Biomedical subjects

Johannes Winning

Publications and source records attributed to Johannes Winning.

11 recordsLinked to original sources

PubMed2006

Dobutamine improves liver function after hemorrhagic shock through induction of heme oxygenase-1.

RATIONALE: Induction of heme oxygenase-1 (HO-1) protects the liver against reperfusion injury after hemorrhagic shock. Previous data suggest that the beta(1)-adrenoceptor agonist dobutamine induces HO-1 in hepatocytes. OBJECTIVES: To investigate the functional significance of dobutamine pretreatment for liver function after hemorrhagic shock in vivo. METHODS: Anesthetized rats received either Ringer's (Vehicle/Shock), 10 microg/kg/min of the beta(1)-adrenoceptor agonist dobutamine (Dob/Shock), or 10 microg/kg/min dobutamine and 500 microg/kg/min of the beta(1)-adrenoceptor antagonist esmolol (Dob/Esmolol/Shock) for 6 h. Hemorrhagic shock was induced thereafter (mean arterial pressure, 35 mm Hg for 90 min). Animals were resuscitated with shed blood and Ringer's. In addition, the HO pathway was blocked after dobutamine pretreatment with 10 micromol/kg tin-mesoporphyrin-IX (Dob/SnMP/Shock) or animals received 100 mg/kg of the carbon monoxide donor dichloromethane (DCM/Shock). MEASUREMENTS: Hepatocellular metabolism and liver blood flow were measured by plasma disappearance rate of indocyanine green (PDR(ICG)) as a sensitive marker of liver function. MAIN RESULTS: Pretreatment with dobutamine induced HO-1 in pericentral hepatocytes and improved PDR(ICG) (Vehicle/Shock: 11.7 +/- 8.12%/min vs. Dob/Shock: 19.7 +/- 2.46%/min, p = 0.006). Blockade of the HO pathway after preconditioning and the combined pretreatment with dobutamine and esmolol decreased PDR(ICG) (Dob/SnMP/Shock: 12.6 +/- 4.24%/min, p = 0.011; Dob/Esmolol/Shock: 10.2 +/- 4.34%/min, p = 0.008). Pretreatment with a carbon monoxide donor improved PDR(ICG) (DCM/Shock: 18 +/- 3.19%/min, p = 0.022) compared with Vehicle/Shock. CONCLUSIONS: These results suggest a beta(1)-adrenoceptor-dependent hepatic up-regulation of HO-1 and a better maintained hepatocellular function after hemorrhagic shock in animals pretreated with dobutamine. The improved hepatocellular function may be in part mediated by carbon monoxide because of up-regulation of HO-1. Pretreatment with dobutamine might be a potential means of pharmacologic preconditioning before ischemia-reperfusion of the liver.

Adrenergic beta-Agonists↗

PubMed2006

Post-pleuropneumonectomy herniation of liver mimicking major pulmonary embolism.

Following right-sided pneumonectomy and hemidiaphragm resection in a 58-year-old man with epithelioid mesothelioma, acute respiratory insufficiency and life-threatening circulatory collapse developed after a forced Valsalva maneuver. Major pulmonary embolism was diagnosed on clinical grounds, however computed tomography revealed herniation of the liver into the right hemithorax.

Diagnosis, Differential↗

PubMed2005

Endothelin activation and postoperative renal failure after human liver transplantation.

Renal failure is an established risk factor for impaired patient outcome after orthotopic liver transplantation (OLT). As the endothelin pathway is known to be involved in the development of acute renal failure (ARF), we designed a study to clarify its role in ARF following OLT. Twenty consecutive patients with intact kidney function scheduled for their first OLT were prospectively studied. Plasma big endothelin-1 (ET-1) levels were measured before surgery, after graft reperfusion, and on the first and second postoperative day. According to postoperative glomerular filtration rate (GFR), patients were assigned to the acute renal dysfunction group (ARDF) and the non-ARDF group. Each patient's GFR was estimated according to the 4-variable formula used in the modification of diet in renal disease before surgery, daily within the first postoperative week, and at 1, 3, 12, and 24 months after surgery. Postoperative mean big ET-1 levels correlated significantly with the maximum percent decrease of GFR within 3 days after OLT (P < 0.01). The proportion of patients who developed ARDF was significantly correlated to mean postoperative big ET-1 quartiles (P < 0.01). In the ARDF group, the percent decrease of GFR within 24 months was significantly higher (P < 0.05) as compared to the non-ARDF group. In conclusion, patients who develop ARDF immediately after OLT do not fully recover to baseline regarding long-term kidney function. Short-term GFR was significantly correlated with postoperative big ET-1 plasma levels, suggesting renal dysfunction is mediated by the activated endothelin system.

