Mucosal Oxygen Research Articles

Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs*

The effect of levosimendan, a novel inotropic vasodilator (inodilator), on the microvascular gastric mucosal hemoglobin oxygenation (muHbo(2)) is unknown. A possible effect could thereby be selective for the splanchnic region or could primarily reflect changes in systemic oxygen transport (Do(2)) and/or oxygen consumption (Vo(2). We compared systemic and regional effects of levosimendan with those of established inotropes, milrinone and dobutamine. Laboratory experiment. University animal research laboratory of experimental anesthesiology. Chronically instrumented dogs with flow probes for cardiac output measurement. Anesthetized, mechanically ventilated dogs (each group n = 6) on different days randomly received levosimendan (10 microg.kg, followed by four infusion steps: 0.125-1.0 microg.kg.min), milrinone (5.0 microg.kg, followed by 1.25-10 microg.kg.min), or dobutamine (2.5-10.0 microg.kg.min). Since these drugs may modify regional or systemic responses to fluid load, an additional predefined volume challenge was subsequently performed with hydroxyethyl starch 6% (10 mL.kg). We measured muHbo(2) (reflectance spectrophotometry), Do(2), Vo(2), and systemic hemodynamics. Levosimendan significantly increased muHbo(2) from baseline (approximately 55% for all groups) to 64 +/- 4% and further to 69 +/- 2% with volume challenge (mean +/- sem). At the systemic level, levosimendan alone only slightly increased Do(2) at a Vo(2). Milrinone elicited similar systemic effects (Do(2), Vo(2), hemodynamics) but failed to increase muHbo(2). Dobutamine, conversely, increased muHbo(2) to a similar extent as levosimendan; however, this was accompanied by marked increases in Do(2) and Vo(2). The gastric mucosa selectivity of these interventions, expressed as slope of the muHbo(2)/Do2 relation, was highest for levosimendan (+1.89 and +1.14, without and with volume challenge), compared with milrinone (+0.45 and + 0.47) and dobutamine (+0.48 and + 0.33). Levosimendan is superior to milrinone (no significant regional effects) and dobutamine (marked systemic effects) in increasing gastric mucosal oxygenation selectively (i.e., at only moderately increased Do(2) and stable Vo(2). If our experimental data apply to the clinical setting, levosimendan may serve as an option to selectively increase gastrointestinal mucosa oxygenation in patients at risk to develop splanchnic ischemia.

Effects of thoracic epidural anaesthesia on microvascular gastric mucosal oxygenation in physiological and compromised circulatory conditions in dogs

The effects of thoracic epidural anaesthesia (TEA) on gastric mucosal microvascular haemoglobin oxygenation (microHbO(2)) are unclear. At the splanchnic level, reduction of sympathetic tone may promote vasodilation and increase microHbO(2). However, these splanchnic effects are counteracted by systemic effects of TEA (e.g., decreased cardiac output (CO) and mean arterial pressure (MAP)), thus making the net effect on microHbO(2) difficult to predict. In this respect, effects of TEA on microHbO(2) may differ between physiological and compromised circulatory conditions, and additionally may depend on adequate fluid resuscitation. Furthermore, TEA may alter the relationship between regional microHbO(2) and systemic oxygen-transport (DO(2)). Chronically instrumented dogs (flow probes for CO measurement) were anaesthetized, their lungs ventilated and randomly received TEA with lidocaine (n=6) or epidural saline (controls, n=6). Animals were studied under physiological and compromised circulatory conditions (PEEP 10 cm H(2)O), both with and without fluid resuscitation. We measured gastric mucosal microHbO(2) by reflectance spectrophotometry, systemic DO(2), and systemic haemodynamics (CO, MAP). Under physiological conditions, TEA preserved microHbO(2) (47 (3)% and 49 (5)%, mean (sem)) despite significantly decreasing DO(2) (11.3 (0.8) to 10.0 (0.7) ml kg(-1) min(-1)) and MAP (66 (2) to 59 (3) mm Hg). However, during compromised circulatory conditions, TEA aggravated the reduction in microHbO(2) (to 32 (1)%), DO(2) (to 6.7 (0.8) ml kg(-1) min(-1)) and MAP (to 52 (4) mm Hg), compared with controls. During TEA, fluid resuscitation completely restored these variables. TEA preserved the correlation between microHbO(2) and DO(2), compared with controls. TEA maintains microHbO(2) under physiological conditions, but aggravates the reduction of microHbO(2) induced by cardiocirculatory depression, thereby preserving the relationship between gastric mucosal and systemic oxygenation.

