[Hyperthyroidism, eosinophilia, and fever in a 64-year-old patient]. / Hyperthyreose, Eosinophilie und Fieber bei einem 64-jährigen Patienten.

We report on a male patient suffering from loss of weight, fatigue, fever, eosinophilia, and hyperthyreoidism. The echocardiogram revealed a left atrial mass originating from the posterior mitral leaflet. In combination with the constitutional symptoms a left atrial myxoma was diagnosed. The tumor was surgically removed. Postoperatively therapy with corticosteroids and thiamazole was stopped. During follow-up, eosinophilia and hyperthyreodism could no longer be detected.

[Surgical atrial fibrillation ablation therapy and postoperative monitoring]. / Rhythmuschirurgie des Vorhofflimmerns und postoperatives Monitoring.

Atrial fibrillation represents the most common atrial arrhythmia seen in clinical practice. The surgical treatment of atrial fibrillation is recommended in symptomatic patients as well as in asymptomatic patients at low postoperative risk. As a "stand alone" procedure, surgical ablation therapy is indicated after failed catheter ablation therapy, which occurs increasingly due to the high number of catheter-based ablation techniques. In order to gain acceptance among patients as well as referring cardiologists, the surgical ablation procedure ought to be performed in a minimally invasive fashion and with a very high success rate. When applied in an interdisciplinary approach by cardiologists/electrophysiologists and cardiothoracic surgeons, both ablative techniques have the potential to treat atrial fibrillation effectively and in the long-term. In order to document the true heart rhythm after ablation therapy, intermittent "snapshot" ECG documentation ought to be avoided. Small leadless devices that can be implanted subcutaneously enable full heart rhythm disclosure with documentation of atrial arrhythmias. The modern technique of implantable loop recorders permits individualized treatment for each patient.

[Diagnostic pathways and pitfalls in acute thoracic aortic dissection: practical recommendations and an awareness campaign]. / Diagnostische Wege und Irrwege der akuten thorakalen Aortendissektion: Praktische Empfehlungen und Aufklärungskampagne.

Despite significant improvements in the surgical therapy of acute aortic dissection (AAD), mortality rates in the initial phase remain unacceptably high. Early diagnosis and therapy are essential to improving prognosis in these patients. A prerequisite of prompt and correct diagnosis is"thinking of it". Delayed or incorrect diagnosis can often have catastrophic results.The reported acute chest and back pain of a tearing, stabbing nature combined with the physiognomy of Marfan syndrome often arouse the clinical suspicion of AAD, prompting immediate imaging of the thoracic aorta and therapy. For less clear cases, additional hints drawn from the patient history and special findings from the medical examination are presented schematically in a diagnostic pathway. As an innovative form of diagnosis, preventive echocardiographic screening in high risk groups is discussed.To heighten awareness of AAD and the importance of its correct diagnosis, the poster campaign "Thinking of it can save lives" has been initiated. The poster depicts AAD schematically, indicates Marfan syndrome as a risk factor for AAD in young people and illustrates a CT scan as the most frequently performed imaging technique with high sensitivity and specificity.

Differences in human and sheep platelet adherence, aggregation and activation induced by glass beads in a modified chandler loop-system.

In human cardiovascular research, sheep in particular are used as a large animal model in addition to pigs. In these animals, medical products, developed and tested for human medical purposes, are almost exclusively used in interventional studies. Therefore, the extent to which platelets from human and ovine blood differ in terms of adherence, aggregation and activation after a 4- or 8-minutes exposure to glass was investigated. Testing was performed with platelet-rich plasma (PRP) and a modified chandler loop-system, with 4- and 8-minute blood-material exposure times corresponding to 20 and 40 test cycles, respectively, through the entire silicone tube loop of the test system.In sheep and human PRP, contact with the silicone tubing resulted in a decrease in platelet count after 4 minutes and 20 test cycles, respectively. Four more minutes (20 additional test cycles) caused a further decrease of the platelet count only in sheep PRP. When the silicon tube was partly filled with glass beads, these effects were more pronounced and stronger in sheep then in human PRP.The mean platelet volume, which was used as parameter for platelet aggregation, did not change over time in human PRP without glass exposure. With glass exposure in human and sheep PRP the mean platelet volume increased within 40 test cycles, but this increase was stronger in sheep than in human PRP.Regarding activation behavior, the activation markers CD62P and CD63 were detectable only in < 30% (sheep) and < 45% (human) of platelets, whereas after 8 min of glass exposure, the proportion of CD62P+ and CD63+ cells was more increased than before only in sheep. These results indicate that ovine platelets adhere more strongly to glass and show stronger aggregation behavior after glass contact than human platelets, but that ovine and human platelets differ only slightly in activability by glass.

Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system.

The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs' 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4-8 min exposure to glass.

Transmyocardial laser revascularization combined with intramyocardial endothelial progenitor cell transplantation in patients with intractable ischemic heart disease ineligible for conventional revascularization: preliminary results in a highly selected small patient cohort.

OBJECTIVE: Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease. METHODS: Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively. RESULTS: One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias. CONCLUSIONS: In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function.

Cutaneous microcirculation in patients with peripheral arterial occlusive disease: Comparison of capillary blood circulation in the nail fold of finger and toe.

In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area -was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries.

Pododermal angioarchitecture in the equine hoof wall: A light and scanning electron microscopic study of the wall proper.

BACKGROUND: Blood supply is an important factor for the normal function of the equine hoof, but earlier studies present conflicting data on functional characteristics of its angioarchitecture. OBJECTIVE: Emphasis was laid on demonstration of the microvascularisation in the different hoof wall regions, aiming at assessment of specialised vascular structures, e.g. vascular sphincter mechanisms and arteriovenous anastomoses. METHODS: The angioarchitecture of the adult pododerma in the equine hoof wall was examined by scanning electron microscopy of micro-corrosion casts assisted by exemplary histological and immuno-histochemical characterisation of the pododermal vasculature. RESULTS: The microvasculature of the lamellae and terminal papillae in all hoof wall regions was described in detail. Focal dilations and microvascular sphincters were a common feature. In contrast to former investigations, true arteriovenous anastomoses were detected at the base of the primary lamellae and the terminal papillae only, while thoroughfare channels proved a regular element within the microvasculature of the wall proper. Bicuspid venous valves were detected as regular feature. For the first time, the alpha-smooth muscle actin-reactivity of the microvascularisation in the hoof wall was systematically assessed, verifying its specialised vasomotor devices. CONCLUSIONS: The vasculature of the hoof wall displays specific angio-adaptations to high pressure and tensile load.

Impact of graft size and commissural resuspension height on aortic valve competence in valve-sparing aortic replacement under physiological pressures.

BACKGROUND: Valve competence in valve-sparing aortic root replacement has been described as being influenced by commissural height as well as graft size. The aim of this study was to investigate the impact of a gradual reduction of commissural height and graft diameter on aortic insufficiency under physiological conditions in an IN VITRO model. METHODS: Porcine aortic valves were reimplanted into a tubular graft and a native commissural height was obtained. Subsequently the height was reduced by 10 % and 20 %, respectively. To investigate the impact of graft size, a 30 % reduction of the prosthesis diameter was carried out in valves with both native and reduced commissural heights. All conditions were investigated under pulsatile flow simulation and static pressure exposure. RESULTS: Reduction of commissural height caused regurgitation at both 10 % and 20 % lower heights, which was more pronounced in grafts with 20 % reduction. Graft undersizing resulted in significant reflux, with regurgitation even occurring with valves in a native commissural position. CONCLUSIONS: Valve competence is impaired both by the reduction of commissural height and by reduced graft size. In particular, reimplantation of aortic valves into undersized grafts promotes valve insufficiency even if commissural height is well adjusted.

Growth-related micromorphological characteristics of the porcine femoral artery.

BACKGROUND: In cardiovascular research small pigs breeds like Göttingen® minipigs (GM) are established animal models, but systematic data about the micromorphology of the GM vasculature at different ages are scarce. OBJECTIVE: The study was aimed at gaining knowledge about the micromorphology of the femoral artery (FA) from German Landrace pigs (DL) and GM during the period of growth over a body weight range of 10-40 kg. METHODS: FA samples from DL aged two or three months were compared to GM ones, aged 18 or 40 months using transmitted light microscopy. RESULTS: All FA samples showed typical characteristics of muscular arteries. Growth was associated with increased vessel wall thickness. In the GM this resulted in a slight decrease of the luminal diameter (LD), while in the DL pigs, an increase of the LD and smooth muscle cell content (10%) with decreased elastic fiber content (10%) has been detected. In contrast, within the 22 months lasting growth period of the GM, the tunica media content of smooth muscle cells and elastic fibers remained stable. CONCLUSIONS: FA maturation strongly depends on the pig breed and age. It can be different from what is described in humans.

