Alexander Hoetzel

Alexander Hoetzel
University Medical Center Freiburg · Department of Anesthesiology and Intensive Care Medicine

About

88
Publications
6,705
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3,232
Citations
Citations since 2016
20 Research Items
1376 Citations
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250

Publications

Publications (88)
Article
Full-text available
Hydrogen sulfide (H2S) protects against stretch-induced lung injury. However, the impact of H2S on individual cells or their crosstalk upon stretch remains unclear. Therefore, we addressed this issue in vitro using relevant lung cells. We have explored (i) the anti-inflammatory properties of H2S on epithelial (A549 and BEAS-2B), macrophage (RAW264....
Article
Zusammenfassung Das perioperative Management von Patienten mit pulmonaler Hypertonie erfordert von den behandelnden Anästhesisten fundierte Kenntnisse über die zugrunde liegenden Ursachen, die Pathophysiologie, den Einfluss anästhesiologischer und chirurgischer Maßnahmen wie z. B. die mechanische Beatmung sowie intraoperative Behandlungsoptionen. I...
Article
Inhaled anaesthetics (inhalation(al) anaesthesia, balanced anaesthesia) as well as intravenous anaesthetics (total intravenous anaesthesia, TIVA) can be used for the induction and maintenance of anaesthesia. Among others, the advantages of TIVA are smooth induction and emergence from anaesthesia, reduced reflexes, lower incidence of postoperative n...
Article
Full-text available
Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H2S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received...
Article
Full-text available
Mechanical ventilation is a life-saving clinical treatment but it can induce or aggravate lung injury. New therapeutic strategies, aimed at reducing the negative effects of mechanical ventilation such as excessive production of reactive oxygen species, release of pro-inflammatory cytokines, and transmigration as well as activation of neutrophil cel...
Article
Full-text available
Acute lung injury (ALI) caused by septic stimuli is still a major problem in critical care patients. We have shown previously that hydrogen sulfide (H2S) mediates anti-inflammatory and lung protective effects. In the present study, we aimed to investigate the underlying mechanisms. C57BL/6N mice were instilled with lipopolysaccharide (LPS) intranas...
Chapter
Medical advances over the last decades have led to a growing patient population with end-stage liver disease and transplanted livers. These patients might present for elective or emergency surgery. In these patients several aspects need to be considered in order to provide safe anesthesia. This chapter focuses on the preoperative and intraoperative...
Article
Full-text available
Although essential in critical care medicine, mechanical ventilation often results in ventilator-induced lung injury. Low concentrations of hydrogen sulfide have been proven to have anti-inflammatory and anti-oxidative effects in the lung. The aim of this study was to analyze the kinetic effects of pre- and posttreatment with hydrogen sulfide in or...
Data
Effect of expanded delayed H2S treatment on physiological parameters. Mice were mechanically ventilated with 12ml/kg either with air alone (6h air, 10h air) or air supplemented with 80ppm H2S (6h H2S). Another group of mice was first mechanically ventilated with air alone for 5h, followed by ventilation with 80ppm H2S for another 5h. pH, arterial o...
Data
Effect of H2S pretreatment on physiological parameters. Mice were mechanically ventilated with 12ml/kg for 6h either with air alone (6h air) or air supplemented with 80ppm H2S (6h H2S). All other mice spontaneously breathed air supplemented with 80ppm H2S 1h, 3h, or 5h prior to mechanical ventilation with air for another 6h as indicated. pH, arteri...
Data
Effect of H2S posttreatment on physiological parameters. Mice were mechanically ventilated with 12ml/kg for 6h either with air alone (6h air) or air supplemented with 80ppm H2S (6h H2S). All other mice were first mechanically ventilated with air alone for 5, 3, or 1h, followed by ventilation with 80ppm H2S for another 1, 3, or 5h as indicated. pH,...
