PubMed Health⌕ Search

Biomedical subjects

J Grünenfelder

Publications and source records attributed to J Grünenfelder.

At least 19 recordsLinked to original sources

Off-pump coronary artery bypass grafting: the Zurich experience.

Coronary artery bypass grafting (CABG) is the surgical procedure of choice for treatment of multi-vessel coronary artery disease. The rising risk profile of the patients requiring isolated CABG and the economic pressure have prompted us to devise new operative strategies to treat these patients. Elimination of the cardiopulmonary bypass is one possible answer to the dilemma of maintaining the quality of care and reducing the exploding costs of our health system. Therefore, we developed the off-pump coronary artery bypass grafting (OPCAB) for patients requiring isolated CABG. In our experience the key to successful OPCAB relies on the order of revascularization of the myocardial walls (anterior, inferior, lateral), use of intracoronary shunt, no-touch technique for the proximal aortic anastomosis with heart string â (Guidant, IN, USA), close collaboration with the anesthesiologists, early and aggressive administration of anti-platelet therapy, endoscopic vein harvest by perfusionists, and improved body temperature control. Following these concepts, we have been able to offer the OPCAB procedure to over 90% of our patients and to reduce perioperative morbidity and global costs.

Aged↗

Experiences in robotically enhanced IMA-preparation as initial step towards totally endoscopic coronary artery bypass grafting.

AIM: To evaluate the feasibility of robotically enhanced preparation of internal mammary arteries (IMA). METHOD: Via three trocars in left thoracic wall the left, right or both IMA were skeletonized under CO(2) insufflation and single lung ventilation using electrocautery. RESULTS: In 12 months, 26 LIMA, five BIMA and one RIMA were dissected. In five patients, the procedure had to be determined (IMA injury (two), respiratory insufficiency (two), and heart penetration (one)). Mean intrathoracic pressure was 9.7+/-1.5 mmHg. Mean time for LIMA and RIMA dissection was 66.7+/-21.1 and 99.2+/-8.7 min, respectively. In 10 patients, pericardium was incised and course of LAD assessed. However, in two patients, this coronary did not correlate with LAD. Time for instrument change depended on type of tool (cautery blade: 24.9+/-13.1 s, clip applier 72.8+/-28.4 s). CONCLUSION: Robotic dissection of IMA is reasonable. However, life-threatening complications can barely be managed due to inadequate tools and excessive time for instrument change. Incorrect determination of coronaries can result in misplaced anastomoses.

Aged↗

Regulation of matrix metalloproteinases and effect of MMP-inhibition in heart transplant related reperfusion injury.

PURPOSE: Metalloproteinases (MMPs) regulate extracellular matrix turnover and degrade basal lamina. Aim of the study was to examine the regulation of MMPs and the effect of an MMP inhibitor in transplant related ischemia/reperfusion injury. METHODS: Heterotopic cardiac transplantation was performed after 4 h of ischemia in three groups of six rats: allografts (black hooded inbred strain, PVG donor/August Copenhagen Irish inbred strain recipient); allografts treated with a competitive MMP-inhibitor (Batimastat) 15 mg/kg every 24 h; isografts (PVG donor and recipient). Normal PVG hearts served as a control. Hearts were explanted after 72 h of reperfusion. Expression of MMP-2 and -9 was measured using gelatin zymography. Proteolytic activity was measured using a gelatinase activity assay. Myeloperoxidase activity and tumor necrosis factor-alpha (TNF-alpha) were measured as markers of inflammatory response. Immunostaining for collagen IV and laminin was used to study degradation of basal lamina. RESULTS: There was a significant increase of MMP-2 expression in allografts (2271+/-571 microg/ml) as compared to normal (683+/-139 microg/ml) and the Batimastat-treated (259+/-140 microg/ml, P<0.05) groups. Although pro-MMP-2 expression was equally high in the untreated iso- and allograft group (75+/-23 versus 62+/-30 microg/ml) MMP-2 expression in the isograft hearts was significantly lower (359+/-267 microg/ml) suggesting activation of the pro-form by an immunologic mechanism. Pro-MMP-9 levels were significantly higher in the untreated iso- and allograft groups as opposed to normal hearts and MMP-inhibited hearts. MMP-9 was completely inhibited by Batimastat treatment. Collagenolytic activity was lower in the treated group as compared to untreated allografts (538+/-140 versus 384+/-97 microg/ml, P<0.05), demonstrating effective inhibition of MMPs by Batimastat. In the treated group a lesser extent of basement membrane component alterations could be demonstrated by laminin and collagen IV staining. There was a significant reduction in myeloperoxidase activity (P=0.027) as well as lower TNF-alpha levels (ns) in the in the Batimastat treated group. CONCLUSION: Ischemia leads to an increase in MMP expression and degradation of basal lamina. This process is enhanced in allografts as compared to isografts suggesting additional activation of MMPs by immunologic mechanisms. MMP-inhibition is effective in preventing the proteolytic activity of MMPs and may alter the host rejection response by preserving extracellular matrix components and basement membranes.

