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Biomedical subjects

Peter Radermacher

Publications and source records attributed to Peter Radermacher.

At least 37 records · Page 2Linked to original sources
PubMed2005

Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO2 balance during endotoxemia in pigs.

OBJECTIVE: We examined whether selective inhibition of inducible nitric oxide synthase (iNOS) promotes intestinal microvascular oxygenation (microPO2) and CO2 off-load after endotoxic shock. DESIGN AND SETTING: Prospective, controlled experimental study in a university animal research laboratory. SUBJECTS: 13 domestic pigs. INTERVENTIONS: After baseline measurements shock was induced by 1 microg kg-1 h-1 endotoxin until mean arterial pressure fell below 60 mmHg. After 30 min in shock the animals were resuscitated with either fluid alone (control, n=6) or fluid and the iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine hydrochloride (1400W, n=7). As final experimental intervention all animals received the nonselective NOS inhibitor L-NAME. MEASUREMENTS AND RESULTS: Systemic and regional hemodynamic and oxygenation parameters were measured at baseline, during endotoxemia and shock, hourly for 3 h of 1400W therapy, and 30 min after the final L-NAME administration. microPO2 was assessed by the Pd-porphyrin phosphorescence technique, and the arterial to intestinal PCO2 gap was determined by air tonometry. Endotoxemia and shock resulted in a decrease in ileal mucosal and serosal microPO2 and a rise in PCO2 gap. The combination of 1400W and fluid resuscitation, but not fluid alone, normalized both the serosal microPO2 and the intestinal PCO2 gap. Administration of L-NAME decreased cardiac output and oxygen delivery and intestinal microPO2 and blood flow in both groups. CONCLUSIONS: Partial blockade of NO production by 1400W increased serosal microvascular oxygenation and decreased the intestinal CO2 gap. This findings are consistent with the idea that 1400W corrects pathological flow distribution and regional dysoxia within the intestinal wall following endotoxic shock.

Animals↗
PubMed2005

Interaction of hyperbaric oxygen, nitric oxide, and heme oxygenase on DNA strand breaks in vivo.

Hyperbaric oxygen (HBO), e.g. pure oxygen breathing at supra-atmospheric pressures, represents a well-suited model for investigating oxidative stress-induced DNA damage as well as protective mechanisms. While the induction of heme oxygenase-1 (HO-1) seems to be crucial for this protection against this DNA damage, the role of nitric oxide (NO) remains unclear. HO-1 expression is a major regulator of the inducible NO synthase (iNOS), and therefore we investigated the effect of the interaction between HBO, NO, and HO-1 on DNA damage. Prior to exposure to HBO (3 h at 3 bar ambient pressure) rats randomly received vehicle (HBO alone, 1 mL 0.9% saline, n=8), the NO donor molsidomine (SIN-10, 40 mg/kg, n=8) or the HO-1 blocker tin-mesopophyrin (Sn-MP, 50 micromol/kg, n=8). Additional groups received SIN-10 without exposure to HBO, i.e. breathing air under normobaric conditions for 3h (SIN-10 alone, 40 mg/kg, n=6), vehicle without HBO (negative controls, n=6), and ethylmethanesulfonate without HBO (EMS, 200 mg/kg) (positive controls n=4). Immediately after the 3 h HBO or air breathing period blood was analysed for DNA strand breaks (tail moment in the alkaline comet assay) and nitrite+nitrate (chemoluminescence). Whereas the tail moment was ten-fold higher after EMS than in the negative controls, there was no effect of HBO nor SIN-10 alone. Together with HBO, pretreatment with SIN-10 doubled the tail moment, and Sn-MP increased it by 50%. In contrast to Sn-MP or HBO alone, SIN-10 resulted in a five-fold increase of nitrite+nitrate concentrations. We conclude that both HO-1 blockade and excess NO release promote DNA damage during HBO exposure in vivo. The effect of HO-1 inhibition is probably independent of the regulatory function of HO-1 for iNOS.

Animals↗
PubMed2005

Physiological and clinical aspects of apnea diving.

