with a high antioxidant capacity may reduce the oxidative damage and inflammation. We investigated total antioxidant capacity and individual scavengers during the preparation of 2 different prime solutions. METHODS: The prime solutions were prepared with either pasteurized human albumin or fresh frozen plasma. The total antioxidant capacity was measured with the total radical antioxidant parameter assay and with the ferric-reducing ability of plasma assay. The individual scavengers vitamin C, sulfhydryl groups, uric acid, and total protein were measured before, during, and after the prime preparation. Malondialdehyde was measured as a parameter for lipid peroxidation. RESULTS: Neither prime solution showed a total radical antioxidant parameter value. The ferric-reducing ability of plasma value of prime solutions was lower than that of undiluted human albumin or fresh frozen plasma. Addition of mannitol did not increase the ferric-reducing ability of plasma value. Vitamin C was only found in the fresh frozen plasma prime. Both prime solutions contained sulfhydryl groups and uric acid in low concentrations. During ultrafiltration, low-molecular-weight antioxidants were lost into the ultrafiltrate. CONCLUSIONS: We showed that prime solutions based on either albumin or fresh frozen plasma had very low antioxidant capacity and that ultrafiltration of the prime solution further lowers this capacity. A prime solution with a low antioxidant capacity may increase oxidative stress in neonates undergoing cardiopulmonary bypass.

Outcome and follow-up of aortic valve replacement with the freestyle stentless bioprosthesis.

BACKGROUND: The aim of this study was to determine the morbidity, mortality, and hemodynamics after implantation of the Freestyle stentless bioprosthesis in the aortic position. METHODS: A total of 280 patients were operated on from June 1993 to July 1999 as part of a multicenter investigation. Factors influencing hospital mortality and long-term survival were assessed by logistic regression and Cox proportional hazards analysis. Patients were evaluated postoperatively at discharge, at 3 to 6 months, and yearly by clinical examination and color flow Doppler echocardiography. RESULTS: Hospital mortality in this group was relatively high (9.6%). Logistic regression analysis showed that cross-clamp time, age, myocardial infarction, diabetes, left ventricular hypertrophy, coronary artery disease, New York Heart Association class III or IV and female gender were the independent predictive factors. According to the Kaplan-Meier method, the 4-year survival for hospital survivors was 94%. In the multivariate Cox proportional hazard analysis, only coronary artery disease proved to be prognostic. During follow-up, 11 patients developed paravalvular leakage due to prosthetic dehiscence at the side of the noncoronary cusp. Performance of the prosthesis as assessed by echocardiography was excellent. Mean gradient decreased significantly between discharge and follow-up at 3 to 6 months. At 1-year follow-up trivial regurgitation was found in 6 patients (3%) and mild regurgitation in 4 (2%). Regurgitation did not increase with time. The effective orifice area increased significantly from discharge to follow-up at 3 to 6 months. CONCLUSIONS: Hospital mortality after implantation of a stentless bioprosthesis was higher compared to conventional prosthesis. A high incidence of prosthesis dehiscence at the proximal suture line was found, which was probably due to technique. Hemodynamic performance up to 3 years showed low transvalvular gradients. There is echocardiographic evidence for reduction of left ventricular hypertrophy and improvement of left ventricular function.

Hemodynamics of the Freestyle bioprosthesis in young patients.

The objective of this study was to analyze hemodynamics of the Freestyle stentless bioprosthesis in young patients compared with the older age group. The Freestyle aortic bioprosthesis is a stentless aortic xenograft. Hemodynamics are proven to be good in older patients for a long period. Experience is limited in the younger age group. Therefore the hemodynamics of 71 patients younger than 60 years (14-59 years) were compared with the data of 471 patients older than 60 years (60-86 years) during a follow-up period of 6 years. In the study, 542 consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and then every year. Mean gradients of the young patients were 8.7 +/- 5.3 mm Hg at discharge and remained between 5.2 +/- 3.9 mm Hg and 11 +/- 5.6 mm Hg during the complete follow-up period. Gradients of the older patients were 8.3 +/- 5.4 mm Hg at discharge and remained between 5.1 +/- 3.7 mm Hg and 6.5 +/- 7.9 mm Hg. Cardiac index during the follow-up period was equal in both groups. Doppler values were evaluated for the Freestyle stentless porcine bioprostheses in the aortic root both for patients younger than 60 years and patients over 60 years of age. Midterm hemodynamic performance is equal in both groups.

Echocardiographic imaging of stentless aortic valve prostheses.

