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Biomedical subjects

Gregor Zünd

Publications and source records attributed to Gregor Zünd.

At least 19 recordsLinked to original sources

Geometric models of the aortic and pulmonary roots: suggestions for the Ross procedure.

OBJECTIVE: To discuss geometric factors, which may influence long-term results relating to homograft competence following the Ross procedure, we describe the 3D morphology of the pulmonary and aortic roots. MATERIALS: Measurements were made on 25 human aortic and pulmonary roots. Inter-commissural distances and the heights of the sinuses were measured. For geometrical reconstruction the three commissures and their vertical projections at the root base were used as reference points. RESULTS: In the pulmonary root, the three inter-commissural distances were of similar dimensions (17.9+/-1.6mm, 17.5+/-1.4mm and 18.6+/-1.5mm). In the aortic root, the right inter-commissural distance was greatest (18.8+/-1.9mm), followed by the non-coronary (17.4+/-2.0mm) and left coronary sinus commissures (15.2+/-1.9mm). The mean height of the left pulmonary sinus was greatest (20+/-1.7mm) followed by the anterior (17.5+/-1.4mm) and right pulmonary sinus (18+/-1.66mm). In the aortic root, the height of the right coronary sinus was the greatest (19.4+/-1.9mm) followed by the heights of the non-coronary (17.7+/-1.8mm) and left coronary sinus (17.4+/-1.4mm). Measured differences between parameters determine the tilt angle and direction of the root vector. The tilt angle in the pulmonary root averaged 16.26 degrees , respectively; for the aortic roots, it was 5.47 degrees . CONCLUSIONS: Herein we suggest that the left pulmonary sinus is best implanted in the position of the right coronary sinus, the anterior pulmonary in the position of the non-coronary sinus and the right pulmonary sinus in the position of the left coronary sinus. In this way, the direction of the pulmonary root vector will be parallel to that of the aortic root vector.

Adult↗

Does retrograde cerebral perfusion via superior vena cava cannulation protect the brain?

OBJECTIVE: The retrograde cerebral perfusion via cannulation of the superior vena cava is a widespread method for optimising protection of the brain during hypothermic circulatory arrest. METHODS: In 14 cadavers (8 females, 6 males) of the local department of pathology, an examination was performed to check the competence of the valves of the internal jugular veins. After a complete preparation of the superior vena cava, the innominate vein and both internal jugular veins, ligating all side branches, a retrograde perfusion on 7 cadavers was installed, documenting flow and pressure of each internal jugular vein (IJV) in vitro. Afterwards, the veins were opened and their valves inspected. RESULTS: In all 14 cadavers, anatomically and functionally competent valves on the right proximal IJV were found. Only 1/14 cadaver had no valve in the left proximal IJV. Additional rudimentary and incompetent valves could be identified in 1/14 cadaver on the distal right IJV, and in 2/14 cadavers on the left IJV. Retrograde flow measurement of 7/14 cadavers revealed 0 ml/min in 4/7 cadavers, 6 ml/min in 1/7, 340 ml/min in 1/7 and 2500 ml/min in 1/7 cadaver. CONCLUSIONS: As a rule, anatomically and functionally competent valves in the proximal IJV are present. In human beings, they obstruct the direct retrograde inlet to the intracranial venous system, which suggests an unbalanced and unreliable perfusion of the brain. Therefore, retrograde cerebral perfusion by cannulating the superior vena cava may help flushing out embolism and supporting 'the cold jacket' of the brain. However, its effect of retrograde backflow cannot be a sign of adequate cerebral perfusion.

Brain Ischemia↗

Autologous human tissue-engineered heart valves: prospects for systemic application.