Effects of thoracic epidural anesthesia (TEA) on microvascular gastric mucosal oxygenation during physiological and compromised circulatory conditions in dogs

Effects of thoracic epidural anesthesia (TEA) on microvascular gastric mucosal oxygenation during physiological and compromised circulatory conditions in dogs

Levosimendan is superior to Milrinone and Dobutamine in selectively increasing microvascular gastric mucosal oxygenation

Department of Anesthesiology, Experimental Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany

Gastroduodenal perfusion and mortality in mechanical ventilation-dependent patients with systemic inflammatory response syndrome.

The role of gastrointestinal blood flow determination in predicting mortality is not known. We tested the hypothesis that when mechanical ventilation-dependent (MVD) patients with systemic inflammatory response syndrome (SIRS) develop a significant reduction in gastroduodenal blood flow, high mortality will ensue. The design was a prospective, observational study at the intensive care unit (study patients) and outpatient endoscopy suite (controls) of a tertiary care Veterans Affairs Hospital. There were 6 study patients and 10 control subjects. Interventions were endoscopic reflectance spectrophotometry recorded indexes of gastroduodenal mucosal oxygen saturation (ISO2) and hemoglobin concentration (IHB). Data for Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were gathered. All study patients had septic SIRS at enrollment. Gastroduodenal blood flow measurements ranged from 32 to 55% (ISO2) and from 42 to 51% (IHB) of those in control subjects. The significant hypoperfusion upgraded diagnosis to severe sepsis. The APACHE II score of 16.8 +/- 2.8 (mean +/- SE) predicted approximately 25% mortality. Observed in-hospital mortality was 83%. Our study confirmed that MVD patients with severe sepsis have a significant impairment of gastroduodenal blood flow. Such a dramatic reduction is associated with a grave prognosis. The impact of these measurements on physicians' predictions of the likelihood of survival in patients receiving intensive care deserves to be assessed.

Cysteamine alters redox state, HIF-1α transcriptional interactions and reduces duodenal mucosal oxygenation: novel insight into the mechanisms of duodenal ulceration

Our recent studies demonstrated a critical role of enhanced transcriptional activity of early growth response factor-1 (Egr-1) in early stages of cysteamine-induced duodenal ulcer in rats. Since cysteamine is also a reducing agent, the aims of this study were to determine the effect of cysteamine on proximal duodenal mucosa: (a) redox status, (b) mucosal oxygenation, (c) expression of hypoxia-inducible factor 1 (HIF-1α) and its binding to DNA, and (d) HIF-1α interaction with Egr-1 and other redox-sensitive transcription factors. Here we demonstrate for the first time that cysteamine treatment reduced the duodenal oxygenation by 19% (vs. baseline) and markedly increased the redox status in duodenal mucosa ( p<0.05). Cysteamine increased HIF-1α expression, its binding to DNA, and enhanced the HIF-1α interactions with Egr-1 and other transcription factors (e.g., AP-1, AP-2, L-III BP, NF-E1, NF-E2, STAT4, and MRE), their binding to DNA. Thus, these data demonstrate the involvement of the redox-dependent regulatory mechanisms in the early stages of duodenal ulceration.

Hyperoxic Ventilation in Critical Dilutional Anemia: Intestinal O2 Transport and Tissue Oxygenation

