Biomedical subjects

Markus J Wilhelm

Publications and source records attributed to Markus J Wilhelm.

14 recordsLinked to original sources

PubMed2005

Partial left ventriculectomy and mitral valve repair: favorable short-term results in carefully selected patients with advanced heart failure due to dilated cardiomyopathy.

BACKGROUND: Because of the scarcity of donor hearts, surgical alternatives to heart transplantation, such as partial left ventriculectomy (PLV), were introduced for treatment of advanced heart failure. Here, we report our experience with this procedure performed in combination with mitral valve repair. METHODS: Twelve patients with dilated cardiomyopathy (DCM), New York Heart Association (NYHA) class exceeding III on maximal medical therapy, cardiac index of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end-diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral incompetence, were selected for PLV and mitral valve reconstruction (MVR). Echocardiography, hemodynamics, spiroergometry, and clinical assessment were performed before and 1 year after the operation. RESULTS: One-year survival was 83.3%. All 10 surviving patients were free from failure of the procedure 1 year post-operatively. From pre-operatively to 1 year post-operatively, NYHA functional class improved from 3.3 +/- 0.3 to 1.9 +/- 0.2 (p < 0.001), cardiac index increased from 2.0 +/- 0.2 liter/min/m2 to 2.9 +/- 0.2 liter/min/m2 (p < 0.001), stroke volume index from 25.9 +/- 4.8 ml/m2 to 40.3 +/- 7.3 ml/m2 (p = 0.008), and VO2max from 10.9 +/- 2.4 ml/kg/min to 16.0 +/- 3.6 ml/kg/min (p = 0.016), whereas LVEDD decreased from 8.4 +/- 0.6 cm to 6.6 +/- 0.3 cm (p < 0.001), left ventricular end-systolic diameter from 6.8 +/- 0.8 cm to 5.3 +/- 0.5 cm (p < 0.001), and mitral incompetence from 2.4 +/- 0.6 to 0.9 +/- 0.6 (p < 0.001). Pulmonary pressures and fractional shortening did not change significantly (p > 0.05). Four patients received an implantable cardioverter/defibrillator as a result of their pathologic electrophysiologic examination. CONCLUSIONS: In carefully selected patients, PLV combined with MVR achieves short-term results comparable to that after heart transplantation. However, long-term results and multicenter evaluation will be needed to define its place in the treatment of advanced heart failure.

Cardiac Surgical Procedures↗

PubMed2005

Aortic dissection with potential origin from a mechanical bypass anastomosis.

Ascending aortic dissection is a known complication of cardiac surgery. Off-pump coronary artery bypass surgery seems to be associated with a higher risk for this event as compared with on-pump bypass surgery. This increased risk may result from aortic side-clamping under pulsatile flow as opposed to continuous flow in conventional bypass surgery. Mechanical devices allowing performance of proximal bypass anastomoses without aortic side-clamping are supposed to reduce the risk for aortic dissection. We report a case in which ascending aortic dissection occurred 8 days after off-pump bypass surgery, most likely arising from a mechanically performed proximal bypass anastomosis.

Aged↗

PubMed2005

Respiratory dependent compression of a venous bypass: therapy by stenting.

Although coronary artery bypass surgery has provided major advances in the treatment of coronary artery disease, narrowing of bypass vessels still constitutes a drawback of this therapy. Although this event is most frequently caused by intraluminal processes, obstruction from external structures is extremely rare. We report such a case in which external bypass compression was provoked by deep inspiration causing typical anginal symptoms. Percutaneous coronary intervention including stent placement provided bypass patency independent from the patient's respiratory phase. Disappearance of symptoms and absence of myocardial ischemia in perfusion scans confirmed successful treatment.

Angioplasty, Balloon, Coronary↗

PubMed2005

Long-term support of 9 patients with the DeBakey VAD for more than 200 days.

