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Study Objectives: To study the location, distribution, and intensity of pain in a sample of adult cardiac surgery patients during their postoperative hospital stay.Design: In a prospective study, pain location, distribution (number of pain areas per patient), and intensity (0 to 10 numerical rating scale) were documented on the first, second, third, and seventh postoperative day (POD). Patient characteristics (age, sex, size, and body mass index) were analyzed for their impact on pain intensity.Setting: A university hospital.Patients: Two hundred consecutive adult patients who underwent median sternotomy for open heart surgery. There were 121 male and 79 female patients, with a mean (+/- SD) age of 60.9 +/- 19.2 years.Measurement and Results: The maximal pain intensity was significantly higher on POD 1 and 2 (3.7 +/- 2 and 3.9 +/- 1.9, respectively) and lower on POD 3 and 7 (3.2 +/- 1.5 and 2.6 +/- 1.8, respectively). The pain distribution did not vary significantly throughout the hospital stay, but the location did, with more shoulder pain on POD 7. Only age was found to have an impact on pain intensity, with patients < 60 years having a higher pain intensity than older patients on POD 2 (4.3 +/- 2.2 vs 3.6 +/- 2.4; p = 0.02).Conclusions: In this patient population, the pain intensity diminished from POD 3 onward, although its distribution did not vary significantly during the first postoperative week. Moreover, pain location changed with time, with more osteoarticular type pain at the end of the first postoperative week. Among the patients' characteristics, only younger age had an impact on pain intensity, with a higher value on POD 2. [ABSTRACT FROM AUTHOR]

Despite an overall improvement in cardiopulmonary bypass (CPB) technology and materials, air emboli still occur. The latest generation membrane oxygenator from Bentley Laboratories, the SpiralGold, was tested ex vivo for its air handling ability. The study was conducted on four calves. Bolus amounts of air of 10, 15 and 20 cm3 were each injected three times, upstream of the oxygenator and a bubble detector located directly downstream. The amount of bubbles was measured semiquantitatively on a 10 unit scale (U one semiquantitative unit). The animals were killed 10 days after the CPB. When 10 cm3 of air was injected, no bubbles were detected. With 15 and 20 cm3, respectively, 1 +/- 1.5 and 5 +/- 3.3 U of bubbles were detected. Despite a total of 135 cm3 of air injected as large bolus amounts, all the animals survived without any obvious neurological deficit secondary to air bubble manipulation. In conclusion, the SpiralGold oxygenator per se can reliably trap an air bolus of up to 10 cm3. This feature should be taken into account when choosing an oxygenator, as it offers an additional barrier to air bubbles in the CPB circuit. [ABSTRACT FROM AUTHOR]

Objective: Myocardial unloading with ventricular assist devices in patients with severe heart failure (HF) can lead to reversal of certain aspects of pathological remodeling. However, these effects do not translate into recovery of myocardial function in the human heart, possibly due to detrimental atrophic processes also elicited through unloading. We have studied the effects of long-term unloading on sarcomeric morphology and function in a small animal model of ventricular unloading, heterotopic heart transplantation (HTX) in rats.Methods: Native rat hearts were unloaded via HTX for 30 days, CMs from control and unloaded hearts were isolated (n=8 hearts/>250 individual cells/group). CM overall size was determined, sarcomere length/contractility assessed and Calcium transients as well as E-C coupling gain analyzed in patch-clamped CMs. Additionally, phosphorylation of Troponin I, indicative of sarcomere activation, was measured with western blotting.Results: CM cross-sectional area was diminished in unloaded cells by about one third (2787±345 vs 1993±230 μm2) as was cell capacitance in patched cells. Accordingly, baseline sarcomere length was significantly reduced by ~0.2μm (Figure). However, this reduction did not diminish contractile function: fractional shortening was significantly higher in unloaded CMs (8.0 ± 3 % vs 6.6 ± 2.5 % in CTR, p = 0.01). Departure velocity of the transients was similar (-135.2 ± 48 vs -119.4 ± 40 dL/dt), and return velocity was slightly increased in unloaded cells (120.7 ± 54 vs 94.0 ± 46 dL/dt, p < 0.05), indicating preserved relaxation. Calcium transient amplitudes and current-voltage relationship under basal condition and isoproterenol stimulation was not changed. Troponin I phosphorylation was elevated and may contribute to the maintenance of sarcomeric function in long-term unloaded CMs.Conclusion: Although there are limitations regarding assessment of contractility in isolated cells, we may conclude that the considerable size reduction in CMs induced by unloading does not translate into diminished contractile function or E-C coupling. [ABSTRACT FROM PUBLISHER]

Objectives: Postoperative permanent pacemaker implantation (PPI) after conventional aortic valve replacement (AVR), due to new-onset severe conduction system disorders, is required in approximately 7% of patients. This study investigated the need for PPI after AVR with conventional stented Perimount Magna compared with the Freedom SOLO (FS) stentless valve (Sorin Group, Saluggia, Italy), now LivaNova plc (London, UK) that uses a strictly supra-annular, subcoronary running suture implantation technique, sparing the vulnerable interleaflet triangles in the region of the septum membranaceum., Methods: A total of 413 consecutive patients (71.4±9.2 yrs, 178 [43.1%] female) underwent isolated AVR using the stented Perimount Magna (n=264) or the stentless FS (n=149) bioprosthesis. Propensity score weighted analysis was used to account for patient-specific and procedural-specific variables, and to identify the prosthesis-specific need for early postoperative PPI within 30 days of AVR., Results: Twenty (20) patients required PPI, which was associated with longer intensive care unit (2.1±1.7 vs 1.5±3.0 days, p<0.001) and overall hospital stays (13.8±5.2 vs 10.7±5.3 days, p<0.001) compared with no PPI. Propensity weighted logistic regression including cross-clamp times identified that use of the stented Perimount Magna was associated with increased need for PPI, as compared with the FS, with an odds ratio 5.8 (95% CI, 1.09-30.76; p=0.039)., Conclusions: After corrections for all plausible confounders, AVR with the stented Perimount valve was associated with an odds ratio of almost 6 for an increased early postoperative need for pacemaker implantation compared with the FS stentless valve. This finding can be explained by the conventional implantation technique, which is potentially associated with mechanical trauma to the conducting system., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Introduction: In outcome research, incomplete follow-up is a major, yet potentially correctable source of bias. Cross-sectional surveys may theoretically increase completeness of follow-up, but low response rates are reported typically. We investigated whether a pre-notification letter improved patient availability for follow-up phone interviews and thereby improved cross-sectional survey yield., Methods: A consecutive series of vascular patients was randomly divided into a trial and a validation population. The trial population was then randomized 1:1 to one of two cross-sectional contact strategies: Strategy 1 consisted of direct contact attempts by up to 12 systematically timed phone calls, whereas Strategy 2 used a personalized pre-notification letter to arrange for scheduled phone call interviews. Response rates, average time and efforts needed per patient and overall survey duration were compared. Subsequently, trial findings were externally validated in the validation population., Results: Of 728 consecutive patients, 370 were allocated to the trial population. Trial patients contacted by strategy 1 (n = 183) had a similar profile when compared to trial patients contacted by strategy 2 (n = 187). Follow-up periods following surgery (54.3 versus 53.6 months) and all-cause mortality rates (21.3% versus 18.7%) were comparable between the trial groups. Cross-sectional information on survival outcomes was almost complete after both contact strategies (99.5% versus 98.9%, P = 1.0). In 144/187 strategy 2 patients (77%) interviews were scheduled successfully necessitating significantly less contact attempts (median of 1.3 versus 2.3 per patient, P<0.0001). However, invested time per patient was similar between the groups (median of 10.1 versus 9.6 minutes), and survey strategy 1 completed earlier (median time to contact 4 versus 11 days, P<0.0001). Therefore, strategy 1 was validated in the validation population (n = 358): a low lost to follow-up rate below 1% (P = 1.0) was reconfirmed necessitating an average of 2.3 contact attempts per patient., Conclusions: Both contact strategies were equally successful in contacting almost all patients cross-sectionally. If systematically timed, direct phone calls were less complicated to organize and faster completed. Given the low time and effort per patient, outcome studies should invest in systematic follow-up surveys to minimize attrition bias., Competing Interests: The authors have declared that no competing interests exist.