Types of reconstructive surgery of the aortic valve.

The aortic valve is part of the aortic root which is wedged between the heart and the ascending aorta, maintaining a directional flow throughout life-span. Beside different types of aortic valve replacements, reconstructive techniques are increasingly performed to restore normal aortic valve function. To apply these operations, understanding of normal and pathological valve anatomy and physiology is of basic importance. In addition, a widely accepted uniform aortic valve and root terminology is desirable for a proper scientific communication. Reconstructive techniques themselves can be divided into isolated reconstruction of aortic valve/root structures and the isolated replacement of one or more structures. Examples for the former ones are commissurotomy, cusps plication, decalcification or extension as well as plications of other aortic root structures (i.e. the intercusp triangles or the basal annulus). Examples for the latter ones are the remodeling and reimplantation techniques and their modifications. Replacement of the ascending aorta at the sinotubular level for the adjustment of the commissures to restore aortic root geometry also belongs to this group of techniques for aortic valve reconstruction. In this review article a systematic description of the current reconstructive techniques to restore adequate aortic valve function as well as clinical data are presented.

Use of botanicals in food supplements. Regulatory scope, scientific risk assessment and claim substantiation. 2005.

BACKGROUND/AIMS: In the European Union, an elaborate legal framework regulates botanical products both under food and medicinal law. The decision as to which legal framework applies to an individual product may differ between the Member States. In the case of botanical food supplements, all food law provisions apply to their manufacturing, composition and marketing, including the new claims legislation. METHODS: Elements from EU and national law, scientific and other publications are brought together to investigate how to clarify the differentiation between the use of botanicals for medicinal and health-promoting purposes on a scientific basis. RESULTS: Guidance on the safety assessment and quality evaluation of botanicals is proposed in light of the different approaches described in the scientific literature with particular attention to the concept of long-term use as an integral part of safety evaluation. Guidance on claims substantiation is also included, taking into consideration the proposed legislation, the concept of long-term experience and grading of evidence. CONCLUSIONS: A model for safety and efficacy assessment of botanical food supplements in the EU is proposed, and should be taken into consideration in the development of legislation and scientific research on botanicals.

Efficacy and tolerability of a spray with Salvia officinalis in the treatment of acute pharyngitis - a randomised, double-blind, placebo-controlled study with adaptive design and interim analysis.

OBJECTIVE: This randomised, double-blind, parallel group phase II/III study with adaptive two-stage design and interim analysis compared the efficacy and tolerability of spray (containing a Salvia officinalis fluid extract) against placebo in the treatment of patients with acute viral pharyngitis. - STUDY PARTICIPANTS: in two study parts, a total of 286 patients with subjective and objective evidence of pharyngitis were randomized. In the first study part 122 patients were enrolled. In the second study part 164 patients were included. The treatment duration per patient was 3 days, including one baseline visit and one final visit. - MAIN OUTCOME MEASURES: Area under Curve for change of throat pain intensity (spontaneous pain), documented every 15 minutes within the first 2 hours after the first application as compared to baseline using a visual analog scale (VAS 100 mm). - RESULTS: Following the interim analyses of the first study part the 15 % spray containing 140 microl sage extract per dose was the most promising preparation for the second study part (main study) whereas for the 30% and the 5% preparation results made superiority over placebo unlikely in the final analysis. Overall, the 15 % spray was significantly superior to placebo for the primary efficacy variable with regard to a reduction of the throat pain intensity score. Only minor side effects such as dry pharynx or burning of mild intensity were seen. - CONCLUSIONS: The efficacy and tolerability profile of a 15 % sage spray indicated that this preparation provides a convenient and safe treatment for patients with acute pharyngitis. A symptomatic relief occurred within the first two hours after first administration and was statistically significantly superior to placebo.

Autonomously contracting human cardiomyocytes generated from adult pancreatic stem cells and enhanced in co-cultures with myocardial biopsies.

