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Biomedical subjects

Uwe Mehlhorn

Publications and source records attributed to Uwe Mehlhorn.

At least 19 recordsLinked to original sources
PubMed2006

Induction of cardioplegic arrest immediately activates the myocardial apoptosis signal pathway.

Myocardial ischemia-reperfusion, including cardioplegic arrest (CA), has been associated with cardiac apoptosis induction. However, the time course of apoptosis activation and the trigger mechanisms are still unclear. Because apoptosis inhibition may represent a novel therapeutic strategy for long-term myocardial preservation, we sought to investigate the time course of apoptosis signal-pathway induction during CA. As to method, Sprague-Dawley rats (300-350 g) were anesthetized, intubated, and mechanically ventilated. CA was initiated by infusion of ice-cold crystalloid solution (Custodiol, 10 ml/kg) into the aortic root, and hearts were rapidly excised and stored for 0, 30, 60, and 120 min in 0.9% sodium chloride solution (28 degrees C). In controls, no CA was initiated before removal and storage at 28 degrees C. In another group, calcium-rich cardioplegia was used, and an additional group received a caspase-8 inhibitor before CA induction. Left ventricular cytosolic extracts were isolated and investigated for the activity of caspase-3 and -6 (effector caspases) and caspase-8 and -9 (involved in extrinsic and intrinsic pathways of apoptosis induction). Fluorometric activity assays were performed by using specific substrates. As a result, activities of all tested caspases were significantly increased immediately after CA induction compared with controls. Administration of the caspase-8 inhibitor significantly reduced activities of all caspases. With calcium-rich cardioplegia, caspase activities were significantly lower compared with low-calcium CA. Control hearts also showed an increase of caspase activities during cold-storage ischemia without CA but had significantly different time courses compared with hearts with CA. In conclusion, our data show rapid apoptosis signal-pathway induction immediately following CA exposure. Thus apoptosis signal-pathway inhibition as a potential strategy for improved myocardial preservation would have the greatest effect when applied before CA exposure.

Animals↗
PubMed2006

No evidence of myocardial restoration following transplantation of mononuclear bone marrow cells in coronary bypass grafting surgery patients based upon cardiac SPECT and 18F-PET.

BACKGROUND: We tested the hypothesis, that intramyocardial injection of mononuclear bone marrow cells combined with coronary artery bypass grafting (CABG) surgery improves tissue viability or function in infarct regions with non-viable myocardium as assessed by nuclear imaging techniques. METHODS: Thus far, 7 patients (60 +/- 10 [SD] years) undergoing elective CABG surgery after a myocardial infarction were included in this study. Prior to sternotomy, bone marrow was harvested by sternal puncture. Mononuclear bone marrow cells were isolated by gradient centrifugation and resuspended in 2 ml volume of Hank's buffered salt solution. At the end of CABG surgery 10 injections of 0.2 ml each were applied to the core area and borderzones of the infarct. Global and regional perfusion and viability were evaluated by ECG-gated 99mTc-tetrofosmin myocardial single-photon emission computed tomograph (SPECT) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in all study patients < 6 days before and 3 months after the intervention. RESULTS: Non-viable segments indicating transmural defects were identified in 5 patients. Two patients were found to have non-transmural defects before surgery. Concomitant surgical revascularisation and bone marrow cell injection was performed in all patients without major complications. The median total injected mononuclear cell number was 7.0 x 10(7) (range: 0.8-20.4). At 3 months 99mTc-tetrofosmin SPECT and 18F-FDG-PET scanning showed in 5 patients (transmural defect n = 4; non-transmural defect n = 1) no change in myocardial viability and in two patients (transmural defect n = 1, non-transmural defect n = 1) enhanced myocardial viability by 75%. Overall, global and regional LV ejection fraction was not significantly increased after surgery compared with the preoperative value. CONCLUSION: In CABG surgery patients with non-viable segments the concurrent use of intramyocardial cell transfer did not show any clear improvement in tissue viability or function by means of non-invasive bioimaging techniques.

Journal Article↗
PubMed2006

Mesenchymal stem cells transmigrate over the endothelial barrier.