Endothelins↗

PubMed2005

The impact of cardiac ischemia and reperfusion on markers of activated haemostasis and fibrinolysis during cardiopulmonary bypass: comparison of plasma levels in arterial and coronary venous blood.

INTRODUCTION: Activation of coagulation and fibrinolysis is common among patients undergoing cardiopulmonary bypass (CPB) surgery. Little is known, however, about the impact of myocardial ischemia and reperfusion on coagulation activation and fibrinolysis in this clinical setting. STUDY DESIGN AND METHODS: We determined the levels of coagulation activation and fibrinolysis markers (CAFM) in 19 patients with severe coronary heart disease (CHD) during CPB surgery. FXIIa, tissue factor (TF), FVIIa, tissue plasminogen activator/plasminogen activator inhibitor-1 complexes (tPA/PAI-1), prothrombin fragments 1+2 (F1+2), D-dimers (DD) and plasmin-plasmin inhibitor complexes (PPI) were measured at baseline, prior to and after cardioplegic myocardial ischemia. Simultaneous blood samples were drawn from the aorta and the coronary sinus to evaluate arteriovenous CAFM plasma level gradients. RESULTS: Myocardial ischemia induced significant increases in gradients of FXIIa and F1+2 levels across the coronary circulation without influencing systemic levels of these markers significantly. Systemic levels of FXIIa, tPA/PAI-1, F1+2, DD and PPI increased significantly during CPB operation. There was a significant linear correlation between FXIIa, FVIIa, F1+2, DD and PPI. CONCLUSIONS: Myocardial ischemia induces contact activation and thrombin generation rather than release of tPA and might thus contribute to postoperative thromboembolic complications. Surgery itself and CPB cause activation of coagulation and fibrinolysis as already described. A significant association between FXIIa, FVIIa, F1+2, DD and PPI suggests a relationship between contact activation, thrombin generation, fibrin formation and fibrinolysis.

Aged↗

PubMed2005

Liver failure.

PURPOSE OF REVIEW: Liver failure is a rare but life-threatening condition affecting a multitude of other organ systems, most notably the brain and kidneys, following severe hepatocellular injury. Liver failure may develop in the absence ('acute') or presence ('acute-on-chronic') of liver disease with substantial differences in pathophysiology and therapeutic options. Within the last 12 months substantial progress has been made in identifying patients who will potentially benefit from extracorporeal support of their failing liver. RECENT FINDINGS: In addition to traditional 'static' laboratory tests to assess liver function, the significance of 'dynamic' tests, such as indocyanine green clearance, has been better defined, and these tests are becoming more easily available. Transplantation remains the treatment of choice for fulminant, acute and subacute liver failure with predicted unfavorable outcome according to King's College or Clichy criteria, most notably in the absence of pre-existing liver disease, and should be performed before extrahepatic complications emerge. Encouraging results have been obtained with the use of support systems in patients with acute and acute-on-chronic liver failure in relatively small patient collectives, making well-conducted randomized trials a necessity to define their role in this high-risk population. Current (pre)clinical data suggest that programmed cell death is an important mechanism for the pathogenesis of acute and acute-on-chronic liver failure and, thus, antiapoptotic strategies are promising pharmacologically. SUMMARY: Although mortality remains high, substantial progress has been made in 2004 regarding the understanding of pathophysiology, and the monitoring and support of the patient presenting with a failing liver.

Journal Article↗

PubMed2005

Design and effectiveness of a membrane-pump-driven ventilator for mice.

