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Thomas Frietsch

Publications and source records attributed to Thomas Frietsch.

8 recordsLinked to original sources
PubMed2006

Reduced cerebral blood flow but elevated cerebral glucose metabolic rate in erythropoietin overexpressing transgenic mice with excessive erythrocytosis.

To examine the impact of excessive erythrocytosis on local cerebral blood flow (CBF) and cerebral glucose metabolic rate (CMR(glc)), we made use of our constitutively erythropoietin (Epo)-overexpressing transgenic mouse line (tg-6) that reach a mean hematocrit of 0.87. Compared with wild-type (wt) control siblings, CBF decreased by 44% in tg-6 mice, while upon hemodilution (tg-6-HD) to a physiologic hematocrit (e.g., 0.44) tg-6-HD mice returned the CBF to wt levels. Cerebral blood flow was determined in another transgenic mouse line that overexpresses human Epo in the brain only (tg-21): CBF increased by 17% compared with wt controls. However, oxygen delivery was similar in all four mouse groups tested (wt, tg-6, tg-6-HD and tg-21). Mean CMR(glc) was higher in tg-6 (+72%), tg-6-HD mice (+43%) and tg-21 (+22%) than in wt mice. Local CMR(glc) was higher in all 40 brain regions in tg-6 but only in 15 and 8 regions in tg-6-HD and tg-21 mice. These results show that prolonged increases in hematocrit did not alter cerebral oxygen delivery at a decreased CBF and increased CMR(glc). Hemodilution suggests that high blood viscosity is a cause of the decrease in CBF and partly of the increase in CMR(glc). Cerebral glucose metabolic rate may also be increased by a direct effect of Epo in the brain (tg-21 mice).

Animals↗
PubMed2006

In-line filtration of autologous whole blood.

BACKGROUND: Experimental data suggest that autologous white blood cells (WBCs) might exert an immunomodulatory effect. Leukodepletion of autologous blood is considered to prevent this unwanted side effect of autologous transfusion. In some cases, however, prolonged filtration or filtration failures occur. Because such autologous units cannot simply be discarded, the interest was in the storage variables of autologous whole blood (AWB) units after prolonged filtration. STUDY DESIGN AND METHODS: AWB of patients undergoing orthopedic surgery was leukodepleted before storage or left unmodified. Filtration times, volume, WBC count, hemoglobin level, hemolysis, potassium, and ATP were determined in all units with filtration times of more than 60 minutes that had not been transfused by the time of expiry and in representative samples of units that had been filtered normally or that had not been filtered. RESULTS: In AWB filtration, the rate of prolonged filtrations or filter blockades is three to four times higher than in allogeneic whole-blood filtration. Filtration or prolonged filtration leads to a mean loss of red blood cell (RBC) mass of 7.3 or 18.2 percent, respectively. Even in units with filtration times of more than 3 hours, storage variables were not significantly different from normally filtered or unfiltered units. Filtration times showed a high intraindividual correlation. CONCLUSION: Leukodepletion of AWB results in a diminished preoperative deposit of RBCs that is pronounced in units with prolonged filtration. The quality of the latter suggests that it is not justified to discard AWB units with prolonged filtration times. Prolonged filtrations are related to patient characteristics that have yet to be defined.

Adult↗
PubMed2004

Strategies of neuroprotection for intracranial aneurysms.

Neuroprotection for patients with intracranial aneurysms encompasses the preservation of brain cells endangered by a limited blood and oxygen supply due to aneurysm rupture, clipping or coiling, as well as vasospasm. A large variety of prophylactic and therapeutic neuroprotective strategies have been proposed, but success in human disease is quite limited. Topics of this chapter are the pathophysiology and treatment options of aneurysms, as well as promising neuroprotective strategies in further developmental stages: both physiologically based (hyperoxygenation, hypothermia, avoidance of hyperthermia and hyperglycaemia, hypertension, haemodilution and hypervolaemia) and pharmacologically based (antifibrinolytic drugs, calcium antagonists, anaesthetics, magnesium, erythropoietin and others). New concepts are ischaemic preconditioning, growth factors, and gene therapy. Each strategy is rated on underlying evidence, and research agendas are mentioned.