Background: Current reporting guidelines do not call for standardised declaration of follow-up completeness, although study validity depends on the representativeness of measured outcomes. The Follow-Up Index (FUI) describes follow-up completeness at a given study end date as ratio between the investigated and the potential follow-up period. The association between FUI and the accuracy of survival-estimates was investigated., Methods: FUI and Kaplan-Meier estimates were calculated twice for 1207 consecutive patients undergoing aortic repair during an 11-year period: in a scenario A the population's clinical routine follow-up data (available from a prospective registry) was analysed conventionally. For the control scenario B, an independent survey was completed at the predefined study end. To determine the relation between FUI and the accuracy of study findings, discrepancies between scenarios regarding FUI, follow-up duration and cumulative survival-estimates were evaluated using multivariate analyses., Results: Scenario A noted 89 deaths (7.4%) during a mean considered follow-up of 30±28months. Scenario B, although analysing the same study period, detected 304 deaths (25.2%, P<0.001) as it scrutinized the complete follow-up period (49±32months). FUI (0.57±0.35 versus 1.00±0, P<0.001) and cumulative survival estimates (78.7% versus 50.7%, P<0.001) differed significantly between scenarios, suggesting that incomplete follow-up information led to underestimation of mortality. Degree of follow-up completeness (i.e. FUI-quartiles and FUI-intervals) correlated directly with accuracy of study findings: underestimation of long-term mortality increased almost linearly by 30% with every 0.1 drop in FUI (adjusted HR 1.30; 95%-CI 1.24;1.36, P<0.001)., Conclusion: Follow-up completeness is a pre-requisite for reliable outcome assessment and should be declared systematically. FUI represents a simple measure suited as reporting standard. Evidence lacking such information must be challenged as potentially flawed by selection bias.

Recent findings in the field of biomaterials and tissue engineering provide evidence that surface immobilised growth factors display enhanced stability and induce prolonged function. Cell response can be regulated by material properties and at the site of interest. To this end, we developed scaffolds with covalently bound vascular endothelial growth factor (VEGF) and evaluated their mitogenic effect on endothelial cells in vitro. Nano- (254±133 nm) or micro-fibrous (4.0±0.4 μm) poly(ɛ-caprolactone) (PCL) non-wovens were produced by electrospinning and coated in a radio frequency (RF) plasma process to induce an oxygen functional hydrocarbon layer. Implemented carboxylic acid groups were converted into amine-reactive esters and covalently coupled to VEGF by forming stable amide bonds (standard EDC/NHS chemistry). Substrates were analysed by X-ray photoelectron spectroscopy (XPS), enzyme-linked immuno-assays (ELISA) and immunohistochemistry (anti-VEGF antibody and VEGF-R2 binding). Depending on the reaction conditions, immobilised VEGF was present at 127±47 ng to 941±199 ng per substrate (6mm diameter; concentrations of 4.5 ng mm(-2) or 33.3 ng mm(-2), respectively). Immunohistochemistry provided evidence for biological integrity of immobilised VEGF. Endothelial cell number of primary endothelial cells or immortalised endothelial cells were significantly enhanced on VEGF-functionalised scaffolds compared to native PCL scaffolds. This indicates a sustained activity of immobilised VEGF over a culture period of nine days. We present a versatile method for the fabrication of growth factor-loaded scaffolds at specific concentrations., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Cardiac tissue engineering approaches can deliver large numbers of cells to the damaged myocardium and have thus increasingly been considered as a possible curative treatment to counteract the high prevalence of progressive heart failure after myocardial infarction (MI). Optimal scaffold architecture and mechanical and chemical properties, as well as immune- and bio-compatibility, need to be addressed. We demonstrated that radio-frequency plasma surface functionalized electrospun poly(ɛ-caprolactone) (PCL) fibres provide a suitable matrix for bone-marrow-derived mesenchymal stem cell (MSC) cardiac implantation. Using a rat model of chronic MI, we showed that MSC-seeded plasma-coated PCL grafts stabilized cardiac function and attenuated dilatation. Significant relative decreases of 13% of the ejection fraction (EF) and 15% of the fractional shortening (FS) were observed in sham treated animals; respective decreases of 20% and 25% were measured 4 weeks after acellular patch implantation, whereas a steadied function was observed 4 weeks after MSC-patch implantation (relative decreases of 6% for both EF and FS)., (Copyright © 2014. Published by Elsevier Ltd.)

The constant shortage of available organs is a major obstacle and limiting factor in heart transplantation; the discrepancy between the number of donors and potential recipients leads to waiting-list mortality of 10-12% per year in Europe and the USA. If adopted for heart transplantation, donation after circulatory determination of death (DCDD) would be expected to improve the availability of organs substantially for both adults and children. With DCDD, however, hearts to be transplanted undergo a period of warm ischaemia before procurement, which is of particular concern because tissue damage occurs rapidly and might be sufficient to preclude transplantation. Nonetheless, the heart is able to withstand limited periods of warm ischaemia, which could provide a window of opportunity for DCDD. Development of clinical approaches specifically for DCDD is critical for the exploitation of these organs, because current practices for donor heart procurement, evaluation, and storage have been optimized for conventional donation after brain death, without consideration of warm ischaemia before organ procurement. Establishment of clinical protocols and ethical and legal frameworks for DCDD of other organs is underway. This Review provides a timely evaluation of the potential for DCDD in heart transplantation.