To perform mechanical ventilation of mice in the absence of highly expensive commercially available devices, we developed a membrane-pump-driven respirator and studied its practicability. The continuous airflow generated by the membrane pump was changed into an intermittent flow by using a multifunction timer. Tidal volume was adjusted by a rotary dimmer regulating the electric power onto the pump. The expiration air left the circuit through openings at the tube connection. Mice were ventilated with room air for 5 h with a tidal volume of approximately 200 muL. In group 1 (n = 6), ventilation was performed with a frequency of 110 min-1, in group 2 (n = 6) with a frequency of 150 min-1. Spontaneously breathing anesthetized mice (n = 6) served as controls. In addition we performed single-lung open-chest ventilation for 1 h in two animals. The parameters of arterial blood gas analyses were within the normal range except for moderate hyperventilation in group 2. Single-lung ventilation led to a significant decline (P < 0.05) of pO2 and SO2, whereas the pCO2 remained within the normal range. Respiratory rate, tidal volume and pressure limitation can be adjusted for optimal ventilation. In addition, the device provides a minimalized dead space and impedes potential alveolar damage caused by negative pressure generated by spontaneous inspiration during positive-pressure ventilation.

Animals↗

PubMed2004

Alterations of mesenteric blood flow after cardiopulmonary bypass: a Doppler sonographic study.

OBJECTIVE: Mesenteric ischemia after cardiopulmonary bypass is a serious complication associated with high mortality. It was the aim of this study to investigate mesenteric blood flow with the help of Doppler sonography in asymptomatic patients before and after cardiopulmonary bypass and cardiac surgery. DESIGN: Observational study of consecutive patients. SETTING: Nonuniversity cardiac center. PARTICIPANTS: Twenty-five patients undergoing elective coronary revascularization with normal left ventricular function and stable postoperative circulations with no need for catecholamines. MEASUREMENTS AND MAIN RESULTS: Preoperative and postoperative color and CW-Doppler sonography of the superior mesenteric artery. Diameter of the superior mesenteric artery and the Doppler flow profile were analyzed. Preoperative and postoperative hemodynamic data were measured by using a pulmonary artery thermodilution catheter. Mesenteric systolic flow velocity was 135 +/- 11 cm/s preoperatively and 193 +/- 13 cm/s postoperatively (p < 0.05). The corresponding preoperative and postoperative values of diastolic flow velocity were 14 +/- 4 and 4 +/- 2 cm/s (p < 0.05) and the values of mean flow velocity were 24 +/- 3 and 17 +/- 2 cm/s (p < 0.05), respectively. The preoperative Pourcelot resistive index was 0.87 +/- 0.05, and the preoperative Gosling pulsatility index was 4.6 +/- 0.5. Both indices increased postoperatively to values of 0.98 +/- 0.04 and 9.5 +/- 0.7, respectively (p < 0.05). Preoperative and postoperative hemodynamic data did not differ significantly. CONCLUSION: The postoperative changes in the flow velocities and the increases of the resistive and pulsatility index are indications of rigidity of the mesenteric vascular bed and decreased mesenteric perfusion after cardiopulmonary bypass.

Blood Flow Velocity↗

PubMed2004

Heme oxygenase-1 gene expression in pericentral hepatocytes through beta1-adrenoceptor stimulation.

Induction of heme oxygenase (HO)-1 may confer hepatocellular protection, e.g., in reperfusion injury. Previous reports suggest that intracellular cAMP up-regulates HO-1. The aim of the present study was to assess the role of adrenoceptor agonists as a means to induce HO-1 and to assess molecular mechanisms of HO-1 gene expression by adrenoceptor agonists. Induction of HO-1 in primary cultures of hepatocytes and in rat liver in vivo was assessed by Northern blot, Western blot, and immunohistochemistry. The beta-receptor agonists (+/-)isoproterenol and (-)isoproterenol induced HO-1 in primary cultures of hepatocytes but not the inactive enantiomer (+)isoproterenol. No induction of HO-1 was observed after alpha1, alpha2, beta2, or beta 3 agonists. beta1-Receptor agonists dobutamine and xamoterol induced HO-1 dose dependently, whereas the beta1-receptor antagonist metoprolol attenuated HO-1 induction by beta1-receptor agonists. Furthermore, 8 Br-cAMP and forskolin induced HO-1. Inhibition of protein kinase A (PKA) abolished induction by dobutamine and 8 Br-cAMP. Parallel changes were observed for the transcription factor AP-1. In vivo infusion of dobutamine for 6 h induced HO-1 in rat livers. Immunohistochemical detection of HO-1 revealed a pericentral expression pattern of HO-1 in hepatocytes, i.e., the area at risk for ischemia/reperfusion injury. These results suggest induction of HO-1 by beta1-adrenoceptor agonists via the PKA pathway in hepatocytes, reflecting a potential means for "pharmacological preconditioning."

