Patterned oscillating topographical changes in photoresponsive polymer coatings.

The light-induced surface topography of a liquid crystal polymer coating is brought into a patterned oscillatory deformation. A dichroic photo-responsive azobenzene is co-aligned with the planar oriented nematic liquid crystal network molecules which makes the surface deformation sensitive to polarized UV light. Locally selective actuation is achieved in coatings with a complex alignment pattern. Dynamic oscillation, as controlled by the actuation and relaxation kinetics of the polymer, is obtained by a continuous change in the polarization of the UV source. The atypical deformation at the defect lines between the domains is of special interest. The amplitude and presence of the oscillation can be manipulated by changing the ratio between blue and UV light and by varying the ambient temperature of the coating.

Clinical-scale in vitro expansion preserves biological characteristics of cardiac atrial appendage stem cells.

OBJECTIVES: Cardiac atrial appendage stem cells (CASCs) have recently emerged as an attractive candidate for cardiac regeneration after myocardial infarction. As with other cardiac stem cells, CASCs have to be expanded ex vivo to obtain clinically relevant cell numbers. However, foetal calf serum (FCS), which is routinely used for cell culturing, is unsuitable for clinical purposes, and influence of long-term in vitro culture on CASC behaviour is unknown. MATERIALS AND METHODS: We examined effects on CASC biology of prolonged expansion, and evaluated a culture protocol suitable for human use. RESULTS: In FCS-supplemented medium, CASCs could be kept in culture for 55.75 ± 3.63 days, before reaching senescence. Despite a small reduction in numbers of proliferating CASCs (1.37 ± 0.52% per passage) and signs of progressive telomere shortening (0.04 ± 0.02 kb per passage), their immunophenotype and myocardial differentiation potential remained unaffected during the entire culture period. The cells were successfully expanded in human platelet plasma supernatant, while maintaining their biological properties. CONCLUSIONS: We successfully developed a protocol for long-term culture, to obtain clinically relevant CASC numbers, while retaining their cardiogenic potential. These insights in CASC biology and optimization of a humanized platelet-based culture method are an important step towards clinical application of CASCs for cardiac regenerative medicine.

Radiotherapy-induced mitral incompetence.

Radiotherapy-induced cardiac disease is a progressive condition with symptoms beginning several years after treatment. The following article reports the case of a 48-year-old woman who had undergone mediastinal radiation therapy for Hodgkin's lymphoma at age of 15 and, more than thirty years later, suffered from congestive heart failure due to fibrotic thickening of the mitral valve. She successfully underwent mitral valve repair with patch augmentation of the anterior leaflet. Long-term cardiac follow-up of patients treated by mediastinal radiation therapy is warranted.

Suppressed increase in blood endothelial progenitor cell content as result of single exhaustive exercise bout in male revascularised coronary artery disease patients.

Endothelial progenitor cells (EPCs) significantly affect endothelial repair capacity and, hence, cardiovascular disease incidence. In healthy subjects, blood EPC content increases significantly as result of a single maximal exercise test, hereby stimulating endothelial repair capacity. It remains to be shown whether a single exercise positively affects blood EPCs in revascularised coronary artery disease (CAD) patients. From male revascularised CAD patients (n = 60) and healthy volunteers (n = 25) blood samples were collected before and immediately after a maximal cardiopulmonary exercise test. Blood samples were analyzed by optimised flow cytometry methodology for EPC content (CD34+, CD34+ CD133+, CD34+VEGFR2+, CD34+CD133+VEGFR2+, and CD34+CD133-VEGFR2+ cells) and compared between groups. CFU-Hill colonies were additionally assessed. As a result of a maximal exercise test, blood CD34+, CD34+VEGFR2+ (all EPCs), CD34+CD133+, and CD34+ CD133-VEGFR2+ (mature EPCs) cells increased significantly in CAD patients (p < 0.05), but less than in healthy subjects (p < 0.05, and p = 0.06 for CD34+VEGFR2+). CD34+CD133+VEGFR2+ cells (immature EPCs) did not change as result of exercise (p > 0.05). No changes in CFU-Hill colonies as result of exercise were observed. This study shows that blood mature EPCs (CD34+CD133-VEGFR2+) increase significantly as result of a single exercise bout in revascularised CAD patients, but with smaller magnitude compared to healthy subjects. Blood immature EPCs (CD34+CD133+VEGFR2+) did not change significantly as result of exercise.

