Florian Simon

Effects of ventilation with 100% oxygen during early hyperdynamic porcine fecal peritonitis.

Objective: Early goal-directed therapy aims at balancing tissue oxygen delivery and demand. Hyperoxia (i.e., pure oxygen breathing) has not been studied in this context, since sepsis increases oxygen radical production, which is believed to be directly related to the oxygen tension. On the other hand, oxygen breathing improved survival in various shock models. Therefore, we hypothesized that hyperoxia may be beneficial during early septic shock. Design: Laboratory animal experiments. Setting: Animal research laboratory at university medical school. Subjects: Twenty domestic pigs of either gender. Interventions: After induction of fecal peritonitis, anesthetized and instrumented pigs were ventilated with either 100% oxygen or supplemental oxygen as needed to maintain arterial hemoglobin oxygen saturation ≥90%. Normotensive and hyperdynamic hemodynamics were achieved using hydroxyethyl starch and norepinephrine infusion. Measurements and Main Results: Before and at 12, 18, and 24 hrs of peritonitis, we measured lung compliance; systemic, pulmonary, and hepatosplanchnic hemodynamics; gas exchange; acid-base status; blood isoprostanes; nitrates; DNA strand breaks; and organ function. Gluconeogenesis and glucose oxidation were calculated from blood isotope and expiratory 13CO2 enrichments during continuous intravenous 1,2,3,4,5,6-13C6-glucose. Apoptosis in lung and liver was assessed postmortem (TUNEL staining). Hyperoxia did not affect lung mechanics or gas exchange but redistributed cardiac output to the hepatosplanchnic region, attenuated regional venous metabolic acidosis, increased glucose oxidation, improved renal function, and markedly reduced the apoptotic death rate in liver and lung. Conclusions: During early hyperdynamic porcine septic shock, 100% oxygen improved organ function and attenuated tissue apoptosis without affecting lung function and oxidative or nitrosative stress. Therefore, it might be considered as an additional measure in the first phase of early goal-directed therapy.

Effects of intravenous sulfide during porcine aortic occlusion-induced kidney ischemia/reperfusion injury.

In rodents, inhaled H2S and injection of H2S donors protected against kidney ischemia/reperfusion (I/R) injury. During porcine aortic occlusion, the H2S donor Na2S (sulfide) reduced energy expenditure and decreased the noradrenaline requirements needed to maintain hemodynamic targets during early reperfusion. Therefore, we tested the hypothesis whether sulfide pretreatment may also ameliorate organ function in porcine aortic occlusion-induced kidney I/R injury. Anesthetized, ventilated, and instrumented pigs randomly received either sulfide or vehicle and underwent 90 min of kidney ischemia using intraaortic balloon-occlusion, and 8 h of reperfusion. During reperfusion, noradrenaline was titrated to maintain blood pressure at baseline levels. Sulfide attenuated the fall in creatinine clearance and the rise in creatinine blood levels, whereas renal blood flow and fractional Na+ excretion were comparable. Sulfide also lowered the blood IL-6, IL-1&bgr;, and nitrite + nitrate concentrations, which coincided with reduced kidney oxidative DNA base damage and iNOS expression, and attenuated glomerular histological injury as assessed by the incidence of glomerular tubularization. While expression of heme oxygenase 1 and cleaved caspase 3 did not differ, sulfide reduced the expression Bcl-xL and increased the activation of nuclear transcription factor &kgr;B. During porcine aortic occlusion-induced kidney I/R injury, sulfide pretreatment attenuated tissue injury and organ dysfunction as a result of reduced inflammation and oxidative and nitrosative stress. The higher nuclear transcription factor &kgr;B activation was probably due to the drop in temperature.

