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H R Zerkowski

Publications and source records attributed to H R Zerkowski.

At least 19 recordsLinked to original sources
PubMed2001

FK506 does not affect cardiac contractility and adrenergic response in vitro.

FK506 (tacrolimus) is a new immunosuppressant being used in cardiac allograft transplantation. While cyclosporine A has been shown to exert an acute negative inotropic effect on isolated heart muscle preparations, little is known of the inotropic influence of FK506. The Ca(2+) release channel of human skeletal muscle and cardiac muscle is associated with FK506 binding proteins (FKBP), FKBP12 and FKBP12.6, respectively. FKBPs can be dissociated by treatment with FK506. As a consequence of FK506 exposure, isolated skeletal muscle and cardiac muscle ryanodine receptors show altered gating characteristics. Therefore, we analyzed the direct inotropic effect of FK506 exposure to isolated, intact heart muscle preparations from the human and rabbits. Experiments were performed on isolated, electrically stimulated right atrial auricular muscle strips obtained from human myocardium during elective open heart surgery and on intact right ventricular trabeculae from rabbit hearts. The human preparations were exposed to concentrations of 8 x 10(-9), 8 x 10(-8) and 8 x 10(-6) M FK506 followed by a cumulative dose-response curve with isoprenaline as a non-selective beta-adrenoceptor agonist. Our data suggest that FK506 does not exert any positive or negative inotropic effect in either human or rabbit myocardium.

Adrenergic beta-Agonists↗
PubMed2001

Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy.

BACKGROUND: Elevated oxidative stress and superoxide anion formation in vascular cells could promote conversion of LDL to atherogenic oxidized LDL (oxLDL), contributing to endothelial dysfunction and atherosclerosis. As a major source of vascular superoxide anion formation, an endothelial NAD(P)H oxidase, similar to the leukocyte enzyme, has been identified. METHODS AND RESULTS: To elucidate functional differences between NAD(P)H oxidases of endothelial cells and leukocytes, DNA sequences of endothelial NAD(P)H oxidase subunits were determined. Gp91phox cDNA sequence showed no difference between the 2 cell types. Endothelial p67phox cDNA sequence revealed 2 known polymorphisms, which do not affect NAD(P)H oxidase function. Next, we analyzed relative mRNA expression of NAD(P)H subunits in human umbilical vein endothelial cells (HUVECs) and leukocytes using a common cRNA standard in competitive reverse transcription-polymerase chain reaction. NAD(P)H oxidase subunits p22phox and p47phox are expressed at a similar level in both cell types, whereas p67phox (2.5%) and gp91phox (1.1%) are expressed at a much lower level in endothelial cells than in leukocytes. Differences of gp91phox expression in leukocytes and HUVECs correlate with differences in superoxide release. Gp91phox mRNA and endothelial superoxide anion formation are induced in response to oxLDL in HUVECs. Furthermore, a lower gp91phox mRNA expression was found in internal mammary artery biopsy samples of patients with coronary artery disease treated with HMG-CoA reductase inhibitors before coronary bypass surgery. CONCLUSIONS: We conclude that oxLDL induces proatherosclerotic NAD(P)H oxidase expression and superoxide anion formation in human endothelial cells and an antioxidative potential of HMG-CoA reductase inhibition via reduction of vascular NAD(P)H oxidase expression.

Antioxidants↗
PubMed2001

New surface biopolymers for oxygenators: an in vitro hemocompatibility test of poly(2-methoxyethylacrylate).