Background: Mechanical unloading of failing hearts can trigger functional recovery but results in progressive atrophy and possibly detrimental adaptation. In an unbiased approach, we examined the dynamic effects of unloading duration on molecular markers indicative of myocardial damage, hypothesizing that potential recovery may be improved by optimized unloading time., Methods: Heterotopically transplanted normal rat hearts were harvested at 3, 8, 15, 30, and 60 days. Forty-seven genes were analyzed using TaqMan-based microarray, Western blot, and immunohistochemistry., Results: In parallel with marked atrophy (22% to 64% volume loss at 3 respectively 60 days), expression of myosin heavy-chain isoforms (MHC-α/-β) was characteristically switched in a time-dependent manner. Genes involved in tissue remodeling (FGF-2, CTGF, TGFb, IGF-1) were increasingly upregulated with duration of unloading. A distinct pattern was observed for genes involved in generation of contractile force; an indiscriminate early downregulation was followed by a new steady-state below normal. For pro-apoptotic transcripts bax, bnip-3, and cCasp-6 and -9 mRNA levels demonstrated a slight increase up to 30 days unloading with pronunciation at 60 days. Findings regarding cell death were confirmed on the protein level. Proteasome activity indicated early increase of protein degradation but decreased below baseline in unloaded hearts at 60 days., Conclusions: We identified incrementally increased apoptosis after myocardial unloading of the normal rat heart, which is exacerbated at late time points (60 days) and inversely related to loss of myocardial mass. Our findings suggest an irreversible detrimental effect of long-term unloading on myocardium that may be precluded by partial reloading and amenable to molecular therapeutic intervention., (© 2013 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.)

Gene therapy may represent a promising alternative strategy for cardiac muscle regeneration. In vivo electroporation, a physical method of gene transfer, has recently evolved as an efficient method for gene transfer. Here, we describe two protocols involving in vivo electroporation for gene transfer to the beating heart.

Background: Peak levels of troponin T (TnT) reliably predict morbidity and mortality after cardiac surgery. However, the therapeutic window to manage CABG-related in-hospital complications may close before the peak is reached. We investigated whether early TnT levels correlate as well with complications after coronary artery bypass grafting (CABG) surgery., Methods: A 12 month consecutive series of patients undergoing elective isolated CABG procedures (mini-extra-corporeal circuit, Cardioplegic arrest) was analyzed. Logistic regression modeling was used to investigate whether TnT levels 6 to 8 hours after surgery were independently associated with in-hospital complications (either post-operative myocardial infarction, stroke, new-onset renal insufficiency, intensive care unit (ICU) readmission, prolonged ICU stay (>48 hours), prolonged need for vasopressors (>24 hours), resuscitation or death)., Results: A total of 290 patients, including 36 patients with complications, was analyzed. Early TnT levels (odds ratio (OR): 6.8, 95% confidence interval (CI): 2.2-21.4, P=.001), logistic EuroSCORE (OR: 1.2, 95%CI: 1.0-1.3, P=.007) and the need for vasopressors during the first 6 postoperative hours (OR: 2.7, 95%CI: 1.0-7.1, P=.05) were independently associated with the risk of complications. With consideration of vasopressor use during the first 6 postoperative hours, the sum of specificity (0.958) and sensitivity (0.417) of TnT for subsequent complications was highest at a TnT cut-off value of 0.8 ng/mL., Conclusion: Early TnT levels may be useful to guide ICU management of CABG patients. They predict clinically relevant complications within a potential therapeutic window, particularly in patients requiring vasopressors during the first postoperative hours, although with only moderate sensitivity.

Objectives: Donation after circulatory declaration of death (DCDD) could significantly improve the number of cardiac grafts for transplantation. Graft evaluation is particularly important in the setting of DCDD given that conditions of cardio-circulatory arrest and warm ischaemia differ, leading to variable tissue injury. The aim of this study was to identify, at the time of heart procurement, means to predict contractile recovery following cardioplegic storage and reperfusion using an isolated rat heart model. Identification of reliable approaches to evaluate cardiac grafts is key in the development of protocols for heart transplantation with DCDD., Methods: Hearts isolated from anaesthetized male Wistar rats (n = 34) were exposed to various perfusion protocols. To simulate DCDD conditions, rats were exsanguinated and maintained at 37°C for 15-25 min (warm ischaemia). Isolated hearts were perfused with modified Krebs-Henseleit buffer for 10 min (unloaded), arrested with cardioplegia, stored for 3 h at 4°C and then reperfused for 120 min (unloaded for 60 min, then loaded for 60 min). Left ventricular (LV) function was assessed using an intraventricular micro-tip pressure catheter. Statistical significance was determined using the non-parametric Spearman rho correlation analysis., Results: After 120 min of reperfusion, recovery of LV work measured as developed pressure (DP)-heart rate (HR) product ranged from 0 to 15 ± 6.1 mmHg beats min(-1) 10(-3) following warm ischaemia of 15-25 min. Several haemodynamic parameters measured during early, unloaded perfusion at the time of heart procurement, including HR and the peak systolic pressure-HR product, correlated significantly with contractile recovery after cardioplegic storage and 120 min of reperfusion (P < 0.001). Coronary flow, oxygen consumption and lactate dehydrogenase release also correlated significantly with contractile recovery following cardioplegic storage and 120 min of reperfusion (P < 0.05)., Conclusions: Haemodynamic and biochemical parameters measured at the time of organ procurement could serve as predictive indicators of contractile recovery. We believe that evaluation of graft suitability is feasible prior to transplantation with DCDD, and may, consequently, increase donor heart availability.

Engineered muscle constructs provide a promising perspective on the regeneration or substitution of irreversibly damaged skeletal muscle. However, the highly ordered structure of native muscle tissue necessitates special consideration during scaffold development. Multiple approaches to the design of anisotropically structured substrates with grooved micropatterns or parallel-aligned fibres have previously been undertaken. In this study we report the guidance effect of a scaffold that combines both approaches, oriented fibres and a grooved topography. By electrospinning onto a topographically structured collector, matrices of parallel-oriented poly(ε-caprolactone) fibres with an imprinted wavy topography of 90 µm periodicity were produced. Matrices of randomly oriented fibres or parallel-oriented fibres without micropatterns served as controls. As previously shown, un-patterned, parallel-oriented substrates induced myotube orientation that is parallel to fibre direction. Interestingly, pattern addition induced an orientation of myotubes at an angle of 24° (statistical median) relative to fibre orientation. Myotube length was significantly increased on aligned micropatterned substrates in comparison to that on aligned substrates without pattern (436 ± 245 µm versus 365 ± 212 µm; p < 0.05). We report an innovative, yet simple, design to produce micropatterned electrospun scaffolds that induce an unexpected myotube orientation and an increase in myotube length.

Although heart donation after cardiac death (DCD) could greatly improve graft availability, concerns regarding warm ischemic damage typically preclude transplantation. Improving tolerance to warm ischemia may thus open a window of opportunity for DCD hearts. We investigated the hypothesis that, compared with normothermia, mild hypothermia (32° C) initiated after ischemic onset improves cardiac functional recovery upon reperfusion. Isolated, working hearts from adult, male Wistar rats underwent global, no-flow ischemia, and reperfusion (n = 28). After ischemic onset, temperature was maintained at either 37° C for 20 or 30 min or reduced to 32° C for 40, 50, or 60 min. Recovery was measured after 60-min reperfusion. Following normothermic ischemia, recovery of rate-pressure product (RPP; per cent of preischemic value) was almost complete after 20-min ischemia (97 ± 9%), whereas no recovery was detectable after 30-min ischemia. After mildly hypothermic ischemia (32° C), RPP also recovered well after 40 min (86 ± 4%). Markers of metabolism and necrosis were similar in 37° C/20 min and 32° C/40 min groups. Simple reduction in cardiac temperature by a few degrees after the onset of global ischemia dramatically prolongs the interval during which the heart remains resistant to functional deterioration. Preservation of hemodynamic function is associated with improved metabolic recovery and reduced necrosis. The application of mild hypothermia may be a simple first step towards development of clinical protocols for DCD heart recovery., (© 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.)