Comparison of cardiac, hepatic, and renal effects of arginine vasopressin and noradrenaline during porcine fecal peritonitis: a randomized controlled trial

IntroductionInfusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock.MethodsAfter intraperitoneal inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned to noradrenaline alone (increments of 0.05 μg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1 to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension. Parameters of systemic and regional hemodynamics (ultrasound flow probes on the portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose production and whole body glucose oxidation derived from blood glucose isotope and expiratory 13CO2/12CO2 enrichment during 1,2,3,4,5,6-13C6-glucose infusion), visceral organ function (blood transaminase activities, bilirubin and creatinine concentrations, creatinine clearance, fractional Na+ excretion), nitric oxide (exhaled NO and blood nitrate + nitrite levels) and cytokine production (interleukin-6 and tumor necrosis factor-α blood levels), and myocardial function (left ventricular dp/dtmax and dp/dtmin) and injury (troponin I blood levels) were measured before and 12, 18, and 24 hours after peritonitis induction. Immediate post mortem liver and kidney biopsies were analysed for histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining).ResultsAVP decreased heart rate and cardiac output without otherwise affecting heart function and significantly decreased troponin I blood levels. AVP increased the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which coincided with less severe kidney dysfunction and liver injury, attenuated systemic inflammation, and decreased kidney tubular apoptosis.ConclusionsDuring well-resuscitated septic shock low-dose AVP appears to be safe with respect to myocardial function and heart injury and reduces kidney and liver damage. It remains to be elucidated whether this is due to the treatment per se and/or to the decreased exogenous catecholamine requirements.

Erythropoietin during porcine aortic balloon occlusion-induced ischemia/reperfusion injury.

Background:Aortic occlusion causes ischemia/reperfusion injury, kidney and spinal cord being the most vulnerable organs. Erythropoietin improved ischemia/reperfusion injury in rodents, which, however, better tolerate ischemia/reperfusion than larger species. Therefore, we investigated whether erythropoietin attenuates porcine aortic occlusion ischemia/reperfusion injury. Materials and Methods:Before occluding the aorta for 45 mins by inflating intravascular balloons, we randomly infused either erythropoietin (n = 8; 300 IU/kg each over 30 mins before and during the first 4 hrs of reperfusion) or vehicle (n = 6). During aortic occlusion, mean arterial pressure was maintained at 80% to 120% of baseline by esmolol, nitroglycerine, and adenosine 5’-triphosphate. During reperfusion, noradrenaline was titrated to keep mean arterial pressure >80% of baseline. Kidney perfusion and function were assessed by fractional Na-excretion, p-aminohippuric acid and creatinine clearance, spinal cord function by lower extremity reflexes and motor evoked potentials. Blood isoprostane levels as well as blood and tissue catalase and superoxide dismutase activities allowed evaluation of oxidative stress. After 8 hrs of reperfusion, kidney and spinal cord specimens were taken for histology (hematoxylin–eosin, Nissl staining) and immunohistochemistry (TUNEL assay for apoptosis). Results:Parameters of oxidative stress and antioxidative activity were comparable. Erythropoietin reduced the noradrenaline requirements to achieve the hemodynamic targets and may improve kidney function despite similar organ blood flow, histology, and TUNEL staining. Neuronal damage and apoptosis was attenuated in the thoracic spinal cord segments without improvement of its function. Conclusion:During porcine aortic occlusion-induced ischemia/reperfusion erythropoietin improved kidney function and spinal cord integrity. The lacking effect on spinal cord function was most likely the result of the pronounced neuronal damage associated with the longlasting ischemia.

Hemodynamic, metabolic, and organ function effects of pure oxygen ventilation during established fecal peritonitis-induced septic shock.

Objective:To test the hypothesis whether pure oxygen ventilation is equally safe and beneficial in fully developed fecal peritonitis-induced septic shock as hyperoxia initiated at the induction of sepsis. Design:Prospective, randomized, controlled, experimental study with repeated measures. Setting:Animal research laboratory at a university medical school. Subjects:Twenty anesthetized, mechanically ventilated, and instrumented pigs. Interventions:Twelve hours after induction of fecal peritonitis by inoculation of autologous feces, swine, which were resuscitated with hydroxyethyl starch and norepinephrine to maintain mean arterial pressure at baseline values, were ventilated randomly with an Fio2 required to keep Sao2 >90% (controls: n = 10) or Fio2 1.0 (hyperoxia, n = 10) during the next 12 hrs. Measurements and Main Results:Despite similar hemodynamic support (hydroxyethyl starch and norepinephrine doses), systemic and regional macrocirculatory and oxygen transport parameters, hyperoxia attenuated pulmonary hypertension, improved gut microcirculation (ileal mucosal laser Doppler flowmetry) and portal venous acidosis, prevented the deterioration in creatinine clearance (controls 61 (44;112), hyperoxia: 96 (88;110) mL·min−1, p = .074), and attenuated the increase in blood tumor necrosis factor-&agr; concentrations (p = .045 and p = .112 vs. controls at 18 hrs and 24 hrs, respectively). Lung and liver histology (hematoxyline eosine staining) were comparable in the two groups, but hyperoxia reduced apoptosis (Tunel test) in the liver (4 (3;8) vs. 2 (1;5) apoptotic cells/field, p = .069) and the lung (36 (31;46) vs. 15 (13;17) apoptotic cells/field, p < .001). Parameters of lung function, tissue antioxidant activity, blood oxidative and nitrosative stress (nitrate + nitrite, 8-isoprostane levels; deoxyribonucleic acid (DNA) damage measured using the comet assay) were not further affected during hyperoxia. Conclusions:When compared with the previous report on hyperoxia initiated simultaneously with induction of sepsis, i.e., using a pretreatment approach, pure oxygen ventilation started when porcine fecal peritonitis-induced septic shock was fully developed proved to be equally safe with respect to lung function and oxidative stress, but exerted only moderate beneficial effects.

