SFRR-E Young Investigator AwardeeNOXing out stroke: Identification of NOX4 and 5as targets in blood-brain-barrier stabilisation and neuroprotection.

Stroke is the second leading cause of death with high blood pressure and female gender being the main risk factors. However, only one treatment is available and with many contraindications, which leaves more than 80% of patients untreated. Over a thousand experimental stroke treatments have remained unsuccessful in the clinic. In preclinical research, low reproducibility and publication bias have been suggested as causes of low translatability success. NADPH oxidases might be key players in stroke via their unique role as a major and/or early source of reactive oxygen species (ROS). To clarify the role of the different NOX isoforms (1, 2, 4, and 5) we analysed different KO and KI models. Previous literature claimed a role for NOX2. Using both a meta-analytical and a blinded randomised controlled trial approach, we however find that NOX2 plays only a minor role and publication bias and lack of power perturbed the published literature. We earlier showed a detrimental role of NOX4 in stroke and extend this based on cell-specific KO animals that endothelial but not vascular smooth muscle cells are the major source of NOX4 in stroke. Mice do not express the human NOX5 gene. Using a NOX5 KI model, we show that endothelial NOX5 induces hypertension and increased stroke risk, particularly in females. In human hypertension, NOX5 is upregulated, and women have a higher stroke risk. Thus NOX5 might be a missing link in this context. In conclusion, NOX4 and NOX5, but not NOX2, are promising targets for the development of new neuroprotective therapies for ischemic stroke. A priori power and sample size calculation as well as reporting of also negative data is essential with respect to preclinical validation of therapeutic targets.

Cardiovascular effects of ketanserin in the treatment of hypertension during coronary artery bypass surgery.

The cardiovascular effects of ketanserin (5-HT2-receptor antagonist with alpha 1-receptor blocking property) were studied during coronary artery surgery. Sixteen patients were anesthetized with flunitrazepamfentanyl-nitrous oxide-oxygen-pancuronium. Ketanserin (10 mg i.v.) was used to decrease elevated blood pressure unresponsive to deepening of anesthesia before extracorporeal circulation. Ketanserin caused a marked vasodilation in all patients, significant (p less than 0.05) decreases of systolic, diastolic, and mean arterial blood pressure, and of pulmonary artery pressure and pulmonary capillary wedge pressure. As a result, indirect indices of myocardial oxygen demand (rate-pressure product and "triple index") also decreased. Heart rate and right atrial pressure remained unchanged, while cardiac index and stroke volume index increased slightly. Ketanserin was found to be effective in the treatment of prebypass hypertension; the elevated blood pressure returned to normal; unwanted hypotension was not observed.

[Experiences with Swan-Ganz-catheter placement in the external jugular vein]. / Erfahrungen mit der Swan-Ganz-Katheter-Plazierung über die Vena jugularis externa.

Clinical experience concerning the placement of Swan-Ganz catheters (SGC) via the external jugular vein is presented. After puncture of either the right or left external jugular vein, placement of SGC was possible in 90 per cent of patients. Compared to techniques involving puncture of the internal jugular vein this method has less complications. The placement of 167 SGC could be done without any problems, thus proving that the external jugular vein is a safe way of insertion. The external jugular vein as a primary route can be recommended if the vein is visible, especially in cases where puncture of the internal jugular vein may be difficult and could only be performed with an increased risk of complications.

[Antithrombin III substitution for optimization of the heparin effect during extracorporeal circulation in heart surgery]. / Antithrombin-III-Substitution zur Optimierung der Heparinwirkung während extrakorporaler Zirkulation in der Herzchirurgie.