Summary Objective: The onset of hyperoxic ventilation after hemodilution to the critical hematocrit (Hctcrit) improves myocardial and peripheral tissue oxygenation. However, it is unknown whether at Hctcrit hyperoxemia is also beneficial to intestinal oxygenation, since intestinal tissue hypoxia might even worsen as a result of hyperoxic vasoconstriction. To study this, we investigated whether hyperoxic ventilation started at Hctcrit is beneficial in terms of intestinal oxygenation. Method: 18 anesthetized pigs were hemodiluted to their individual Hctcrit (onset of myocardial ischemia; ECG) by 1:1 exchange of blood with 6% pentastarch (200,000/0.5). At Hctcrit hyperoxic ventilation was initiated. Nine complete datasets were obtained and analyzed at baseline, at Hctcrit and during hyperoxic ventilation. Analysis included intestinal O2 transport parameters (portal blood gases), intestinal mucosal O2 partial pressure (MDO‐Electrode) and regional intestinal blood flow (microsphere method). Results: At Hctcrit (7.2 ±1.2%), intestinal O2 delivery was reduced. Despite increased O2 extraction, local tissue hypoxia was documented by markedly reduced portal venous (26 ± 2 Torr) and jejunal O2 (9 ± 3 Torr) partial pressures. Portal venous base excess (‐10 ± 3 mmol/L) and lactate concentration (4.3 ± 1.4 mmol/L) evidenced anaerobic intestinal metabolism (all p &lt; 0.05). During hyperoxic ventilation, intestinal O2 delivery increased (p &lt; 0.05) requiring a less intensive O2 extraction; physically dissolved O2 extracted from plasma was predominantly responsible for the restoration of portal and intestinal mucosal O2 partial pressure (49 ± 2 Torr and 17 ± 4 Torr; p &lt; 0.05 vs. Hctcrit). Portal base excess (‐12 ± 6 mmol/L) and lactate concentration (4.3 ± 1.9 mmol/L) did not recover. Conclusion: Hyperoxic ventilation at Hctcrit did improve intestinal O2 transport and mucosal oxygenation after 15 min. However, intestinal O2 debt persisted during the observation time.SummaryHyperoxic ventilation reverses manifest intestinal mucosal tissue hypoxia at Hctcrit due to the efficacious utilization of physically dissolved O2. There is no evidence that at Hctcrit hyperoxia‐induced vasoconstriction further does impair microvascular intestinal blood flow and O2 transport. It remains unclear, to which extent hyperoxic ventilation may induce relevant O2 shunts. Hence, the true value of this technique for a possible use in humans remains to be elucidated.

Effects of arginine–vasopressin on jejunal mucosal oxygen supply in healthy pigs

Arginine–vasopressin (AVP) may promote intestinal ischemia. We studied the effects of increasing doses of AVP on mucosal tissue oxygen tension (PO2muc), microvascular haemoglobin oxygen saturation (HbO2), and microvascular blood flow (PU) in a jejunal segment.

Visceral and Renal Tissue Oxygenation During Supraceliac Aortic Crossclamping and Left Heart Bypass with Selective Organ Perfusion

Introduction. Left-heart bypass (LHB) and selective organ perfusion (SOP) are used during thoracoabdominal aortic surgery to prevent ischemic damage to the kidneys and visceral organs after supraceliac aortic crossclamping. We studied the hypothesis, in a porcine model, that despite LHB and maximal SOP, visceral and renal ischemia still occured during surgery.Material and methods. Eleven pigs (54–70 kg) were coupled to a non-pulsatile LHB with inflow and outflow at the lower thoracic and distal infrarenal aorta, respectively. After supracoeliac and infrarenal aortic crossclamping, SOP was started using perfusion catheters. The proximal and distal mean aortic blood pressures were kept above 70 and 50 mmHg, respectively, while the mean blood pressure within the SOP system was above 60 mmHg. The visceral and renal tissue oxygenation was measured by intermittent blood gas analysis, from the portal and both renal veins. The jejunal mucosal oxygenation was measured by tonometric measurement of the luminal pCO2.Results. Measured median blood blood flow through the LHB and the SOP system were 800 and 1140 ml/min, respectively. Median blood flow prior to, and during LHB and SOP through the celiac artery, superior mesenteric artery, and left renal artery were 300 and 240, 762 and 295, and 235 and 235 ml/min, respectively. During 3 h of LHB and SOP no significant changes in the renal tissue oxygenation were noted compared with the physiological situation prior to supracoeliac aortic crossclamping and cannulation. However, in the visceral vascular bed median mixed venous oxygen saturation dropped from 79 to 63% (p<0.001), and median oxygen extraction ratio increased from 26 to 41% (p<0.001). Median tonometric measured intraluminal jejunal pCO2 increased from 9.9 to 12.15kPa (p>0.05). During 3 h of LHB and SOP no hemolysis was detected, as there was no rise in serum LDH.Conclusion. LHB and SOP preserves renal but not visceral tissue oxygenation during supraceliac aortic crossclamping and does not induce hemolysis.