Myocardial regeneration with artificially applied cardiomyocytes is emerging as a promising issue of significant scientific and clinical impact. Nevertheless the source of cells for human cardiomyocyte differentiation especially from adult tissue is still unclear. We hypothesized that human pancreatic stem cells may differentiate into cardiomyocyte-like cells and may increase in number when co-cultured with myocardial tissue. Adult stem cells were harvested from pancreatic tissue of patients undergoing operative procedures including the pancreas. The cells were selected, cultured and passaged. To promote self-differentiation into cardiomyocytes, human pancreatic stem cells were co-cultered with biopsies of human myocardium. After co-culture and breeding, cells were phenotyped as well with respect to RNA, protein and cardiomyocyte specificity at the electron-microscopic level.Pancreatic stem cells have already differentiated spontaneously into cardiomyocyte-like cells performing netlike cell clusters with rare but distinct multilocular cellular autonomous contractions with a frequency of about 20 beats per minute. The number of contracting areas however could be enhanced by co-culture with human myocardial biopsies. On RNA and protein levels as well as in electron-microscopy, evidence for cardiomyocyte specificity is shown. To the best of our knowledge this is the first report demonstrating the feasibility of generating autonomously contracting cardiomyocyte-like cells from adult human pancreatic stem cells and their enhancement by myocardial co-culture. This procedure might prove to be an alternative source and method for myocardial regenerative medicine.

Time course of aortic valve function and root dimensions after subcoronary ross procedure for bicuspid versus tricuspid aortic valve disease.

BACKGROUND: The freestanding aortic root, which is the currently preferred operative technique for pulmonary autografts, is reported to dilate and potentially promote aortic insufficiency, which has led to a controversial debate on the appropriate surgical technique, especially for congenital bicuspid aortic valve disease. Desirable data on the time course of valve function and root dimensions for the alternative subcoronary technique comparing bicuspid and tricuspid aortic valve disease are scarce. METHODS AND RESULTS: Echocardiographic examinations of 31 patients with congenital bicuspid aortic valve disease (group A; age 50.5+/-11.0 years) and 51 patients with acquired tricuspid aortic valve disease (group B; age 48.1+/-15.7 years) who were operated on between June 1994 and August 1998 were performed twice postoperatively. At first and second follow-up, respectively, maximum (mean) pressure gradients were 6.0+/-2.0 (3.6+/-1.0) and 5.1+/-2.1 (2.9+/-1.1) mm Hg in group A and 6.5+/-3.5 (3.9+/-1.9) and 5.0+/-1.7 (2.9+/-1.0) mm Hg in group B (P>0.05 between groups). In group A, grade 0 aortic insufficiency at first and second follow-up occurred in 8 and 7 patients, respectively, grade 0-I in 12 and 9 patients, grade I in 9 and 11 patients, grade I-II in 1 and 0 patients, and grade II in 1 and 4 patients; in group B, grade 0 aortic insufficiency occurred in 16 and 18 patients, grade 0-I in 16 and 8 patients, grade I in 17 and 21 patients, grade I-II in 0 and 1 patient, and grade II in 0 and 1 patient (P>0.05). Aortic insufficiency decreased in 10 patients (17%). However, there was an overall tendency for aortic insufficiency to increase over time (n=23, 38%), although it remained subclinical. Aortic root dimensions did not differ between groups and were constant during follow-up. CONCLUSIONS: This study provides some evidence that the function of the subcoronary pulmonary autograft in bicuspid aortic valve disease is excellent, with stable root dimensions, and is not different from that of tricuspid aortic valves at least up to 5.5 years postoperatively, which suggests the subcoronary technique should be reconsidered.

Opening and closing characteristics of the aortic valve after different types of valve-preserving surgery.