Ex vivo evaluation of a new neonatal/infant oxygenator: comparison of the Terumo CAPIOX Baby RX with Dideco Lilliput 1 and Polystan Safe Micro in the piglet model.

OBJECTIVE: A newly developed neonatal and infant oxygenator with a nonheparin biocompatible polymer coating, low priming volume (43 mL), high oxygen transfer, wide operating range (<1.5 L/min) and low pressure drop represents a promising solution for cardiac surgery in neonates and infants. We compared the new CAPIOX Baby RX, Terumo (BRX) with two commonly used neonatal oxygenators: Dideco Lilliput 1 (DL1) and Polystan Safe Micro (PSM) in a piglet model. METHODS: Fifteen piglets (5.6 +/- 1.3kg) were placed on standardized cardiopulmonary bypass (CPB) for 6 hours using one of the three oxygenators (n = 5 in each group). After 120 min, the system was cooled to 25 degrees C for 60 min and then returned to normothermia. Arterial and venous blood gas data and temperature were recorded continuously by a CDI500 System (Terumo). Pressure drop, FiO2 and gas flow were recorded. Blood samples were taken before CBP, after 10 min, before and after cooling, and at the end. Total blood counts, thrombin-antithrombin complex and plasma-free haemoglobin (PfHb) were measured. RESULTS: All oxygenators showed acceptable performance for the duration of CPB. The BRX had lower mean gas flow (0.33 +/- 0.05 L/min) and FiO2 (0.43 +/- 0.02%) throughout CPB than the DL1 (1.14 +/- 0.25 L/min, p = 0.006 and 0.60 +/- 0.02%, p = 0.009, respectively) or the PSM (1.47 +/- 0.87 L/min and 0.54 +/- 0.08%, p = ns). Pressure drop in the BRX group ranged from 12 to 22 mmHg. This was significantly lower than in the DL1 group (39-65 mmHg, p = 0.005). In the PSM group, values ranged between 24 and 33 mmHg (p = ns). The increase in PfHb at six hours was significantly lower in the BRX (11.3 +/- 4.2 ng/dL) versus the DL1 (42.2 +/- 6.1 ng/dL, p = 0.004) and the PSM (56.7 +/- 15.5 ng/dL, p = 0.045). CONCLUSIONS: The BRX is as safe as the DL1 and the PSM, with superior performance in pressure drop, efficient blood gas management and lower haemolysis. The BRX exhibited the lowest prime, hold-up volume and breakthrough time.

Evaluation of a novel synthetic sealant for inhibition of cardiac adhesions and clinical experience in cardiac surgery procedures.