Animals↗

Upregulation of Bcl-2 through caspase-3 inhibition ameliorates ischemia/reperfusion injury in rat cardiac allografts.

BACKGROUND: Oxidative stress after ischemia/reperfusion of cardiac allografts leads to cytokine production. Bcl-2, an inhibitor of apoptosis, also has strong antioxidant properties. Caspase-3 is known to cleave bcl-2. This study tests the hypothesis that bcl-2 is downregulated while tumor necrosis factor-alpha (TNF-alpha) levels increase after cardiac transplantation. Furthermore, the use of caspase-3 inhibition was investigated as a strategy for preserving myocardial bcl-2 and mitochondrial cytochrome c after transplantation. METHODS AND RESULTS: PVG-to-ACI rat heterotopic cardiac transplantations were performed in 4 groups designed with 30 minutes' ischemia and 4 or 8 hours of reperfusion (n=4 per group). Treatment consisted of DEVD-CHO 500 microgram IP per animal to donor and recipient 2 hours before transplantation and 250 microgram IC into allograft. Controls were treated with saline. Grafts were analyzed by reverse transcription-polymerase chain reaction for bcl-2 mRNA, by ELISA for TNF-alpha, for myeloperoxidase activity, and by Western blot for cytochrome c. In untreated groups, bcl-2 mRNA decreased significantly over time, whereas TNF-alpha increased significantly at 4 hours (P=0.003) and returned to baseline after 8 hours' reperfusion (P=NS compared with normal hearts). Treatment with caspase-3 inhibitor showed significant upregulation of bcl-2 mRNA expression after 4 and 8 hours of reperfusion (P<0.001 versus control), with a concomitant decrease in TNF-alpha to baseline levels. Myeloperoxidase activity in all groups was no different from that of normal hearts. Mitochondrial cytochrome c release increased in both control and treatment groups. CONCLUSIONS: Bcl-2 is actively downregulated and TNF-alpha is upregulated in this model of cardiac allograft ischemia/reperfusion. Furthermore, the caspase-3 pathway is linked to this process, and blockade of caspase-3 can ameliorate reperfusion injury by upregulating bcl-2 and inhibiting TNF-alpha without affecting cytochrome c release.

Animals↗

Influence of three-dimensional vision on surgical telemanipulator performance.

BACKGROUND: Different viewing conditions (two- and three-dimensional National Television Standard Committee [2D-NTSC and 3D-NTSC] and two-dimensional high-definition television [2D-HDTV]) on telemanipulator performance were evaluated. METHODS: Six taskes were performed by 15 endoscopic surgeons using the daVinci telemanipulation system. Performance time and errors were measured. Encoder data from the system were used for kinematic analysis of motion. A self-evaluation questionnaire regarding performance under various viewing conditions was obtained. RESULTS: Resolution was better with 2D-HDTV. The estimate of relative distance was not influenced by the different visualization systems. Motor skill tasks were performed faster with binocular vision (3D-NTSC) than with monocular vision (2D-NTSC, 2D-HDTV). For both 2D settings, the deceleration phase of motion was prolonged (p < 0.05 vs 3D). Peak velocity was reduced with 2D-HDTV as compared with 3D-NTSC (p = 0.01). The surgeons tended to favor the 3D system despite their use of 2D systems in their own practice. CONCLUSIONS: Three-dimensional vision enhances telemanipulator performance as compared with a 2D system at the same or higher level of resolution. Because it allows faster and more precise movement, future surgical systems should focus on 3D visualization.