BACKGROUND: The surgical approach to aortic root aneurysm and/or dissection remains controversial. The use of valve-sparing operations, which are thought to have many advantages, is increasing. We hypothesized that the particular technique and type of surgery could influence valve motion characteristics and function. Therefore, we studied the instantaneous opening and closing characteristics of the aortic valve after the main 2 types of valve-sparing surgery. METHODS AND RESULTS: In 20 patients (10 with tube replacement of the aortic root, group A; and 10 with separate replacement of the sinuses of Valsalva, group B) and 10 controls (group C), transthoracic and transesophageal studies on aortic valve dynamics were performed. Three distinct phases of aortic valve motion were identified. They were as follows: (1) a rapid opening, with a velocity of 20.9+/-4.2 cm/s in group C, 27.1+/-10.9 cm/s in group B (P=NS), and 58.3+/-18.4 cm/s in group A (group A versus group C, P<0. 001; group A versus group B, P=0.001); (2) a slow systolic closure, with 12.5+/-6.6% and 10.8+/-2.2% of maximal opening in groups C and B, respectively (P=NS), and 3.8+/-1.6% in group A (group A versus group C, P=0.001; group A versus group B, P<0.001); and (3) a rapid closing movement, with a velocity of 26.3+/-5.6 cm/s in group C, 32. 4+/-11.4 cm/s in group B (P=NS), and 21.8+/-3.5 cm/s in group A (group A versus group C, P=NS; group A versus group B, P=0.008). The pressure strain of the elastic modulus was different in groups C and B only at the commissures (682+/-145 g/cm(2) versus 1896+/-726 g/cm(2), respectively; P<0.001). At all root levels, the distensibility was reduced in group A (P<0.001). Systolic contact of aortic cusps and wall occurred only in group A. CONCLUSIONS: Near-normal opening and closing characteristics can be achieved by a technique that preserves the shape and independent mobility of the sinuses of Valsalva.

Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease.

BACKGROUND: Chemotherapeutic treatment for patients with symptomatic coronary artery disease to reduce cardiovascular events may be initiated in response to elevated antibody titers against Chlamydia pneumoniae or cytomegalovirus. How antibody titers are associated with the endovascular presence of these microorganisms is still unclear. METHODS AND RESULTS: Antibody titers against C pneumoniae (microimmunofluorescence) and cytomegalovirus (ELISA) in patients undergoing primary (coronary desobliterates, n=80) or repeated CABG (occluded vein grafts, n=45) were correlated with the endovascular presence of the 2 microorganisms. C pneumoniae was detected by means of a nested polymerase chain reaction (PCR) and by culturing. Both conventional PCR and quantitative PCR were applied for detection of cytomegalovirus. C pneumoniae (PCR/culture) was detected in 19/9% (15/80 and 7/80) of coronary desobliterates and in 18/11% (8/45 and 5/45) of occluded vein grafts. There was no statistical evidence that IgG values differed between patients with or without C pneumoniae detection who were undergoing primary CABG. In contrast, repeated-CABG patients with a positive PCR (P=0.0027) or C pneumoniae culture (P=0.0018) had distinctly elevated IgG titers compared with patients in whom C pneumoniae was not detected. Cytomegalovirus could not be detected in the examined specimens. CONCLUSIONS: Cytomegalovirus infection does not seem to be associated with advanced coronary artery lesions. C pneumoniae antibody titers are not associated with the endovascular presence of C pneumoniae in patients with coronary artery disease. The observed strong association between elevated IgG titers and the detection of C pneumoniae in occluded vein grafts warrants further investigation.

Does histocompatibility affect homograft valve function after the Ross procedure?

BACKGROUND: Homograft valves have been shown to be immunogenic, but it is unknown whether this affects valve function. Therefore, we prospectively studied the degree of histoincompatibility (defined as the number of human leukocyte antigen [HLA] mismatches between valve donor and recipient) and the response of the recipient (measured by antibodies against HLA) in relation to echocardiographic parameters of homograft valve function after the Ross procedure. METHODS AND RESULTS: Twenty-six patients (mean age 41+/-14 years; 20 males, 6 females) and the cryopreserved pulmonary homograft valves that were implanted during a Ross procedure were typed for HLA-A, HLA-B, and HLA-DR. After a mean follow-up of 15+/-6 months, 14 (54%) of the patients were anti-HLA class I antibody positive. In all but 1 patient, these antibodies were shown to be donor specific. During follow-up, there was a significant increase of the maximal (+6.2+/-7.1 mm Hg) and mean (+3.2+/-4.3 mm Hg) transhomograft pressure gradients but not of homograft regurgitation. Neither the number of HLA mismatches nor antibody status was found to have significant impact on homograft valve function. In a multivariate analysis, smaller homograft size (P=0.001) and younger recipient age (P=0.044) were shown to be significantly associated with increased transhomograft pressure gradients. CONCLUSIONS: Implantation of a cryopreserved pulmonary homograft during the Ross procedure can induce a specific humoral response. We observed a significant increase of the transhomograft pressure gradients within 15+/-6 months after surgery. For this period, we were unable to demonstrate a relationship between this increase and the degree of histoincompatibility.