UNLABELLED: Homografts and stentless xenografts are increasingly used in aortic valve surgery. Echocardiography technicians and cardiologists have to know what they will find when performing an echo-Doppler examination in patients who received a stentless valve. We therefore evaluated echocardiographic images of 74 patients who received a Freestyle stentless bioprosthesis with three techniques and a follow-up of 2 years in two high-volume hospitals. Of the patients studied, 81% were operated using the subcoronary technique, 12% using the root-inclusion technique, and 7% using the full-root technique. RESULTS: Transvalvular gradients across the stentless valves were low: 8.0 mmHg when implanted with the subcoronary technique, 8.2 +/- 5.1 mmHg using the root-inclusion technique, and 6.5 mmHg using the full-root technique. Trivial aortic insufficiency (grade 1) was observed in 10.7% of the patients (8.9% for the subcoronary technique, 13% for the root-inclusion technique, and 0% for the full-root technique). When the bioprosthesis was implanted using the subcoronary technique or the root-inclusion technique, the prosthesis was placed inside the recipient aortic root. Using these techniques, a lumen between the double layer of the xenograft and the aortic wall could be observed. With the root-replacement technique, the porcine root became the most proximal part of the ascending aorta. As the native aortic wall was removed, in most cases, no double lumen could be observed with imaging of the ascending aorta.

Remodeling of the porcine pulmonary autograft wall in the aortic position.

OBJECTIVE: Dilatation and valve regurgitation are disturbing sequelae of the pulmonary root functioning at systemic pressures. We tried to characterize the histologic mode of adaptation of the neoaortic wall. METHODS: We compared routine histologic studies, immunohistochemical staining, and computer-assisted morphometric analysis of aortic, pulmonary autograft, and native pulmonary wall specimens from pigs in which, as a newborn, a valveless pulmonary autograft had been implanted in the aorta. RESULTS: Histologic examination of the pulmonary autograft revealed a viable, normally revascularized wall without degenerative phenomena. Smooth muscle cells were enlarged and rearranged. The characteristic "pulmonary" medial elastin lamellar structure was retained, which was confirmed by morphometry. Immunohistochemistry of the autograft revealed relatively strong staining of type III collagen and alpha smooth muscle actin, exclusive staining of basic fibroblast growth factor, and no staining of proliferation markers proliferating cell nuclear antigen and Ki67. CONCLUSION: The developing pulmonary autograft in the aortic position becomes normally revascularized, lacks major degenerative phenomena, and retains its own typical pulmonary morphologic features. Remodeling is accomplished by increased extracellular matrix deposition with collagen as an important constituent. The marked expression of growth factors in the autograft suggests the persistence of increased metabolic activity.

Stentless bioprostheses have ideal haemodynamics, even in the small aortic root.

OBJECTIVE: To determine normal Doppler and 2D gradients and flow characteristics of the Freestyle stentless aortic bioprosthesis related to valve size. BACKGROUND: The Freestyle stentless aortic bioprosthesis is one of the newer aortic xenografts. Only limited data are available of the echocardiographic flow characteristics during a mid-term follow-up period of this valve. Therefore valve performance related to valve size was measured during a follow-up period of two years. METHODS: 175 consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1 and 2 years. RESULTS: With a valve size from 19 to 27 mm mean gradients decreased from 8.0 +/- 5.1 mmHg at discharge to 5.8 +/- 3.8 mmHg after 3-6 months (p < 0.001). Thereafter gradients remained stable. The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro increased from 69 +/- 20% at discharge to 79 +/- 29% after one, two and three years. Performance index was especially very high in the smaller sized valves with a performance index of 85 +/- 17% for the 21 mm valve. During follow-up mean gradients remained below 10 mmHg even in the 21 mm valve. CONCLUSION: Stentless xenografts have ideal haemodynamics, even in the small aortic root.

Dynamic obstruction, an unusual complication after aortic valve replacement with a stentless porcine valve.

In the early nineties, the stentless porcine aortic bioprosthesis has been reintroduced successfully. Because of the limited experience, knowledge of clinical complications is limited. Therefore, we describe an unusual complication of dynamic obstruction after aortic valve replacement with a stentless porcine valve in a 70 year old man 18 months after implantation. We discuss the complications of stentless aortic prostheses known so far, describe operative techniques used and their characteristic two dimensional echocardiographic images.

Echocardiographic parameters of the freestyle stentless bioprosthesis in aortic position: the European experience.