Depth Perception↗

Preoperative administration of steroids: influence on adhesion molecules and cytokines after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with tissue damage mediated by adhesion molecules and cytokines. Prebypass steroid administration may modulate the inflammatory response, resulting in improved postoperative recovery. METHODS: Fifty patients undergoing elective coronary operations under normothermic CPB were randomized into two groups: group A (n = 24) received intravenous methylprednisolone (10 mg/kg) 4 hours preoperatively, and group B (n = 26) served as controls. Cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-2R [IL-2R], IL-6, IL-8), soluble adhesion molecules (sE-selectin, sICAM-1), C-reactive protein, and leukocytes were measured before steroid application, then 24 and 48 hours, and 6 days postoperatively. Adhesion molecules were measured by enzyme-linked immunosorbent assay, cytokines by chemiluminescent immunoassay. Postoperatively, hemodynamic measurements, inotropic agent requirements, blood loss, duration of mechanical ventilation, and intensive care unit stay were compared. RESULTS: Aortic cross-clamp and CPB time was similar in both groups. Prednisolone administration reduced postoperative levels of IL-6 (611 versus 92.7 pg/mL; p = 0.003), TNF-alpha (24.4 versus 11.0 pg/L, p = 0.02), and E-selectin (327 versus 107 ng/mL, p = 0.02). Postoperative recovery did not differ between groups. CONCLUSIONS: Preoperative administration of methylprednisolone blunted the increase of IL-6, TNF-alpha, and E-selectin levels after CPB but had no measurable effect on postoperative recovery.

Aged↗

Tissue engineering of small caliber vascular grafts.

OBJECTIVE: Previous tissue engineering approaches to create small caliber vascular grafts have been limited by the structural and mechanical immaturity of the constructs. This study uses a novel in vitro pulse duplicator system providing a 'biomimetic' environment during tissue formation to yield more mature, implantable vascular grafts. METHODS: Vascular grafts (I.D. 0.5 cm) were fabricated from novel bioabsorbable polymers (polyglycolic-acid/poly-4-hydroxybutyrate) and sequentially seeded with ovine vascular myofibroblasts and endothelial cells. After 4 days static culture, the grafts (n=24) were grown in vitro in a pulse duplicator system (bioreactor) for 4, 7, 14, 21, and 28 days. Controls (n=24) were grown in static culture conditions. Analysis of the neo-tissue included histology, scanning electron microscopy (SEM), and biochemical assays (DNA for cell content, 5-hydroxyproline for collagen). Mechanical testing was performed measuring the burst pressure and the suture retention strength. RESULTS: Histology showed viable, dense tissue in all samples. SEM demonstrated confluent smooth inner surfaces of the grafts exposed to pulsatile flow after 14 days. Biochemical analysis revealed a continuous increase of cell mass and collagen to 21 days compared to significantly lower values in the static controls. The mechanical properties of the pulsed vascular grafts comprised supra-physiological burst strength and suture retention strength appropriate for surgical implantation. CONCLUSIONS: This study demonstrates the feasibility of tissue engineering of viable, surgically implantable small caliber vascular grafts and the important effect of a 'biomimetic' in vitro environment on tissue maturation and extracellular matrix formation.

Absorbable Implants↗

Genetic predisposition in patients undergoing cardiopulmonary bypass surgery is associated with an increase of inflammatory cytokines.