As opposed to culture on standard tissue-treated plastic, cell culture on three-dimensional scaffolds impedes additional challenges with respect to substrate preparation, cell seeding, culture maintenance, and analysis. We herewith present a general route for the culture of primary cells, differentiated cells, or stem cells on plasma-coated, electrospun scaffolds. We describe a method to prepare and fix the scaffolds in culture wells and discuss a convenient method for cell seeding and subsequent analysis by scanning electron microscopy or immunohistology.

Vascular endothelial growth factor (VEGF) can induce normal angiogenesis or the growth of angioma-like vascular tumors depending on the amount secreted by each producing cell because it remains localized in the microenvironment. In order to control the distribution of VEGF expression levels in vivo, we recently developed a high-throughput fluorescence-activated cell sorting (FACS)-based technique to rapidly purify transduced progenitors that homogeneously express a specific VEGF dose from a heterogeneous primary population. Here we tested the hypothesis that cell-based delivery of a controlled VEGF level could induce normal angiogenesis in the heart, while preventing the development of angiomas. Freshly isolated human adipose tissue-derived stem cells (ASC) were transduced with retroviral vectors expressing either rat VEGF linked to a FACS-quantifiable cell-surface marker (a truncated form of CD8) or CD8 alone as control (CTR). VEGF-expressing cells were FACS-purified to generate populations producing either a specific VEGF level (SPEC) or uncontrolled heterogeneous levels (ALL). Fifteen nude rats underwent intramyocardial injection of 10(7) cells. Histology was performed after 4 weeks. Both the SPEC and ALL cells produced a similar total amount of VEGF, and both cell types induced a 50%-60% increase in both total and perfused vessel density compared to CTR cells, despite very limited stable engraftment. However, homogeneous VEGF expression by SPEC cells induced only normal and stable angiogenesis. Conversely, heterogeneous expression of a similar total amount by the ALL cells caused the growth of numerous angioma-like structures. These results suggest that controlled VEGF delivery by FACS-purified ASC may be a promising strategy to achieve safe therapeutic angiogenesis in the heart.

Introduction: Small animal models are widely used in basic research. However, experimental systems requiring extracorporeal circuits are frequently confronted with limitations related to equipment size. This is particularly true for oxygenators in systems with limited volumes. Thus we aimed to develop and validate an ultra mini-oxygenator for low-volume, buffer-perfused systems., Methods: We have manufactured a series of ultra mini-oxygenators with approximately 175 aligned, microporous, polypropylene hollow fibers contained inside a shell, which is sealed at each of the two extremities to isolate perfusate and gas compartments. With this construction, gas passes through hollow fibers, while perfusate circulates around fibers. Performance of ultra mini-oxygenators (oxygen partial pressure (PO2), gas and perfusate flow, perfusate pressure and temperature drop) were assessed with modified Krebs-Henseleit buffer in an in vitro perfusion circuit and an ex vivo rat heart preparation., Results: Mean priming volume of ultra mini-oxygenators was 1.2±0.5 mL and, on average, 86±6% of fibers were open (n=17). In vitro, effective oxygenation (PO2=400-500 mmHg) was achieved for all flow rates up to 50 mL/min and remained stable for at least 2 hours (n=5). Oxygenation was also effective and stable (PO2=456±40 mmHg) in the isolated heart preparation for at least 60 minutes ("venous" PO2=151±11 mmHg; n=5)., Conclusions: We have established a reproducible procedure for fabrication of ultra mini-oxygenators, which provide reliable and stable oxygenation for at least 60-120 min. These oxygenators are especially attractive for pre-clinical protocols using small, rather than large, animals.

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Gene therapy of the heart has been attempted in a number of clinical trials with the injection of naked DNA, although quantitative information on myocellular transfection rates is not available. The present study aimed to quantify the efficacy of electropulsing protocols that differ in pulse duration and number to stimulate transfection of cardiomyocytes and to determine the impact on myocardial integrity., Methods: Reporter plasmid for constitutive expression of green fluorescent protein (GFP) was injected into the left ventricle of beating hearts of adult, male Lewis rats. Four electrotransfer protocols consisting of repeated long pulses (8 × 20 ms), trains of short pulses (eight trains of either 60 or 80 × 100 µs) or their combination were compared with control procedures concerning the degree of GFP expression and the effect on infiltration, fibrosis and apoptosis., Results: All tested protocols produced GFP expression at the site of plasmid injection. Continuous pulses were most effective and increased the number of GFP-positive cardiomyocytes by more than 300-fold compared to plasmid injection alone (p < 0.05). Concomitantly, the incidence of macrophage infiltration, fibrosis and cell death was increased. Trains of short pulses reduced macrophage infiltration and fibrosis by four- and two-fold, respectively, although they were 20-fold less efficient in stimulating cardiomyocyte transfection. GFP expression co-related to delivered electric energy, infiltration and fibrosis, although not apoptosis., Conclusions: The data imply that electropulsing of the myocardium promotes the overexpression of exogenous protein in mature cardiomyocytes in relation to an injury component. Fractionation of pulses is indicated as a option for sophisticated gene therapeutic approaches to the heart., (Copyright © 2012 John Wiley & Sons, Ltd.)

Aims: Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs., Methods and Results: Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *10(3) mmHg*beats*min(-1) (p<0.01)., Conclusion: Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.

Cell therapies have gained increasing interest and developed in several approaches related to the treatment of damaged myocardium. The results of multiple clinical trials have already been reported, almost exclusively involving the direct injection of stem cells. It has, however, been postulated that the efficiency of injected cells could possibly be hindered by the mechanical trauma due to the injection and their low survival in the hostile environment. It has indeed been demonstrated that cell mortality due to the injection approaches 90%. Major issues still need to be resolved and bed-to-bench followup is paramount to foster clinical implementations. The tissue engineering approach thus constitutes an attractive alternative since it provides the opportunity to deliver a large number of cells that are already organized in an extracellular matrix. Recent laboratory reports confirmed the interest of this approach and already encouraged a few groups to investigate it in clinical studies. We discuss current knowledge regarding engineered tissue for myocardial repair or replacement and in particular the recent implementation of nanotechnological approaches.