Article
Objectives: Hydrogen sulfide reduces ventilator-induced lung injury in mice. Here, we have examined the underlying mechanisms of hydrogen sulfide-mediated lung protection and determined the involvement of cyclooxygenase 2, 15-deoxy Δ-prostaglandin J2, and peroxisome proliferator-activated receptor gamma in this response. Design: Randomized, expe...
Article
Full-text available
The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H 2 S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H 2 S to affect oxidative processes...
Article
Background: Mechanical ventilation is an important perioperative tool in anesthesia and a lifesaving treatment for respiratory failure, but it can lead to ventilator-associated lung injury. Inhaled anesthetics have demonstrated protective properties in various models of organ damage. We compared the lung-protective potential of inhaled sevoflurane...
Article
Full-text available
Recently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical v...
Conference Paper
Full-text available
Our group has recently shown that inhalation of hydrogen sulfide (H2S) during mechanical ventilation protects against VILI [1]. Here we explored the gene expression profile of this model in order to identify underlying molecular mechanisms.
Article
Oxygen therapy is a life-sustaining treatment for patients with respiratory failure. However, prolonged exposure to high oxygen concentrations often results in hyperoxia-induced acute lung injury (HALI). At present, no effective therapeutic intervention can attenuate the development of HALI. In the present study, we investigated whether H2S can con...
Article
Full-text available
Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protecti...
Article
Despite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new and effective strategies in order to improve the outcome of these patients. Carbon monoxide, endogenously produced by the heme oxygenase enzyme system, has e...
Article
Carbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoning in industrial countries. However, after two decades of intensive research, there is ample evidence that CO endogenously produced by heme oxygenase enz...
Article
Full-text available
Mechanical ventilation causes ventilator-induced lung injury (VILI), and contributes to acute lung injury/acute respiratory distress syndrome (ALI/ARDS), a disease with high morbidity and mortality among critically ill patients. Carbon monoxide (CO) can confer lung protective effects during mechanical ventilation. This study investigates the time d...
Article
An increasing number of patients requiring surgery are presenting with chronic or end stage liver disease. The management of these patients demands anesthesiologists with in-depth knowledge of the consequences of hepatic dysfunction, the effects on other organs, the risk of surgery, and the impact of anesthesia. Chronic or end stage liver disease i...
Article
Mechanical ventilation leads to ventilator-induced lung injury in animals, and can contribute to acute lung injury/acute respiratory distress syndrome in humans. Acute lung injury/acute respiratory distress syndrome currently causes an unacceptably high rate of morbidity and mortality among critically ill patients. Volatile anesthetics have been sh...
Article
Full-text available
To characterize the inductive effects of isoflurane (ISO) on hepatic heme oxygenase-1 (HO-1) in an animal model of hepatic steatosis. Lean (LEAN) and obese (FAT) Zucker rats were randomized into 4 groups: 1: LEAN + pentobarbital sodium (PEN); 2: LEAN + ISO; 3: FAT + PEN; 4: FAT + ISO. The animals were mechanically ventilated for 6 h. In vitro analy...
Article
The carbon monoxide releasing molecule tricarbonyldichlororuthenium (CORM-2) displays protective actions like carbon monoxide. The molecular mechanism underlying this effect remains controversial. We hypothesized that CORM-2 mediates cytoprotection via induction of heat shock proteins through activation of p38 mitogen-activated kinase. Embryonic bo...
Article
Pancreatic stellate cells (PSCs) play a crucial role during pancreatic fibrosis development. Hydrogen sulfide (H2S) is a recently discovered gaseous transmitter, whose role in PSCs has not been explored yet. In the present study, we examined the effects of sodium hydrosulfide (NaHS), an H2S donor, on rat PSCs and elucidated the mechanisms involved....
Article
As an enzyme, heme oxygenase (HO) can provide substantial cellular protection. By eliminating free heme and generating iron, biliverdin, as well as carbon monoxide, HO exerts anti-inflammatory, anti-proliferative, antioxidative, and vasodilatory effects. The inducible form of HO, heme oxygenase-1 (HO-1) can be upregulated by harmful stimuli in most...