BACKGROUND: Pericardial adhesions subject patients requiring reoperation to potential injuries to the heart, great vessels, and cardiac grafts during the re-sternotomy. These adhesions can severely complicate re-operations by making re-entry hazardous, impeding orientation and visibility, increasing the amount of blood loss, and prolonging the operation time. The efficacy of an in situ-forming polyethylene glycol (PEG) material, CoSeal surgical sealant (CoSeal), for inhibiting cardiac adhesions in an animal model is reported. It is currently estimated that 10-20% of patients undergoing aortic valve replacement and coronary artery bypass grafting (CABG) will require a second operation later in their lives. Successful clinical experience using CoSeal for sealing suture lines of the aorta and CABGs with the data reported here suggest that CoSeal may have multiple applications in cardiac surgery. METHODS: In rabbits, a sternotomy and pericardiotomy were performed to expose the heart and the epicardium of the left ventricular surface. The epicardium was abraded for five minutes with dry gauze and cotton to develop punctate bleeding. In treated animals, CoSeal(R) or Tissucol(R) was applied directly to the abraded bleeding epicardium while retracting the pericardium. The pericardium was released, and the material over-sprayed to the cut edges of the pericardium. No material was applied in control animals. RESULTS: At necropsy, CoSeal(R) was found to significantly reduce the formation of adhesions, the tenacity of the adhesions, and the percent of the abraded site with adhesions as compared to surgical control and Tissucol. Tissucol showed no significant difference from the surgical control in any adhesion parameter. CoSeal treated hearts showed re-establishment of the mesothelial layer and tissue morphology similar to a normal un-operated heart. During the clinical cardiac procedures, CoSeal was easily mixed and applied to the suture lines of the aorta and coronary artery grafts. No bleeding was found at the suture lines. CONCLUSIONS: In the rabbit cardiac adhesion model, CoSeal significantly reduced the formation of adhesions as compared to surgical control and Tissucol, and demonstrated good biocompatibility. In CoSeal treated patients undergoing cardiopulmonary bypass or vessel repair, sealing was achieved comparable to previous cases using Tissucol fibrin sealant. CoSeal effectively sealed the suture lines of the aorta and coronary artery bypass grafts.

Na(+)/H(+)-exchange inhibition and aprotinin administration: promising tools for myocardial protection during minimally invasive CABG.

OBJECTIVE: Minimally invasive coronary artery bypass grafting (CABG), carried out on the warm beating heart, does not allow conventional myocardial protection. The objective was to investigate the possibility of enhancing tolerance to ischemia during short episodes of coronary artery occlusion, based on a pharmacological approach using a selective Na(+)/H(+)-exchange inhibitor (cariporide) or a serine protease inhibitor (aprotinin). METHODS: Four groups (n=6 in each group) of sheep were subjected to 20 min of normothermic regional ischemia (first lateral branch of the circumflex artery occlusion) followed by 1 h of reperfusion. Regional wall thickening was measured using sonomicrometry, and expressed as the percentage of thickening fraction compared with baseline. Group I was the control with no treatment, group II received cariporide (1 mg/kg administered over 2 min prior to ischemia), group III was treated with aprotinin (2.10(6) kallikrein inactivation units (KIU) load followed by 500.000 KIU/h). Group IV was treated with a combination of cariporide and aprotinin at the same concentrations as in groups II and III, respectively. RESULTS: Wall thickening measurements showed that, compared with control, cariporide was largely able to suppress secondary loss of wall thickening after initial recovery during early reperfusion. Wall thickening in the ischemic/reperfused myocardial area improved from 10+/-31 to 51+/-17% at 1 h of reperfusion (P=0.002). Aprotinin improved wall thickening at the end of 1 h of reperfusion to 70+/-13% (P=0.0001). However, in this group, there was a transient loss of regional contractility similar in amplitude and time course to the one observed in the control group. A combination of cariporide and aprotinin suppressed transient contractile loss and resulted in improved wall thickening at the end of 1 h of reperfusion (65+/-22%, P=0.0002 vs. control). This value was not significantly different from the cariporide (P=0.263) or aprotinin (P=0.704) group. CONCLUSION: These data indicate that both Na(+)/H(+)-exchange inhibition and aprotinin administration are promising tools for cardioprotection during minimally invasive CABG. A combination of both treatments is able to adequately suppress loss of contractility during early reperfusion as a consequence of reperfusion injury, and results in significantly improved wall thickening at the end of 1 h of reperfusion.

[Overdentures covering natural roots. The use of chlorhexidine gel]. / Overkappingsprothesen op natuurlijke pijlers. Het gebruik van chloorhexidinegel.

To prevent caries and periodontal disease in overdenture abutment teeth, daily application of chlorhexidine gel is recommended. In order to get insight into the use of the gel, 29 overdenture wearing patients were interviewed. In addition the patients were requested to show the use of the gel. It was concluded that at any time the patients were instructed about the use of the gel. Nevertheless, a majority of the patients did not use the gel daily and in accordance with the instructions given. Application of the gel in the abutment depressions of the overdenture appeared to be a heavy task.