Clenbuterol-supported dynamic training of skeletal muscle ventricles against systemic load: a key for powerful circulatory assist?

BACKGROUND: The profound loss of power that occurs in skeletal muscle after electrical conditioning has been the major limiting factor in its clinical application. This study investigates a 3-fold approach for chronic conditioning of skeletal muscle ventricles (SMVs) combining electrical transformation, dynamic training against systemic load, and pharmacological support with clenbuterol. METHODS AND RESULTS: In 10 adult male goats, SMVs were constructed from latissimus dorsi muscle wrapped around an intrathoracic training device with windkessel characteristics. SMVs were stimulated electrically and trained dynamically by shifting volume against systemic load. Group 1 goats were controls (n=5), and group 2 goats (n=5) were supported with clenbuterol (150 microg 3 times a week). SMV dynamics were recorded weekly over 5 to 8 months: peak pressure (P(max)), stroke volume (SV), volume displacement per minute (VD), stroke work per day (SW/d), and maximum rates of pressure generation, +dP/dt(max), and decay, -dP/dt(max). In group 1, after 149.5+/-2.7 days (n=4), data were P(max)=70.8+/-4.7 mm Hg, SV=3.2+/-1.2 mL, VD=62.3+/-21.1 mL/min, SW/d=0.8+/-0.4 kJ, +dP/dt(max)=64+/-13 mm Hg/s, and -dP/dt(max)=156+/-32 mm Hg/s. These parameters were significantly improved (P<0.007) in the clenbuterol-treated group 2 after 151+/-2.7 days: P(max)=176.2+/-43.8 mm Hg, SV=23.3+/-6.1 mL, VD=568.2+/-186.1 mL/min, SW/d=9.1+/-2.2 kJ, +dP/dt(max)=1134+/-267 mm Hg/s, and -dP/dt(max)=1028+/-92 mm Hg/s. In 2 SMVs of group 2, VD increased to 1090 and 1235 mL/min after 202 and 246 days of training, respectively. At termination, myosin heavy chains were totally transformed into myosin heavy chain-1 in all SMVs. CONCLUSIONS: This clenbuterol-supported dynamic training provides powerful SMVs that may have important clinical implications for the treatment of end-stage heart failure by muscular blood pumps.

Biomechanical hearts: muscular blood pumps, performed in a 1-step operation, and trained under support of clenbuterol.

BACKGROUND: As shown previously in goats, clenbuterol increased the power of electrically conditioned skeletal muscle ventricles (SMVs) of clinically relevant size (150 mL), which were constructed around a mock system. They pumped against a pressure of 60 to 70 mm Hg immediately during surgery and up to several months after, finally at >1 L/min. SMVs without clenbuterol administration failed. Thus, we expected that clenbuterol-supported SMVs might become integrated into the circulation by a 1-step operation instead of the 2-step procedure required up to now. METHODS AND RESULTS: In adult Boer goats (n=5), latissimus dorsi muscle was wrapped around a polyurethane chamber of 150 mL that was connected to the descending aorta. This muscular flow-through pumping chamber containing a stabilizing inner layer (called a biomechanical heart [BMH]) was formed and immediately made to work against a systemic load with the support of clenbuterol (5x150 microg/wk). During surgery, the mean stroke volume of BMHs was 53.8+/-22.4 mL. One month after surgery, in peripheral arterial pressure, the mean diastolic (P(MD)) and minimal diastolic (P(min)) pressures of BMH-supported heart cycles differed significantly from unsupported ones (P(MD)=+2.9+/-1.1 mm Hg [P<0.04], P(min)=-2.4+/-0.9 mm Hg [P<0.04]). After BMH-supported heart contractions, the subsequent maximal rate of pressure generation, dP/dt(max), increased by 20.5+/-8.1% (P<0.02). One BMH, catheterized 132 days after surgery, shifted a volume of 34.8 mL per beat and 1.4 L/min with a latissimus dorsi muscle of 330 g. Depending on duration of training, the percentage of myosin heavy chain type 1 ranged between 31% and 100%. CONCLUSIONS: Under support of clenbuterol, BMHs of a clinically relevant size can be trained effectively in the systemic circulation after a 1-step operation and offer the prospect of a sufficient volume shift and probably unloading of the left ventricle.