Mesenchymal stem cells (MSCs) seem to be a useful tool for cellular therapy in injured tissues, e.g. myocardial infarction or cardiomyopathies resulting in heart failure. For therapeutic approaches it is crucial that MSCs cross the endothelial barrier especially in intravascular or rather intracoronary application. Until today little is known about MSCs transmigrating across the endothelium. We performed co-culture experiments of MSCs on an endothelial monolayer to analyse direct interactions. An increasing flattened morphology of the MSCs was followed by a total integration into the monolayer after 2h. We repeated these experiments in isolated heart perfusions with gold-labelled MSCs. Using electron microscopy we detected MSCs exhibited direct cell-cell contacts. Tight junctions between the endothelial cells became abolished resulting in a distinct split between the cells. MSCs developed tight cell-cell contacts and became integrated into the endothelial wall of the capillary vessel. Finally, using confocal laser scanning microscopy, we assessed the ability of the MSCs to fully pass the endothelial barrier. Within the first 30 min, 30+/-8% of MSCs transmigrated, increasing to about half at 60 min (50+/-8%), whereas after 120 min the rate remained nearly unchanged (53+/-10%). This work demonstrates the capability of MSCs for transendothelial migration. Moreover we showed that the vast majority of MSCs migrated within 30 min, an important finding for the exposure times in clinical settings.

Animals↗
PubMed2006

ENOS is not activated by nebivolol in human failing myocardium.

Nebivolol is a highly selective beta(1)-adrenoceptor blocker with additional vasodilatory properties, which may be due to an endothelial-dependent beta(3)-adrenergic activation of the endothelial nitric oxide synthase (eNOS). beta(3)-adrenergic eNOS activation has been described in human myocardium and is increased in human heart failure. Therefore, this study investigated whether nebivolol may induce an eNOS activation in cardiac tissue. Immunohistochemical stainings were performed using specific antibodies against eNOS translocation and eNOS serine(1177) phosphorylation in rat isolated cardiomyocytes, human right atrial tissue (coronary bypass-operation), left ventricular non-failing (donor hearts) and failing myocardium after application of the beta-adrenoceptor blockers nebivolol, metoprolol and carvedilol, as well as after application of BRL 37344, a specific beta(3)-adrenoceptor agonist. BRL 37344 (10 microM) significantly increased eNOS activity in all investigated tissues (either via translocation or phosphorylation or both). None of the beta-blockers (each 10 microM), including nebivolol, increased either translocation or phosphorylation in any of the investigated tissues. In human failing myocardium, nebivolol (10 microM) decreased eNOS activity. In conclusion, nebivolol shows a tissue-specific eNOS activation. Nebivolol does not activate the endothelial eNOS in end-stage human heart failure and may thus reduce inhibitory effects of NO on myocardial contractility and on oxidative stress formation. This mode of action may be of advantage when treating heart failure patients.

Adrenergic beta-Antagonists↗
PubMed2006

First year changes of myocardial lymphatic endothelial markers in heart transplant recipients.

OBJECTIVE: The lymphatic system plays an important role in interstitial fluid balance, lipid metabolism, and immune response. The recent introduction of specific lymphatic endothelial cell markers has made the investigation of lymphangiogenesis under various conditions and from small tissue samples feasible. It was the purpose of the study to investigate the changes of myocardial lymphatic endothelial markers during the first 12 months after heart transplantation and to analyze if a correlation between lymphatic markers and rejection can be found. METHODS: Right ventricular endomyocardial biopsies taken for routine rejection monitoring from 26 heart transplant recipients were investigated. Selected time points were 0.5, 1, 1.5, 6, and 12 months after human heart transplantation (HTX). Immunohistostaining was performed for VEGFR-3, the receptor for lymphangiogenic vascular endothelial growth factors C and D, for LYVE-1, a novel hyaluronan receptor, restricted to lymphatic vessels, and PROX-1, a homeobox gene product, which plays a key role in lymph vessel development and differentiation. RESULTS: Density of VEGFR-3 positive lymphatics did not change during the first 12 months after transplantation. However, in comparison to the 0.5-month biopsy, density of LYVE-1 and PROX-1 positive lymphatics was significantly decreased at 1 month after transplantation (p<0.03) and at the subsequent time points (p<0.01). Patients with only moderate rejection during the first 12 months (ISHLT<IIIa) had a significantly higher density of VEGFR-3 at 0.5 month in comparison to patients with at least one episode of clinically relevant rejection (ISHLT IIIa or worse, p<0.03). CONCLUSION: Myocardial lymphatics show a significant change of endothelial phenotype after transplantation, as demonstrated by significant quantitative changes of lymphatic endothelial marker density. Patients with at least one rejection of ISHLT IIIa or higher had a significantly lower density of VEGFR-3 at 0.5 month after transplantation. The results of this study warrant further investigation on the impact of transplantation on the lymphatic endothelium. The cause-effect relation between rejection and lymphatic endothelium remains to be investigated.

