Hypothermia improves oral and gastric mucosal microvascular oxygenation during hemorrhagic shock in dogs.

Hypothermia is known to improve tissue function in different organs during physiological and pathological conditions. The aim of this study was to evaluate the effects of hypothermia on oral and gastric mucosal microvascular oxygenation (µHbO2) and perfusion (µflow) under physiological and hemorrhagic conditions. Five dogs were repeatedly anesthetized. All animals underwent each experimental protocol (randomized cross-over design): hypothermia (34°C), hypothermia during hemorrhage, normothermia, and normothermia during hemorrhage. Microcirculatory and hemodynamic variables were recorded. Systemic (DO2) and oral mucosal (µDO2) oxygen delivery were calculated. Hypothermia increased oral µ HbO2 with no effect on gastric µHbO2. Hemorrhage reduced oral and gastric µHbO2 during normothermia (-36 ± 4% and -27 ± 7%); however, this effect was attenuated during additional hypothermia (-15 ± 5% and -11 ± 5%). The improved µ HbO2 might be based on an attenuated reduction in µ flow during hemorrhage and additional hypothermia (-51 ± 21 aU) compared to hemorrhage and normothermia (-106 ± 19 aU). µDO2 was accordingly attenuated under hypothermia during hemorrhage whereas DO2 did not change. Thus, in this study hypothermia alone improves oral µHbO2 and attenuates the effects of hemorrhage on oral and gastric µ HbO2. This effect seems to be mediated by an increased µDO2 on the basis of increased µ flow.

Hypercapnia counteracts captopril-induced depression of gastric mucosal oxygenation.

Hypercapnia (HC) increases systemic oxygen delivery (DO2) and gastric mucosal oxygenation. However, it activates the renin-angiotensin-aldosterone system (RAAS), which conversely reduces mesenteric perfusion. The aims of this study were to evaluate the effect of RAAS inhibition during normocapnia and HC on oral and gastric mucosal oxygenation (µHbO2) and to assess the effect of blood pressure under these circumstances. Five dogs were repeatedly anesthetized to study the effects of ACE inhibition (ACE-I; 5 mg/kg captopril, followed by 0.25 mg/kg per h) on µHbO2 (reflectance spectrophotometry) and hemodynamic variables during normocapnia (end-tidal CO2=35 mmHg) and HC (end-expiratory carbon dioxide (etCO2)=70 mmHg). In the control group, the dogs were subjected to HC alone. To exclude the effects of reduced blood pressure, in one group, blood pressure was maintained at baseline values via titrated phenylephrine (PHE) infusion during HC and additional captopril infusion. ACE-I strongly reduced gastric µHbO2 from 72±2 to 65±2% and mean arterial pressure (MAP) from 64±2 to 48±4 mmHg, while DO2 remained unchanged. This effect was counteracted in the presence of HC, which increased gastric µHbO2 from 73±3 to 79±6% and DO2 from 15±2 to 22±4 ml/kg per min during ACE-I without differences during HC alone. However, MAP decreased similar to that observed during ACE-I alone from 66±3 to 47±5 mmHg, while left ventricular contractility (dPmax) increased from 492±63 to 758±119 mmHg/s. Titrated infusion of PHE had no additional effects on µHbO2. In summary, our data suggest that RAAS inhibition reduces gastric mucosal oxygenation in healthy dogs. HC not only abolishes this effect, but also increases µHbO2, DO2, and dPmax. The increase in µHbO2 during ACE-I under HC is in accordance with our results independent of blood pressure.

Vasopressin V(1A) receptors mediate the increase in gastric mucosal oxygenation during hypercapnia.

Hypercapnia (HC) improves systemic oxygen delivery (DO2) and microvascular hemoglobin oxygenation of the mucosa (µHbO2). Simultaneously, HC increases plasma levels of vasopressin. Although vasopressin is generally regarded a potent vasoconstrictor particularly in the splanchnic region, its effects on splanchnic microcirculation during HC is unclear. The aim of this study was to evaluate the role of endogenous vasopressin on gastric mucosal oxygenation and hemodynamic variables during physiological (normocapnia) and hypercapnic conditions. Five dogs were repeatedly anesthetized to study the effect of vasopressin V(1A) receptor blockade ([Pmp¹,Tyr(Me)²]-Arg8-Vasopressin, 35  µg/kg) on hemodynamic variables and µHbO2 during normocapnia or HC (end-tidal CO2 70  mmHg). In a control group, animals were subjected to HC alone. µHbO2 was measured by reflectance spectrophotometry, systemic DO2 was calculated from intermittent blood gas analysis, and cardiac output was measured by transpulmonary thermodilution. Data are presented as mean±s.e.m. for n=5 animals. During HC alone, DO2 increased from 12±1 to 16±1 ml/kg per min and µHbO2 from 70±4 to 80±2%. By contrast, additional vasopressin V(1A) receptor blockade abolished the increase in µHbO2 (80±2 vs. 69±2%) without altering the increase in DO2 (16±1 vs. 19±2  ml/kg per min). Vasopressin V1A receptor blockade (VB) during normocapnia neither affected DO2 (13±1 vs. 14±1  ml/kg per min) nor µHbO2 (75±3 vs. 71±5%). Vasopressin V(1A) receptor blockade abolished the increase in µHbO2 during HC independent of DO2. Thus, in contrast to its generally vasoconstrictive properties, the vasopressin V1A receptors seem to mediate the increase in gastric microcirculatory mucosal oxygenation induced by acute HC.