The objective of this study was to determine normal Doppler and 2-dimensional characteristics of the Freestyle stentless aortic bioprosthesis. The Freestyle aortic bioprosthesis is a new type of aortic xenograft, and experience is limited. We therefore determined the normal range of echocardiographic and Doppler examinations of this valve. Three hundred thirty-nine consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1, 2, and 3 years. With a valve size from 19 to 27 mm, mean gradients decreased from 7.9 +/- 5.1 mm Hg at discharge to 5.5 +/- 3. 8 mm Hg after 3 to 6 months (P <.001). Thereafter, gradients remained stable. Effective orifice area 1 year after implantation was 1.59 +/- 0.58 cm(2) for the 21-mm valves, 1.92 +/- 0.74 cm(2) for the 23-mm valves, 2.03 +/- 0.64 cm(2) for the 25-mm valves, and 2.52 +/- 0.72 cm(2) for the 27-mm valves (P <.001). The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro, increased from 67% +/- 20% at discharge to 82% +/- 29% after 1, 2, and 3 years. Performance index was especially very high in the smaller-sized valves. After implantation with the subcoronary technique or root-inclusion technique, small cavities could be seen between the native aortic root and the Freestyle valve. Doppler values were evaluated for the Freestyle stentless porcine bioprostheses in the aortic root. Gradients appear to be close to those measured in native valves over a time period of 3 years.

Brom's three-patch technique for repair of supravalvular aortic stenosis.

OBJECTIVE: Case histories of all patients (n = 29) operated on for supravalvular aortic stenosis from 1962 to the present were reviewed to study different techniques and outcomes. The technique of symmetric aortoplasty with 3 patches (1 in each sinus) is described and compared with other methods. METHODS: Case reports were reviewed and follow-up was completed by contacting the patient's (pediatric) cardiologist. We aimed for a last follow-up visit, including Doppler echocardiographic studies, in a period no more than 12 months earlier than December 1997. Supravalvular aortic stenosis was discrete in 25 and diffuse with involvement of the aortic arch and arch vessels in 4 patients. Additional anomalies were bicuspid aortic valve (n = 5), coarctation (n = 3), ascending aortic aneurysm (n = 1), mitral valve insufficiency (n = 2), pulmonary valvular stenosis (n = 1), and peripheral pulmonary artery stenosis (n = 2). Eleven patients had Williams syndrome and 1 patient had Noonan syndrome. Symmetric aortoplasty with 3 patches (1 in each sinus) was used in 13 patients, whereas other nonsymmetric methods (1, 2, or Y-shaped patches) were used in 16 patients. Mean follow-up was 10.5 years (range: 4 months-36 years). RESULTS: All techniques adequately decreased the pressure gradient. Progression of preoperative aortic valve insufficiency or de novo regurgitation was not observed except in 1 patient in whom the patches inserted were too large. CONCLUSIONS: No difference could be demonstrated in outcome for any surgical technique; however, reconstruction of the aortic root with autologous pericardial patches in each sinus after transection of the aorta has the advantage of symmetry while restoring the normal aortic root anatomy.

Aortic valve replacement with Medtronic Freestyle bioprosthesis: 5-year results.

The Medtronic Freestyle aortic root bioprosthesis has been implanted in patients since August 1992. This study reviews clinical and echocardiographic results at midterm (5 years) after implantation. The Freestyle bioprosthesis was implanted in 1,100 patients in a 21-center Food and Drug Administration clinical trial from August 1992 to October 1998. The device was implanted (1) as a subcoronary valve replacement, (2) as a complete aortic root replacement (full-root), or (3) as a root inclusion. Patients were followed annually by clinical examination and echocardiography. There were 47 deaths early after operation (7.1%). There were 2,478 patient-years of follow-up during which there were 99 deaths or 4.0/pt.-yr. Before implantation, 73% of patients were in New York Heart Association functional class III or IV. After operation, 95% were in class I or II. Transvalvular gradient 4 years after operation was low (7.5+/-5.3 mm Hg) for all valve sizes (subcoronary implant). Small valves (19 and 21 mm) had mean gradients (10.2+/-3.0, 9.1+/-4.4 mm Hg). There was no or mild valve insufficiency in 98% of patients. Actuarial analysis at 5 years showed the rate for freedom from thromboembolism of 86% in subcoronary implant and 93% in full root replacement. Freedom from endocarditis was 98%. Freedom from reoperation for explant of the valve highest in patients having full root replacement (98%) and lower with root inclusion (94%). There were 20 bioprostheses explanted; 10 for endocarditis, 8 for technical reasons, and 2 for structural deterioration. The Medtronic Freestyle bioprosthesis (1) has excellent hemodynamic performance, (2) techniques for insertion that result in a competent valve, (3) low rates of thromboembolism and endocarditis, and (4) a rare rate of structural deterioration at 5 years.

Dehiscence of the Freestyle stentless bioprosthesis.

This study aimed to identify and characterize patients who developed prosthetic dehiscence after aortic valve replacement with the Freestyle Stentless bioprosthesis. Review of patients' records and preoperative echocardiogram was performed. Prosthetic dehiscence developed in 10 patients after 2.5 to 49 months (mean 19). Most patients were symptomatic at presentation. Nine patients were reoperated. Dehiscence was typically located at the inflow suture line beneath the noncoronary cusp. Four patients died. The cause of dehiscence is assumed to be related primarily to surgical technique.