OBJECTIVE: Cardiopulmonary bypass (CPB) surgery induces a transient rise in pro-inflammatory cytokines typically released by activated monocytes. The E4 variant of apolipoprotein E is a recognized risk factor for atherosclerosis. It has recently been shown that apolipoprotein E affects monocyte functions in vitro and leads to higher levels of median lipoprotein (a) in humans. The aim of the study is to investigate if the E4 genetic variant of apolipoprotein E affects cytokine release after CPB surgery. METHODS: 22 patients were operated on with standard coronary artery bypass grafting. Concentrations of interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha) were measured by automated Immulite immunoassay at regular intervals within 48 h after surgery. Total apparent cytokine outputs were calculated as area under the curve. Results are expressed as mean+/-standard deviation and compared by unpaired t-test. RESULTS: In the presented patient population 6 (27%) carried the E4 allele. Sixteen (63%) showed no E4 allele. Mean cross clamp time (CCT) was 56.2+/-13.5 min versus 55.7+/-12.1 min and CPB time was 91.8+/-17.5 versus 93.5+/-15.7 min. No statistical difference between E4-carriers and E4 non-carriers regarding CCT and CPB was observed. The total amount of IL-8 and TNF-alpha was higher in patients carrying the E4 genetic variant of apolipoprotein E in comparison to E4 non-carriers (P<0.08, P<0.039). CONCLUSION: The presence of the E4 allele is associated with increased release of IL-8 and TNF-alpha after CBP surgery. The preoperative determination of E4 in patients undergoing cardiac surgery may lead to additional perioperative measures for the treatment of an increased systemic inflammatory response.

Aged↗

Long-term results and determinants of mortality after surgery for native and prosthetic valve endocarditis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the long-term results and determinants of mortality after operative treatment of native and prosthetic valve endocarditis at a single institution. METHODS: Between March 1985 and October 1999, 171 patients underwent surgery for native (NVE) or prosthetic valve endocarditis (PVE). NVE was present in 98 patients (57%), and PVE in 73 patients (43%). Mean follow up was 5.6+/-3.9 years (range: 0 to 15 years). RESULTS: Overall hospital mortality was 9.9% (n = 17). Hospital mortality was higher among patients with PVE (15.1%) than those with NVE (6.1%; p = 0.05). Overall survival at 10 years was 46+/-5%. Patients with NVE had a higher 10-year survival rate (53+/-7%) than those with PVE (37+/-7%; p = 0.02). At 10 years, overall freedom from any late complication was 47+/-6% and from residual or recurrent endocarditis was 78+/-5%. Predictors of hospital death were emergency surgery (p <0.003) and preoperative renal insufficiency (p <0.008). Predictors of late death were age >70 years (p <0.002), renal failure (p <0.03) and fungal endocarditis (p <0.04). CONCLUSION: These findings demonstrate the increased perioperative, as well as postoperative, risks associated with PVE versus NVE. Cardiac and extracardiac manifestations of the disease, as well as fungal organisms, but not the activity of the endocarditis, were significant adverse determinants of late outcome.

Endocarditis↗

Endoscopic computer-enhanced beating heart coronary artery bypass grafting.

BACKGROUND: Telemanipulation systems have enabled coronary revascularization on the arrested heart. The purpose of this study was to develop a technique for computer-enhanced endoscopic coronary artery bypass grafting on the beating heart. METHODS: The operation was performed using the daVinci telemanipulation system. Through three ports, the left internal thoracic artery was harvested in 10 mongrel dogs (30 to 35 kg) using single right-lung ventilation and CO2 insufflation. Through a fourth port an articulating stabilizer, manipulated from a second surgical console, was inserted to stabilize the heart. The left anterior descending artery was snared using silicone elastomer slings anchored in the stabilizer cleats and the graft to coronary artery anastomosis was performed. RESULTS: In 7 of 10 dogs, total endoscopic beating heart bypass grafting, cardiac stabilization, arteriotomy, and arterial anastomosis were performed using computer-enhanced technology. Endoscopic stabilization and temporary left anterior descending artery occlusion were well tolerated. All grafts were patent although minor strictures were found in 2. In 3 dogs, the procedure could not be completed (1 ventricular arrhythmia, 1 left atrial laceration, and 1 right ventricular outflow tract compression). CONCLUSIONS: Endoscopic beating heart coronary artery bypass grafting is possible in a canine model using a computer-enhanced instrumentation system and articulating stabilization.

Animals↗

Role of myocardial revascularization in postinfarction ventricular septal rupture.