Adolescent↗
PubMed2006

Crataegus special extract WS 1442 induces an endothelium-dependent, NO-mediated vasorelaxation via eNOS-phosphorylation at serine 1177.

PURPOSE: This study investigates the influence of WS(R) 1442, a special extract of Crataegus leaves with flowers, on the relaxation of rat aorta and human mammarian artery (coronary bypass patients). METHODS: Experiments were performed in the presence and absence (mechanical disruption) of endothelium. In addition, we investigated three fractions of WS(R) 1442 (fraction A: lipophilic, containing flavonoids and oligomeric procyanidins (OPC), fraction B: hydrophilic, containing flavonoids and low molecular weight OPC, fraction C: hydrophilic, essentially flavonoid-free and rich in high molecular weight OPC). RESULTS: WS 1442 induced a concentration-dependent vasodilation in isolated vessel rings that had been precontracted by 10 microM phenylephrine (concentration for halfmaximal relaxation (IC(50)): rat: 15.1 +/- 0.6 microg/ml (n = 7), human: 19.3 +/- 3.4 microg/ml (n = 6)). The maximal vasorelaxation induced after application of 100 microg of WS 1442 was 75.0 +/- 5.7% (rat) and 79.2 +/- 5.8% (human) of the papaverine (0.1 mM)-induced vasodilation. If the experiments were performed in the presence of L-nitroarginine methylester (10 microM, eNOS-inhibition) or after mechanical disruption of the endothelium, no vasorelaxation was observed in the presence of WS 1442. The vasorelaxant properties of WS 1442 were mediated by fraction C. WS 1442 induced an NO-liberation from human coronary artery endothelial cells as measured by diaminofluorescein. WS 1442 induced eNOS-activation was due to a phosphorylation at serine 1177. No eNOS-translocation or phosphorylation at serine 114 or threonine 495 was observed after application of WS 1442. CONCLUSIONS: It is concluded that WS 1442, induces an endothelium-dependent, NO-mediated vasorelaxation via eNOS phosphorylation at serine 1177.

Adult↗
PubMed2006

Effect of thawing on nitric oxide synthase III and apoptotic markers in cryopreserved human allografts.

BACKGROUND: Previous investigations suggested apoptosis as a contributing factor to early failure of allograft heart valves. As myocardial apoptosis may be induced by nitric oxide (NO) release, this study investigated NO synthase [NOS-III] activation and apoptosis induction in human cryopreserved allografts during the thawing process. METHODS: Frozen myocardial tissue from ten human allograft heart valves, unsuitable for implantation, was submitted to the following conditions: (1) thawing in paraformaldehyde (Control), thawing according to the standard clinical protocol (Standard), standard-thawing with addition of the NOS-inhibitor N-omega-nitro-l-arginine (L-NA; Standard-LNA), and standard thawing with the NOS-stimulator angiotensin II (Standard-AT-II). Cryo-thin sections were investigated by immunostaining for activated NOS-III, cyclic guanosine monophosphate (cGMP), activated caspase-3, and poly-ADP-ribose polymerase (PARP). Quantitative analyses was performed by television densitometry. RESULTS: For activated NOS-III, gray unit values were significantly higher in the Standard and Standard-AT-II group than in the Control and Standard-LNA groups (p < 0.001). Gray unit values for cGMP, a downstream NO-signal-pathway molecule, showed results grossly corresponding to NOS-III activation. Activated caspase-3 and PARP showed high levels of expression in all groups with no significant differences. CONCLUSIONS: Significant activation of NOS-III and subsequent NO-cGMP signal pathway occurs in human cryopreserved allografts during the thawing process and can be significantly reduced by a NOS-III inhibitor administered during thawing. Activation of the apoptosis pathway is also present after thawing, which was not correlated to NOS-III activation. Further experimental investigation focused on the time course and mechanisms of apoptosis and NOS-III activation are required to evaluate NOS and(or) apoptosis inhibitors as therapeutic strategies for improved allograft preservation.