Endoscopic components separation for abdominal compartment syndrome

Background Sustained intraabdominal pressures of 14 to 20 mm Hg have significant pathophysiological consequences, but there is currently no satisfactory low-morbidity procedure appropriate for intervention early in the disease process of abdominal compartment syndrome (ACS). The anatomical principles of abdominal wall components separation were used to develop a percutaneous procedure that increased abdominal capacity and decreased abdominal pressure. Methods Using a porcine model, we determined abdominal capacity changes by helium insufflation. Corn oil was then used to create an episode of sustained intraabdominal hypertension and changes in intraabdominal pressure and intestinal mucosal oxygenation were determined. Results Endoscopic abdominal wall components separation (EACS) increased abdominal capacity by 1 L (from 0.89 ± 0.39 L to 1.95 ± 0.48 L; P <0.001). During intraabdominal hypertension, EACS decreased abdominal pressure by 31.6% (from 15.9 ± 2.1 to 11.0 ± 1.5 mm Hg; P <0.001). Intestinal P o 2 was increased by 61% (18.8 ± 11.4 to 30.3 ± 11.7; P = 0.012) Conclusions A minimally invasive procedure (EACS) is feasible and has demonstrated effectiveness in a porcine model of ACS.

The Effect of Inhibition of Renin-Angiotensin System by Valsartan during Hypovolemic Shock and Low Flow Sigmoideal Ischaemia in Pigs

The aim of this experiment was to study the effect of Renin-Angiotensin System (RAS) blockade by means of valsartan on the colonic and systemic circulation in pigs during low flow sigmoideal ischemia in combination with hypovolemic shock. This condition resembles the situation that occurs in patients suffering from a ruptured aneurysm and a compromised colonic circulation. An experimental study in pigs was performed: 6 pigs with low flow sigmoideal ischemia and hypovolemic shock were treated with valsartan and a control group of 5 pigs with low flow sigmoideal ischemia and hypovolemic shock without medical treatment. Valsartan, 3 mg/kg, was administered intravenously. The operation was performed via left sided lumbotomy. The distal aorta was partially occluded to a flow reduction of 30% of the initial value. Hypovolemic shock was induced by withdrawing 20 ml/kg blood in 45 min. Resuscitation with 30 ml/kg haemaccel was iniated after 2 h of shock. The following parameterswere measured: blood pressure, cardiac output; hemoglobin, lactate, angiotensin II in mixed venous blood (obtained from pulmonary artery) and in splanchnic blood (obtained from caudal mesenteric vein); and endoluminal pulse oximetry of the sigmoideal mucosa. Statistical analysis was performed by ANOVA and Wilcoxon signed rank test. There was a significant increase of lactate levels both in systemic and splanchnic circulation (P&lt;0.05) in both groups. In the control group, the mean angiotensin II concentrations in the systemic circulation increased, after induction of ischaemia and shock. In the experimental group, the increase in angiotensin concentrations after resuscitation was significantly more prominent. In the colonic circulation, in both groups, there was a significant increase in angiotensin II levels in the splanchnic circulation following ischaemia and reperfusion (P&lt;0.05), but there was no significant difference between the groups. There were no detectable mucosal signals measured by pulse oximetry after induction of shock throughout the experiment, whereas in the experimental group, median mucosal oxygen saturations of 81. 74.5 and 85% were achieved after resuscitation and declamping (P&lt;0.01). In conclusion, angiotensin II inhibition during hypovolemic shock improves the colonic circulation, measured by pulse oximetry. However, other parameters of tissue ischaemia did not improve.

The effect of inhibition of renin-angiotensin system by valsartan during hypovolemic shock and low flow sigmoideal ischaemia in pigs

The aim of this experiment was to study the effect of Renin-Angiotensin System (RAS) blockade by means of valsartan on the colonic and systemic circulation in pigs during low flow sigmoideal ischemia in combination with hypovolemic shock. This condition resembles the situation that occurs in patients suffering from a ruptured aneurysm and a compromised colonic circulation. An experimental study in pigs was performed: 6 pigs with low flow sigmoideal ischemia and hypovolemic shock were treated with valsartan and a control group of 5 pigs with low flow sigmoideal ischemia and hypovolemic shock without medical treatment. Valsartan, 3 mg/kg, was administered intravenously. The operation was performed via left sided lumbotomy. The distal aorta was partially occluded to a flow reduction of 30% of the initial value. Hypovolemic shock was induced by withdrawing 20 ml/kg blood in 45 min. Resuscitation with 30 ml/kg haemaccel was iniated after 2 h of shock. The following parameterswere measured: blood pressure, cardiac output; hemoglobin, lactate, angiotensin II in mixed venous blood (obtained from pulmonary artery) and in splanchnic blood (obtained from caudal mesenteric vein); and endoluminal pulse oximetry of the sigmoideal mucosa. Statistical analysis was performed by ANOVA and Wilcoxon signed rank test. There was a significant increase of lactate levels both in systemic and splanchnic circulation ( P<0.05) in both groups. In the control group, the mean angiotensin II concentrations in the systemic circulation increased, after induction of ischaemia and shock. In the experimental group, the increase in angiotensin concentrations after resuscitation was significantly more prominent. In the colonic circulation, in both groups, there was a significant increase in angiotensin II levels in the splanchnic circulation following ischaemia and reperfusion ( P<0.05), but there was no significant difference between the groups. There were no detectable mucosal signals measured by pulse oximetry after induction of shock throughout the experiment, whereas in the experimental group, median mucosal oxygen saturations of 81, 74.5 and 85% were achieved after resuscitation and declamping ( P<0.01). In conclusion, angiotensin II inhibition during hypovolemic shock improves the colonic circulation, measured by pulse oximetry. However, other parameters of tissue ischaemia did not improve.