Objective: The use of radial artery conduits in coronary artery bypass grafting (CABG) surgery is associated with improved long-term patency and patient survival rates as compared with saphenous vein conduits. Despite increasing popularity, relative incidence of local harvest-site complications and subjective perception of adverse long-term sequelae remain poorly described., Methods: To allow for direct comparison, we investigated a consecutive series of patients in whom both the radial artery and the saphenous vein had been harvested for isolated CABG during a 36-month period. Patients were identified from a prospective database that collects baseline clinical information. The patients' own perceptions were assessed by a standardized direct telephone survey regarding any persistent functional impairment from their arm and leg operation sites., Results: Out of 1756 CABG patients during the study period, 168 (10%) were eligible (78% men, median age: 60.1 ± 9.6 years, range: 29.6-82.4 years). Of these, 123 (73%) could be contacted and interviewed at a median follow-up time of 2.5 ± 0.9 years. Surgical wound complications at harvest sites (arms and legs) had occurred in 3% and 12%, respectively, and persistent symptoms (arms and legs) were self-reported as follows: chronic pain (5% and 8%), numbness (32% and 34%) and paresthesia/dysesthesia (14% and 7%). Overall, 39% of the patients reported persistent discomfort at the arm and 39% at the leg. Both sites were simultaneously affected in 21% (P = n.s., paired testing). Logistic regression modeling showed that patients with adverse long-term sequelae were younger (P < 0.005), had a higher body mass index (P < 0.05) and a lower EuroSCORE (P < 0.001) at the time of operation (EuroSCORE, European System for Cardiac Operative Risk Evaluation). Perioperative wound complications, however, did not predict persistence of symptoms., Conclusions: Persistent harvest-site discomfort occurs with astonishing frequency after CABG surgery and affects arms and legs equally. Although usually considered a minor complication, long-term limitation to quality of life may be substantial, particularly in younger and relatively healthy patients. Thus, harvest-site discomfort clearly belongs to the list of possible post-CABG complications of which patients need to be aware., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Gene therapy may represent a promising alternative strategy for cardiac muscle regeneration. In vivo electroporation, a physical method of gene transfer, has recently evolved as an efficient method for gene transfer. In the current study, we investigated the efficiency and safety of a protocol involving in vivo electroporation for gene transfer to the beating heart. Adult male rats were anesthetised and the heart exposed through a left thoracotomy. Naked plasmid DNA was injected retrograde into the transiently occluded coronary sinus before the electric pulses were applied. Animals were sacrificed at specific time points and gene expression was detected. Results were compared to the group of animals where no electric pulses were applied. No post-procedure arrhythmia was observed. Left ventricular function was temporarily altered only in the group were high pulses were applied; CK-MB (Creatine kinase) and TNT (Troponin T) were also altered only in this group. Histology showed no signs of toxicity. Gene expression was highest at day one. Our results provide evidence that in vivo electroporation with an optimized protocol is a safe and effective tool for nonviral gene delivery to the beating heart. This method may be promising for clinical settings especially for perioperative gene delivery.

Background: Mechanisms underlying improvement of myocardial contractile function after cell therapy as well as arrhythmic side effect remain poorly understood. We hypothesised that cell therapy might affect the mechanical properties of isolated host cardiomyocytes., Methods: Two weeks after myocardial infarction (MI), rats were treated by intramyocardial myoblast injection (SkM, n=8), intramyocardial vehicle injection (Medium, n=6), or sham operation (Sham, n=7). Cardiac function was assessed by echocardiography. Cardiomyocytes were isolated in a modified Langendorff perfusion system, their contraction was measured by video-based inter-sarcomeric analysis. Data were compared with a control-group without myocardial infarction (Control, n=5)., Results: Three weeks post-treatment, ejection fraction (EF) further deteriorated in vehicle-injected and non-injected rats (respectively 40.7+/-11.4% to 33+/-5.5% and 41.8+/-8% to 33.5+/-8.3%), but was stabilised in SkM group (35.9+/-6% to 36.4+/-9.7%). Significant cell hypertrophy induced by MI was maintained after cell therapy. Single cell contraction (dL/dt(max)) decreased in SkM and vehicle groups compared to non-injected group as well as cell shortening and relaxation (dL/dt(min)) in vehicle group. A significantly increased predisposition for alternation of strong and weak contractions was observed in isolated cardiomyocytes of the SkM group., Conclusion: Our study provides the first evidence that injection of materials into the myocardium alters host cardiomyocytes contractile function independently of the global beneficial effect of the heart function. These findings may be important in understanding possible adverse effects., (Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.)

Tissue engineering represents an attractive approach for the treatment of congestive heart failure. The influence of the differentiation of myogenic graft for functional recovery is not defined. We engineered a biodegradable skeletal muscle graft (ESMG) tissue and investigated its functional effect after implantation on the epicardium of an infarcted heart segment. ESMGs were synthesized by mixing collagen (2 mg/mL), Matrigel (2 mg/mL), and rat skeletal muscle cells (10(6)). Qualitative and quantitative aspects of ESMGs were optimized. Two weeks following coronary ligation, the animals were randomized in three groups: ESMG glued to the epicardial surface with fibrin (ESMG, n = 7), fibrin alone (fibrin, n = 5), or sham operation (sham, n = 4). Echocardiography, histology, and immunostaining were performed 4 weeks later. A cohesive three-dimensional tissular structure formed in vitro within 1 week. Myoblasts differentiated into randomly oriented myotubes. Four weeks postimplantation, ESMGs were vascularized and invaded by granulation tissue. Mean fractional shortening (FS) was, however, significantly increased in the ESMG group as compared with preimplantation values (42 +/- 6 vs. 33 +/- 5%, P < 0.05) and reached the values of controlled noninfarcted animals (control, n = 5; 45 +/- 3%; not significant). Pre- and postimplantation FS did not change over these 4 weeks in the sham group and the fibrin-treated animals. This study showed that it is possible to improve systolic heart function following myocardial infarction through implantation of differentiated muscle fibers seeded on a gel-type scaffold despite a low rate of survival.

Aprotinin is widely used in cardiac surgery to reduce postoperative bleeding and the need for blood transfusion. Controversy exists regarding the influence of aprotinin on renal function and its effect on the incidence of perioperative myocardial infarction (MI) and cerebrovascular incidents (CVI). In the present study, we analyzed the incidence of these adverse events in patients who underwent coronary artery bypass grafting (CABG) surgery under full-dose aprotinin and compared the data with those recently reported by Mangano et al [2006]. For 751 consecutive patients undergoing CABG surgery under full-dose aprotinin (>4 million kalikrein-inhibitor units) we analyzed in-hospital data on renal dysfunction or failure, MI (defined as creatine kinase-myocardial band > 60 iU/L), and CVI (defined as persistent or transient neurological symptoms and/or positive computed tomographic scan). Average age was 67.0 +/- 9.9 years, and patient pre- and perioperative characteristics were similar to those in the Society of Thoracic Surgeons database. The mortality (2.8%) and incidence of renal failure (5.2%) ranged within the reported results. The incidence rates of MI (8% versus 16%; P < .01) and CVI (2% versus 6%; P < .01) however, were significantly lower than those reported by Mangano et al. Thus the data of our single center experience do not confirm the recently reported negative effect of full-dose aprotinin on the incidence of MI and CVI. Therefore, aprotinin may still remain a valid option to reduce postoperative bleeding, especially because of the increased use of aggressive fibrinolytic therapy following percutaneous transluminal coronary angioplasty.