Effects of pretreatment hypothermia during resuscitated porcine hemorrhagic shock.

Objectives:Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. Design:Prospective, controlled, randomized study. Setting:University animal research laboratory. Subjects:Twenty domestic pigs of either gender. Interventions:Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38°C, 35°C, or 32°C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values. Measurements and Main Results:Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32°C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis. Conclusions:During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase.

Implantation of an Iliac Branch Device After EVAR via a Femoral Approach Using a Steerable Sheath

Purpose: To describe a contralateral femoral approach for iliac branch device implantation using a steerable sheath in the setting of an existing bifurcated stent-graft. Technique: The method is demonstrated in an 80-year-old man who developed a 4-cm iliac aneurysm 3 years after implantation of an Endurant bifurcated stent-graft. Both femoral arteries were cannulated after surgical cutdown. The steerable sheath was advanced from the contralateral side over the neobifurcation of the bifurcated stent-graft. A 0.014-inch Roadrunner wire was used as a through-and-through wire to stabilize the curve of the sheath and to get proper push. The bridging stent-graft for the iliac branch was advanced over this sheath to seal the iliac aneurysm. During the entire procedure, the sheath was stable over the neobifurcation without pulling it down. Conclusion: The contralateral femoral approach for iliac branch graft implantation is feasible in cases with an extant bifurcated stent-graft using a steerable sheath and a through-and-through wire.

Acute Limb Ischemia—Much More Than Just a Lack of Oxygen

Acute ischemia of an extremity occurs in several stages, a lack of oxygen being the primary contributor of the event. Although underlying patho-mechanisms are similar, it is important to determine whether it is an acute or chronic event. Healthy tissue does not contain enlarged collaterals, which are formed in chronically malperfused tissue and can maintain a minimum supply despite occlusion. The underlying processes for enhanced collateral blood flow are sprouting vessels from pre-existing vessels (via angiogenesis) and a lumen extension of arterioles (via arteriogenesis). While disturbed flow patterns with associated local low shear stress upregulate angiogenesis promoting genes, elevated shear stress may trigger arteriogenesis due to increased blood volume. In case of an acute ischemia, especially during the reperfusion phase, fluid transfer occurs into the tissue while the vascular bed is simultaneously reduced and no longer reacts to vaso-relaxing factors such as nitric oxide. This process results in an exacerbative cycle, in which increased peripheral resistance leads to an additional lack of oxygen. This whole process is accompanied by an inundation of inflammatory cells, which amplify the inflammatory response by cytokine release. However, an extremity is an individual-specific composition of different tissues, so these processes may vary dramatically between patients. The image is more uniform when broken down to the single cell stage. Because each cell is dependent on energy produced from aerobic respiration, an event of acute hypoxia can be a life-threatening situation. Aerobic processes responsible for yielding adenosine triphosphate (ATP), such as the electron transport chain and oxidative phosphorylation in the mitochondria, suffer first, thus disrupting the integrity of cellular respiration. One consequence of this is irreparable damage of the cell membrane due to an imbalance of electrolytes. The eventual increase in net fluid influx associated with a decrease in intracellular pH is considered an end-stage event. Due to the lack of ATP, individual cell organelles can no longer sustain their activity, thus initiating the cascade pathways of apoptosis via the release of cytokines such as the BCL2 associated X protein (BAX). As ischemia may lead to direct necrosis, inflammatory processes are further aggravated. In the case of reperfusion, the flow of nascent oxygen will cause additional damage to the cell, further initiating apoptosis in additional surrounding cells. In particular, free oxygen radicals are formed, causing severe damage to cell membranes and desoxyribonucleic acid (DNA). However, the increased tissue stress caused by this process may be transient, as radical scavengers may attenuate the damage. Taking the above into final consideration, it is clearly elucidated that acute ischemia and subsequent reperfusion is a process that leads to acute tissue damage combined with end-organ loss of function, a condition that is difficult to counteract.