Neither inhalative nor intravenous application of carbon monoxide modifies gastric mucosal oxygenation.

This study was designed to compare the effects of different ways of administering carbon monoxide (intravenous and inhalative) on gastric mucosal oxygenation in a canine model of hemorrhage. Six chronically instrumented dogs were repeatedly anesthetized and randomized to each of the following protocols: In a first series the animals were ventilated either with 100 ppm carbon monoxide (CO) or without followed by hemorrhage and re-transfusion. In a second series a saturated CO solution was infused, compared to normal saline, again followed by hemorrhage and re-transfusion. In a control series, animals received either CO-saline or saline without any further intervention. Microvascular oxygenation of the gastric mucosa (µHbO2) was assessed continuously by tissue reflectance spectrophotometry. Cardiac output was measured intermittently and oxygen delivery (DO2) was calculated. The application of CO, inhalative and intravenous, increased carboxyhemoglobin levels without effect on µHbO2. Hemorrhage reduced µHbO2 in all groups, paralleled by a reduction in DO2 without any differences between groups related to the application of CO. Neither intravenous nor inhalative application of CO alters µHbO2 during physiological conditions or during hemorrhage. Thus, independent of the application way, low dose CO does not seem to modulate regional mucosal oxygenation in cytoprotective concentrations.

The effects of levosimendan and glibenclamide on circulatory and metabolic variables in a canine model of acute hypoxia.

PURPOSE: To study the effects of pretreatment with levosimendan (LEVO, a Ca²(+)-sensitizer and K (ATP) (+) channel opener) and/or the K (ATP) (+) channel antagonist glibenclamide (GLIB) on systemic hemodynamics, metabolism, and regional gastromucosal oxygenation during hypoxic hypoxemia. METHODS: Chronically instrumented, healthy dogs (24-32 kg, n = 6 per group, randomized cross-over design) were repeatedly sedated, mechanically ventilated (FiO2 ~0.3) and subjected to the following interventions: no pretreatment, LEVO pretreatment, GLIB pretreatment, or combined LEVO + GLIB pretreatment, each followed by hypoxic hypoxemia (FiO2 ~0.1). We measured cardiac output (CO, ultrasonic flow probes), oxygen consumption (VO2, indirect calorimetry), and gastromucosal microvascular hemoglobin oxygenation (µHbO2, spectrophotometry). STATISTICS: data are presented as mean ± SEM and compared by one-way ANOVA (direct drug effects within group) and two-way ANOVA (between all hypoxic conditions) both with Bonferroni corrections; p < 0.05. RESULTS: In LEVO-pretreated hypoxemia, CO was significantly higher compared to unpretreated hypoxemia. The increased CO was neither associated with an increased VO2 nor with markers of aggravated anaerobiosis (pH, BE, lactate). In addition, LEVO pretreatment did not further compromise gastromucosal µHbO2 in hypoxemia. After combined LEVO + GLIB pretreatment, systemic effects of GLIB were apparent, however, CO was significantly higher than during unpretreated and GLIB-pretreated hypoxemia, but equal to LEVO-pretreated hypoxemia, indicating that GLIB did not prevent the increased CO in LEVO-pretreated hypoxia. CONCLUSIONS: LEVO pretreatment resulted in improved systemic circulation (CO) during hypoxemia without fueling systemic VO2, without aggravating systemic anaerobiosis markers, and without further compromising microvascular gastromucosal oxygenation. Thus, LEVO pretreatment may be an option to support the systemic circulation during hypoxia.

Endocrine and psychological stress responses in a simulated emergency situation.