Background: Minimal extracorporeal circulation (MECC) is a promising perfusion technology, taking the advantage of an ECC while having a significantly reduced priming volume. We analyzed the actual possible benefits of using MECC in patients undergoing CABG procedures and compared the results with conventional extracorporeal circulation (CECC)., Methods: One thousand fifty-three consecutive patients underwent CABG surgery using the MECC perfusion technique. Subgroup analyses focused on perioperative myocardial markers (cardiac troponin I [cTnI]), incidence of atrial fibrillation (AF), and perioperative evaluation of inflammatory markers and data were compared with those of patients who underwent CABG using CECC. A propensity score analysis was performed., Results: Patient characteristics and distribution of EuroSCORE risk were similar in both groups. Severity of coronary artery disease and extent of revascularization were also comparable in both groups (number of distal anastomoses: 3.2 +/- 1.1 in CECC vs 3.2 +/- 0.9 in MECC; p = not significant [ns]). The cTnI was significantly lower in the MECC group (11.0 +/- 10.8 microg/L in MECC vs 24.7 +/- 25.3 microg/L in CECC; p < 0.05). Incidence of AF was 11.1% in MECC and 39.0% in CECC (p < 0.05). Inflammatory markers (interleukin-6, SC5b-9) were lower in MECC patients (p < 0.05). Propensity score analysis confirmed faster recovery in MECC patients and lower incidence of AF., Conclusions: Minimal extracorporeal circulation is a safe perfusion technique for CABG and may therefore concurrence OPCAB and traditional CABG under CECC.

Myocardial tissue engineering aims to repair, replace, and regenerate damaged cardiac tissue using tissue constructs created ex vivo. This approach may one day provide a full treatment for several cardiac disorders, including congenital diseases or ventricular dysfunction after myocardial infarction. Although the ex vivo construction of a myocardium-like tissue is faced with many challenges, it is nevertheless a pressing objective for cardiac reparative medicine. Multidisciplinary efforts have already led to the development of promising viable muscle constructs. In this article, we review the various concepts of cardiac tissue engineering and their specific challenges. We also review the different types of existing biografts and their physiological relevance. Although many investigators have favored cardiomyocytes, we discuss the potential of other clinically relevant cells, as well as the various hypotheses proposed to explain the functional benefit of cell transplantation.

Intramyocardial transplantation of skeletal myoblasts augments postinfarction cardiac function. However, poor survival of injected cells limits this therapy. It is hypothesized that implantation of myoblast-based scaffolds would result in greater cell survival. Rat skeletal myoblasts were seeded on highly porous polyurethane (PU) scaffolds (7.5 x 7.5 x 2.0 mm). The effect of several scaffold pretreatments, initial cell densities, and culture periods was tested by DNA-based cell count and viability assessment. Seeded PU scaffolds were implanted on infarcted hearts and immunohistology was performed 4 weeks later. Precoating with laminin allowed the most favorable cell attachment. An initial inoculation with 5 x 10(6) cells followed by a 15-day culture period resulted in optimal myoblast proliferation. Four weeks after their implantation in rats, numerous myoblasts were found throughout the seeded patches although no sign of differentiation could be observed. This myoblast seeding technique on PU allows transfer of a large number of living myoblasts to a damaged myocardium.

Pulmonary embolism is very rarely reported early after cardiac surgery, most probably due to full heparinisation during cardiopulmonary bypass. We report a 66-year-old man without thromboembolic history who presented three days after a coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic instability. A CT scan confirmed paracentral bilateral pulmonary embolism requiring an urgent and successful embolectomy. Review of the literature confirms that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass patients. The possibility of pulmonary embolism must be taken into consideration in post-cardiopulmonary bypass patients with acute onset of chest pain and respiratory insufficiency.

Recently, a new oxygenator (Dideco 903 [D903], Dideco, Mirandola, Italy) has been introduced to the perfusion community, and we set about testing its oxygen transfer performance and then comparing it to two other models. This evaluation was based on the comparison between oxygen transfer slope, gas phase arterial oxygen gradients, degree of blood shunting, maximum oxygen transfer, and diffusing capacity calculated for each membrane. Sixty patients were randomized into three groups of oxygenators (Dideco 703 [D703], Dideco; D903; and Quadrox, Jostra Medizintechnik AG, Hirrlingen, Germany) including 40/20 M/F of 68.6 +/- 11.3 years old, with a body weight of 71.5 +/- 12.1 kg, a body surface area (BSA) of 1.84 +/- 0.3 m(2), and a theoretical blood flow rate (index 2.4 times BSA) of 4.4 +/- 0.7 L/min. The maximum oxygen transfer (VO(2)) values were 313 mL O(2)/min (D703), 579 mL O(2)/min (D903), and 400 mL O(2)/min (Quadrox), with the D903 being the most superior (P < 0.05). Oxygen (O(2)) gradients were 320 mm Hg (D703), 235 mm Hg (D903), and 247 mm Hg (Quadrox), meaning D903 and Quadrox are more efficient versus the D703 (P < 0.05). Shunt fraction (Qs/Qt) and diffusing capacity (DmO(2)) were comparable (P = ns). Diffusing capacity values indexed to BSA (DmO(2)/m(2)) were 0.15 mL O(2)/min/mm Hg/m(2) (D703), 0.2 mL O(2)/min/mm Hg/m(2) (D903), and 0.18 mL O(2)/min/mm Hg/m(2) (Quadrox) with D903 outperforming D703 (P < 0.0005). During hypothermia (32.0 +/- 0.3 degrees C), there was a lower absolute and relative VO(2 )for all three oxygenators (P = ns). The O(2) gradients, DmO(2) and DmO(2)/m(2), were significantly lower for all oxygenators (P < 0.01). Also, Qs/Qt significantly rose for all oxygenators (P < 0.01). The oxygen transfer curve is characteristic to each oxygenator type and represents a tool to quantify oxygenator performance. Using this parameter, we demonstrated significant differences among commercially available oxygenators. However, all three oxygenators are considered to meet the oxygen needs of the patients.

Seromas occurring around a vascular graft are a rare complication. We report a life-threatening plasma leakage that occurred through the polytetrafluoroethylene vascular prosthesis of an Impella right ventricular assist device (Impella RD [Impella Cardiosystems GmbH, Aachen, Germany]) implanted in a 62-year-old patient with acute right ventricular failure after cardiac transplantation. The leakage became progressively massive. Weaning the patient from the right ventricular assist device was not possible. The prosthesis was thus wrapped within a pericardial patch to contain the leakage. Three days later the patient could be successfully weaned and the pump was removed. The clinical evolution was favorable.

Objective(s): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds., Methods: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction (48.3% +/- 1.1%) were randomized to (1) implantation of myoblast-seeded polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2) implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies., Results: The ejection fraction significantly decreased in the PU (39.1% +/- 2.3%; P = .02) and Sham (39.9% +/- 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB (48.4% +/- 3.1%) and MyoB (47.9% +/- 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB (4960 +/- 266 mm Hg/s) and MyoB (4748 +/- 304 mm Hg/s) than in groups PU (3909 +/- 248 mm Hg/s, P = .01) and Sham (4028 +/- 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation., Conclusions: Myoblast-seeded polyurethane scaffolds prevent post-myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.