Gastric Tonometry in the Care of the Newborn

Gastric Tonometry in the Care of the Newborn

Sigmoid colonic reflectance pulse oximetry and tonometry in a porcine experimental hypoperfusion shock model.

The objective of the present study was to determine if colonic endoluminal mucosal oxygen saturation, as determined by reflectance pulse oximetry, is an appropriate method to monitor colonic ischemia produced by a gradual partial constriction of the aorta in a porcine experimental model. Piglets were anesthetized and mechanically ventilated. A Nellcor RS-10 reflectance pulse oximeter probe was attached to a Foley balloon catheter and passed transanally to record the oxygen saturation of the sigmoid colonic mucosa. For comparison, a tonometry catheter was introduced into the sigmoid colon. Hypoperfusion shock was induced by partial gradual constriction of the aorta. The same measurements but no intervention was performed in the control group. During one-third reduction of the aortic blood flow, the plethysmographic signal disappeared suddenly and the sigmoid colonic mucosa oxygen saturation (ScO2) measurements showed zero in seven out of the eight pigs. During two-thirds flow reduction, no plethysmographic signals were observed in any of the piglets. During the reperfusion period, ScO2 measurements with a good plethysmographic signal were obtained immediately after complete release of the aortic constriction in all pigs. Significantly decreased intramucosal pH and increased difference between the arterial and regional PCO2 (PCO2 gap) were observed during two-thirds blood flow reduction. In contrast to the results of previous investigations, the sigmoid colonic pulse oximetry was not useful because the method proved to be overly sensitive and non-linear in relation to regional blood flow.

Clinical evaluation of reflectance spectrophotometry for the measurement of gastric microvascular oxygen saturation in patients undergoing cardiopulmonary bypass

Objective: To evaluate the impact of cardiopulmonary bypass (CPB) on gastric mucosal oxygen saturation assessed by reflectance spectrophotometry in patients undergoing coronary artery bypass graft surgery. Design: Prospective, observational study. Setting: A division of cardiothoracic anesthesia in a university hospital. Participants: Twelve consecutive patients undergoing CPB. Interventions: Monitoring, anesthesia, surgical procedure, and CPB for the patients followed routine clinical protocol as established in the departments. Microvascular oxygen saturation in gastric mucosa was assessed by reflectance spectrophotometry before, during, and after CPB. Measurements and Main Results: Gastric mucosal oxygen saturation averaged 65 ± 7% (mean ± SD) before CPB, decreased significantly to 57 ± 9% during CPB (p < 0.01), and was 59 ± 8% after CPB. These changes in regional oxygen saturation were not mirrored in variables of systemic oxygenation. Gastric mucosal oxygen saturation always showed instantaneous reactions to various surgical and pharmacologic interventions. Conclusion: Reflectance spectrophotometry allowed the authors to assess gastric mucosal oxygen saturation with a high repetition rate, regardless of spontaneous circulation with pulsatile flow or nonpulsatile flow during CPB. This technique provided the means to monitor on-line the course of tissue oxygen saturation throughout the operative procedure. Reflectance spectrophotometry is an appropriate and sensitive assessment tool to monitor gastric mucosal oxygen saturation in patients undergoing CPB. Copyright 2002, Elsevier Science (USA). All rights reserved.

