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Biomedical subjects

M C Deng

Publications and source records attributed to M C Deng.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of modification of the allocation system on ischemia duration and costs of heart transplantation. Transplantation Cooperation UNI-NRW.

BACKGROUND: In order to optimize regional utilization of transplantable thoracic organs, the seven university hospitals in North-Rhine-Westfalia have formed a transplant cooperation meanwhile approved by Eurotransplant. METHODS: Heart transplant and organ donation activities of the cooperating hospitals in the year before the foundation of the cooperation (period A, 7/95 - 6/96) and in the year thereafter (period B, 7/96 - 6/97) were retrospectively analysed. RESULTS: In period A, a total of 39 heart transplants and 74 heart donations were performed, whereas in period B 67 heart transplantations and 78 heart donations could be achieved. The regional utilization of the donor organs increased from 4% to 30% with a significantly shorter ischemia time of regionally or locally allocated donor hearts than of nationally or internationally allocated ones. CONCLUSIONS: A high rate of regional or local heart transplant procedures with short ischemia times clearly demonstrate the benefits of a regionalization of heart transplant medicine for medical as well as economical reasons.

Cost-Benefit Analysis↗
PubMed1999

Left ventricular assist system support is associated with persistent inflammation and temporary immunosuppression.

BACKGROUND: In patients undergoing left-ventricular assist system support, it has not been elucidated to which extent mechanical circulatory support itself as opposed to the underlying condition of endstage heart-failure contributes to perturbation of immune homeostasis. METHODS: In eleven heart transplant candidates who had to undergo Novacor left-ventricular assist device bridging, we prospectively sampled interleukin-6, T-cell and monocyte subsets and compared them to fifteen UNOS status II patients awaiting cardiac transplantation on medical heart failure treatment as outpatients at the time of LVAS implantation/listing decision as well as 2.0+/-1.2 months and 4.5+/-2.3 months later. In order to assess deviations in both groups from normal values, thirty-two healthy subjects served as reference group. RESULTS: Patients undergoing Novacor bridging had higher C-reactive protein, leukocyte, neutrophil, and monocyte levels at all three times, and exhibited lower CD3 +, CD4+, CD3+/CD45 RO T-cell and natural killer cell counts than medically treated patients awaiting transplantation 2 months after the LVAS implantation/listing decision. In comparison to controls, both groups had higher levels of inflammatory activation and lower levels of immunocompetence at all three times. CONCLUSIONS: While both groups of endstage heart failure patients show immunological alterations compared to controls, patients who have to be bridged by the Novacor LVAS exhibit a more pronounced activation of inflammatory markers. This may be due to more advanced heart failure but the device itself also may contribute to more pronounced inflammation and a temporary suppression of immunocompetent cells.

Adult↗
PubMed1999

Identification and characterization of diadenosine 5',5"'-P1,P2 -diphosphate and diadenosine 5',5"'-P1,P3-triphosphate in human myocardial tissue.

We examined whether human cardiac tissue contains diadenosine polyphosphates and investigated their physiological role. Extracts from human cardiac tissue from transplant recipients were fractionated by size exclusion-, affinity-, anion exchange- and reversed-phase chromatography. MALDI-MS analysis of two absorbing fractions revealed molecular masses of 676.2 Da and 756.0 Da. The UV spectra of both fractions were identical to that of adenosine. Postsource decay MALDI mass spectrometry indicated that the molecules with a mass of 676.2 Da and 757.0 Da contained AMP and ATP, respectively. As shown by enzymatic cleavage, both molecules consist of two adenosines interconnected by either two or three phosphates in 5'-positions of the riboses. Two substances can be identified as 5',5"'-P1,P2-diphosphate (Ap2A) and 5',5"'-P1, P3-triphosphate (Ap3A). Ap2A and Ap3A, together with ATP and ADP, are stored in myocardial-specific granules in biologically active concentrations. In the isolated perfused rat heart, Ap2A and Ap3A caused dose-dependent coronary vasodilations. In myocardial preparations, Ap2A and Ap3A attenuated the effect of isoproterenol, exerting a negative inotropic effect. The calcium current of guinea pig ventricular myocytes, stimulated by isoproterenol, was also attenuated by Ap2A and Ap3A. The presence of Ap2A and Ap3A in cardiac-specific granules and the actions of these substances on the myocardium and coronary vessels indicate a role for these substances as endogenous modulators of myocardial functions and coronary perfusion.

Animals↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor (GM-CSF) modulates the expression of type VIII collagen mRNA in vascular smooth muscle cells and both are codistributed during atherogenesis.