Acute myocardial ischemia is a critical adverse effect potentially occurring during cardiac procedures. A peptide inhibitor of the beta-adrenergic receptor kinase (betaARK1), betaARKct, has been successful in rescuing chronic myocardial ischemia. The present study focused on the effects of adenoviral-mediated betaARKct (Adv-betaARKct) delivery on left ventricle (LV) dysfunction induced by acute coronary occlusion. Rabbits received intracoronary delivery of phosphate-buffered saline (PBS) (n=9) or 5x10(11) viral particles of betaARKct (n=8). A loose prolene 5-0 Potz-loop suture was placed around the circumflex coronary artery (LCx) with both ends buried under the skin. Four days later, the suture was retrieved and pulled to occlude the LCx. Ischemia was confirmed by immediate ECG changes. LV function was continuously recorded for 45 min. Contractility (LVdP/dtmax), relaxation (LVdP/dtmin) and end diastolic pressure (EDP) were less impaired in the betaARKct group as compared to PBS (P<0.05, two-way ANOVA). betaAR density was higher in the ischemic area of the LV in the betaARKct group (betaARKct: 71.9+/-4.6 fmol/mg protein, PBS: 54.5+/-4.0 fmol/mg protein, P<0.05). Adenylyl cyclase activity was also improved basally and in response to betaAR stimulation. betaARK1 activation was less in the betaARKct group (P<0.05). Therefore, inhibition of myocardial betaARK1 may represent a new strategy to prevent LV dysfunction induced by acute coronary ischemia., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

In humans, the lateral recumbent position has a beneficial effect on haemodynamics. If this effect is substantial in small animals too, there is a risk of misinterpretation in preclinical investigations. Therefore, the aim of this study was to analyse the impact of acute changes in body position on haemodynamics in rats. Healthy rats (n=21) and rats post myocardial infarction (n=20) were randomly positioned supine, prone, or on the right or left side. In each position, we measured haemodynamic parameters by pressure-tip catheter and thermodilution. We found that left ventricular contractility (dP/dtmax) was significantly elevated in both lateral positions as compared to the supine position in healthy rats. In healthy rats and following infarction, cardiac index (CI) and stroke volume index (SVI) were significantly higher in both lateral positions as compared to the supine or prone position. Of importance, if SVI values in the supine position in healthy rats (0.095 +/- 0.003 ml (100 g)(-1)) are compared to SVI values measured in different positions after myocardial infarction, the SVI can be either significantly lower in the supine (0.084 +/- 0.003 ml (100 g)(-1)) or significantly higher in the left lateral position (0.105 +/- 0.003 ml (100 g)(-1)). We conclude that post myocardial infarction and in healthy control rats, important haemodynamic values are increased in lateral positions as compared to prone or supine positions. Analysing haemodynamic data in rats may therefore result in misinterpretation if the body position is inconsistent.

beta-adrenergic receptor (betaAR) antagonists, or beta blockers, are now a part of the standard therapeutic arsenal in the medical management of chronic heart failure (HF). Conversely, betaAR stimulation remains the most efficient way to enhance cardiac contractile function acutely, although long-term inotropic therapy based on enhanced betaAR stimulation is likely detrimental. Although altered betaAR signaling plays a pivotal role in the genesis of HF, the choice to therapeutically agonize or antagonize this receptor pathway remains an area of ongoing investigation. Research from the authors' laboratory as well as other research conducted over the last 10 years has produced evidence to support the fact that "normalizing" the betaAR system at a molecular level and improving signaling, instead of blocking it, leads to significant enhancement of cardiac contractile function and prevents ventricular remodeling in HF. This review summarizes the extensive in vivo animal model experimentation that supports the still-controversial hypothesis that increasing the myocardial density of beta(2)-ARs or, more effectively, inhibiting the activity of the betaAR kinase (also referred to as G-protein-coupled receptor kinase 2), represent potential novel therapeutic strategies for HF.

Objectives: Prevalence of abdominal aortic aneurysms (AAA) is not exactly known among patients with coronary artery disease (CAD) who are considered for surgical revascularisation. We evaluated the value of screening AAA among coronary patients admitted in our cardiovascular surgery unit., Methods: Over a 24-month period, an abdominal echography was proposed to male patients aged 60 or more while hospitalised for surgical coronary revascularisation. Patients with previous investigation of the aorta were excluded. The aorta was considered aneurysmal when the anterior-posterior diameter was of 30 mm or more., Results: Three hundred and ninety-five consecutive patients all accepted a proposed abdominal echographic screening for AAA. Forty unsuspected AAA were detected (10.1%). The mean diameter was 38.9 +/- 1.3 mm. Four AAA were larger than 50 mm and considered for surgery after the CABG procedure. Surveillance was proposed to the other 36, especially the 10 patients with an AAA larger than 40 mm. Patients with AAA were significantly older than those without AAA (71.3 +/- 0.8 vs. 69.4 +/- 0.3 years, P<0.05). Smoking history (P<0.05) and hypertension (P<0.05) were also associated more frequently with AAA. More than 16% of the patients being smokers and suffering hypertension presented with unsuspected AAA., Conclusions: In-hospital screening of AAA is very efficient among patients with coronary artery disease. Therefore, patients with CAD may be considered for routine AAA screening.

Vacuum-assist venous drainage (VAVD) can increase venous blood return during cardiopulmonary bypass (CPB) procedures. However, the negative pressure created in the closed cardiotomy reservoir can be transmitted to the oxygenator if a nonocclusive or centrifugal arterial pump is used, resulting in bubble transgression (BT) from the gas to blood compartment of the oxygenator. We analyzed the vacuum pressure required to produce BT using an in vitro circuit including successively a closed reservoir, a pump (centrifugal or roller), and an oxygenator. A constant hydrostatic pressure was maintained onto the oxygenator. Vacuum was applied on the cardiotomy reservoir, progressively increasing negative pressure from 0 to -80 mmHg and monitoring BT with a bubble detector. Six different oxygenators were compared. A partially occlusive roller pump and a centrifugal pump were compared to a control, which was without any pump. A mean negative pressure of -53 +/- 7 mmHg was necessary to produce BT in all the oxygenators in the absence of a pump. The presence of a centrifugal pump between the reservoir and the oxygenator significantly increased the negative pressure required to produce BT compared to the control (-67 +/- 7 mmHg, p < .05). No bubbles were detected using the roller pump (> -80 mmHg needed for BT), thus statistically significant when compared to the centrifugal pump (p < .05). The centrifugal pump offers significant resistance to BT but not as much compared to the roller pump, though BT cannot be prevented if the pump is turned off while the vacuum remains on the reservoir. Therefore, VAVD is a safe technique as long as the perfusionist stops the vacuum when the arterial pump is no longer in use.