OBJECTIVE: Pulsatile left ventricular assist devices serving as mechanical circulatory support for patients with end-stage heart failure are associated with complications, including bleeding, thromboembolism, and infection. Axial-flow pumps might overcome some of these shortcomings. Here we report our experience with long-term application of the DeBakey VAD (MicroMed Technology, Inc, Houston, Tex). METHODS: Nine male transplant candidates (37 +/- 14 years) with severe hemodynamic compromise (cardiac index, 1.6 +/- 0.5 L . min(-1) x m(-2); pulmonary capillary wedge pressure, 27 +/- 6 mm Hg) and beginning end-organ failure despite inotropic and intra-aortic balloon pump support received the DeBakey VAD. Clinical outcome was evaluated. RESULTS: Cumulative support was 7.8 years, and the mean duration of support was 314 +/- 75 days (range, 229-438 days). Eight patients were transplanted, and one died from intracerebral bleeding. Peripheral circulation and end-organ function recovered rapidly after implantation. Continuous flow was able to maintain adequate organ perfusion over the long term. Eight patients were discharged during support, with good quality of life. There were no early bleedings, but there were late bleedings in 3 patients caused by excessive anticoagulation and platelet inhibition. Neurologic events occurred in 4 patients. Three patients recovered completely from symptoms, and one had lethal intracerebral bleeding. Because of thrombus formation, the device was exchanged in 4 patients. With increasing experience, thrombolysis was performed in similar situations. All such patients underwent successful transplantation. Hemolysis occurred, with events indicating thrombus formation. Device-related infection was found in one patient. CONCLUSIONS: The DeBakey VAD demonstrated its potential for long-term bridge to transplantation. The risk for thrombus formation needs to be addressed by improvement of pump technology and new strategies for platelet inhibition.

Adolescent↗

PubMed2004

Donor hypertension increases graft immunogenicity and intensifies chronic changes in long-surviving renal allografts.

BACKGROUND: Marginal donor organs are used increasingly for transplantation. To define the influences of donor hypertension, we compared the behavior of kidney allografts from hypertensive and normotensive donors in an established rat model of chronic rejection. METHODS: Donor hypertension was induced by partial occlusion of the right renal artery with a silver clip. After 10 weeks, the left kidney was removed and transplanted. Normotensive animals served as controls. All recipients were treated with a low dose of cyclosporine for 10 days (1.5 mg/kg). Blood pressure and proteinuria were determined weekly four times after transplantation. To examine the effects of donor hypertension on late events, grafts (n=6/time point) were examined morphologically and by quantitative reverse transcriptase-polymerase chain reaction analysis at serial intervals. RESULTS: Recipients of kidneys from hypertensive donors developed systemic hypertension in contrast with normotensive controls (P<0.05). Allografts from hypertensive animals showed accelerated deterioration in structure and function after transplantation. Proteinuria became significantly elevated as early as 6 weeks (P<0.05) compared with controls and increased progressively thereafter (P<0.005). Grafts from hypertensive donors, histologically normal at the time of engraftment, developed significant morphologic deterioration after 12 weeks (P<0.01). Changes in allografts from normotensive donors remained minor. mRNA of proinflammatory mediators in hypertensive donor grafts (P<0.01) was up-regulated before transplantation and increased progressively over time (P<0.01). CONCLUSIONS: Donor hypertension intensifies the chronic injury associated with allogeneic kidney transplantation in the rat model used. This condition also leads to induction of recipient hypertension and may be a more important risk factor for chronic graft dysfunction than previously appreciated.

Animals↗

PubMed2004

Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support.

BACKGROUND: Nonpulsatile axial or centrifugal pumps are the latest generation of left ventricular assist devices (LVAD). Whether left ventricular (LV) unloading and outcome in these devices is similar to pulsatile LVADs during long-term support has not been investigated. We compared LV unloading and mortality between different types of LVAD support (pulsatile versus nonpulsatile). METHODS: In 31 patients undergoing long-term LVAD implantation (nonpulsatile = 10, pulsatile = 21) preoperative and postoperative echocardiographic and hemodynamic assessment with right heart catheterization had been obtained. RESULTS: All patients had similar echocardiographic, hemodynamic, and clinical heart failure characteristics at baseline. The degree of LV pressure unloading was the same in both device types, caused by similar reduction of mean pulmonary pressure (18.6 +/- 5.1 versus 18.3 +/- 7.5 mm Hg) and pulmonary capillary wedge pressure (8.9 +/- 4.4 versus 8.0 +/- 7.0 mm Hg). Left ventricular volume unloading was pronounced with a pulsatile device owing to a statistically significant higher pump output (5.1 +/- 1.0 L/min) in comparison with nonpulsatile LVADs (3.6 +/- 0.9 L/min, p < 0.001). Echocardiographic-determined end-systolic indicators confirm this augmentation in pulsatile LVADs. Etiology or the time interval of hemodynamic reassessment had no impact in left ventricular pressure unloading, but LV volume unloading decreased between day 60 and 120 in patients with nonpulsatile LVADs. The preoperative and postoperative transplant mortality was comparable in both groups. CONCLUSIONS: Left ventricular pressure unloading is similar in patients with nonpulsatile as compared with pulsatile implantable long-term assist devices. Left ventricular volume unloading is pronounced in pulsatile LVADs.

Adolescent↗

PubMed2004

Functional changes after partial left ventriculectomy and mitral valve repair assessed by gated perfusion SPECT.