In a prospective randomised study 20 patients undergoing coronary bypass surgery were assigned to two groups. Patients in group I (n = 10) received initially 250 IU heparin X kg-1 before the start of extracorporeal circulation. Patients in group II (n = 10) were given the same amount of heparin and in addition 1 000 units of purified human antithrombin III (AT III) concentrate. A highly significant lower heparin coefficient [2.69 +/- 0.57 IU X kg-1 X min-1, which is a parameter of heparin consumption (units of heparin X kg-1 given per minute during the time of heparinisation)], was found in group II compared to group I (3.73 +/- 0.56 IU X kg-1 min-1). Heparin sensitivity, measured as an increase in the ratio of activated coagulation time (ACT) X IU heparin-1 X kg-1 as a response to initial heparin dose, was found to be significantly higher (1.22 +/- 0.30 sec X IU heparin-1 X kg-1) in patients receiving AT III as measured in the control group (0.95 +/- 0.23 s X IU heparin-1 X kg-1). Mean values of ACT during the period of heparinisation were comparable (group I: 533 +/- 81 s, group II: 512 +/- 62 s) in the two groups. The substitution of AT III led to an increase of plasma AT III activity of 1.4% per substituted unit AT III X kg-1. AT III plasma activity, corrected to initial haematocrit levels to avoid dilution dependency, decreased as a consequence of extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reduction of whole blood requirements in coronary surgery with hemoseparation and isovolemic hemodilution]. / Reduzierung des Fremdblutverbrauchs in der Koronarchirurgie durch Hämoseparation und isovolämische Hämodilution.

Because of relative shortage of homologous stored blood, and the dangers of transmission infectious diseases and isoimmunisation, we tried to reduce blood requirement in cardiac surgery. In 139 patients undergoing coronary artery bypass surgery different techniques of autotransfusion were applied. A 52% reduction of whole blood transfusion compared to a control group of patients could be obtained by preoperative isovolaemic haemodilution. The application of haemoseparation reduced the amount of whole blood used by 55%. When the two techniques were combined the use of whole blood was reduced by 70% compared to the control group of patients. In contrast retransfusion of blood remaining in the oxygenator is not advisable because only a small amount of blood can be saved in this way and in addition it results in a higher risk of postoperative bleeding. Our results will be discussed reviewing the literature.

Control of hypertension during cardiopulmonary bypass with urapidil and phentolamine.

The vasodilating effect of 6-(3-[4-(o-methoxy-phenyl)-piperazin-1-yl]-propylamino)-1,3-dimethyluracil (urapidil, Ebrantil) and phentolamine was investigated during extracorporeal circulation in patients undergoing coronary artery bypass (CABG) operations. To compare the vasodilating effect, 10 patients received 2 times 25 mg urapidil, and another 10 patients 2 times 5 mg phentolamine when mean arterial blood pressure (MAP) exceeded 100 mgHg. Both drugs caused a significant (p less than 0.01) decrease in mean arterial blood pressure and total peripheral resistance (TPR), using constant flow (Qecc). Central venous pressure (CVP), measured in the inferior vena cava, showed no significant change, while a marked volume loss (delta V) in the oxygenator was observed. There was no significant difference in the measured cardiovascular parameters in the two groups of patients. The peripheral vasodilating effect of urapidil, expressed in mg was found 5 times weaker than that of phentolamine. Urapidil was found effective in the treatment of hypertension during extracorporeal circulation.

[Electrical stimulation anaesthesia in abdominal surgery in special consideration of selective proximal vagotomie (author's transl)]. / Elektro-Stimulationsanaesthesie in der Abdominalchirurgie unter besonderer Berücksichtigung der selektiven proximalen Vagotomie

107 abdominal operations were performed using in a combined electrostimulating anaesthesia. Anaesthesia was indued by etomidate (about 15 mg) and fentanly (about 0,2 mg). After administration of pancuronium (5-7 mg) intubation was performed. During continuous intermittent relaxation anaesthesia was maintained by a mixture of nitrous oxide/oxygen 4:2 (in poor risk patients: 3:3) and electrical stimulation at certain body-and ear-points. Electrical stimulation was done using impulse currents with frequencies of 10 to 15 Hz and a current intensity of about 40 mA. During extremly painful periods of operations 30% of the patients showed maximal heart rates and only in 5% of cases did blood pressure exceed preoperative values by about 50%. Especially in poor risk pateints the results of electro-stimulating anaesthesia are excellent. At this time, however, it should not be recommanded as a routine method for general surgery; questions concerning regulating mechanisms need to be answered first.