The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and type VIII collagen was studied in human arteries. GM-CSF and type VIII collagen were codistributed in all layers of the walls of nondiseased arteries and during early atherogenesis with up to type V lesions. The number of cells expressing both mRNAs increased during the development of advanced atherosclerotic lesions. Whereas type VIII collagen expression increased further in complicated lesions, GM-CSF was downregulated. During early atherogenesis smooth muscle cells (SMC) and endothelial cells were the principal GM-CSF and type VIII collagen mRNA-expressing cell types. In advanced lesions monocytes/macrophages also expressed the mRNAs. In complicated lesions the number of GM-CSF mRNA-expressing SMC was markedly reduced. In in vitro experiments transforming growth factor-beta1, platelet-derived growth factor, and GM-CSF, but not basic fibroblast growth factor, stimulated the expression of type VIII collagen mRNA by SMC. GM-CSF transiently stimulated type VIII collagen transcription. Thus GM-CSF is a prominent component of the regulatory network influencing collagen metabolism during atherogenesis. By modulating the synthesis of type VIII collagen in SMC, GM-CSF may influence the course of plaque development and may govern processes such as cell movement, plaque stability, and thrombus organization.

Arteriosclerosis↗
PubMed1999

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Animals↗
PubMed1998

T-cell and monocyte subsets, inflammatory molecules, rejection, and hemodynamics early after cardiac transplantation.

BACKGROUND: In the early period after cardiac transplantation, differential diagnosis of graft failure due to rejection, infection, and other causes is important but difficult. METHODS: In 22 consecutive patients undergoing heart transplantation, we prospectively determined levels of interleukin-6 as well as T-cell and monocyte subsets at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first 3 months after transplantation. RESULTS: Worse hemodynamic parameters, as characterized by dichotomization according to median values (pulmonary capillary wedge pressure >10 mmHg, mean pulmonary arterial pressure > 18 mmHg, pulmonary vascular resistance > 115 dyn x sec x cm(-5), right atrial pressure > 5 mmHg, cardiac index <3 L/min/m2, early mitral deceleration time < 135 msec, and isovolumic relaxation time <80 msec), were associated with higher levels of interleukin-6, C-reactive protein, polymorphonuclear cells, CD71+/CD14+ monocytes, and IgM levels and, in contrast, with lower levels of immunocompetence markers such as CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+/CD25+ T cells, CD4+/ CD45RO+ T cells, NK cells, and lower biopsy scores. CONCLUSION: Early after cardiac transplantation, elevated levels of inflammatory cells and soluble inflammatory molecules and lower levels of immunocompetence markers are associated with impaired allograft function in the absence of cellular rejection.

Adult↗
PubMed1998

Possible relationship between heat shock protein 70, cardiac hemodynamics, and survival in the early period after heart transplantation.

BACKGROUND: Heat shock proteins (HSPs) are produced by cells in response to a wide variety of stresses. To determine a possible relationship between hemodynamic parameters and HSP 70 in the early postoperative period after heart transplantation, we examined immunohistochemically the inducible HSP 70 (anti-HSP 72) response in human heart biopsies, as well as the effect of myocardial rejection on HSP. METHODS: A total of 105 routinely processed endomyocardial biopsies from 15 consecutive patients who underwent heart transplantation were examined. Analysis of hemodynamic and echocardiographic parameters were performed within 30 min and 12 hr after the biopsies. RESULTS: Immunohistochemically detected inducible HSP 70 was mainly located in the cytoplasm and nucleus/nucleolus of cardiomyocytes. Two specimens additionally showed HSP 70-positive interstitial cells and smooth muscle cells of arteries, whereas lymphocytes were consistently negative. There was a significant relation between the echocardiographically determined increased relaxation time and positive HSP 70 staining (P < 0.011). Patients with elevated right atrial pressure (P < 0.098), as well as those with increased left ventricular end systolic diameter (P < 0.06), showed a trend to higher HSP expression. Three patients who died of sepsis or multiorgan failure showed significantly higher cytoplasmic HSP 70 expression compared with 12 patients with stable clinical course. In case of rejection, significantly more patients showed no HSP expression. CONCLUSION: Although only five patients showed organ rejection, our results suggest an inverse relationship between HSP expression and rejection with the possibility of a role for HSP 70 as a graft marker to assess graft function.

Biopsy↗
PubMed1998

Transplant vasculopathy.

Transplant vasculopathy constitutes the major impediment to long-term survival in heart transplant recipients. Within the "response to immune injury" paradigm, it can best be understood as the resultant of an orchestrated recipient immune response to the initial allogenic stimulus by graft vascular endothelium. This response incorporates the elaboration of complex coordinated cytokine patterns and corresponding cell types including B-lymphocytes, T-helper1- and T-helper2-cells, cytotoxic T-cells, macrophages, and polymorphonuclear cells. These attack the alloantigenic vascular endothelium and lead, by complex cytokine signaling, to migration of donor smooth muscle cells from the media into the intima, associated with a switch from the contractile to a synthetic phenotype. In conjunction with recipient T-cells, macrophages, and lipids, the intimal fibroproliferative growth of the donor vessel is hereby initiated.