Animals↗
PubMed2003

Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity.

Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. However, some individuals such as high altitude dwellers cope well with an increased hematocrit level. We analyzed adaptive mechanisms to excessive erythrocytosis in our transgenic (tg) mice that, due to hypoxia-independent erythropoietin (Epo) overexpression, reached hematocrit values of 0.8 to 0.9 without alteration of blood pressure, heart rate, or cardiac output. Extramedullar erythropoiesis occurred in the tg spleen, leading to splenomegaly. Upon splenectomy, hematocrit values in tg mice decreased from 0.89 to 0.62. Tg mice showed doubled reticulocyte counts and an increased mean corpuscular volume. In tg mice, plasma volume was not elevated whereas blood volume was up to 25% of the body weight compared with 8% in wild-type (wt) siblings. Although plasma viscosity did not differ between tg and wt mice, tg whole-blood viscosity increased to a lower degree (4-fold) than expected from corresponding hemoconcentrated wt blood (8-fold). This moderate increase in viscosity is explicable by the up to 3-fold higher elongation of tg erythrocytes at physiologic shear rates. Apart from the nitric oxide-mediated vasodilation we reported earlier, adaptation to high hematocrit levels in tg mice involves regulated elevation of blood viscosity by increasing erythrocyte flexibility.

Adaptation, Physiological↗
PubMed2002

Cerebral transcriptome analysis of transgenic mice overexpressing erythropoietin.

Erythropoietin (EPO) and its receptor are expressed in the brain, and one of its roles appears to be neuroprotection. This study investigates whether chronic overexpression of EPO changes brain mRNA expression in the brains of transgenic mice. Therefore, cerebral mRNA expression was investigated in transgenic mice overexpressing EPO. Microarray analysis revealed an upregulation (2.8- to 3.6-fold) of N-acetylglucosamine-6-O-sulfotransferase (prolongation of the EPO effect), a translocase of the inner mitochondrial membrane (mitochondrial matrix import of nuclear encoded proteins), a mitochondrial ribosomal protein (mitochondrial protein translation), and a peroxisomal biogenesis factor (formation of peroxisomes). In conclusion, components of oxidative metabolism pathways were activated at the level of transcription which could be related to neuroprotective effects of EPO or could indicate compromised tissue.

Animals↗
PubMed2002

Early effects of acid-base management during hypothermia on cerebral infarct volume, edema, and cerebral blood flow in acute focal cerebral ischemia in rats.

BACKGROUND: Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and alpha-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats. METHODS: Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33 degrees C). Animals were artificially ventilated with either alpha- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[(14)C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS). RESULTS: Compared with the alpha-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm(3) vs. 53.6 +/- 21.6 mm(3); P > or = 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0% vs. 3.1 +/- 2.4%; P > or = 0.05). Global CBF during pH-stat management exceeded that of alpha-stat animals (69.5 +/- 12.3 ml x 100 g(-1) x min(-1) vs. 54.7 +/- 13.3 ml x 100 g(-1) x min; P > or = 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml x 100 g(-1) x min(-1) in the pH-stat group versus 48.2 +/- 7.2 ml x 100 g(-1) x min(-1) in the alpha-stat group ( P> or = 0.05). CONCLUSIONS: In the very early reperfusion period (5 h), pH-stat management significantly decreases cerebral infarct volume and edema as compared with alpha-stat during moderate hypothermia, probably by increasing CBF.

Acid-Base Equilibrium↗
PubMed2002

Sickle cell disease--pathophysiology, clinical and diagnostic implications.

We review the current knowledge of the pathophysiology of sickle cell disease (SCD), the clinical complications and the state of the art in SCD diagnostics. Today, a flexible laboratory concept allows the fast and economic clarification of the patients' sickle cell hemoglobin (HbS) status, e.g. additional compound heterozygosities. In contrast to a well-investigated pathophysiology of the disease, factors influencing the severity of symptoms as well as some laboratory findings in SCD still lack a final explanation. In this review, we focus on red cell lysis resistance as an additional diagnostic tool in SCD. There is a need for further studies regarding lysis resistance in blood samples from patients with HbS.

Anemia, Sickle Cell↗