Apoptosis↗
PubMed2006

Effect of prophylactic bisoprolol plus magnesium on the incidence of atrial fibrillation after coronary bypass surgery: results of a randomized controlled trial.

OBJECTIVE: Bisoprolol, a highly cardioselective beta(1)-blocker, is widely used to treat elderly patients with hypertension, coronary artery disease and heart failure. The current literature lacks evidence regarding its potency to prevent atrial fibrillation (AF) following cardiac surgery. Therefore the aim of this study was to evaluate the efficacy of bisoprolol plus magnesium (Mg) in the prophylaxis of AF after coronary artery bypass graft (CABG) surgery. RESEARCH DESIGN AND METHODS: A total of 100 consecutive patients subjected to elective on-pump CABG (84 men, age 65 +/- 8 [SD] years), with no prior AF history, were randomly assigned to the prophylaxis group (n = 50) receiving after surgery bisoprolol (5 mg/day) plus Mg (intravenous infusion of 2 g of Mg on arrival in the intensive care unit, followed by oral Mg at 1800 mg/day for 1 week), or to the control group (n = 50), receiving no combined study medication but remaining on their preoperative drugs, including beta-blockers. All patients were continuously monitored to identify the onset of AF. RESULTS: In the prophylaxis group the incidence of postoperative AF was significantly lower, with 20% (10 / 50) compared to 42% (21 / 50) among controls (p = 0.030, 95% confidence interval [CI] for absolute risk reduction [ARR], 2-42%). Particularly in the elderly, bisoprolol plus Mg was effective in preventing AF; in the prophylaxis group only six of 36 (17%) patients > or = 65 years of age developed AF, compared to 13 of 20 (65%) in the control group (p < 0.001, 95% CI for ARR, 17-65%). This was associated with significantly (p = 0.022) shorter hospital stays in the prophylaxis group (median of 7 vs. 9 days, 95% CI for difference in medians, 0-3 days). CONCLUSIONS: The combination of bisoprolol plus Mg effectively reduces the incidence of postoperative AF following on-pump CABG, particularly in elderly patients, and is associated with a shorter hospital length of stay.

Aged↗
PubMed2006

Basic fibroblast growth factor controls migration in human mesenchymal stem cells.

Little is known about the migration of mesenchymal stem cells (MSCs). Some therapeutic approaches had demonstrated that MSCs were able to regenerate injured tissues when applied from different sites of application. This implies that MSCs are not only able to migrate but also that the direction of migration is controlled. Factors that are involved in the control of the migration of MSCs are widely unknown. The migratory ability of isolated MSCs was tested in different conditions. The migratory capability was examined using Boyden chamber assay in the presence or absence of basic fibroblast growth factor (bFGF), erythropoietin, interleukin-6, stromal cell-derived factor-beta, and vascular endothelial growth factor. bFGF in particular was able to increase the migratory activity of MSCs through activation of the Akt/protein kinase B (PKB) pathway. The results were supported by analyzing the orientation of the cytoskeleton. In the presence of a bFGF gradient, the actin filaments developed a parallelized pattern that was strongly related to the gradient. Surprisingly, the influence of bFGF was not only an attraction but also routing of MSCs. The bFGF gradient experiment showed that low concentrations of bFGF lead to an attraction of the cells, whereas higher concentrations resulted in repulsion. This ambivalent effect of bFGF provides the possibility to a purposeful routing of MSCs.

Actins↗
PubMed2005

eNOS translocation but not eNOS phosphorylation is dependent on intracellular Ca2+ in human atrial myocardium.