BACKGROUND: Postinfarction ventricular septal rupture requires urgent closure. The role of systematic coronarography and coronary revascularization needs clarification. METHODS: Fifty-four patients who underwent patch closure of postinfarction ventricular septal defect were reviewed. A coronarography had been systematically and myocardial revascularization selectively (when significant coronary artery stenosis existed) performed. RESULTS: No patient died or deteriorated during coronarography. Twenty-six patients showed no coronary artery disease besides the infarct-related artery, and 28 had associated disease. Threatened myocardial territories were revascularized usually with venous grafts (mean number of distal anastomosis, 2.5). Operative mortality was 19% and 32% (p = 0.36) and late mortality 43% and 53% (p = 0.75) in patients without and in patients with associated coronary artery disease, respectively. Survival curve in both group was similar, at least up to 8 years after operation. CONCLUSIONS: Myocardial revascularization controlled the added risk of associated coronary artery disease in the postoperative period and in median term. A coronarography should be performed in all patients who can be stabilized hemodynamically and myocardial revascularization performed in case of significant stenosis.

Aged↗

Expression of adhesion molecules and cytokines after coronary artery bypass grafting during normothermic and hypothermic cardiac arrest.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) results in vascular injury and tissue damage which involves leukocyte-endothelial interactions mediated by cytokines and adhesion molecules. This study was designed to demonstrate the effect of normothermic and hypothermic CPB to cytokine and soluble adhesion molecule levels in adults and to determine whether these levels correlate to the patients postoperative course. DESIGN AND PATIENTS: In 25 patients after normothermic and in 25 patients after hypothermic coronary artery bypass grafting with cardiopulmonary bypass (CPB), blood samples for cytokine and soluble adhesion molecule analysis were taken preoperatively, 24, 36, 48 h, and 6 days postoperatively. Soluble adhesion molecules (sE-selectin, sICAM-1) were measured by ELISA and cytokines (TNF-alpha, IL-6, IL-8) by chemilumenscent-immunoassay. Clinical data were collected prospectively. RESULTS: Postoperatively, adhesion molecule and cytokine levels were significantly elevated after CPB. Mean plasma levels of sICAM-1 was 2.4-fold higher after 6 days. Mean plasma concentration of sE-selectin peaked after 48 h with a 2-fold increase compared to normothermic conditions. In the hypothermia group sICAM-1, sE-selectin, IL-6, and IL-8 showed significantly higher levels (P<0.0057, P<0.0012, P<0.0419, P<0.0145) after 24 h compared to the normothermia group. No clinical differences were seen. CONCLUSION: Adhesion molecules and cytokines are elevated after CPB. Patients after hypothermic CPB show significant higher sICAM-1, sE-selectin, IL-6, and IL-8 levels after 24 h compared to normothermic conditions. These results are mainly due to longer CPB and crossclamp times but do not alter the patient's postoperative course.

Adult↗

Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) results in expression of cytokines and adhesion molecules (AM) with subsequent inflammatory response. The purpose of the study was to evaluate the clinical impact of modified ultrafiltration (MUF) and its efficacy in reducing cytokines and AM following coronary artery bypass grafting (CABG) in adults. METHODS: A prospective randomized study of 97 patients undergoing elective CABG was designed. Fifty patients were operated on using normothermic and 47 patients using hypothermic CPB. The normothermic group was subdivided into a group with modified ultrafiltration (n = 30) and a group without MUF (n = 20). In the hypothermic group 30 patients received MUF compared to 17 patients serving as controls. MUF was instituted after CPB for 15 min through the arterial and venous bypass circuit lines. Cytokines (IL-6, IL-8, TNF-alpha, IL-2R) and adhesion molecules (sE-selectin, sICAM-1) were measured preoperatively, pre-MUF, in the ultrafiltrate, 24 h, 48 h and 6 days after surgery by chemiluminescent enzyme immunometric assay or enzyme-linked immunosorbent assay (ELISA). Clinical parameters were collected prospectively until discharge. RESULTS: In all patients AM and cytokines were significantly elevated after normothermic and hypothemic CPB. AM and cytokines were significantly higher in hypothermia compared to normothermia. In hypothermic CPB sE-selectin was decreased after 24 h by 37% (P < 0.0063) and by 40% (P < 0.0027) after 48 h postoperatively. ICAM-1 was reduced by 43% (P < 0.0001) after 24 h and by 60% (P < 0.0001) after 6 days. Similar results were seen in cytokines with reduction up to 60% after 24 h. Changes after 48 h were noticeable but not significant. Reduction of AM and cytokines after normothermic CPB was minimal. Neither in normothermia, nor in hypothermia has sIL-2R been effectively removed from the circulation. There were no significant differences in the clinical variables between the patients with or without MUF. CONCLUSION: AM and cytokines are significantly elevated after hypothermic CPB compared to normothermic CPB. MUF led to a significant reduction in cytokine and AM levels after hypothermic CPB, except for IL-2R. MUF showed minimal effect in normothermia. We conclude that MUF is an efficient way to remove cytokines and AM. However, we were unable to demonstrate any significant impact of MUF in outcome of adults after elective CABG.