BACKGROUND: Tissue engineering represents a promising approach for the development of living heart valve replacements. In vivo animal studies of tissue-engineered autologous heart valves have focused on pulmonary valve replacements, leaving the challenge to tissue engineer heart valves suitable for systemic application using human cells. METHODS AND RESULTS: Tissue-engineered human heart valves were analyzed up to 4 weeks and conditioning using bioreactors was compared with static culturing. Tissue formation and mechanical properties increased with time and when using conditioning. Organization of the tissue, in terms of anisotropic properties, increased when conditioning was dynamic in nature. Exposure of the valves to physiological aortic valve flow demonstrated proper opening motion. Closure dynamics were suboptimal, most likely caused by the lower degree of anisotropy when compared with native aortic valve leaflets. CONCLUSIONS: This study presents autologous tissue-engineered heart valves based on human saphenous vein cells and a rapid degrading synthetic scaffold. Tissue properties and mechanical behavior might allow for use as living aortic valve replacements.

Absorbable Implants↗

Coronary artery imaging with 64-slice computed tomography from cardiac surgical perspective.

INTRODUCTION: 64-Slice computed tomography (CT) has been introduced with high expectations. This study illustrates the value of 64-slice CT for the diagnosis of significant coronary artery stenoses when images are analysed by cardiovascular surgeons. METHODS: Fifty patients (39 males, 11 females) underwent invasive coronary angiography and 64-slice CT. In these patients, 40 had coronary artery disease and 10 patients had valvular disease. Evaluation of right coronary artery (RCA), left main (LM), left anterior descending artery (LAD), diagonal branch 1 (D1), circumflex branch (CX), and 1st marginal branch was performed by two cardiovascular surgeons. All vessels with a diameter >/=1.5 mm were analysed and a lumen restriction of >50% was considered a significant stenosis. CT image quality was classified as excellent, reduced but still diagnostic, and not assessable. Invasive coronary angiography was taken as gold standard for calculations of diagnostic accuracy. RESULTS: Mean heart rate during CT scan was 65+/-11 beats per minute (bpm). Image quality of 92% (506/550) of all segments was rated as excellent, 5% (27/550) were rated as being of reduced quality but still diagnostic, and 3% (17/550) were considered not assessable. The sensitivity for diagnosing a significant stenosis with CT when including all reliably evaluated segments was 93% (106/114), specificity was 97% (381/392), positive predictive value was 91% (106/117), and negative predictive value was 98% (381/389). CONCLUSION: 64-Slice CT provides a high diagnostic accuracy in assessing significant coronary artery stenosis. Nevertheless, still exist some disadvantages such as strong vessel wall calcifications reducing the reliability for image interpretation. At the moment, 64-slice CT should be used as a complementary imaging modality to invasive coronary angiography.

Aged↗

Activation of human microvascular endothelial cells with TNF-alpha and hypoxia/reoxygenation enhances NK-cell adhesion, but not NK-Cytotoxicity.

BACKGROUND: Ischemia/reperfusion injury (I/R) and cellular rejection in solid organ transplantation are characterized by adhesion molecule up-regulation on the graft endothelium, a prerequisite for leukocyte recruitment. The contribution of NK cells to I/R and allograft rejection is not well understood. The aim of the present study was to investigate allogeneic interactions between human NK cells and microvascular endothelial cells (MVEC) with special regard to the differential impact of TNF-alpha and hypoxia/reoxygenation in an in vitro model of I/R. METHODS: MVEC were stimulated in vitro for 8 h with TNF-alpha, exposed to hypoxia (1% O2), hypoxia/reoxygenation, and combinations thereof in a hypoxia chamber. Cell surface expression of adhesion molecules on MVEC was analyzed by flow cytometry, and adhesion molecule shedding by ELISA. NK cell adhesion on MVEC was determined under shear stress, and NK cytotoxicity using Cr-release assays. RESULTS: Surface expression of ICAM-1, VCAM-1, and E-/P-selectin on MVEC was up-regulated by TNF-alpha but unaffected by hypoxia/reoxygenation in the absence of TNF-alpha. ICAM-1 expression was further increased by a combination of TNF-alpha and hypoxia/reoxygenation, whereas TNF-alpha-induced E-/P-selectin expression was strongly reversed by hypoxia/reoxygenation. NK cell adhesion increased after exposing MVEC to TNF-alpha and hypoxia/reoxygenation. Susceptibility of MVEC to NK cytotoxicity was enhanced by TNF-alpha and slighty reduced by hypoxia/reoxygenation. CONCLUSIONS: Endothelial activation with TNF-alpha, but not hypoxia/reoxygenation, induced NK cytotoxicity whereas the combination thereof induced the strongest NK cell adhesion. Our findings suggesting a role for NK cells in allograft responses support the development of anti-inflammatory treatment strategies to prevent I/R.