In endothelial cells, two ways of endothelial nitric oxide (NO) synthase (eNOS) activation are known: 1) translocation and 2) Akt-dependent phosphorylation of the enzyme at Ser(1177) (Ser(1177) eNOS). We have recently shown that agonist-induced Ser(1177) eNOS phosphorylation also occurs in human myocardium (10). In this study, we investigated the Ca(2+) dependency of these two mechanisms in human atrium. Therefore, atrial tissue was obtained from patients who underwent coronary artery bypass operations. In immunohistochemical experiments, the translocated form of eNOS and phosphorylated Ser(1177) eNOS were labeled using specific antibodies. eNOS translocation was measured in the absence and presence of the Ca(2+) chelator BAPTA before and after application of BRL 37344 (BRL), a beta(3)-adrenoceptor agonist that increases eNOS activity (34). In the absence of BAPTA, BRL time dependently increased the staining intensity of translocated eNOS, whereas in the presence of BAPTA, this effect was blunted. In contrast, BRL clearly increased the staining of phosphorylated Ser(1177) eNOS even in the presence of BAPTA. This observation was confirmed using Western blot analysis. Using the NO-sensitive dye diaminofluorescein, we have demonstrated that BRL induced a strong NO release. This effect was completely abolished in the presence of BAPTA but was unaffected by LY-292004, an inhibitor of phosphatidylinositol 3-kinase activity and eNOS phosphorylation. Although Ca(2+) dependent, neither the translocation of eNOS nor NO release was changed by the adenylate cyclase activator forskolin. In conclusion, 1) in human atrial myocardium, BRL-induced eNOS translocation but not Ser(1177) eNOS phosphorylation is dependent on intracellular Ca(2+). 2) In atrial myocardium, eNOS-translocation and not Ser(1177) eNOS phosphorylation is responsible for generating the main amount of NO. 3) Although Ca(2+) dependent, eNOS translocation and NO release could not be mimicked by adenylate cyclase activation as a mediator of beta-adrenergic stimulation.

Calcium↗
PubMed2005

Daily assessment of organ dysfunction and survival in intensive care unit cardiac surgical patients.

BACKGROUND: The purpose of this study was to develop a specific postoperative score for intensive care unit (ICU) cardiac surgical patients for assessment of organ dysfunction and survival. METHODS: This prospective study consisted of all consecutive adult patients admitted after cardiac surgery to our ICU over a period of 3 years. Evaluation of variables was performed using the first year patients who stayed in the ICU for at least 24 hours. The reproducibility was then tested in two validation sets using all patients. Performance was assessed with the Hosmer-Lemeshow (chi2 statistics) goodness-of-fit test and receiver operating characteristic (ROC) curves and compared with the Acute Physiology and Chronic Health Evaluation (APACHE II) and Multiple Organ Dysfunction Score (MODS). RESULTS: A total of 3,230 patients were admitted to the ICU after cardiac surgery. Mean chi2 values for the new score were 5.8 (APACHE II, 11.3; MODS, 9.7) for the construction set, 7.2 (APACHE II, 8.0; MODS, 4.5) for the validation set I, and 5.9 for the validation set II. The mean area under the ROC curve was 0.91 (APACHE II, 0.86; MODS, 0.84) for the new score in the construction set, 0.88 (APACHE II, 0.84; MODS, 0.84) in the validation set I, and 0.92 in the validation set II. CONCLUSIONS: Our new 10-variable risk index performs very well, with calibration and discrimination very high, better than general severity systems; and it is an appropriate tool for daily risk stratification in ICU cardiac surgery patients. Thus, it may serve as an "expert system" for diagnosing organ failure, decision making, resource evaluation, and predicting mortality among ICU cardiac surgical patients.

APACHE↗
PubMed2005

LIFEBRIDGE: a portable, modular, rapidly available "plug-and-play" mechanical circulatory support system.

PURPOSE: We describe the LIFEBRIDGE, a portable, modular, rapidly available "plug-and-play" mechanical circulatory support system, and report its experimental safety evaluation. DESCRIPTION: The modular construction consists of a disposable patient module with cardiopulmonary bypass circuit, control module, and base module with power supply, embedded PC, and user interface. The system weighs about 20 kg, has a modular design, and has semi-automatic priming that allows action within 5 minutes, and a 7-step air elimination program that prevents air embolization. EVALUATION: In eight pigs (85 +/- 10 kg) we investigated this system using central (right atrium and ascending aorta) cannulation (n = 4) or peripheral (iliac) cannulation (n = 4). Pump flows were 5.7 +/- 0.2 L/min with central and 4.1 +/- 0.2 L/min with peripheral cannulation, yielding sufficient animal perfusion and gas exchange. Using an intraaortic 8-MHz Doppler device, we demonstrated that venous air boluses of up to 100 mL were effectively removed, thus avoiding air embolization. Changing heights between animals and LIFEBRIDGE did not affect its proper action. CONCLUSIONS: This initial evaluation demonstrates that the LIFEBRIDGE is rapidly available, provides adequate perfusion and gas exchange, and operates safely even under simulated transport conditions.

Animals↗
PubMed2005

Phospho-eNOS Ser-114 in human mesenchymal stem cells: constitutive phosphorylation, nuclear localization and upregulation during mitosis.