BACKGROUND/OBJECTIVE: The continuous interaction of blood with artificial contact surfaces under cardiopulmonary bypass can lead to a substantial damage of blood cells and plasma factors. Surface biopolymers in oxygenation systems can help increasing the hemocompatibility, often combined with anticoagulative agents such as heparin. The poly(2-methoxyethylacrylate) [PMEA] is a new heparin-free polymer. The objective of this experimental study was to evaluate the hemocompatibility of a PMEA-coated oxygenator (Terumo Capiox RX-25) (PTX) under standardized in vitro conditions compared to two ionic-bound and one covalent-bound heparin-coated models. METHOD: Each oxygenator was mounted in a separate standardized closed circulation system. Heparinized (5 IE/mL) fresh human blood from the same donor (hemodilution: Ringer's solution) was used. Circulation time: 120 - 180 min with a flow rate of 4.0 L/min. Blood samplings: at the beginning, 5. min and every 30 min of the circulation. PARAMETERS: platelets, granulocytes, plasma factors (p-selectin, alpha-granulomeres expression, and TAT(III)-complex). After the experiment, oxygenators were dismantled and examined by scanning electron microscopy. RESULTS: All of the oxygenators led to an initial reduction of platelets and granulocytes. PTX had the lowest platelet and granulocyte reduction rates. With a lower p-selectin release compared to covalent-bound heparin-coated oxygenator and higher expression of alpha-granulomeres compared to ionic-bound heparin-coated oxygenators, the results of PTX indicated that a high number of circulating platelets were intact on the PMEA surface. TAT(III)-complex showed a steady increase in all of the oxygenators during the tests, more remarkably in PTX. In contrast to ionic-bound heparin-coated oxygenators, the electron microscopy displayed virtually no cellular accumulation on hollow fiber and housing surfaces of PTX and covalent-bound heparin-coated oxygenator. CONCLUSIONS: 1. The hemocompatibility characteristics of PTX were remarkably better than ionic-bound heparin-coated oxygenators and slightly better than the covalent-bound heparin-coated model under in vitro conditions. 2. The PMEA coating can be a useful alternative for patients with heparin-associated disorders. 3. The clinical feasibility of PTX should be evaluated under in vivo conditions.

Acrylates↗
PubMed2001

Translocation of S100A1(1) calcium binding protein during heart surgery.

Myocardial ischemia during cardiopulmonary bypass terminated by reperfusion generally leads to different degrees of damage of the cardiomyocytes induced by transient cytosolic Ca(2+) overload. Recently, much attention has been paid to the role of heart-specific Ca(2+)-binding proteins in the pathogenesis of myocardial ischemia-reperfusion injury. S100A1 is a heart-specific EF-hand Ca(2+)-binding protein that is directly involved in a variety of Ca(2+)-mediated functions in myocytes. The aim of our study was to investigate the localization and translocation of S100A1 in the human heart under normal (baseline) conditions and after prolonged ischemia and reperfusion of the myocardium. Our data suggest that S100A1 is directly involved in the transient perioperative myocardial damage caused by ischemia during open heart surgery in humans. Given its role in the contractile function of muscle cells, this S100 protein could be an important "intracellular link" in ischemia-reperfusion injury of the heart.

Calcium-Binding Proteins↗
PubMed2001

Invasive pulmonary fungal infection in hematologic patients: is resection effective?

INTRODUCTION: Invasive pulmonary aspergillosis carries a high mortality in neutropenic patients. Descriptive reports have shown early surgery to be feasible with acceptably low morbidity. The possible benefit of surgery has not been investigated in comparative studies. MATERIALS AND METHODS: In a retrospective cohort study encompassing a 15-year period, 54 (8%) of 697 consecutive patients with severe hematological disease required treatment for localized invasive pulmonary aspergillosis. Patients treated by antifungal drugs (medical group, n = 24) were compared to patients treated with additional early lung resection (surgical group, n = 30). Outcomes analysed were fungal progression and survival. RESULTS: Fungal progression at six months was 17% (95% CI 3-31) in the surgical group and 52% (95% CI 34-73) in the medical group (P = 0.005). Survival at six months was 70% (95% CI 53-87) in surgically and 42% (95% CI 24-62) in medically treated patients (P = 0.009). Adjusting for differences in WHO performance score (worse in the medical group) and duration of neutropenia (longer in the surgical group) in a multivariate analysis, a difference in relative risk of death (0.26; 95% CI 0.08-0.88; P = 0.03) remained in favor of surgery. CONCLUSION: In this retrospective study surgical intervention to treat invasive pulmonary fungal disease appeared to have a beneficial effect on the impact of disease control and survival. Differences in baseline characteristics of the two patient groups calls for cautious interpretation. A prospective randomized trial seems warranted.

Adolescent↗
PubMed2001

Age-dependent myocardial reinduction of apoptosis inhibitors under VAD in heart failure.