Animals↗
PubMed1998

Cerebral and systemic embolization during left ventricular support with the Novacor N100 device.

BACKGROUND: Patients undergoing implantation of left ventricular assist systems (LVAS) are prone to thromboembolic complications. We analyzed the incidence, clinical findings, and outcome of neurologic and systemic thromboembolic events (TE) in patients with the Novacor N100 LVAS. In a subset of patients, transcranial Doppler sonography was used to detect microembolic signals. METHODS: Thirty-six patients underwent implantation of a Novacor N100 LVAS for various reasons. The surgical procedure was elective in 18 patients and scheduled on an urgent or emergency basis in another 18 patients. The assist period lasted from 17 to 336 days (109 +/- 88 days); 22 patients were forwarded to heart transplantation after being supported for 140 +/- 87 days. RESULTS: Clinical cerebral embolism was evident in 17 patients (47%). Thromboembolic events were singular in 8 and multiple in 9 patients; in the latter up to 10 TE occurred (mean +/- SD, 1.4 +/- 2 TE). Leading neurologic symptoms were unilateral hemiplegia in 11, as well as ocular symptoms and aphasia in 12 patients each. Noncerebral TE were detected in 4 patients, 2 of whom underwent an emergency operation for intestinal and iliac artery occlusion. The incidence of TE did not correlate strongly with the interval of LVAS support. Cerebral computed tomography confirmed lesions in 58% of patients. Transcranial Doppler sonography detected microembolic signals on 67% of all recordings, with the microembolic signals being more frequent on days with clinically manifest TE. The outcomes were good, as only 2 patients suffer from neurologic sequelae. CONCLUSIONS: Thromboembolism is still a major threat for patients with LVAS implantation. Neurologic sequelae are frequent but have a favorable prognosis, and systemic complications occur considerably less often. Patient selection, adequate anticoagulation, and transcranial Doppler sonography may help to reduce the incidence of TE.

Adult↗
PubMed1998

Successful treatment of a Novacor LVAD malfunction without repeat sternotomy.

Implantable left-ventricular assist devices have been remarkably free of mechanical failures. We describe an uncommon Novacor N100 PCq LVAS malfunction caused by an internal short circuit of the device due to urine aspiration via the vent line. Device replacement was managed via a subcostal approach without sternotomy. Patient recovery was uneventful and successful transplantation was performed one month after the device exchange.

Adult↗
PubMed1998

Left-ventricular expression of interleukin-6 messenger-RNA higher in idiopathic dilated than in ischemic cardiomyopathy.

During end-stage heart failure, plasma levels of interleukin-6 (IL6) are elevated. This cytokine exerts a negative inotropic influence on the myocardium. The production site of IL6 is unclear. We examined the hypothesis that IL6 in end-stage heart-failure patients is produced in the myocardium itself and is differentially regulated according to etiology. Cardiac tissue was obtained from 27 patients (idiopathic dilated cardiomyopathy, (DCM) 9/6 m/f, age 46 +/- 14 y; ischemic cardiomyopathy (ICM), 11/1 m/f, age 55 +/- 8 y) at the time of transplantation. The tissue was subjected to IL6 Northern-blot analysis. Signals were quantified by densitometric scanning after normalization to G3 PDH mRNA. Data were compared by Mann-Whitney test between DCM and ICM patients, divided by chamber origin. IL6 transcripts were found in all patients. In DCM, left-ventricular IL6 mRNA expression was higher than in ICM (p = 0.006). Median right-ventricular as well as left- and right-atrial IL6 mRNA expression was not significantly different in both groups. In summary, in end-stage heart failure, IL6 mRNA is consistently expressed in the myocardium. Left-ventricular expression is higher in DCM than in ICM. These data support the concept of a potentially reversible inflammatory component in the etiology of DCM which is more pronounced than in patients with ICM of comparable clinical severity.

Adult↗
PubMed1998

Effect of platelet inhibitors on thromboembolism after implantation of a Novacor N100--preliminary results.