BACKGROUND: Several studies have assessed the effects of training using patient simulation systems on medical skills. However, endocrine and psychological stress responses in a patient simulation situation and the relationship between stress reactivity and medical performance have been studied rarely, so far. METHODS: Medical students (18 males and 16 females) who had completed at least two months anaesthesiology training participated in the study. In a counterbalanced cross-over design they were subjected to three conditions: rest, laboratory stress (LS; public speaking), and simulated emergency situation (SIM; myocardial ischemia and ventricular fibrillation). Salivary cortisol and psychological responses (visual analogue scales, VAS) were assessed every 15 min from 15 min prior to until 60 min after intervention. Differences between stress and rest conditions were analysed. Medical performance was assessed according to the European Resuscitation Council's Guidelines for Resuscitation. RESULTS: As compared to rest, cortisol increased significantly in both stress conditions with different time courses in LS and SIM. Psychological responses in SIM exceeded those in LS. Cortisol increase in LS (r(s)=.486; p=.019) but not in SIM (r(s)=.106; p=.631) correlated significantly with medical performance. DISCUSSION: A simulated emergency situation is a profound stressor. The positive relationship between endocrine stress responsiveness in a standard laboratory situation and medical performance in a simulated emergency situation indicates that high stress responsiveness might be a predictor of good performance. At the same time the high stress response might counteract educational efforts associated with training using high-fidelity patient simulation.

Hypercapnic acidosis preserves gastric mucosal microvascular oxygen saturation in a canine model of hemorrhage.

The authors aimed to clarify the effects of hypercapnic acidosis and its timing on gastric mucosal oxygenation in a canine model of hemorrhage. This was designed as a prospective, controlled, randomized animal study set in a university research laboratory. Five chronically instrumented dogs were used. Dogs were repeatedly anesthetized (sevoflurane 1.5 MAC), mechanically ventilated, and randomized to each of the following protocols. In a control series (CON), animals underwent hemorrhage during normoventilation (etCO2, 35 mmHg). In a second series, hypercapnia (etCO2, 70 mmHg) was applied before onset of hemorrhage (prophylactic hypercapnia), whereas in the third series, hypercapnia was applied after hemorrhage (therapeutic hypercapnia, THE). Microvascular oxygenation (µHbO2) of the gastric mucosa was continuously assessed by tissue reflectance spectrophotometry. Cardiac output was continuously measured, and oxygen delivery (DO2) was intermittently calculated. In CON, hemorrhage decreased DO2 (from 11 ± 3 mL·kg⁻¹·min⁻¹ to 8 ± 2 mL·kg⁻¹·min⁻¹ and 8 ± 2 mL·kg⁻¹·min⁻¹ after 30 and 75 min, respectively) and µHbO2 (from 57% ± 4% to 43% ± 11% and 50% ± 11%). Prophylactic hypercapnia attenuated the effects of hemorrhage on DO2 (12 ± 2 mL·kg⁻¹·min⁻¹ to 10 ± 2 mL·kg⁻¹·min⁻¹ and 11 ± 2 mL·kg⁻¹·min⁻¹) and preserved µHbO2 (52% ± 3% to 47% ± 5% and 57% ± 3%). Initial effects of hemorrhage in THE were comparable to CON (DO2 from 11 ± 2 mL·kg⁻¹·min⁻¹ to 8 ± 1 mL·kg⁻¹·min⁻¹; µHbO2 from 56% ± 7% to 43% ± 9%), but after application of hypercapnic acidosis, baseline levels were restored (DO2 10 ± 3 mL·kg⁻¹·min⁻¹; µHbO2 52% ± 14%). Hypercapnic acidosis applied before or after hemorrhage (THE) preserves microvascular mucosal oxygenation. If these experimental findings may be transferred to the clinical setting, deliberate hypercapnic acidosis could serve to augment oxygenation of the splanchnic region in states of compromised circulation, e.g., hemorrhage.

Perioperative liver protection.

PURPOSE OF REVIEW: This review presents important pathophysiological alterations associated with impaired liver function and discusses protective perioperative strategies and the various anaesthetic agents recommended. RECENT FINDINGS: Perioperative liver impairment is a serious complication of anaesthesia and surgery. Unfortunately, clinicians are provided with only crude macrohaemodynamic monitoring devices to optimize their therapy. Technical improvements have revealed some complex mysteries of perioperative microcirculatory alterations and have disclosed a large heterogeneity between different vascular beds. The present review will critically discuss current clinical concepts of optimizing global haemodynamic variables and the often contrasting effects of vasoactive agents on the microcirculatory nutritional blood flow. Finally, promising protective experimental interventions of pharmacological or ischaemic preconditioning are presented and their often disillusioning transition into recent clinical trials is highlighted. SUMMARY: Targeted perioperative liver protection still lacks adequate monitoring tools and is currently based on optimization of global haemodynamic variables. While there is currently no evidence suggesting a positive effect of ischaemic preconditioning, promising experimental results of pharmacological preconditioning and therapeutic hypothermia require further evaluation in larger randomized clinical trials.