Hemodynamic unloading using the ventricular assist device [VAD] results in partial functional recovery of failing hearts that show increased susceptibility to cardiomyocyte apoptosis. The caspase cascade is the central element of the apoptotic process in cells. We therefore tested expression shifts of left ventricular mRNA of caspases and their endogenous inhibitors from 15 patients with VAD support and successful bridging to transplantation using semiquantitative RT-PCR. Cardiac unloading was shown by the reduction in ventricular Pro-ANP mRNA under VAD. No alteration of mRNA expression under VAD could be observed for initiator caspases, for their selective inhibitors or for apoptotic signal molecules from the mitochondrial intermembrane space. Only two unselective cardiac IAPs (inhibitor of apoptosis protein) were increased under VAD with better recovery in younger patients. In conclusion, our findings indicate that successful hemodynamic unloading by VAD support causes only minor, age-dependent recovery in the expression of IAPs, while presumed alterations in antiapoptotic modulator systems upstream of the caspase cascade still remain to be identified.

Age Factors↗
PubMed2001

Doppler microembolic signals in patients with two different types of bileaflet valves.

OBJECTIVES: This study was performed to evaluate the prevalence and counts of Doppler microembolic signals in patients with St Jude Medical valves (St Jude Medical, Inc, St Paul, Minn) and patients with ATS valves (ATS Medical, Inc, Minneapolis, Minn) and their relation to clinical parameters. METHODS: A total of 179 outpatients of the department of cardiothoracic surgery were examined. They included 98 men and 81 women, aged 61 +/- 11 years, with ATS (n = 91) or St Jude Medical (n = 88) valves in the aortic (n = 110), mitral (n = 39), or both positions (n = 30). Neurologic examination was followed by transcranial Doppler monitoring for microembolic signals. Monitoring was performed bilaterally over the middle cerebral arteries for 1 hour per session. RESULTS: Microembolic signal counts and prevalence were significantly higher in patients with St Jude Medical as compared with ATS valves. Valve type and presence of diabetes mellitus were the only predictors of microembolic signal prevalence on multivariate analysis. No influence of microembolic signals on cerebral embolic complications was established. Additionally, patients with a postoperative history of cerebral embolic complications did not have a higher number of microembolic signals than remaining patients. Interobserver variability was satisfactory. CONCLUSIONS: Patients with St Jude Medical valves were shown to have significantly higher microembolic signal counts than patients with ATS valves. However, our results suggest that microembolic signal counts cannot be used to predict cerebral embolic complications. Their relation to neuropsychologic deficits remains to be evaluated.

Aged↗
PubMed2001

[Intravascular detection of myocardial ischemia by spectrometry in the near infrared spectrum in experimental animals].

Interruption of oxygen supply in acute myocardial ischaemia reduces venous return of oxygen at the coronary sinus. In this study, the oxygen content of venous return in the coronary sinus was measured by using spectrometry in the near infrared spectrum. The authors developed a new intravascular catheter made of fibre optics. After in vitro calibration by blood flow based on a standard gas mixture used in in vitro experiment, an in vivo application in 12 domestic pigs was undertaken. The catheter was positioned in the coronary sinus and ischaemia induced by temporary occlusion of the left anterior descending artery. Recordings of the near infrared spectrum and haemodynamic data were obtained during 90 minutes' ischaemia followed by 90 minutes reperfusion. Spectrometry in the near infrared range detected a marked difference between oxyhaemoglobin and deoxyhaemoglobin, especially when the oxygen concentration was less than 30%. The near infrared spectrum of liaison between haemoglobin and oxygen in the coronary sinus shows significant and reproducible differences between pre-ischaemia occlusion of the left anterior descending artery and reperfusion. The recordings of the near infrared also show variation in CO2, pH and temperature. The authors conclude that the use of intravascular spectrometry of the near infrared spectrum could be a permanent reliable tool for detection and follow-up of acute myocardial ischaemia.

Animals↗
PubMed2001

[Multiple heart valve diseases: differential therapeutic considerations].

After more than 40 years of heart valve surgery, the indication for double valve procedures still represents a problem in the presence of an obviously leading single valve disease. If the isolated valves do not already represent a clear indication for surgery then this situation is the best example for a good deal of thought in cardiac surgery and discussion with competent cardiologists.

Adult↗
PubMed2000

Deloading of the left ventricle by ventricular assist device normalizes increased expression of endothelin ET(A) receptors but not endothelin-converting enzyme-1 in patients with end-stage heart failure.