BACKGROUND: Left-ventricular assist device implantation (LVAD) is still associated with thromboembolism as the optimal anticoagulation is still unclear. We report on the effects of adding platelet inhibitors to our anticoagulation regimen in our Novacor LVAD program. METHODS: Oral platelet aggregation inhibitors (aspirin 330 mg + dipyridamole 75 mg, three times per day) were added to the heparin/phenprocoumon treatment in 9 patients starting on postoperative day 3 to 7 (group A). Of the previous 41 patients, the last 20 patients served as a control group (group B), to reduce any learning curve effect. RESULTS: The mean interval of mechanical support between the two groups was comparable (group A vs B: 148 +/- 127 vs 104 +/- 61 days, n.s.). Accordingly, the cumulative support was much lower in group A (1051 days) as compared to group B (2091 days). In group B, 10 patients (50%) developed clinically evident thromboembolism. The number of events ranged from 1 to 10 (mean 1.4 +/- 2.3), with a total of 32. With addition of platelet inhibitors, the incidence of cerebral embolism dramatically dropped, as only one patient presented with transient ischemic attacks in group A (p < 0.05). Thoracic bleeding as defined by excessive drainage losses requiring redo thoracotomy did not increase (group A vs B: 22% vs 20%, n.s.). CONCLUSION: Addition of platelet inhibitors to heparin/phenprocoumon effectively prevents thromboembolism. However, platelet inhibitors should be postponed until sufficient hemostasis is achieved, since too early administration is associated with an increased risk of bleeding.

Anticoagulants↗
PubMed1998

Selection and outcome of ventricular assist device patients: the Muenster experience.

BACKGROUND: Because the number of patients on the waiting list for transplantation is increasing and the stagnation in the number of organs donated has led to a more restrictive listing for transplantation, an increased fraction of patients needs to be bridged mechanically. We examined the hypothesis that selection of these patients with regard to urgency status is critical in determining outcome. METHODS: A cohort of 631 patients referred for transplantation to our center between January 1, 1990, and December 31, 1996, was analyzed. Two hundred ninety-seven patients were listed for transplantation and 157 were given transplantation. Forty-one patients had to undergo ventricular assist device implantation (n=34, Novacor; n=6, TCI Heartmate; n=1, Medos), 39 for bridging to transplantation and 2 for permanent support. Initial transplantation evaluation data were analyzed in 3 subgroups (elective bridging, urgent bridging, emergency bridging) and compared with another and with other patients referred for transplantation, specifically those who did not have to be bridged on the waiting list. RESULTS: Patients who underwent elective or urgent assist device bridging were younger and more compromised than the rest of patients accepted on the waiting list (higher functional class, lower mean arterial pressure, lower cardiac index, lower serum sodium, higher pulmonary capillary wedge pressure). In the elective group, overall survival including perioperative mortality rate was better than in the urgent/emergency group and at least as good as in patients who were stable on the waiting list and did not undergo heart transplantation during follow-up. This should prompt cardiologists and cardiac surgeons to consider assist device implantation earlier.

Adult↗
PubMed1997

Ischemic versus idiopathic cardiomyopathy: differing neurohumoral profiles despite comparable peak oxygen uptake.

OBJECTIVE: We tested the hypothesis that neurohormonal and immunological activation differs in ischemic and idiopathic dilated cardiomyopathy since recent intervention trials indicate that ischemic cardiomyopathy seems to carry a worse prognosis than idiopathic cardiomyopathy of comparable clinical severity. METHODS: In ten patients with ischemic cardiomyopathy undergoing spiroergometric evaluation venous levels of norepinephrine, epinephrine, renin, angiotensin, atrial natriuretic peptide as well as soluble interleukin-2-receptor were determined before, during and 10 min after exercise. Results were compared to sixteen patients with idiopathic cardiomyopathy with similar peak oxygen uptake (13.3+/-3 vs. 13.6+/-3 ml/kg/min; P=ns). RESULTS: In ischemic patients, norepinephrine, angiotensin, and interleukin-2 receptor levels were significantly higher before, during and after exercise. Interleukin-2-receptor levels correlated with angiotensin. CONCLUSIONS: We conclude that in ischemic as compared to idiopathic cardiomyopathy, a more pronounced activation of the sympathetic, renin-angiotensin and T-cell immune system is present at rest, during and after exercise. These data may contribute to explain differences in response to intervention and in prognosis. They warrant further investigation.

Adult↗
PubMed1997

Quantification of the cAMP response element binding protein in ventricular nuclear protein from failing and nonfailing human hearts.

Alterations in the expression of myocardial regulatory proteins (e.g. beta-adrenoceptor, inhibitory G-proteins) in human heart failure are associated with excessive stimulation of the cAMP signalling pathway by endogenous catecholamines. The transcription factor cAMP response element binding protein (CREB) mediates cAMP-dependent transcriptional activation and is expressed in the human heart. Here, CREB protein was immunologically quantified in ventricular nuclear protein preparations from nonfailing donor hearts (n = 8) and from failing hearts transplanted due to dilative (n = 10) or ischemic cardiomyopathy (n = 6). CREB expression was unchanged in ventricular nuclei from failing hearts compared to the nonfailing controls suggesting that expressional alterations in human heart failure cannot be explained by altered expression of CREB.

Cyclic AMP Response Element-Binding Protein↗