Activity of endothelial nitric oxide synthase (eNOS) is modulated by protein-protein interaction and phosphorylation at specific serine or threonine residues. Using immunofluorescence analysis we show here that proliferating mesenchymal stem cells (MSCs) derived from human bone marrow exhibit cytosolic and pronounced nuclear localization of eNOS. Examination of phosphorylated eNOS subspecies revealed that eNOS phosphorylated at Ser-114 is heavily enriched in the nucleus, whereas eNOS phosphorylated at Ser-1177 is localized at filamentous structures in the cytosol that are abundant in the perinuclear region. Phosphorylation of eNOS at Ser-114 but not at Ser-1177 was strongly increased in cells shortly before mitosis and decreased to normal level after completed cell division. Double immunofluorescence analysis revealed that subcellular localization of 8-hydroxyguanosine immunoreactivity was overlapping with eNOS phosphorylated at Ser-114 in human MSCs providing evidence that phosphorylation at this residue is linked to the generation of superoxide anions. As expected there was only a weak colocalization between eNOS phosphorylated at Ser-1177 and caveolin-1. Different from many other cell systems, human MSCs accumulate eNOS in the nucleus without an acute stimulus. eNOS constitutively phosphorylated at distinct amino acid residues is targeted to different subcellular compartments pointing to an important role of specific phosphorylation events in the life cycle of proliferating human MSCs.

Active Transport, Cell Nucleus↗
PubMed2005

Increased vascular selectivity and prolonged pharmacological efficacy of the L-type Ca2+ channel antagonist lercanidipine in human cardiovascular tissue.

1. The present study investigates the vasoselectivity of lercanidipine (LER), a 1,4-dihydropyridine calcium channel blocker, compared with amlodipine (AML) and nifedipine (NIF) in human cardiovascular tissue. Experiments were performed either in human left ventricular failing myocardium (orthotopic heart transplants) or in isolated right atrial trabeculae and isolated vessel preparations of arteria mammaria obtained from patients undergoing aortocoronary bypass operation. 2. The obtained rank order for the L-type Ca2+ channel affinity in human tissue was LER > NIF >or= AML. Lercanidipine had the lowest negative inotropic efficacy (1 micromol/L LER: 60.3% basal < AML: 79.1% basal < NIF: 92.4 basal) and potency (IC50 NIF: 3.5 nmol/L < AML: 48 nmol/L < Ler: 127 nmol/L) in right atrial trabeculae. 3. The vasorelaxant potency of LER (IC50 0.5 nmol/L) and AML (IC50 0.8 nmol/L) was similar and significantly increased compared with that of NIF (IC50 5.9 nmol/L) in arteria mammaria preparations of the very same patients. 4. The following rank order was obtained for vasoselectivity: LER (260) < AML (60) < NIF (0.6). 5. The pharmacological effects of LER and AML were still present 2 h after drug washout. 3. Lercanidipine is characterized by a high vasoselectivity and a prolonged interaction with the L-type calcium channel in human cardiovascular tissue This may be advantageous, especially in the treatment of patients with arterial hypertension.

Adolescent↗
PubMed2005

Renal protection by radical scavenging in cardiac surgery patients.

OBJECTIVE: Renal function impairment is a common complication in cardiac surgery patients. Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals, which have been shown to impair various organs including the kidneys, radical scavenging may protect renal function. Therefore, the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine (NAC) versus placebo on peri-operative renal function in cardiac surgery patients. RESEARCH DESIGN AND METHODS: We reanalyzed the data of our previous study in which 40 coronary artery surgery patients (66 +/- 9 [SD] years, 9 women and 31 men) with normal pre-operative renal function had been randomized in a double-blind fashion to receive either NAC (100 mg/kg into the cardiopulmonary bypass prime followed by infusion at 20 mg/kg/h; n = 20) or placebo (n = 20). We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication. Creatinine clearance was calculated according to Cockcroft and Gault. RESULTS: Biometric and intra-operative patient data were similar between both groups. In the placebo group, serum creatinine increased from 93.1 +/- 35.4 micromol/L pre-operatively to 115.9 +/- 47.2 micromol/L on post-op day 1 (p < 0.001). In contrast, serum creatinine in the NAC group remained unchanged (92.3 +/- 31.3 micromol/L pre-op; 99.3 +/- 25.4 micromol/L on post-op day 1; p = 0.084). Accordingly, creatinine clearance decreased by 16.9 +/- 14.3 mL/min in the placebo group as compared to 7.5 +/- 17.7 mL/min in the NAC group (p = 0.039). Urinary output and diuretic medication were similar between NAC and placebo. CONCLUSIONS: Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass.