Cell Adhesion↗

Blood supply of the sternum and its importance in internal thoracic artery harvesting.

BACKGROUND: The internal thoracic artery (ITA) is the conduit of choice in coronary bypass grafting, due to the excellent long-term results achieved using it. However, increased incidence of sternal infections after pedicled ITA harvesting has revived interest in the morphology of sternal blood supply. Our aim was to discuss the topography of the sternal branches with emphasis on internal thoracic artery harvesting. METHODS: This study was conducted on 50 fresh specimens of the anterior thorax wall. Radio-opaque material was injected and angiograms of the ITA were performed. Subsequently, the specimens were preserved and a dry dissection of each ITA and its branches was carried out. RESULTS: In dry dissected specimens, four types of vessels were identified that have the potential to carry blood to the sternum after harvesting the ITA. In the first group, the artery to the sternum also supplies the intercostal space. In the second morphologic variant, the sternal branch gives off the perforating and anterior intercostal arteries. In the third group, we classified the common branch of the sternal and perforating arteries. In the fourth group, the sternal artery originated from the ITA as an independent branch. CONCLUSIONS: For sternal-intercostal, perforating-intercostal, and sternal-perforating branches to function as collaterals after ITA harvesting, the common trunk of origin must remain intact. Based on morphologic data, we recommend ligating the common trunk as close as possible to the ITA; in this way, collateral blood flow to the sternum remains intact.

Adolescent↗

Effects of tacrolimus or sirolimus on proliferation of vascular smooth muscle and endothelial cells.

Local strategies directed against vascular smooth muscle cell (VSMC) proliferation such as drug-eluting stents reduce the occurrence of restenosis. However, these approaches may also inhibit endothelial cell (EC) proliferation and, thus, impair reendothelialization. We compared the effects of tacrolimus on human VSMC and EC proliferation and migration to sirolimus, a compound with similar molecular structure. Thymidine incorporation was determined in growth factor-stimulated VSMC and EC. The drug concentration at which maximal VSMC proliferation was inhibited by 50% (IC50) was about 10-fold higher for tacrolimus (3.8 x 10 M) than for sirolimus (4.1 x 10 M; P = 0.055). It is interesting that the molar IC50 value in EC was around 10-fold higher for tacrolimus (2.3 x 10 M) than for sirolimus (7.1 x 10 M; P < 0.01). The profile of these drugs on VSMC and EC migration was similar to the one found in the proliferation assays. Inhibition of VSMC proliferation by both tacrolimus and sirolimus was associated with upregulation of the cell-cycle inhibitor p27. Thus, tacrolimus is less potent than sirolimus for inhibiting VSMC proliferation or migration. However, tacrolimus exerts markedly less antiproliferative effects on EC compared with sirolimus. In combination with its potent antiinflammatory effects, tacrolimus may represent a promising compound for the use in drug-eluting stents.

Blotting, Western↗

Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin osteoporosis in vitro.

Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.

Calcification, Physiologic↗

Clinical anatomy of the atrioventricular node artery.

BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the topographical relationship of the atrioventricular (AV) node artery and mitral valve annulus fibrosus with regard to AV node dysfunction following mitral valve replacement or ring annuloplasty. METHODS: The anatomy of the AV node artery was analyzed in 55 human hearts without previous pathological alterations. Selective coronary angiograms were performed to identify the AV node origin. Run-off of the AV node artery and its topographical relationship to the mitral valve attachment was analyzed in dry-dissected hearts. The position of the AV node was verified by histological sectioning. RESULTS: The AV node artery originated from the right coronary artery in 73% of examined cases, and from the left coronary artery in 27% of cases. The left AV node artery was closely related to the mitral valve attachment, especially at the area of the left proximal part of the posterior leaflet. CONCLUSION: These morphological data were compared to clinical reports emphasizing the postoperative incidence of AV block after mitral valve implantation and ring annuloplasty. The occurrence of early postoperative AV node block ranged from 20% to 37%. By comparing the present data with available literature, it can be stated that there is a high risk of intraoperative damage to the left AV node artery during manipulation of the mitral valve annulus fibrosus.

Adult↗

Normalization of high pulmonary vascular resistance with LVAD support in heart transplantation candidates.

OBJECTIVE: Pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) lead to poor outcome after heart transplantation due to postoperative failure of the non-conditioned right ventricle. The role of continuous flow left ventricular assist device (LVAD) support in the reduction of elevated PVR was evaluated in a series of clinical implants. METHODS: Among 17 patients with terminal heart failure receiving a MicroMed DeBakey LVAD as bridge to transplant, there were six patients with pulmonary hypertension (mean systolic PAP 47 mmHg) and high PVR (398 dynes/cm5), previously not considered suitable for heart transplantation, who underwent serial right heart catheters during their LVAD support period. RESULTS: In these patients mean systolic pulmonary pressure dropped to 29 mmHg and PVR decreased to a mean 167 dynes/cm5 under LVAD support. Clinical improvement was significant in all patients. Four patients were successfully transplanted without major postoperative difficulties (mean duration 130 days support) and all are doing well to date. Post-transplant-PVR remained in the normal range in all transplanted patients. CONCLUSIONS: Elevated PVR and severe PH were both previously considered as contraindication for heart transplantation. A period of LVAD pumping leads to a progressive decrease of PVR and normalization of pulmonary pressures, making these patients amenable for heart transplantation. LVAD as bridge to heart transplantation is safe and highly beneficial for terminal heart failure patients with severe PH.

Adult↗

Geometrical model of the pulmonary root.

BACKGROUND AND AIM OF THE STUDY: The renaissance of the Ross procedure has attracted much attention to the clinical anatomy of the pulmonary valve. Within the reviewed literature which emphasizes the morphology of the pulmonary root, no detailed anatomy has been reported. The study aim was to describe the cardiosurgical-orientated anatomy of the pulmonary valve. METHODS: Morphometric measurements were made on 20 fixed normal pulmonary roots. The roots were fixed under diastolic pressure (5 mmHg) with closed leaflets. The distances between the commissures, and between the intervalvular triangles, were measured. The heights of the sinuses and of the intervalvular triangles were also defined. RESULTS: The mean (+/- SD) of each parameter was calculated. The distances of the right, left and anterior sinus commissures were approximately similar, as were the distances of the intervalvular triangles at the root base. The mean height of the left coronary sinus was maximal, followed by the right and anterior pulmonary sinuses. The left intervalvular triangle was highest, followed by the posterior and right intervalvular triangles. The difference between the height of the left sinus and right intervalvular triangle indicated a tilt angle of 16.26 degrees between the root base and sinotubular junction. CONCLUSION: Based on these measured parameters, a spatial geometrical model was constructed which clearly described the asymmetrical structure of the pulmonary root.

Adult↗

Validation of Intracoronary Shunt Flow Measurements for Off-Pump Coronary Artery Bypass Operations.