UNLABELLED: A myocardial remodeling in dilated cardiomyopathy (DCM) after partial left ventriculectomy (PLV) has been previously discussed. The aim of this study was to investigate the functional changes in the follow-up of patients with DCM undergoing PLV using electrocardiographically triggered perfusion SPECT (gated SPECT). METHODS: Twelve DCM patients (10 men, 2 women; 56 +/- 9 y [mean +/- SD]), after successful PLV and mitral valve repair (PLV-MVR), were monitored by gated SPECT and echocardiography. Gated SPECT quantified end-diastolic volumes (EDV), end-systolic volumes (ESV), myocardial and scar volumes, as well as ejection fraction (EF) preoperatively, early (38 +/- 28 d), and late (296 +/- 130 d) after PLV-MVR. RESULTS: EDV and ESV showed an immediate reduction after PLV-MVR (EDV from 542 +/- 90 mL to 350 +/- 81 mL, P < 0.001; ESV from 452 +/- 91 mL to 254 +/- 79 mL, P < 0.001) with no significant change in the late follow-up (EDV late, 316 +/- 63 mL; ESV late, 207 +/- 63 mL; both P = not significant vs. early follow-up). PLV-MVR immediately improved EF (preoperative, 16.8% +/- 5.5%; early, 28.8% +/- 7.6%; P = 0.003) with no significant change in the late follow-up (36.0% +/- 9.4%; P = not significant vs. early follow-up). CONCLUSION: In this highly selected DCM patient group, gated perfusion SPECT assessed early responses in volumes and EF after PLV-MVR. However, although statistically nonsignificant in the small patient group, ESV and EDV were further decreased, whereas EF improved toward 1 y, coinciding with the improvement of clinical symptoms (New York Heart Association), potentially indicating a functional remodeling after PLV-MVR. Further studies in larger patient cohorts and longer follow-up are warranted.

Adult↗

PubMed2004

Surgical treatment of infective mitral valve endocarditis.

BACKGROUND AND AIM OF THE STUDY: The approach to mitral valve endocarditis is a surgical challenge, and the optimal procedure remains a matter of debate. In this condition, mitral valve repair appears feasible, but its long-term effects--as opposed to more often practiced valve replacement--have not yet been determined. Herein, the authors' experience of surgical treatment of infective mitral valve endocarditis is presented, with reference to surgical replacement or reconstruction. METHODS: A retrospective analysis was performed of all patients with infective native mitral valve endocarditis treated surgically at the University Hospital Zurich and the City Hospital Triemli Zurich between 1980 and 1996. Of 154 patients, 97 (63%) underwent mitral valve replacement, and 57 (37%) mitral valve reconstruction. RESULTS: The 30-day mortality was 3.2% (5/154); 4% (4/97) after replacement and 1.7% (1/57) after reconstruction (p = 0.67). Survival (Kaplan-Meier) was 93%, 81% and 61% after one, five and 10 years, respectively. There was no significant difference between valve replacement and reconstruction in terms of long-term survival (p = 0.15), but there was a trend towards better survival after reconstruction than replacement if only cardiac deaths were considered (p = 0.1). At follow up, reconstruction patients were significantly less frequently symptomatic (NYHA class III/IV) than replacement patients (0% versus 29%; p = 0.002), had a lower incidence of atrial fibrillation and need for pacemaker implantation (29% versus 47%; p = 0.04), and tended to have less dyspnea in daily life (20% versus 38%; p = 0.07). Reoperation in patients surviving more than 30 days was more common in replacement than in reconstruction patients. CONCLUSION: The present data suggest a trend for better clinical outcome after mitral valve reconstruction than after replacement when treating mitral valve endocarditis. These results encourage mitral valve reconstruction in mitral valve endocarditis, but recommendations to clinicians undertaking surgery on mitral valve endocarditis must be made with caution.

Adolescent↗

PubMed2003

Dynamic regulation of MEK/Erks and Akt/GSK-3beta in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism.