Ischemia and reperfusion injury of the spinal cord：experimental strategies to examine postischemic paraplegia

Thoracoabdominal aortic replacement, necessary in case of injuries, aneurysms and dissections, shows a high complication rate as a consequence of the perioperative ischemia / reperfusion-sequence (I/R). Clamping above and below the lesion leads to the spinal cord suffering from ischemia. Clamping times of less than 30 minutes show only a small risk of neurological deficit, while longer periods increase paraplegia rates disproportionately. The subsequent reperfusion as a second hit causes additional damage to the spinal cord. Up to 30 % of all patients who require being treated in the thoracoabdominal part of the aorta suffer from paraplegia within the first 24 postoperative hours (Kahn et al., 2012).

Aktueller Forschungsstand zur akuten Extremitätenischämie

ZusammenfassungDie akute Extremitätenischämie (AEI) gefährdet sowohl die betroffene Gliedmaße als auch das Leben des Patienten und stellt eine häufige Ursache für eine Extremitätenamputation dar. Deshalb ist die AEI ein vaskulärer Notfall, der einer raschen Revaskularisation bedarf. Die Ursachen sind kardiale Embolien, lokale Thrombosen, postrekonstruktive thrombotische Gefäßverschlüsse, embolisierende Aneurysmen, Aortendissektionen und Gefäßverletzungen. Das 30-Tage-Major-Amputationsrisiko beträgt 10–30 % und die 30-Tage-Mortalität 15–30 %. Die Ausprägung des Krankheitsbilds ist abhängig von der peripheren Restperfusion. Die Einteilung nach Rutherford und die 6 Ps nach Pratt beschreiben die Klinik. Man unterscheidet eine komplette Ischämie mit voller Ausprägung der Symptomatik und eine inkomplette Form mit Erhalt der Sensibilität und Motorik. Als Folgeereignis kann es zu einem Reperfusions- oder einem Kompartmentsyndrom kommen.Bei komplexer Vorgeschichte ist eine CTA für die Therapieplanung hilfreich. Mittel der Wahl zur Diagnostik ist die Duplexsonographie und Angiographie. Als Therapieoptionen stehen die offen chirurgische Therapie, die endovaskuläre Therapie oder eine Kombination aus beidem (Hybridverfahren) zur Verfügung. Mittlerweile haben die endovaskuläre und die offenchirurgische Methode einen vergleichbaren Stellenwert bei der Behandlung einer AEI.AbstractAcute limb ischemia (ALI) is a danger to the life as well as the affected limb of the patient and has a high amputation and mortality rate; therefore, ALI is a vascular emergency which requires immediate revascularization. The causes of ALI are lower extremity embolisms originating from the heart, proximal arterial aneurysms, arterial thrombosis, thrombosis of a bypass graft, aortic dissection and arterial injury. The 30-day risk of major amputation is 10–30 % while the 30-day mortality is 15–20 %. The extent of symptoms is dependent on the presence of sufficient collateral perfusion. The clinical symptoms of ALI can be classified according to the 6 Ps of Pratt and the Rutherford classification. There are two kinds of ischemia: complete ischemia with the full extent of symptoms and an incomplete form of ischemia without sensory loss and muscle weakness. Acute limb compartment syndrome and a life-threatening reperfusion syndrome may be complications of ALI. The use of computed tomography angiography (CTA) in cases with a complex history can be helpful for therapy planning. The standard procedures for diagnostics are duplex sonography and angiography. Treatment options are open surgery, endovascular therapy and a combination of both (hybrid procedure). Endovascular therapy and open surgery now have a comparable status in the treatment of ALI.