Abstract Introduction: Intracoronary shunting is a useful, easy and inexpensive technique to maintain blood flow during off-pump surgery to lessen myocardial ischemia. Intracoronary shunts should provide a minimal flow for adequate myocardial protection. Material and Methods: Two commercially available shunts were used to measure flow from a bulb-size diameter of 1.00 mm to 3.00 mm (n = 10) in an in vitro setup. Shunts were perfused with Glycerin 47% solution at 37 degrees C. Inlet pressure was raised continuously from 0 to 160 mmHg in all intracoronary shunts. Results: In both groups (recipients of either type A shunt or type B shunt), mean pressure of 40 mmHg was necessary in shunts with diameter of 3.0 mm to provide a flow of approximately 50 mL/min. At mean pressure of 100 mmHg, a maximum flow of 126 mL/min was measured. Shunt B of 2.5-mm and 3.0-mm diameter showed similar flow patterns: 50 versus 52 mL/min at 40 mmHg and 98 versus 108 mL/min at 100 mmHg. Shunt A at 2.5-mm diameter showed 37 mL/min at 40 mmHg and 80 mL/min at 100 mmHg ( P =.01). Shunt B at 1.5-mm diameter required 75 mmHg for approximately 40mL/min and showed maximum flow of 51 mL/min at 100 mmHg ( P <.001). Only minimal flow was measured in 1.0-mm shunts of both groups. Conclusions: There is a clear pressure/flow correlation in 2.0-mm to 3.0-mm shunts with maximum flow of 126 mL/min. Type B shunt of 1.5-mm and 2.5-mm diameter showed significant better flow rates. The possible value of 1.0-mm shunts is only in stenting and facilitating anastomosis and to obtain better visibility during anastomosis.

Journal Article↗

Trajectory of coronary motion and its significance in robotic motion cancellation.

OBJECTIVES: To characterize remaining coronary artery motion of beating pig hearts after stabilization with an 'Octopus' using an optical remote analysis technique. METHODS: Three pigs (40, 60 and 65 kg) underwent full sternotomy after receiving general anesthesia. An 8-bit high speed black and white video camera (50 frames/s) coupled with a laser sensor (60 microm resolution) were used to capture heart wall motion in all three dimensions. Dopamine infusion was used to deliberately modulate cardiac contractility. Synchronized ECG, blood pressure, airway pressure and video data of the region around the first branching point of the left anterior descending (LAD) coronary artery after Octopus stabilization were captured for stretches of 8 s each. Several sequences of the same region were captured over a period of several minutes. Computerized off-line analysis allowed us to perform minute characterization of the heart wall motion. RESULTS: The movement of the points of interest on the LAD ranged from 0.22 to 0.81 mm in the lateral plane (x/y-axis) and 0.5-2.6 mm out of the plane (z-axis). Fast excursions (>50 microm/s in the lateral plane) occurred corresponding to the QRS complex and the T wave; while slow excursion phases (<50 microm/s in the lateral plane) were observed during the P wave and the ST segment. The trajectories of the points of interest during consecutive cardiac cycles as well as during cardiac cycles minutes apart remained comparable (the differences were negligible), provided the hemodynamics remained stable. Inotrope-induced changes in cardiac contractility influenced not only the maximum excursion, but also the shape of the trajectory. Normal positive pressure ventilation displacing the heart in the thoracic cage was evident by the displacement of the reference point of the trajectory. CONCLUSIONS: The movement of the coronary artery after stabilization appears to be still significant. Minute characterization of the trajectory of motion could provide the substrate for achieving motion cancellation for existing robotic systems. Velocity plots could also help improve gated cardiac imaging.