Release of cardiac troponin I in antegrade crystalloid versus cold blood cardioplegia.

OBJECTIVE: The purpose of this study was to assess the efficacy of myocardial protection, comparing antegrade crystalloid cardioplegia with cold blood cardioplegia, in patients with preserved left ventricular function who were undergoing elective first coronary artery bypass grafting. Release of cardiac troponin I was used as a marker for the effectiveness of myocardial protection. METHODS: A consecutive series of 62 patients were randomly assigned to receive crystalloid or blood cardioplegia. Cardiac troponin I concentrations were determined in venous blood samples before the operation, immediately after unclamping, at 6, 9, 12, and 24 hours, and daily thereafter for 5 days. RESULTS: Rising levels of troponin I were found in all patients. The time course and peak release were similar in the crystalloid cardioplegia and the blood cardioplegia groups. No patients in either group had electrocardiographic evidence of perioperative myocardial infarction. Cardiac troponin I was able to detect small areas of myocardial damage, not revealed by electrocardiography or creatine kinase MB release. Aprotinin administration was associated with lower cardiac troponin I release in both groups. Cardiac troponin I was lower in patients whose conditions did not require electrical defibrillation after aortic unclamping, irrespective of cardioplegia type. The presence of a main stem lesion was associated with higher cardiac troponin I release only in the crystalloid cardioplegia group. CONCLUSIONS: Antegrade cold blood cardioplegia is equally effective as antegrade crystalloid cardioplegia in a randomized group of patients with preserved left ventricular function who were undergoing elective first coronary artery bypass grafting. Aprotinin administration resulted in lower cardiac troponin I release, whereas electrical defibrillation was related to a higher release irrespective of cardioplegia type. The presence of a main stem lesion resulted in higher cardiac troponin I release in the crystalloid cardioplegia group.

The use of a heparin removal device: a valid alternative to protamine.

PURPOSE: Experiments were carried out to test the efficacy and safety of the heparin removal device, a plasmapheresis filter that binds and eliminates heparin, in the context of extracorporeal circulation. PROCEDURES AND FINDINGS: Six dogs were put on cardiopulmonary bypass after heparinization. Upon weaning, additional heparin was administered to obtain an activated clotting time above 900s. The animals were connected to the heparin removal device and with flows of 500 ml/min, activated clotting time, activated partial thromboplastin time and plasma heparin concentrations were normalised to baseline after 30 min. Hemodynamic parameters remained unaffected. A slight decrease in red and white blood cell count and in platelets was observed which however recovered spontaneously two hours after the filter procedure. No damage to blood components could be observed. CONCLUSIONS: The use of a heparin removal device is as efficient as systemic administration of protamine to reverse the effects of heparinization. It may prevent the adverse reactions linked to protamine administration and therefore be indicated in certain subgroups of patients undergoing cardiopulmonary bypass.

Aortic and mitral valve disease induced by ergotamine therapy for migraine: a case report and review of the literature.

A case of aortic and mitral valve disease associated with ergotamine abuse is reported. A 34-year-old woman presented with dyspnea after a long standing history of peripheral vascular pathology associated with ergotamine abuse. Cardiac dysfunction was rapidly progressive. At surgery, nodular thickening of both valves and fusion of the posterior leaflet of the mitral valve were seen. Microscopy revealed proliferation of myofibroblasts with little destruction of normal valvular elements. The similarity to lesions in carcinoid heart disease and in methysergide-associated valvular disease suggests direct stimulation of myofibroblast growth by serotonin agonist effect.

Information processing in patients with early and continuously-treated phenylketonuria.