Apnea diving is a fascinating example of applied physiology. The record for apnea diving as an extreme sport is 171 meters, 8:58 minutes. The short time beneath the surface induces profound cardiovascular and respiratory effects. Variations of blood-gas tensions result from the interaction of metabolism and the rapid sequence of compression and decompression. Decompression sickness is possible. Apnea divers can reach depths beyond the theoretic physiologic limit by using the lung-packing maneuver. Apnea divers exhibit a fall in heart rate, which can be trained and is an oxygen-conserving effect, but increases the incidence of ventricular arrhythmia.

Apnea↗
PubMed2005

How to choose a mechanical ventilator.

PURPOSE OF REVIEW: To provide some practical and clinical considerations that may guide users through the decision process when choosing mechanical ventilators RECENT FINDINGS: Although the complexity of mechanical ventilators is steadily increasing, the importance of many devices developed over the course of the technical evolution is still a matter of discussion. Recent data demonstrate that the technical performance of equivalent ventilators (ie, machines of the same generation and category) is pretty similar, suggesting that the different manufacturers keep in step with new developments. Thus, other factors than technical limitations will probably influence the choice of ventilators. Among them the ability of the staff to understand the rationale of the different devices and controls as well as deal with the complexity of the ventilator may be particularly important. SUMMARY: Choosing mechanical ventilators should begin by defining the algorithms of how to ventilate a patient. Once this is done, a ventilator should allow the transformation of specific strategies into practice and the adaptation of the mechanical support to the needs of the individual patient. This procedure is crucially important, because ventilator therapy should always be determined by the physician and based on solid physiologic rationales rather than by the technical features of the machine.

Artificial Intelligence↗
PubMed2005

Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism.

OBJECTIVE: To investigate whether the vasopressin analog terlipressin might induce hepatosplanchnic ischemia during long-term, hyperdynamic, volume-resuscitated porcine endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Eighteen pigs were divided into two groups receiving either endotoxin alone (control group, n = 10) or endotoxin and terlipressin (n = 8). INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented and received a continuous intravenous infusion of Escherichia coli endotoxin. Animals were resuscitated with hydroxyethyl starch targeted to maintain mean arterial pressure >60 mm Hg. Twelve hours after the start of the endotoxin infusion, terlipressin (5-15 microg.kg.hr titrated to maintain mean arterial pressure at preendotoxin levels) or its vehicle was administered for 12 hrs. MEASUREMENTS AND MAIN RESULTS: Terlipressin increased mean arterial pressure and systemic vascular resistances, which was affiliated with a decrease in cardiac output and global oxygen consumption. Terlipressin restored the hepatic artery buffer response, which led to an increase in hepatic artery flow, ultimately resulting in well-maintained liver oxygen delivery, oxygen uptake, and all other variables of regional metabolism and organ function. Terlipressin markedly attenuated the hepatosplanchnic venous acidosis but was associated with pronounced hyperlactatemia. CONCLUSIONS: During long-term hyperdynamic porcine endotoxemia, the well-known vasoconstrictor properties of terlipressin blunted the progressive decrease in mean arterial pressure without any detrimental effect on hepatosplanchnic perfusion, oxygen exchange, and metabolism. The marked terlipressin-induced hyperlactatemia did not originate from the hepatosplanchnic organs but from extrasplanchnic tissues, possibly muscle and skin.

Animals↗
PubMed2005

Effects of tempol, a free radical scavenger, on long-term hyperdynamic porcine bacteremia.