OBJECTIVE: Left ventricular assist devices (LVAD) are used to 'bridge' patients with end-stage heart failure to transplantation. After long-term LVAD support, ventricular function may partially recover, a process called 'reverse remodeling'. As several kinase-mediated signal transduction pathways have been implicated in the development of cardiac hypertrophy and failure, we examined the activities of the Erks, MEKs, Akt, GSK-3 beta, p70S6K, JNKs and p38 under LVAD support as well as during single myocyte strain and whole heart stretch. METHODS: Western blotting and immunohistochemistry were performed using phospho-specific antibodies in matched samples from ten patients with end-stage heart failure before and after LVAD. Cyclic strain was performed in rat neonatal cardiac myocytes, and tensile stretch applied to Langendorff-perfused mouse hearts via a left ventricular balloon. RESULTS: The activity of Erks and Akt in failing hearts dramatically decreased after LVAD support, while that of GSK-3 beta increased. There was an endo/epicardial gradient for Erk activity which persisted after LVAD despite the reduction of total Erk activity. TUNEL-positivity and myocyte size decreased after LVAD, but independently of changes in kinase activity. In cardiomyocytes and Langendorff-perfused mouse hearts both strain/stretch and its relief regulated the activities of Erks, Akt, and GSK-3 beta. CONCLUSION: Erks and Akt/GSK-3 beta are highly responsive to myocyte stretch in vitro and in vivo, and may be sensitive molecular parameters of 'reverse remodeling' under LVAD support.

Adolescent↗

PubMed2003

The impact of the pro- and anti-inflammatory immune response on ventilation time after cardiac surgery.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass (CPB) may induce a systemic inflammatory response syndrome (SIRS), which is associated with an increased risk of postoperative morbidity and mortality. The intention of this pilot study was to investigate the influence of the pro- and anti-inflammatory cytokine responses as well as of released adhesion molecules and endotoxin on the time requirements for assisted postoperative respiration following CPB surgery. METHODS: One hundred consecutive patients undergoing elective coronary artery bypass grafting (CABG) using CPB were prospectively investigated. Blood levels of cytokines, adhesion molecules, and endotoxins were serially measured at four time points perioperatively. RESULTS: All patients survived the observation period. Eighty-five patients were uneventful (group 1), whereas 15 patients required prolonged ventilation (34.8 +/- 9.2 h; group 2). All patients developed a pro-inflammatory and a compensatory anti-inflammatory cytokine response. An endotoxin liberation was found in parallel. The prediction of prolonged respirator dependence may be possible at completion of surgery using a combined data pattern analysis, including interleukin (IL)-6, IL-8, IL-4, endotoxins, vascular cell adhesion molecule (VCAM)-1, age, and cross clamp (x-clamp) time. Using arbitrary cutoff points improved sensitivity (0.92), specificity (0.90), positive prediction (0.87), and negative prediction (0.85) (all P < 0.02), and the ODD ratio (2.1) was found. CONCLUSIONS: Cardiac surgery and CPB induces both a pro- and anti-inflammatory immune response. The use of a data pattern instead of several individual parameters seems advantageous for individualized predictions on postoperative recovery in CPB surgery.

Aged↗

PubMed2003

Outcome of patients surviving to heart transplantation after being mechanically bridged for more than 100 days.

OBJECTIVE: The effect of long-term mechanical support on subsequent heart transplantation is still debated. METHODS: We report the outcome of 41 patients (42 +/- 12 years) bridged with left ventricular assist devices (VAD; 28 Novacor, 9 HeartMate, 2 Thoratec, and 2 DeBakey) for >100 days (218 +/- 76 days) between April 1994 and March 2000). We compared follow-up with 146 patients (55 +/- 13 years) who underwent heart transplantation during the same time without prior long-term mechanical support. RESULTS: Thirty-two of the 41 patients (78%) underwent heart transplantation, 9 patients (22%) died of multi-organ (n = 5), cardiac (n = 2), or cerebral failure (n = 2). Thirty-day post-transplant mortality includes 5 cases (3 graft failures). Within the following 2 years, another 5 patients expired, 2 of cardiac failure/sudden death. Currently, 21 of 41 patients (51%) are still alive 10 to 77 months (41 +/- 22 months) after heart transplantation (1 patient was lost for follow-up). One-year and 5-year survival rates were compared with the control group (VAD vs control, 1-year survival was 75% vs 74% and 5-year survival was 60% vs 66%). Fifteen patients are doing well in New York Heart Association Class I), and 6 are NYHA Class II despite normal left ventricular ejection fraction. Episodes of moderate acute rejection (International Society for Heart and Lung Transplantation Grade 3) occurred in 10 patients (1.3 episodes per patient), not significantly different from that of the control group (1.2 episodes per patient). Scintigraphy showed regional myocardial ischemia/transplant vasculopathy in 4 patients, and coronary angiography detected the same in 2. One patient has undergone successful retransplantation. Two patients had increased right ventricular pressure. Six patients had impaired kidney function, and 3 had impaired liver function. Seven patients experienced cytomegalovirus infection. CONCLUSIONS: Our data indicate that patients who underwent heart transplantation after long-term mechanical support have a similar survival rate and comparable cardiac morbidity associated with acute rejection episodes.