To limit the morbidity of cardiopulmonary bypass (CPB), a new concept of integrating pumping, oxygenation, and air removal into a single unit has been developed (CardioVention Inc., Santa Clara, CA). The air filtration capacity of this system was tested. Three calves (73.2 +/- 2 kg) were connected to the integrated system by jugular and carotid cannulation. The integrated unit was challenged with injections of boluses of air of 5, 10, and 20 ml, three times each, and for a blood flow of 3 L/min and 5 L/min, respectively. The bubble count and size were recorded downstream of the unit with a Doppler ultrasound. At 3 L/min, bubbles were detected after injections of 20 ml only (n = 7 for the nine boluses). At 5 L/min, 1 bubble was detected with the nine injections of 5 ml, 14 bubbles were detected with nine injections of 10 ml, and 25 bubbles were detected with nine injections of 20 ml. No bubble exceeded 40 microm in diameter as determined by the Doppler ultrasound. The air filtering capacity of the CardioVention system is excellent both in terms of bubble count and of size after injection of large boluses of air. Its integrated concept offers a simplification of the circuit with fewer devices and connections, which further reduces the risk of accidental air introduction.

Objectives: Recent studies have demonstrated cardiac improvement in patients supported with a ventricular assist device, suggesting that reverse remodeling and myocardial recovery are possible. We developed an animal model of cardiac unloading by adapting a heterotopic transplantation technique and used it to examine the pattern of functional recovery in the left ventricle of the failing heart., Methods: Heart failure was induced in adult New Zealand rabbits by coronary artery ligation with subsequent myocardial infarction. Animals undergoing sham operation served as a control group. After 4 weeks or 3 months, failing hearts were transplanted into the necks of recipient rabbits. A left ventricular latex balloon connected to subcutaneous tubing allowed repeated physiologic analysis on days 1 and after transplantation and then every 5 days until day 30., Results: Contractility (left ventricular dP/dt(max)) and relaxation (left ventricular dP/dt(min)) were significantly lower in transplanted postinfarction hearts as compared to control hearts immediately after transplantation. Both left ventricular dP/dt(max) and left ventricular dP/dt(min) responses to increased preload and to beta-adrenergic stimulation progressively improved to a significantly higher level after 30 days of left ventricular unloading for the hearts that were transplanted 4 weeks after myocardial infarction. However, this functional improvement was not detected in failing hearts transplanted 3 months after infarction., Conclusions: This model of cardiac unloading appears at least partially to mimic conditions of ventricular assist devices. If performed early in the development of heart failure, it permits improvement of contractile dysfunction and restoration of cardiac responsiveness to mechanical and beta-adrenergic stimulation. Therefore this model may constitute a novel alternative in the study of reverse remodeling in unloaded failing hearts.

A coaxial atrial cannula connected to a mini-centrifugal pump was developed to bypass the right heart during extreme exposures in off-pump coronary artery bypass surgery. This study was designed to test the effect of this pump, running during 24 hours, on blood elements to evaluate its use as a prolonged right heart support. In a calf model (body weight 68+/-5 kg), the pump was inserted and set to its maximal motor speed of 7000 rpm. Blood samples were drawn every 6 hours for blood gas analyses, as well as for hematology and chemistry. The right heart mini-pump performed perfectly at its maximal speed over the 24 hour period. Blood gas parameters and blood lactate levels reflected adequate tissue perfusion (baseline: 2.2+/-0.5 mmol/L vs. 24 h: 2+/-0.3 mmol/L; p = 0.64). Red blood cell count was stable (baseline: 9.8+/-1.4 x 10(12)/L vs. 24 h: 9.6+/-1.1 x 10(12)/L; p = 0.83). Free plasma hemoglobin remained below 100 mg/L throughout the experiment. Platelet count was stable during the first 6 hours and exhibited a tendency to drop thereafter (baseline: 749+/-104 x 10(9)/L vs. 24 h: 486+/-20 x 10(9)/L; p = 0.01). This right heart mini-pump appears to provide sufficient blood flow during a 24 hour period with minimal impact on red cell and moderate platelet damage after 6 hours. These results suggest a potential application of this system for postcardiotomy right heart support.

Objectives: Reperfusion after myocardial ischemia goes together with alteration of the beta-adrenergic (betaAR) signaling. Especially the level and catalytic activity of beta AR kinase (betaARK1) are increased. We hypothesized that myocardial expression of a betaARK1 inhibitor (betaARKct) may protect from post-reperfusion dysfunction., Methods: Two groups of rabbits were treated by intracoronary delivery of either phosphate-buffered saline (PBS) or a solution of adenovirus carrying the betaARKct transgene (Adeno-betaARKct). At day 5, the hearts were explanted after cold cardioplegic arrest, and preserved at 4 degrees C for 4 h. Reperfusion was hemodynamically standardized on a Langendorff apparatus with oxygenated Krebs solution for 30 min before left ventricular (LV) pressure was recorded using an LV latex balloon connected to a pressure transducer. Non-arrested hearts immediately perfused on the Langendorff apparatus served as controls., Results: LV contractility (LV dP/dt(max), P < 0.05) and relaxation (LV dP/dt(min), P < 0.05) were reduced, and end diastolic pressure (LV EDP) was increased after prolonged exposure to cold preservation solution as compared to normal control hearts, both under basal conditions and when stimulated with the betaAR agonist isoproterenol. However, these parameters remained within a normal range in Adeno-betaARKct-expressing hearts arrested and preserved for 4 h. Biochemical analysis shows a reduced betaAR density and an impaired signaling after reperfusion of hearts arrested for 4 h whereas it is normalized in Adeno-betaARKct-expressing hearts., Conclusion: Myocardial gene-mediated inhibition of betaARK1 via betaARKct expression avoids ventricular dysfunction after prolonged preservation. Therefore, this may represent a way of improving early results of cardiac transplantation and perioperative function., (Copyright 2002 Elsevier Science B.V.)

Background: During percutaneous cannulation, the diameter of the venous cannula is determined by the size of the access site. To limit this restriction, the Smart cannula (Cardiosmart Ltd., Fribourg, Switzerland) has been developed. Because its design allows self-expansion within the recipient vein, diameter restriction is limited to the access site., Methods: In 6 calves (78 +/- 4.3 kg), the jugular vein and the carotid artery were cannulated through a cervicotomy. The Smart cannula was tested against three percutaneous cannulas with a diameter of 27, 25, and 21F, respectively. Stenotic percutaneous access to the vein was simulated by 1-cm wide tape encircling the vein that could be adjusted to a diameter of 27, 25, and 21F, respectively. The maximal flow rate, reached with stable reservoir level and a negative pressure of 44 mm Hg, was determined three times for each access size with the Smart cannula (one size fits all) and the corresponding percutaneous cannula successively., Results: For an access size of 27F, the flow of the Smart cannula was 5.7 +/- 0.4 L/min and that of the percutaneous cannula was 4.3 +/- 0.2 L/min (p < 0.0001); for 25F, flow rates were 5.6 +/- 0.5 and 3.9 +/- 0.2 L/min, respectively (p < 0.0001); and for 21F, the flow rates were 4.3 +/- 0.4 and 2.7 +/- 0.3 L/min, respectively (p < 0.0001). The percentage increase of flow for the 27, 25, and 21F sizes were 34% +/- 9%, 42% +/- 16%, and 53% +/- 18%, respectively (one-way analysis of variance, p = 0.014)., Conclusions: For the present set-up, the Smart cannula outperforms commercially available percutaneous cannulas. The smaller the size of the insertion site, we observed a higher gain of flow with the Smart cannula.