OBJECTIVES: Pretreatment with tempol, a membrane-permeable radical scavenger, has been shown to be protective in rodent models of endotoxic and Gram-positive shock. However, neither the pretreatment design nor hypodynamic endotoxic shock in rodents mimics the clinical scenario. Therefore, we investigated the effects of tempol in a posttreatment model of long-term, volume-resuscitated, hyperdynamic porcine bacteremia. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University animal laboratory. SUBJECTS: Sixteen anesthetized, mechanically ventilated, and instrumented pigs. INTERVENTIONS: Sepsis was induced and maintained for 24 hrs with continuous infusion of live Pseudomonas aeruginosa. After 12 hrs of hyperdynamic sepsis, animals were randomized to receive either vehicle (control, n = 8) or continuous infusion of tempol (n = 8, 30 mg/kg/hr). MEASUREMENTS AND MAIN RESULTS: Systemic and hepatosplanchnic hemodynamics, oxygen exchange, metabolism, ileal mucosal microcirculation, and tonometry as well as oxidative stress and coagulation variables were assessed before and after 12, 18, and 24 hrs of P. aeruginosa infusion. Tempol significantly attenuated reduction in mean arterial pressure. Despite comparable mesenteric macrocirculation, tempol attenuated the otherwise progressive deterioration in ileal mucosal microcirculation and prevented mucosal acidosis. By contrast, treatment with tempol failed to influence the P. aeruginosa-induced derangements of hepatosplanchnic redox state, liver lactate clearance, and regional acidosis but prevented the development of renal dysfunction. In addition, tempol reduced nitrosative stress without significant effect on the gradual increase in plasma 8-isoprostanes. Finally, tempol attenuated sepsis-induced endothelial (von Willebrand factor) and hemostatic dysfunction (thrombin-antithrombin complexes, plasminogen activator inhibitor-type 1). CONCLUSIONS: The radical scavenger tempol partially prevented live bacteria from causing key features of hemodynamic and metabolic derangements in porcine hyperdynamic sepsis and beneficially affected surrogate markers of sepsis-induced endothelial and coagulation dysfunction. Incomplete reduction of oxidative stress because of dilutional effects and/or missed optimal therapeutic window for antioxidant treatment when used in posttreatment approach may account for the only partial protection by tempol in this model.

Animals↗
PubMed2005

Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.

OBJECTIVE: To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Anesthetized, mechanically ventilated, and instrumented pigs. INTERVENTIONS: After 12 hrs of continuous infusion of lipopolysaccharide and hydroxyethyl starch to keep mean arterial pressure >60 mm Hg, swine randomly received placebo (Ringer's solution; control group, n = 11) or ethyl pyruvate in lactated Ringer's solution (n = 8; 0.03 g.kg(-1) loading dose over 10 mins, thereafter 0.03 g.kg(-1)hr(-1) for 12 hrs). MEASUREMENTS AND MAIN RESULTS: Whereas mean arterial pressure significantly decreased in control animals, mean arterial pressure was maintained at the baseline level in pigs treated with ethyl pyruvate. Global oxygen uptake was comparable, so that the trend toward a higher oxygen transport and the significantly higher mixed venous hemoglobin oxygen saturation resulted in a significantly lower oxygen extraction in the ethyl pyruvate group. Ethyl pyruvate reduced intrapulmonary venous admixture and resulted in significantly greater Pa(O2)/F(IO2) ratios. Despite comparable urine production in the two groups during the first 18 hrs of endotoxemia, ethyl pyruvate significantly increased diuresis during the last 6 hrs of the study. Lipopolysaccharide-induced systemic and regional venous metabolic acidosis was significantly ameliorated by ethyl pyruvate. Endotoxemia increased both blood nitrate + nitrite and isoprostane concentrations, and ethyl pyruvate attenuated the response of these markers of nitric oxide production and lipid peroxidation. CONCLUSIONS: Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.

Acidosis↗
PubMed2005

Effect of increased cardiac output on hepatic and intestinal microcirculatory blood flow, oxygenation, and metabolism in hyperdynamic murine septic shock.