Adrenergic Agonists↗

PubMed2004

Noninvasive mechanical ventilation of mice by using a balloon-tipped cannula.

Cardiovascular research in mouse models can lead to respiratory insufficiency with the need for temporary mechanical ventilation to reduce mortality. We developed a noninvasive method for brief ventilation in which a balloon-tipped cannula is inserted into the oral cavity of the mouse. The rubber balloon is constructed in such a way that it becomes inflated when the pressure in the tube rises. We tested the cannula in ten C57BL/6J mice which underwent mechanical ventilation by a membrane-pump-driven ventilator. Results of blood gas analyses in the ten cannulated animals were in the normal range after 1 h of mechanical ventilation and did not differ significantly from those of anesthetized and spontaneously breathing mice (n = 5) and mice mechanically ventilated via tracheal intubation (n = 5). Noninvasive mechanical ventilation by using the balloon-tipped cannula is a useful method which is quick and easy to manipulate.

Animals↗

PubMed2003

Long-term cell survival and hemodynamic improvements after neonatal cardiomyocyte and satellite cell transplantation into healed myocardial cryoinfarcted lesions in rats.

Cell engraftment is a new strategy for the repair of ischemic myocardial lesions. The hemodynamic effectiveness of this strategy, however, is not completely elucidated yet. In a rat model of cryothermia-induced myocardial dysfunction, we investigated whether syngeneic transplantation of neonatal cardiomyocytes or satellite cells is able to improve left ventricular performance. Myocardial infarction was induced in female Lewis rats by a standardized cryolesion to the obtuse margin of the left ventricle. After 4 weeks, 5 x 10(6) genetically male neonatal cardiomyocytes (n = 16) or satellite cells (n = 16) were engrafted into the myocardial scar. Sham-transplanted animals (n = 15) received injections with cell-free medium. Sham-operated animals (n = 15) served as controls. Left ventricular performance was analyzed 4 months after cell engraftment. Chimerism after this sex-mismatched transplantation was evaluated by detection of PCR-amplified DNA of the Y chromosome. The average heart weight of the infarcted animals significantly exceeded that of controls (p < 0.05). In sham-transplanted animals, mean aortic pressure, left ventricular systolic pressure, aortic flow (indicator of cardiac output), and left ventricular systolic reserve were significantly lower (p < 0.05) compared with sham-operated controls. This was associated with deterioration of ventricular diastolic function (maximal negative dP/dt, time constants of isovolumic relaxation; p < 0.05). Transplantation of satellite cells was found more effective than transplantation of neonatal cardiomyocytes, resulting in i) normalization of mean aortic pressure compared with sham-operated controls, and ii) significantly improved left ventricular systolic pressure and aortic flow (p < 0.05) compared with sham-transplanted animals. Left ventricular systolic reserve and diastolic function, however, were improved by neither satellite cell nor neonatal cardiomyocyte transplantation. Analysis of male genomic DNA revealed 3.98 +/- 2.70 ng in hearts after neonatal cardiomyocyte engraftment and 6.16 +/- 4.05 ng in hearts after satellite cell engraftment, representing approximately 10(3) viable engrafted cells per heart. Our study demonstrates i) long-term survival of both neonatal cardiomyocytes and satellite cells after transplantation into cryoinfarcted rat hearts, ii) slight superiority of satellite cells over neonatal cardiomyocytes in improving global left ventricular pump performance, and iii) no effect of both transplant procedures on diastolic dysfunction.

Animals↗

PubMedDate not supplied

Transit thrombus entrapped in a patent foramen ovale.

We describe the case of a 39-year-old man with a diagnosis of inferior vena cava compression caused by metastases of a testicular seminoma, who developed massive pulmonary embolism. Emergency operation was performed because of acute hemodynamic deterioration. Preoperatively, a free-floating mass was seen echocardiographically in the right atrium. Intraoperatively, a thrombus entrapped in a patent foramen ovale with a short free-floating end in the left atrium and a long end in the right atrium was found in addition to the pulmonary emboli. The thrombus was removed, the foramen ovale was closed by direct suture, and pulmonary embolectomy was performed. Histological examination confirmed thrombi but no malignant tissue. Further diagnostic studies documented a malignant seminoma with paraaortic lymph node metastases giving rise to the thrombembolism. Three years after oncologic therapy, he is alive and free from recurrence of embolic and malignant disease.

Adult↗