Article
Sevoflurane is a potent non-toxic inducer of the hepatoprotective enzyme heme oxygenase-1 (HO-1). So far, little is known about the underlying molecular mechanism. Therefore the aim of this study was to characterize the respective signal transduction pathway and in particular to elucidate the role of Kupffer cells in this context. Rats were treated...
Article
Mechanical ventilation still causes an unacceptably high rate of morbidity and mortality because of ventilator-induced lung injury (VILI). Therefore, new therapeutic strategies are needed to treat VILI. Hydrogen sulfide can induce hypothermia and suspended animation-like states in mice. Hydrogen sulfide can also confer antiinflammatory and antiapop...
Article
Full-text available
Proliferation of pancreatic stellate cells (PSCs) plays a cardinal role during fibrosis development. Therefore, the suppression of PSC growth represents a therapeutic option for the treatment of pancreatic fibrosis. It has been shown that up-regulation of the enzyme heme oxygenase-1 (HO-1) could exert antiproliferative effects on PSCs, but no infor...
Article
Carbon monoxide (CO) can confer anti-inflammatory protection in rodent models of ventilator-induced lung injury (VILI). Caveolin-1 exerts a critical role in cellular responses to mechanical stress and has been shown to mediate cytoprotective effects of CO in vitro. We sought to determine the role of caveolin-1 in lung susceptibility to VILI in mice...
Article
We describe a case of hiccup in an awakening patient. Since there was no success in stopping the hiccup by deepening anaesthesia with Desflurane, we used Propofol 1.3 mg/kg BW as a short acting i.v. anaesthetic with a fast onset to provide early recovery after eliminating hiccup in the awakening patient. Recommendations for the therapy of hiccup ra...
Article
Full-text available
Activation of pancreatic stellate cells (PSCs) is the key process in the development of pancreatic fibrosis, a common feature of chronic pancreatitis and pancreatic cancer. In recent studies, curcumin has been shown to inhibit PSC proliferation via an extracellular signal-regulated kinase (ERK)1/2-dependent mechanism. In addition, curcumin is a pot...
Article
Wir schildern einen Fall von plötzlich auftretendem Schluckauf in der Ausleitungsphase der Narkose. Die Vertiefung der Narkose mit Desfluran zeigte keinen Erfolg, so dass 1,3mg/kg KG Propofol als kurzwirksames i.v.–Anästhetikum mit kurzer Halbwertszeit gegeben wurde, um eine schnelle Narkoseausleitung nach Unterbrechung des Schluckaufs zu ermöglich...
Article
Full-text available
Ventilator-induced lung injury (VILI) leads to an unacceptably high mortality. In this regard, the antiinflammatory properties of inhaled carbon monoxide (CO) may provide a therapeutic option. This study explores the mechanisms of CO-dependent protection in a mouse model of VILI. Mice were ventilated (12 ml/kg, 1-8 h) with air in the absence or pre...
Article
Nitric oxide plays a crucial role in the maintenance of liver function and integrity. During stress, the inducible heme oxygenase-1 protein and its reaction products, including carbon monoxide, also exert potent hepatoprotective effects. We investigated a potential relationship between endogenous nitric oxide synthesis and the hepatic regulation of...
Data
Indices of lung injury in bronchoalveolar lavage fluid. wt = wild-type mouse,mkk3 = mkk3−/− mouse, jnk1 = jnk1−/− mouse, n = 5–8mice/group (0.68 MB TIF)
Data
Mean blood pressure during 8 hours mechanical ventilation in wild-type mice. a = significant change 0th versus 8th hour ventilation, p<0.05, n = 3/group, abbreviation:BP = blood pressure (0.12 MB TIF)
Data
103 genes with significant expression change following mechanical ventilation in wild-type and jnk1−/− mice. a wt = gene expression ratio wild-type mouse ventilation/control, jnk1−/− = gene expression ratio jnk1−/− mouse ventilation/control. Genes are ranked by fold-change. Listed genes meet the following statistical criteria significant change: t-...