UNLABELLED: A total of 33 patients with early and continuously-treated phenylketonuria (PKU) between 7 and 16 years of age and 33 matched controls participated in a study examining perceptual, central, and response-related mechanisms of information processing. The specific mechanisms studied were: perceptual filtering, memory search, response selection, response execution, and motor presetting. In addition, groups were compared on mean intelligence level and task oriented behaviour. The performance of the PKU patients practically matched that of the controls on all three tasks, suggesting that PKU patients who are continuously maintained on a well-controlled phenylalanine-restricted diet are not impaired in the elementary mechanisms of information processing. Furthermore, groups did not differ in mean IQ or task-oriented behaviour. CONCLUSION: These results underline the importance of continued, well-controlled dietary treatment. Further studies are recommended to obtain a more complete evaluation of the potential of PKU patients under these stricter dietary treatment conditions.

Social behaviour and task orientation in early-treated PKU.

In the context of the Dutch Collaborative Study on the Psychological Development of Children, early treated for Phenylketonuria (PKU), data were obtained on children's behaviour as perceived by parents (n = 53) and teachers (n = 57), using standardized behavioural questionnaires. Results are compared with a group representative of Dutch school-aged children (n = 1381) with a matched control group (n = 38), and with a group, to be considered as "Attention Deficit Hyperactivity Disorder" (ADHD, n = 38). Especially the clusters "negative task orientation" and "extraversion" distinguish between PKU children and controls. In parents' descriptions as well as in teachers' descriptions PKU children score higher in both clusters. Intriguing differences are found between PKU and ADHD. In parents' but not in teachers' descriptions PKU children show signs of negative task orientation almost to a similar degree as children with ADHD, but not of the signs of "negative social behaviour", characteristic for ADHD children. Data are discussed in terms of the effectiveness of early treatment and guidance.

Information processing deficits in children with early and continuously treated phenylketonuria?

Thirty-three patients with early and continuously treated classical phenylketonuria (PKU) and 33 controls matched for age, gender, and educational level of both parents, participated in a chronometric study exploring elementary mechanisms of information processing. Subjects performed speeded performance tasks designed to systematically vary the load on perceptual, central, and output-related mechanisms of information processing. A preliminary analysis of the data indicated that the overall performance of patients with early and continuously treated PKU practically matched that of the controls on all three tasks. Although this finding must be interpreted with caution as it is based on only a preliminary analysis of the data, it suggests that PKU patients who are continuously maintained on a well-controlled phenylalanine-restricted diet are not deficient in the elementary mechanisms of processing. Given the more recent findings indicating that young children with early-treated classical PKU have specific cognitive deficits in the executive function skills, despite relatively strict dietary control, the authors suggest that future studies should focus on these higher-order cognitive processes.

Phenylketonuria and some aspects of emotional development.

Early dietary treatment of phenylketonuria (PKU) prevents intellectual retardation and gross neurological impairment although not all neuropsychological problems. This study investigates to what extent the illness and its treatment imposes a burden on emotional development of early-treated PKU patients and on rearing practices of their parents. It is concluded that in early-treated PKU it is particularly difficult to find constructive ways to adapt to the situation for children as well as for parents. As coping with PKU and its treatment is so complicated, paediatric control should be combined with psychocounselling.

New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart.