OBJECTIVE: Septic shock-associated organ dysfunction is attributed to derangements of microcirculatory perfusion and/or impaired cellular oxygen utilization. The hepatosplanchnic organs are regarded to play a pivotal role in the pathophysiology of sepsis-related organ failure. In a murine model of septic shock, we tested the hypothesis whether achieving normotensive, hyperdynamic hemodynamics characterized by a sustained increase in cardiac output would allow maintenance of regional microvascular perfusion and oxygenation and, thus, hepatic metabolic capacity. DESIGN: Prospective, controlled, randomized animal study. SETTING: University animal research laboratory. SUBJECTS: Male C57Bl/6 mice. INTERVENTIONS: Fifteen hours after sham operation (n = 11) or cecal ligation and puncture (CLP) (n = 9), mice were anesthetized, mechanically ventilated, and instrumented (central venous and left ventricular pressure-conductance catheter, portal vein and superior mesenteric artery ultrasound flow probes). Animals received continuous intravenous hydroxyethylstarch and norepinephrine to achieve normotensive and hyperdynamic hemodynamics, and glucose was infused to maintain normoglycemia. MEASUREMENTS AND MAIN RESULTS: Measurements were recorded 18, 21, and 24 hrs post-CLP. In CLP mice, titration of hemodynamic targets were affiliated superior mesenteric artery and portal vein flow. Using a combined laser-Doppler flowmetry and remission spectrophotometry probe, we found well-maintained gut and liver capillary perfusion as well as intestinal microcirculatory hemoglobin oxygen saturation, whereas hepatic microcirculatory hemoglobin oxygen saturation was even increased. At 24 hrs post-CLP, the rate of de novo gluconeogenesis as derived from hepatic C-glucose isotope enrichment after continuous intravenous 1,2,3,4,5,6-C6-glucose infusion (condensation biosynthesis modeling after gas chromatography-mass spectrometry isotope measurements) was similar in the two experimental groups. CONCLUSIONS: During murine septic shock achieving normotensive hyperdynamic hemodynamics with fluid resuscitation and norepinephrine, exogenous glucose requirements together with the lack of norepinephrine-induced increase in the rate of gluconeogenesis mirror impaired metabolic capacity of the liver despite well-maintained hepatosplanchnic microvascular perfusion and oxygenation.

Animals↗
PubMed2005

Effects of intrarenal administration of the cox-2 inhibitor parecoxib during porcine suprarenal aortic cross-clamping.

The aim of this study was to investigate the effects of intrarenal administration of the cyclooxygenase-2 inhibitor parecoxib during suprarenal aortic cross-clamping. In a prospective, controlled, blinded, randomized manner, 16 anesthetized and mechanically ventilated pigs were instrumented to measure systemic and right kidney hemodynamics, oxygen exchange, and metabolism. During 45 min of suprarenal aortic cross-clamping, animals received 40 mg of parecoxib (n = 8) or vehicle (n = 8) infused continuously into the right renal artery. Hemodynamic and metabolic data, right kidney venous blood, as well as urine samples were obtained before clamping, as well as before and 75 and 195 min after declamping. Clamping transiently increased mean arterial pressure in both groups. Systemic and renal blood flow did not differ between the pre- and postclamping measurements or between groups. Parecoxib attenuated the otherwise significant fall in right kidney creatinine clearance (controls: from 45 [7;111] to 17 [9;22] mL/min; parecoxib: from 39 [3;59] to 27 [11;45] mL/min, P = 0.039 and P = 0.297, respectively versus before clamping, P = 0.021 versus controls at 195 min) and prevented the impairment of renal lactate balance observed in the control group (controls: from 0.5 [-0.8;3.5] to 0.2 [-0.2;0.6] mumol/kg/min; parecoxib: from 0.6 [-1.0;2.0] to 0.4 [-1.2;0.6] mumol/kg/min, P = 0.038 and P = 0.285, respectively, versus before clamping). In conclusion, intrarenal parecoxib infusion beneficially influenced kidney function in this clinically relevant model of suprarenal aortic cross-clamping.

Angiography↗
PubMed2005

Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies.

Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a "vital poison" for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N(G)-methyl-l-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-to-day care resuscitative measures.

Animals↗
PubMed2004

Positive end-expiratory pressure in acute respiratory distress syndrome - an old yet mysterious tool.

A recent study by Bruhn and colleagues, discussed here, confirms that even high levels of positive end-expiratory pressure (PEEP) - up to 20 cmH2O - may be applied in conditions of moderate acute respiratory distress syndrome. Such levels of PEEP were found to be safe in terms of their impact on cardiac output and adequacy of gastric mucosal perfusion once systemic haemodynamics were stabilized by adequate fluid replacement and catecholamine therapy. However, we strongly recommend that the reader does not oversimplify the conclusions of that study. PEEP therapy is not inherently safe with respect to haemodynamics and regional organ perfusion, but it may be used safely, even at high levels of up to 20 cmH2O, if haemodynamic therapy is appropriate.

Cardiac Output↗