BACKGROUND: Ventricular assist devices (VAD) are implanted in patients with end-stage heart failure for bridging the time until heart transplantation, resulting in hemodynamic unloading of the failing heart, improved cardiac contractile and mitochondrial function, and reversal of cardiac hypertrophy. It is unknown whether VAD unloading may affect the cardiac endothelin (ET) system, which has been proposed as one of the putative pathomechanisms of heart failure. METHODS AND RESULTS: With the use of standard-calibrated, competitive reverse-transcription-polymerase chain reaction mRNA expression of components of the ET system was analyzed in left ventricular myocardium from nonfailing donor hearts, from failing hearts without and with ACE inhibitor therapy, and from patients with end-stage heart failure at the time of VAD implantation and 103+/-15 days after VAD implantation during removal with subsequent heart transplantation. ET receptor A (ET(A)) was markedly upregulated in failing human myocardium. This increased ET(A) expression was not affected by ACE inhibitor treatment but was normalized by VAD unloading. ET(A) expression before or after VAD implantation did not correlate with duration of VAD implantation or suppression of Pro-ANP mRNA. ET(B) mRNA expression was unaffected by heart failure or VAD. In contrast, increased ET-converting enzyme-1 mRNA and ET-1 peptide levels in failing myocardium were partially normalized by ACE inhibition but not by VAD unloading. CONCLUSIONS: We conclude that VAD implantation normalizes ET(A) expression in failing human left ventricular myocardium, probably as the result of the beneficial effects of VAD unloading.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Aberrant right pulmonary artery and double outlet ventricle: one-stage repair.

We report a 13-month-old male child with anomalous origin of the right pulmonary artery from the ascending aorta and a double outlet right ventricle. Aortic wall was used for elongation of the pulmonary artery and side-to-end connection to the pulmonary trunk. Special emphasis is made on this particular operative technique for strictly laterally originating right pulmonary artery that requires no prosthetic material, avoids extreme stretching, and may enable normal growth potential.

Aorta↗
PubMed2000

Expression of secreted frizzled related proteins 3 and 4 in human ventricular myocardium correlates with apoptosis related gene expression.

OBJECTIVE: Overload-induced heart failure is associated with myocyte apoptosis induced by unknown mechanisms. Wnt genes encode secreted signaling molecules that bind to frizzled receptors and stabilize cytosolic beta-catenin which is translocated into the nucleus, acts as transcriptional activator and imparts an apoptosis resistant phenotype. This signaling pathway is antagonized by secreted frizzled related proteins (sFRPs) which modulate apoptosis susceptibility in cell culture models. On the basis of these considerations, the present investigation compares myocardial mRNA expression of sFRPs and the level of soluble beta-catenin in tissue samples from nonfailing and failing hearts. METHODS: Nonischemic transmural samples from human failing left ventricles and from nonfailing donor ventricles were used in the present study. The mRNA concentration of the Wnt-antagonists sFRP 1-4 were determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). The myocardial localization of sFRP 3 and 4 expression was investigated using in situ RT-PCR. The pool of soluble beta-catenin was quantified by Western blot analysis of protein extracts. RESULTS: The mRNA levels of proapoptotic sFRPs 3 and 4 but not of sFRP 1 and 2 were elevated in failing ventricles compared to donor hearts. There was no significant difference between patients suffering from a dilated cardiomyopathy or a coronary heart disease. sFRPs 3 and 4 were expressed in cardiomyocytes and their expression correlated with the mRNA expression of the proapoptotic Fas/Fas-antagonist ratio, but inversely with the mRNA levels of the antiapoptotic bcl-xL. The size of the pool of 0.1% Triton soluble beta-catenin tended to decrease in myocardial samples with high sFRP 3 and 4 expression levels. CONCLUSIONS: The results support the hypothesis that in failing human myocardium the Wnt/beta-catenin pathway is attenuated by enhanced expression of two endogenous Wnt-antagonists. This might contribute to an apoptosis susceptible phenotype of overloaded human myocardium.

Apoptosis↗
PubMed2000

Predictive value of S-100beta and neuron-specific enolase serum levels for adverse neurologic outcome after cardiac surgery.