BACKGROUND: Experiments were carried out using the new Na(+)-H+ exchange inhibitor (3-methylsulfonyl-4-piperidinobenzoyl)guanidine methanesulfonate (HOE 694) to assess the role of Na(+)-H+ exchange in myocardial ischemic and reperfusion injury. METHODS AND RESULTS: Three groups of rabbit hearts (n = 5 in each) were perfused with blood and were subjected to 45 minutes of global normothermic (37 degrees C) ischemia, followed by 1 hour of reperfusion. Group 1 was the control group (vehicle only); in group 2, HOE 694 (1 mumol/L) was administered before ischemia (pretreatment group); and in group 3, HOE 694 was given only during reperfusion to separate actions exerted during ischemia from those specifically obtained during reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 starting before ischemia (from 52.2 +/- 8.5 mm Hg in group 1 to 17.6 +/- 4.5 mm Hg in group 2, P < .01) or starting on reperfusion (28.8 +/- 5.4 mm Hg in group 3, P < .05 versus group 1). Left ventricular developed pressure (LVDP) and its derivative (dP/dt) recovered better in HOE 694-pretreated hearts (LVDP, 79 +/- 9.9 mm Hg in group 2 versus 24.8 +/- 10 mm Hg in group 1; dP/dt, 1580 +/- 198 mm Hg/s versus 340 +/- 221 mm Hg/s, P < .01). In hearts treated only on reperfusion, some improvement was observed, which, however, did not reach statistical significance. Coronary flow on reperfusion was higher in groups 2 and 3 compared with controls, and no "no-reflow" was observed. Two additional groups of hearts were perfused with phosphate-free Krebs-Henseleit solution to enable studies with 31P nuclear magnetic resonance (NMR). ATP was better preserved in HOE 694-pretreated (62 +/- 4.9% of preischemic value) than in control hearts (44 +/- 3.3%) at the end of 30 minutes of reperfusion, and phosphocreatine resynthesis was higher (109 +/- 3.7% versus 86 +/- 5.4%). HOE 694 did not affect the time course of intracellular acidosis during ischemia but suppressed a small alkaline overshoot occurring early in reperfusion (pH 6.96 +/- 0.02 in HOE 694-pretreated hearts versus 7.14 +/- 0.05 in control hearts). Electron microscopy with Ca2+ staining of the blood-perfused hearts showed that clumping of Ca2+ aggregates in mitochondria was prevented by HOE 694. CONCLUSIONS: Postischemic dysfunction was associated with a rise in end-diastolic pressure. This rise was effectively blocked by HOE 694. The drug was most effective when hearts were treated before ischemia, although partial protection was observed when administration was started on reperfusion. The action of HOE 694 strengthens the idea that Na(+)-H+ exchange during both ischemia and reperfusion contributes to contractile dysfunction.

Improved functional recovery after ischemic preconditioning in the globally ischemic rabbit heart is not mediated by adenosine A1 receptor activation.

Experiments were carried out to test the hypothesis that preconditioning reduces the impairment of recovery of cardiac mechanical function and that this effect is mediated by activation of adenosine A1 receptors. Isolated hearts were Langendorff-perfused at 37 degrees C with oxygenated blood and paced at 3 Hz. They were divided into 5 groups, all subjected to 45 min global ischemia followed by one hour of reperfusion: 1) Control hearts (n = 7) which received no treatment or short ischemia before the long ischemia, 2) preconditioned hearts (n = 7), submitted to 5-min zero-flow global ischemia, followed by 5 min reperfusion before the long ischemia, 3) hearts pretreated with sulfophenyltheophylline (SPT 100 microM) before preconditioning and long ischemia (n = 6), 4) hearts in which preconditioning was substituted by administration of 10 microM phenyl-isopropyl-adenosine (PIA) over 5 min, and 5) hearts in which preconditioning was substituted by the administration of 1.5 mg adenosine over 5 min. Hemodynamic results show significant improvement of the postischemic recovery of left ventricular developed pressure (DP) by preconditioning. SPT pretreatment did not reverse the improvement of recovery, obtained by preconditioning, whereas PIA treatment could not mimic preconditioning. Adenosine treatment caused some improvement of recovery of DP, but which remained lower compared to that caused by preconditioning. The contracture developed during ischemia persisted in control hearts, whereas contracture disappeared in non-treated preconditioned hearts. SPT did not prevent the decrease in contracture by preconditioning although values remained slightly higher than in the non-treated preconditioned hearts. PIA did not substitute for preconditioning in preventing contracture. In the adenosine treated group, some decrease of contracture occurred during reperfusion, but values remained significantly higher than in preconditioning. We conclude that receptor A1 activation is not the main mechanism underlying improved functional recovery conferred by preconditioning since an A1 receptor blocker (SPT) cannot reverse the effect of preconditioning and an A1 receptor agonist (PIA) cannot mimic it. Administration of exogenous adenosine reduces functional impairment to a certain extent, but less than preconditioning.