Data
Time course of mechanical ventilation in wild-type, mkk3−/−, jnk1−/− and in mmp8−/− mice. Mice were ventilated with 10 or 20 ml/kg tidal volume and their lung injury parameters were compared to non-ventilated controls. 20 ml/kg tidal volume ventilation experiments for wild-type, mkk3−/− and jnk1−/− mice: Mice were ventilated for 2 hours to assess c...
Article
Full-text available
Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH(...
Article
Treatment of hyperthyroidism by thionamides is associated with immunomodulatory effects, but the mechanism of thionamide-induced immunosuppression is unclear. Here we show that thionamides directly inhibit interleukin-2 cytokine expression, proliferation, and the activation (CD69 expression) of primary human T lymphocytes. Inhibition of immune func...
Article
Despite modern practices in critical care medicine, sepsis or systemic inflammatory response syndrome remains a leading cause of morbidity and mortality in the intensive care unit. Thus, the need to identify new therapeutic tools for the treatment of sepsis is urgent. In this context, carbon monoxide has become a promising therapeutic molecule that...
Article
It was the aim of this study to characterize the influence of isoflurane-induced heme oxygenase-1 (HO-1) expression on hepatocellular integrity after ischemia and reperfusion. Abundant experimental data characterize HO-1 as one of the most powerful inducible enzymes that contribute to the protection of the liver and other organs after harmful stimu...
Article
The involvement of p38 in fundamental physiological processes and the fact that deregulation often leads to disease indicates the potential impact of p38 dependent mechanisms. Here we demonstrate a new pathway that includes the induction of the mitogen activated protein kinase p38 by protein kinase C and results in a specific phosphorylation of c-J...
Article
Full-text available
Reactive oxygen or nitrogen species (ROS/RNS) generated endogenously or in response to environmental stress have long been implicated in tissue injury in the context of a variety of disease states. ROS/RNS can cause cell death by nonphysiological (necrotic) or regulated pathways (apoptotic). The mechanisms by which ROS/RNS cause or regulate apoptos...
Article
Carbon monoxide (CO) is much more than just a toxic gas. Carbon monoxide is produced endogenously by the enzyme heme oxygenase and has important functions under physiological and pathophysiological conditions. Recent studies suggested antioxidative, anti-inflammatory, antiproliferative, anti-apoptotic, and vasodilating characteristics. Regarding cl...
Article
Kohlenmonoxid (CO) ist weit mehr als nur ein toxisches Gas. Es wird endogen durch das Enzym Hmoxygenase synthetisiert und erfllt essenzielle Funktionen unter physiologischen und pathophysiologischen Bedingungen. Untersuchungen der letzten Jahre attestieren CO antioxidative, antiinflammatorische, antiproliferative, antiapoptotische und vasodilatativ...
Article
Impaired hepatic perfusion after hemorrhagic shock frequently results in hepatocellular dysfunction associated with increased mortality. This study characterizes the effect of the vasodilators dihydralazine and urapidil on hepatocellular perfusion and integrity after hemorrhagic shock and resuscitation. Prospective, randomized, controlled experimen...
Article
The heme oxygenase pathway represents a major cell and organ protective system in the liver. The authors recently showed that isoflurane and sevoflurane up-regulate the inducible isoform heme oxygenase 1 (HO-1). Because the activating cascade remained unclear, it was the aim of this study to identify the underlying mechanism of this effect. Rats we...
Article
Volatile anesthetics modulate lymphocyte function during surgery, and this compromises postoperative immune competence. The current work was undertaken to examine whether volatile anesthetics induce apoptosis in human T lymphocytes and what apoptotic signaling pathway might be used. Effects of sevoflurane, isoflurane, and desflurane were studied in...
Article
Barbiturates are known to suppress protective immunity, and their therapeutic use is associated with nosocomial infections. Although barbiturates inhibit T cell proliferation, differentiation, and cytokine synthesis, only thiobarbiturates markedly reduce the activation of immune regulatory transcription factors such as nuclear factor-kappaB and nuc...