Animals↗

Genetic polymorphisms of apolipoprotein E4 and tumor necrosis factor beta as predisposing factors for increased inflammatory cytokines after cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass induces a rise in cytokines released by activated monocytes. The apolipoprotein E and the tumor necrosis factor beta polymorphisms are risk factors for atherosclerosis. The aim of the study was to investigate whether the genetic variants of apolipoprotein E (APOE*E4) and tumor necrosis factor beta (TNFB*A329G) affect cytokine release after cardiopulmonary bypass. METHODS: Thirty-eight patients underwent standard coronary artery bypass grafting procedures. Genotyping for APOE*E4 and TNFB*A329G was performed. Concentrations of interleukin 8 and tumor necrosis factor alpha were measured for 48 hours after surgery. Clinical data were collected prospectively. RESULTS: Fourteen patients (37%) carried the combination non-APOE*E4/wild-type TNFB*A329, 12 patients (32%) showed non-APOE*E4/TNFB*A329G, 9 patients (24%) had APOE*E4/TNFB*A329G, and 3 patients (7%) had APOE*E4/wild-type TNFB*A329. Total amount of tumor necrosis factor alpha was significantly higher in patients carrying the combination APOE*E4/TNFB*A329 than in those carrying non-APOE*E4/wild-type TNFB*A329 (P <.0001). Clinical data were similar except for intubation time and amount of transfusion, which were significantly increased in patients with genetic polymorphisms (P =.022, P =.033). CONCLUSION: Presence of TNFB*A329G polymorphism in addition to APOE*E4 variant is associated with significantly higher releases of interleukin 8 and tumor necrosis factor alpha, prolonged intubation, and increased transfusion relative to patients without genetic variants. Preoperative determination of APOE/TNFB genotypes in patients undergoing coronary artery bypass grafting may lead to additional perioperative measures to ameliorate systemic inflammatory response.

Aged↗

Review article: Tissue engineering of semilunar heart valves: current status and future developments.

Heart valve replacement represents the most common surgical therapy for end-stage valvular heart diseases. One major drawback that all heart valve replacements have in common is the lack of growth, repair, and remodeling capability once implanted into the body. The emerging field of tissue engineering is focusing on the in-vitro generation of functional, living semilunar heart valve replacements. This review presents a state-of-the-art overview of the physiological and biomechanical requirements of semilunar heart valves, focusing on the aortic valve. Moreover, recent heart valve tissue engineering is summarized and future options and improvements on the way towards clinical applications are discussed.

Animals↗

Hypoxia and reoxygenation do not upregulate adhesion molecules and natural killer cell adhesion on human endothelial cells in vitro.

OBJECTIVES: Ischemia/reperfusion injury is characterized by endothelial cell activation leading to increased expression of adhesion molecules such as inter-cellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, endothelial- and platelet-selectin (E- and P-selectin), and to the subsequent recruitment of leukocytes. The aim of the present study was to investigate the respective effects of a proinflammatory cytokine (tumor necrosis factor alpha, TNF-alpha), hypoxia and/or reoxygenation on adhesion molecule expression and natural killer (NK) cell adhesion in an in vitro model of I/R. METHODS: Human aortic endothelial cells (HAEC) were stimulated in vitro for 8h with TNF-alpha (1000 U/ml) and exposed to hypoxia (1% O(2)), reoxygenation (21% O(2)) or different combinations thereof. Cell surface expression of ICAM-1, VCAM-1 and E-/P-selectin on HAEC was analyzed by flow cytometry, and culture supernatants were tested for soluble adhesion molecules by ELISA. Rolling adhesion of NK cells on HAEC was determined using a rotating assay. RESULTS: Untreated HAEC constitutively expressed ICAM-1 on their surface but neither expressed E-/P-selectin, VCAM-1, nor shedded soluble adhesion molecules. Exposure of HAEC to hypoxia or hypoxia and reoxygenation did not upregulate cell surface expression or shedding of adhesion molecules. In contrast, TNF-alpha significantly upregulated cell surface expression of ICAM-1, VCAM-1, and E-/P-selectin and led to the shedding of ICAM-1 and E-selectin. Combined treatment of HAEC with TNF-alpha, hypoxia and reoxygenation reduced E-/P-selectin surface expression and enhanced E-selectin shedding, but did not further influence ICAM-1 and VCAM-1. Soluble VCAM-1 was not detected. NK cell adhesion on HAEC increased 4-fold after TNF-alpha stimulation, but was not affected by hypoxia or hypoxia and reoxygenation. CONCLUSIONS: Both the expression of endothelial adhesion molecules and rolling NK cell adhesion was upregulated by TNF-alpha but not by hypoxia alone or hypoxia followed by reoxygenation supporting the view that anti-inflammatory treatment may reduce ischemia/reperfusion injury.

Aorta↗