Hypercapnia induces a concentration-dependent increase in gastric mucosal oxygenation in dogs.

OBJECTIVE: To clarify the effects of hypercapnia (increased PaCO2) on gastric mucosal oxygenation during anaesthesia in dogs. DESIGN: Prospective, controlled animal study. SETTING: Experimental research laboratory of an university hospital. SUBJECTS: Six chronically instrumented dogs. INTERVENTIONS: Dogs were anaesthetized (sevoflurane 1.5 MAC), mechanically ventilated (etCO2 = 35 mmHg) and randomly assigned to the following protocols: in a first series, ventilation was adjusted to increase etCO(2) to 45, 55, 65 and 70 mmHg. In a second series, animals were ventilated to achieve 70 mmHg of etCO2, which was maintained for 120 min to test if effects are transient or prolonged and to achieve a similar time course in both protocols. MEASUREMENTS AND MAIN RESULTS: Gastric mucosal oxygenation (microHbO2) was assessed continuously by tissue reflectance spectrophotometry. Mean arterial blood pressure (MAP) and cardiac output (CO) were continuously measured. Blood was sampled for blood gas analysis and lactate concentration. Hypercapnia increased gastric mucosal oxygenation concentration dependently from 48 +/- 6% (35 mmHg etCO2) to 51 +/- 4, 54 +/- 5, 56 +/- 5 and 59 +/- 3% (etCO2 45, 55, 65 and 70 mmHg, respectively). This reflected changes in CO (68 +/- 16, 74 +/- 16, 82 +/- 12, 91 +/- 11 and 97 +/- 16 ml kg(-1) min(-1), respectively) and systemic oxygen delivery (10 +/- 2, 11 +/- 3, 13 +/- 2, 14 +/- 2 and 14 +/- 2 ml kg(-1) min(-1), respectively). These effects persisted for 2 h (microHbO2 53 +/- 6 vs. 64 +/- 4%, CO 73 +/- 16 vs. 92 +/- 15 ml kg(-1) min(-1), DO2 12 +/- 4 vs. 14 +/- 3 ml kg(-1) min(-1), etCO2 35 and 70 mmHg, respectively). CONCLUSIONS: Hypercapnia increased systemic and regional oxygenation. If this experimental finding may be transferred to the clinical setting, permissive hypercapnia might be used to augment the oxygenation of the splanchnic region, e.g. gastrointestinal mucosa.

Clonidine elicits a long-term depression in mucosal red cell flux.

OBJECTIVE: To evaluate the impact of clonidine on mucosal red cell flux during baseline sedation with propofol or sevoflurane, respectively. MATERIALS AND METHODS: Six healthy, chronically instrumented dogs for the measurement of cardiac output (CO) were repeatedly studied. During baseline sedation with either propofol (15 mg x kg(-1) x h(-1)) or sevoflurane (1.5 MAC), local tissue cell flux was assessed using laser Doppler flowmetry at the enoral mucosa. After baseline measurements, a bolus of clonidine (2.0 microg/kg) was infused within 1 min. Data are presented as mean +/- SEM; STATISTICS: ANOVA, Scheffé's post hoc test, p < 0.05. RESULTS: Clonidine significantly reduced CO from 75 +/- 4 and 75 +/- 6 ml x kg(-1) x min(-1) (sedation with propofol or sevoflurane, respectively) to 40 +/- 3 and 49 +/- 5 ml x kg(-1) x min(-1), however, with almost complete recovery to baseline after 30 min (70 +/- 4 and 71 +/- 6 ml x kg(-1) x min(-1), NS from baseline). Similarly, clonidine decreased mucosal red cell flux by 44 +/- 8% and 54 +/- 4%. However, mucosal perfusion did not return to baseline (-25 +/- 5% and -27 +/- 3%). CONCLUSIONS: In spite of the rapid return to baseline in systemic perfusion, the mucosal red cell flux of the enoral mucosa remained markedly reduced after a single bolus of clonidine. Given the crucial role of preserved microcirculatory perfusion for an intact mucosal barrier function, our data suggest that clonidine might impair this important mechanism to prevent the translocation of bacteria and endotoxins into the systemic circulation.