Adult↗

Endoscopic Doppler for detecting vessels in closed chest bypass grafting.

A new method of endoscopic ultrasonography during endoscopic bypass grafting is described. Using a 7.5 MHz ultrasonic catheter (AcuNav, Acuson, Mountain View, CA) that was introduced through a 5mm port and manipulated by robotically enhanced endoscopic instruments, detection of the internal thoracic artery (ITA) and the left anterior descending (LAD) artery was possible through layers of fat and muscle in a canine model.

Coronary Artery Bypass↗

Operative results of "repair" of ventricular septal rupture after acute myocardial infraction.

Fifty-four consecutive patients with postinfarction ventricular septal defect were reviewed. The rupture was closed with a patch and the left ventricle remodeled in all patients. Coronary artery bypass surgery was performed in 28 patients (52%). Fourteen patients (26%) died after operation and 19 during follow-up (mean 42 months). Cumulative survival (including operative deaths) was 78%, 65%, and 40% at 1, 5, and 10 years, respectively. A short interval between septal rupture and operation was a risk factor for early mortality (p = 0.03). Treated associated coronary artery disease had no effect. A residual septal shunt, detected in 10 patients (18%), warranted reoperation in 7 and contributed to 2 early and 1 late death. The location and morphology of the septal rupture were not associated with increased risk of residual shunt. Thus, patch closure of the ventricular septal rupture, remodeling of the left ventricle to improve stroke volume and reduce wall stress, and selective myocardial revascularization provided acceptable results.

Aged↗

Aortopulmonary window with anomalous origin of the right coronary artery.

We report a case of an aortopulmonary window with a right coronary artery arising from the pulmonary trunk. This exceedingly rare anomaly with anomalous coronary artery presented without myocardial ischemia owing to the aortopulmonary window. The correct diagnosis was made by angiography and a successful surgical correction was performed.

Aortopulmonary Septal Defect↗

Surgical repair of postinfarction structural failure of the posterobasal part of the heart.

BACKGROUND: This study is an analysis of our results with endoventricular repair of postinfarction structural defects of the posterobasal part of the heart. METHODS: Thirty-four patients who underwent endoventricular repair of a postinfarction structural defect of the posterobasal heart were reviewed. Patients with rupture of the ventricular septum (18 patients) or free wall (1 patient) were operated on acutely and patients with ventricular aneurysm (15 patients) electively. Restitution of the ventricular geometry was achieved by evertion (11 patients), resection (4 patients), or augmentation of the ventriculotomy (4 patients) in patients with ventricular rupture, and by resection of the aneurysm in the others. Coronary artery bypass was performed in 24 patients. RESULTS: Six patients died postoperatively (five due to rupture and one from aneurysm) and nine patients (six due to rupture and three from aneurysm) during follow-up. Survival rate at 5 years (including operative mortality) was 43% for patients with rupture and 61% for patients with aneurysm. The majority of the survivors were in New York Heart Association functional class I or II after a median follow-up of 5 years. CONCLUSIONS: Endocardial repair, ventricular remodeling, and selective myocardial revascularization provided overall good results in the treatment of this difficult cardiac area.

Aged↗