Effects of three different resuscitation regimens on jejunal tissue oxygen supply after hemorrhagic shock

In this study we evaluated effects of blood (B; n = 7), gelatine (G; n = 8) and Ringer's lactate (R; n = 8) resuscitation on jejunal microvascular blood flow (PU), tissue microvascular hemoglobin oxygen saturation (HbO2t) and jejunal mucosal tissue oxygen tension (PO2muc) after severe haemorrhage (50% of estimated blood volume) in pigs.

Lung recruitment manoeuvres decrease gastric mucosal blood flow in ICU patients

The use of recruitment manoeuvres (RM) has recently been introduced into clinical practice for treatment of atelectasis during mechanical ventilation. Transient high airway pressures, such as those employed in RM, may lead to adverse general or regional circulatory effects. The aim of this study was to evaluate effects of RM on gastric mucosal blood flow, systemic oxygenation and respiratory mechanics.

Jejunal luminal nitric oxide during severe hypovolemia and sepsis in anesthetized pigs.

Lowered gut blood perfusion and the associated intestinal mucosal barrier dysfunction is considered important in the pathophysiology leading to critical illness. Intestinal mucosal nitric oxide formation has been attributed a key role in the regulation of epithelial permeability and other properties of the intestinal mucosal barrier. This study was performed to delineate intestinal mucosal NO formation during hypovolemia or sepsis, both of which are associated with intestinal hypoperfusion. Seventeen pigs were subjected to 2 h of severe hypovolemia (bleeding induced) or sepsis (systemic infusion of live Escherichia coli) or no treatment (controls). Jejunal mucosal NO production was monitored by a tonometer. Mesenteric blood flow was measured as portal venous blood flow by an ultrasonic transit time flowmeter probe, and oxygen delivery and consumption were calculated from regional blood samples. Intestinal perfusion and oxygen delivery were reduced by the same order of magnitude in both groups. Jejunal mucosal NO production and oxygen consumption decreased markedly in the hypovolemia group but remained stable in the group subjected to septic shock. These data suggest that blood loss inhibits jejunal mucosal NO production as part of a general downregulation of nonvital organs. Sepsis represents a more complex stress condition with activation/maintenance of host defense mechanisms as reflected by maintained jejunal mucosal NO production despite reduced gut blood perfusion.

Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model.

To study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation. Prospective, controlled animal study. University-affiliated research laboratory. Thirteen fasted, anesthetized, mechanically ventilated landrace pigs. Cardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2 gap), and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelinA/endothelinB antagonist tezosentan at 1 mg.kg-1.hr-1 during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco2 gap increased. The change in tPo2 failed to gain statistical significance (p =.08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo2 above baseline, and decreased Pco2 gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade. Endothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.

Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension.

To investigate effects of intravenous norepinephrine (NE) and phenylephrine (PE) on intestinal oxygen supply in an autoperfused, innervated jejunal segment. Prospective, randomized animal study in an animal research laboratory. In 24 anesthetized and normoventilated pigs a segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension (PO2muc; Clark-type surface oxygen electrodes), microvascular hemoglobin oxygen saturation (HbO2, tissue reflectance spectrophotometry), and microvascular blood flow (perfusion units, PU; laser Doppler velocimetry), systemic hemodynamics, mesenteric-venous acid base and blood gas variables, and systemic acid base and blood gas variables were recorded after a resting period and at 20-min intervals during infusion of NE (0.01, 0.05, 0.1, 0.5, 1, 2 micrograms x kg-1 x min-1; n = 8) or PE (0.1, 0.5, 1, 2, 5, 10 micrograms x kg-1 x min-1; n = 8) and in controls (n = 8) without treatment. NE infusion led to significant tachycardia, an increase in cardiac output, and systemic oxygen delivery and consumption while PE progressively increased mean arterial pressure with only small effects on systemic blood flow. NE or PE infusion did not affect mesenteric venous oxygen tension (baseline: PE 53 +/- 5, NE, 52 +/- 4.2 mmHg), mesenteric oxygen extraction ratio (baseline: PE 0.29 +/- 0.08, NE 0.3 +/- 0.06), jejunal microvascular blood flow (baseline: PE 254 +/- 127, NE 282 +/- 72 PU), PO2muc (baseline: PE 31 +/- 9.1, NE 33 +/- 11 mmHg), and HbO2 (baseline: PE 52 +/- 9.6%, NE 58 +/- 11.6%). Despite major differences in systemic hemodynamics jejunal tissue oxygen supply is not affected by progressively increasing intravenous infusion of norepinephrine and phenylephrine.