Female↗

PubMed2002

Treatment of thrombus formation associated with the MicroMed DeBakey VAD using recombinant tissue plasminogen activator.

BACKGROUND: The latest generation of left ventricular assist devices consists of nonpulsatile impeller pumps. In these small pumps, thrombus formation inside the device does not lead to thromboembolic end-organ dysfunction but may dramatically impair pump flow. We report on our experience with thrombus-related pump dysfunctions of the MicroMed DeBakey left ventricular assist device and its treatment. METHODS: Eight of 22 patients with a MicroMed DeBakey VAD presented with a critically reduced pump flow. In 7 cases, an increased power demand indicative of progressive thrombus formation associated with the device was evident, whereas 1 case presented with thrombus formation within the inflow conduit associated with a very low power demand. Brief spontaneously resolving pump stops had been noted in 6 patients. All 8 patients were treated with 100 mg of recombinant tissue plasminogen activator (rt-PA), administered via an IV line. RESULTS: Rt-PA lysis led to an increase of pump flow along with a reduction of power demand within a short time in all patients. No severe bleeding complications occurred. However, 4 patients experienced transient epistaxis. All patients could be discharged from intensive care immediately after discontinuation of thrombolytic therapy. CONCLUSION: Rt-PA lysis is a very effective tool for thrombus-related pump dysfunction in patients with impeller pumps, which renders emergency surgical exchange unnecessary in most cases.

Adolescent↗

PubMed2002

Anti-CD28 monoclonal antibody therapy prevents chronic rejection of renal allografts in rats.

The effects of a signaling anti-CD28 mAb (JJ319), which interferes with the CD28-B7 T cell costimulation pathway thought to be involved in the development of chronic rejection of organ transplants, was investigated. Functional, morphologic, and molecular changes in rat renal allografts were examined up to 24 wk after placement. Control Lewis rats, recipients of F344 kidneys, received a single dose of a nonspecific mouse mAb intravenously on the day of transplantation (group 1). Group 2 animals were given anti-CD28 mAb in similar fashion. Group 3 animals were treated with a short course of cyclosporin A (CsA), and group 4 received both anti-CD 28 mAb and CsA. The majority (>95%) of animals in groups 2, 3, and 4 survived throughout the follow-up, compared with 28% in group 1 (P < 0.001). Group 2 and 4 recipients produced negligible proteinuria, whereas group 1 controls developed progressively increasing proteinuria after 4 wk and group 3 animals developed proteinuria by 24 wk. Allografts in groups 2 and 4 were morphologically unremarkable at 24 wk. Kidneys of group 1 animals rapidly developed changes of acute rejection, and those that survived long-term showed extensive glomerulosclerosis and interstitial fibrosis. Changes of early chronic rejection were noted in group 3 grafts. By reverse transcriptase-PCR, expression of representative inflammatory factors interferon-gamma and interleukin-10 were significantly elevated at 24 wk only in the surviving group 1 animals. A single dose of a signaling anti-CD28 mAb administered at transplantation or in combination with a short course of CsA significantly prolonged recipient survival, normalized function, and preserved the morphology of renal allografts in an established model of chronic rejection. These data support an important role for T cell costimulation in the evolution of the chronic process.

Animals↗

PubMed2001

Influence of donor brain death on chronic rejection of renal transplants in rats.

The clinical observation that the results of kidney grafts from living donors (LD), regardless of relationship with the host, are consistently superior to those of cadavers suggests an effect of brain death (BD) on organ quality and function. This condition triggers a series of nonspecific inflammatory events that increase the intensity of the acute immunologic host responses after transplantation (Tx). Herein are examined the influences of this central injury on late changes in renal transplants in rats. A standardized model of BD was used. Groups included both allografts and isografts from normotensive brain dead donors and anesthetized LD. Renal function was determined every 4 wk after Tx, at which time representative grafts were examined by morphology and by reverse transcriptase-PCR. Long-term survival of brain-dead donor transplants was significantly less than LD grafts. Proteinuria was significantly elevated in recipients of grafts from BD donors versus LD controls as early as 6 wk postoperatively and increased progressively through the 52-wk follow up. These kidneys also showed consistently more intense and progressive deterioration in renal morphology. Changes in isografts from brain-dead donors were less marked and developed at a slower tempo than in allografts but were always greater than those in controls. The transcription of cytokines was significantly increased in all brain-dead donor grafts. Donor BD accelerates the progression of long-term changes associated with kidney Tx and is an important risk factor for chronic rejection. These results explain in part the clinically noted difference in long-term function between organs from cadaver and living sources.

Animals↗