OBJECTIVES: The aim of this study was to evaluate the time course of S-100beta and neuron-specific enolase serum levels after cardiac surgery and their clinical relevance in predicting postoperative adverse neurologic outcomes; the 2 proteins are only released in peripheral blood in association with nervous system lesions. METHODS: We neurologically assessed 190 consecutive patients undergoing elective cardiac operations for coronary artery bypass (n = 147), valve replacement (n = 29), or both (n = 14), before as well as after the operation. Postoperative outcome was classified as type I (uncomplicated), type II (confusion, agitation, disorientation, or epileptic seizures), or type III (stroke, stupor, or coma). Levels of S-100beta and neuron-specific enolase were evaluated in venous blood samples drawn preoperatively and then daily in the first 5 postoperative days. RESULTS: Levels of S-100beta and neuron-specific enolase differed significantly among the 3 groups (type III > type II > type I) throughout the postoperative period and had a diagnostic specificity and specificity of 89% and 79%, respectively, in identifying patients with type III outcome. S-100beta (but not neuron-specific enolase) levels were identified as significant independent predictors for type II and III outcomes (odds ratio 16.2, P <.0004). The same was true for duration of cardiopulmonary bypass (odds ratio 1.02, P <.006). CONCLUSIONS: Serum levels of S-100beta are reliable markers for adverse neurologic outcomes after cardiac surgery.

Biomarkers↗
PubMed2000

Improved outcome of APACHE II score-defined escalating systemic inflammatory response syndrome in patients post cardiac surgery in 1996 compared to 1988-1990: the ESSICS-study pilot project.

OBJECTIVE: Cardiac surgery using extracorporeal circulation leads to the release of cytokines and subsequently to a systemic inflammatory response syndrome, which is thought to be a negative prognostic factor for patients' outcome. A stratification for the risk of an escalating systemic inflammatory response syndrome had been achieved in a monocenter study carried out in 1988-1990, using APACHE II scoring on the morning of the 1st postoperative day. We now re-evaluated this concept prospectively in three independent centers. METHODS: The APACHE II based risk stratification was put to test in three independent heart surgery centers in the period from June to December 1996. Nine hundred and forty-five patients after elective cardiac surgery (excluding heart transplantation) with the assistance of the cardiopulmonary bypass were prospectively monitored. RESULTS: We found an increase in mortality with higher APACHE II score values determined on the 1st postoperative day. The mortality rose to nearly 50% with an APACHE II score of > or = 28. Patients at high risk for the development of a systemic inflammatory response syndrome (APACHE II score > or = 24) significantly differed from patients at lower risk (APACHE II score < 19) in the duration of mechanical ventilation and extracorporeal circulation, age and New York Heart Association (NYHA) classification (P < 0.05). CONCLUSION: The APACHE II score determined on the morning of the 1st postoperative day helps identifying the subgroup of patients with escalating systemic inflammatory response syndrome. Comparison with the data obtained in the years 1988-1990, suggests a better prognosis in the current trial for patients at high risk with a similar degree of escalating systemic inflammatory response syndrome.

APACHE↗
PubMed2000

The mechanism of cryoinjury: In vitro studies on human internal mammary arteries.

The mechanism of cryoinjury was investigated in human internal mammary arteries (IMA) by monitoring contractile responses to ET-1 and KCl. For cryopreservation segments of IMA were equilibrated for 20 min with the cryomedium (RPMI 1640 culture medium containing 1.8 M DMSO and 0.1 M sucrose), frozen at a mean cooling rate of 1.3 degrees C min(-1) to -70 degrees C and stored in liquid nitrogen. Before use, samples were thawed slowly and the cryomedium removed by dilution. Compared to unfrozen controls, ET-1 stimulated frozen/thawed IMA with similar efficacy but at 3 fold lower concentrations (P<0.001). Addition of ET-1 (100 nM) induced maximal contraction of unfrozen IMA within 10 min, declining thereafter to 25% after 90 min. In frozen/thawed IMA the ET-1-induced contraction was sustained but could be reversed if protein kinase C was blocked by staurosporine (100 nM). Responses to ET-1 of cryostored IMA were 5 fold more susceptible to blockade by nifedipine than those of controls. After cryostorage the efficacy of KCl was diminished to 40% (P<0.05) and the KCl curve was shifted to the left (2 fold, P<0. 001). In both unfrozen and cryostored IMA the KCl (60 mM) effect was sustained and equally susceptible to nifedipine. It is suggested that the smooth muscle cell of IMA is receptive to physical forces which occur during cryopreservation. These forces modify transmembrane signal transduction and intracellular pathways, that are common to pharmacological agonists thereby changing vascular responses to several contractile agonists after thawing.

Calcium↗