Acetylcysteine↗
PubMed2005

Digital frequency analysis of valve sound phenomena in patients after prosthetic valve surgery: its capability as a true home monitoring of valve function.

BACKGROUND AND AIM OF THE STUDY: Depending on the individual risk profile of a patient, disturbances of the functional integrity of mechanical heart valve prostheses occur in up to 2.5% of patients each year. The early phase of prosthetic dysfunction (due to thrombus formation, tissue ingrowth or endocarditis) usually remains undiagnosed, as patients do not present with symptoms in this situation, and imaging techniques (echocardiography, fluoroscopy) demonstrate normal occluder motion. The delay between the onset of prosthetic valve dysfunction and its clinical manifestation may result in complications (e.g. thromboembolism) or extended therapeutic options (e.g. reoperation rather than more intensive anticoagulation). METHODS: A total of 291 patients with mechanical heart valves was allocated to four different sub-groups, and each measured their valve sounds regularly with the 'ThromboCheck' device. Depending on the subgroup, the signals were compared with different reference signals. Patients in whom a suspicious signal was detected were immediately contacted and examined meticulously. RESULTS: Fourteen patients were found to have suspicious signals. In 13 patients, valve dysfunction was confirmed by fluoroscopy, but in four cases neither transthoracic nor transesophageal echocardiography detected abnormal occluder motion or 'musses' adjacent to the prosthesis. Normal valve sounds returned in four patients who underwent thrombolytic therapy. All patients regularly recorded and passed on their signals. Surveys revealed high acceptance and easy handling of the Thrombocheck device. CONCLUSION: Home monitoring of sound pressure measurements of prosthetic valves by digital frequency analysis via a Fast Fourier transformation may detect even very mild alterations of prosthetic valve function. The next evolution of control systems, allowing for registration of flow, frequency spectrum and electrocardiography, opens potential applications for Internet-based, remote monitoring of cardiac patients.

Aged↗
PubMed2004

The mobilization of CD34 positive mononuclear cells after myocardial infarction is abolished by revascularization of the culprit vessel.

BACKGROUND: The mobilization of hematopoietic progenitor cells from bone marrow has been proposed to play a role in cardiac regeneration after myocardial infarction (MI). Accordingly, an increase in CD34 positive cells (CD34+) has been observed in the peripheral blood of patients after acute myocardial infarction. Here, we evaluated the influence of an acute percutaneous coronary intervention (PCI) of the occluded artery on the mobilization of CD34+ in acute MI. METHODS: CD34 positive cells were quantified by flow cytometry (FACS analysis) and expressed as number per million white blood cells. Peripheral blood was obtained and analyzed at day 5 after the onset of symptoms from patients with acute MI without early PCI (n=11, age 63+/-5 years), acute MI with rapid PCI (n=7, age 63+/-3), patients with pneumonia (n=5, age 51+/-6), patients without angiographical signs of coronary artery disease (control, n=5, age 66+/-8) and young healthy volunteers (n=11, age 28+/-1). RESULTS: Patients with MI but without PCI had a higher CD34+ count at day 5 (312+/-48 per 10(6) leukocytes) than control (156+/-40, P=0.03) and MI with PCI (173+/-31, P=0.03). No increase in CD34+ was observed in patients who underwent PCI vs. control. Patients with pneumonia had higher CD34+ (350+/-44) than patients with MI with PCI (P=0.01) and control (P=0.01). Healthy individuals who were much younger than all other groups (28+/-1 years, P<0.0001 vs. all groups) had the highest CD34+ (526+/-51, P=0.006 vs. MI without PCI, P=0.00003 vs. MI with PCI, P=0.02 vs. pneumonia, P=0.00006 vs. control). CONCLUSIONS: Shorter time of ischemia and reduced cell death may be the reasons for reduced CD34+ cell count after acute MI with early percutaneous intervention vs. acute MI without intervention. Besides ischemia, also inflammation as present in pneumonia may cause a mobilization of CD34+ cells. Age may be a major factor that influences the mobilization of CD34+ cells and the regenerative capacity of the heart.

Antigens, CD34↗