M. Theisen

Xenon improves recovery from myocardial stunning in chronically instrumented dogs.

In this study we tested the hypothesis that inhalational administration of xenon improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate; left atrial, aortic, and left ventricular pressure; coronary blood-flow velocity; and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography. An occluder around the left anterior descending artery (LAD) allowed the induction of a reversible LAD ischemia. Animals underwent 2 experimental conditions in a randomized crossover fashion on separate days: (a) 10 min of LAD occlusion under fentanyl (25 μg · kg−1 · h−1) and midazolam (0.6 mg · kg−1 · h−1) (control) and (b) a second ischemic episode under the same basal anesthesia with concomitant inhalational administration of 75 ± 1 vol% xenon (intervention). Anesthesia was induced 35 min before LAD occlusion and was discontinued after 20 min of reperfusion. Dogs receiving xenon showed a significantly better recovery of wall-thickening fraction up to 12 h after ischemia. The increase in plasma epinephrine during emergence from anesthesia and in the early reperfusion period was significantly attenuated in the xenon group. There were no differences between groups concerning global hemodynamics, blood-flow velocity, or regional myocardial blood flow. In conclusion, inhalational administration of 75 vol% xenon improves recovery from myocardial stunning in chronically instrumented dogs under fentanyl/midazolam anesthesia.

Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

We have previously demonstrated that non-selective nitric oxide synthase (NOS) inhibition did not reverse the LPS-induced deterioration of hepato-splanchnic energy status in porcine endotoxic shock. Therefore, this study investigated the effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal and liver perfusion, O2 kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous intravenous infusion of 1400 W was started until the end of the experiment and was titrated to maintain mean blood pressure (MAP) at baseline levels. Twelve, 18, and 24 h after starting LPS, we measured hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal as well as hepatic venous lactate/pyruvate ratios, and endogenous glucose production rate. Expired NO and plasma nitrate levels were assessed as a measure of NO production. 1400 W decreased LPS-induced increase in expired NO and allowed for the maintenance of MAP without modification of cardiac output. Despite unchanged regional macrocirculation, 1400 W prevented the progressive rise of ileal mucosal-arterial PCO2 gap, significantly improved the LPS-induced impairment of hepato-splanchnic redox state, and blunted the decline in liver lactate clearance. Increased glucose production rate was not influenced. Thus, the selective iNOS inhibition with 1400 W prevented circulatory failure and largely attenuated otherwise progressive LPS-induced deterioration of intestinal and hepatocellular energy metabolism.

Adenosine triphosphate-magnesium dichloride during hyperdynamic porcine endotoxemia: Effects on hepatosplanchnic oxygen exchange and metabolism

ObjectiveTo assess the effects of adenosine triphosphate-magnesium dichloride (ATP-MgCl2) on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic normotensive porcine endotoxemia. DesignProspective, randomized, controlled experimental study with repeated measures. SettingInvestigational animal laboratory. SubjectsSeventeen pigs were divided into two groups: eight animals receiving endotoxin served as a control group and nine animals received endotoxin (lipopolysaccharide) and ATP-MgCl2. InterventionsPigs were anesthetized, mechanically ventilated, and instrumented. Endotoxemia was achieved by continuous intravenous infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch targeted to maintain mean arterial pressure of >75 mm Hg. Twelve hours after the start of the endotoxin infusion, ATP-MgCl2, or its vehicle, were administered for 12 hrs. Measurements and Main ResultsMean arterial pressure was maintained in the control group because of a sustained increase in cardiac output achieved by fluid resuscitation, whereas ATP-MgCl2 significantly decreased mean arterial pressure because of further systemic vasodilatation. ATP-MgCl2 markedly increased portal venous flow. In contrast to the controls, hepatic arterial flow remained unchanged until the end of the experiment, despite the further increase in cardiac output. The ileal mucosal-arterial Pco2 gap (&Dgr;Pco2) progressively increased (p < .05) in control animals, whereas it was restored to prelipopolysaccharide levels during ATP-MgCl2 infusion. Changes in &Dgr;Pco2 correlated with those of portal vein blood flow in these animals (r = −.68, p < .05). Moreover, ATP-MgCl2 blunted the lipopolysaccharide-induced decrease in hepatic lactate balance but did not affect portal venous pH, hepatosplanchnic oxygen exchange, splanchnic lactate/pyruvate ratios, isoprostane, NO2− + NO3−, cytokine concentrations, or tissue nucleotide content. ConclusionDuring long-term hyperdynamic porcine endotoxemia, ATP-MgCl2 normalized the otherwise progressive rise of the ileal mucosal-arterial &Dgr;Pco2. Furthermore, it allowed blunting of the continuous decrease in hepatic lactate clearance, thus preserving the metabolic coupling between lactate release from the intestine and lactate utilization by the liver.

Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

Detection and distribution of opioid peptide receptors in porcine myocardial tissue

There is growing evidence that opioid peptide receptors (OPRs) play an important role in cardiovascular function. Many studies have been conducted in swine, in view of their anatomic and physiologic similarities to humans. Until now, the presence and particularly distribution of OPRs has been unclear. Porcine myocardial tissue was obtained from both the left and right atria and ventricles. Expression of mRNA for μ-, δ- and κ-OPR was determined by reverse transcription PCR. OPR proteins were detected by Western blot, distribution and cellular location were identified using immunohistochemistry. Homogenous expression of mRNA and protein for δ- and κ-OPRs were demonstrated in all porcine myocardial tissue tested, whereas expression of μ-OPR mRNA was not demonstrated in any of the tissues tested. This study demonstrates the expression of δ- and κ-OPRs in porcine myocardial tissue. No differences in distribution of δ- and κ-OPRs were found between the four heart cavities. Modulation of cardiac function by δ- and κ-OPR agonists or antagonists is therefore possible, while μ-OPR-mediated direct cardiac effects appear unlikely, due to nonexpression of the receptor. This study demonstrates that porcine studies can further elucidate the role of OPRs in cardiac (patho-)physiology.

Sleep Disturbances after Posterior Scoliosis Surgery with an Intraoperative Wake-up Test Using Remifentanil

Background:The intraoperative wake-up test is a standard procedure for early recognition of neurologic complications after posterior correction of idiopathic scoliosis. In this prospective, single-blinded cohort study, the impact of the wake-up test and the opioid used for anesthesia on the quality of the patients’ sleep after scoliosis surgery was investigated up to 12 months postoperatively. Methods:Patients were classified into three groups: posterior instrumentation with wake-up test using remifentanil, anterior instrumentation without wake-up test using sufentanil, and posterior instrumentation with wake-up test using sufentanil. The quality of sleep was assessed using the Pittsburgh Sleep Quality Index questionnaire preoperatively as well as 3, 6, and 12 months postoperatively. In addition, data were collected on patients’ age, weight, and sex, as well as the duration of the operation and anesthesia, amount of blood loss, specific opioid dosages, and wake-up test times. Statistical analysis was conducted using the Mann–Whitney, Kruskal–Wallis, and Wilcoxon tests. Results:There were no differences between groups with regard to baseline characteristics. No explicit recall was assessed through all groups. At 3 and 6 months postoperatively, the sleep quality in the posterior–remifentanil group was significantly poorer than preoperatively and compared with the anterior– and posterior–sufentanil groups. No significant differences in wake-up test times between groups undergoing posterior instrumentation occurred. Conclusions:This study suggests that patients undergoing scoliosis surgery with an intraoperative wake-up test using remifentanil had impaired sleep quality that lasted up to 6 months postoperatively. No deterioration in sleep quality was observed with sufentanil. Large randomized trials are now needed to confirm these preliminary results.

Opioid Receptor Antagonism Improves Recovery from Myocardial Stunning in Chronically Instrumented Dogs

We tested the hypothesis that the selective &kgr;-opioid receptor antagonist nor-binaltorphimine (nor-BNI) improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), and the maximum rate of LVP increase (LV dP/dtmax) and decrease (LV dP/dtmax), coronary blood flow velocity and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography, and &bgr;-endorphin and dynorphin plasma levels by radioimmunoassay. An occluder around the left anterior descending artery (LAD) allowed induction of a reversible LAD-ischemia. Animals underwent two experiments in a randomized crossover fashion on separate days: (a) 10 min LAD-occlusion (control experiment), (b) second ischemic episode 24 h after nor-BNI (2.5 mg/kg IV) (intervention). Dogs receiving nor-BNI showed an increase in wall-thickening fraction, LV dP/dtmax and LV dP/dtmin before ischemia and during the whole reperfusion (P < 0.05 versus control experiment). After nor-BNI pretreatment, dynorphin levels increased after induction of ischemia to a peak level of 15.1 ± 3.6 pg/mL (P < 0.05 versus control experiment). The increase in plasma &bgr;-endorphin during ischemia and early reperfusion was attenuated after nor-BNI. Compared with the control experiment, nor-BNI left global hemodynamics, regional myocardial blood flow, and catecholamine levels unchanged. In conclusion, nor-BNI improves recovery from myocardial stunning after regional myocardial ischemia in chronically instrumented dogs.

Inhaling Nitrous Oxide or Xenon Does Not Influence Bowel Wall Energy Balance During Porcine Bowel Obstruction

Xenon (Xe) is less soluble than nitrous oxide (N2O) and hence may be more suitable during bowel obstruction. Therefore, we compared the intestinal mechanical and biochemical effects of these two gases with those of total IV anesthesia in a porcine model of small-bowel obstruction. Intestinal obstruction was induced in 33 anesthetized pigs, in 18 of which segmental ileal perfusion was reduced by partial arterial occlusion. Pigs received total IV anesthesia, Xe, or N2O (in 30% oxygen) for 4 h, and we determined the intraluminal pressure and volume, the arterial-ileal Pco2 gap, and the lactate and pyruvate levels in the segmental mesenteric vein. Under both experimental conditions, Xe or N2O ventilation caused the volume to significantly increase with a concomitant significant increase in the intraluminal pressure during N2O ventilation. Regardless of the anesthesia technique, none of the biochemical variables was influenced in the animals with maintained ileal blood supply. In contrast, reducing the segmental perfusion induced pronounced alterations of all variables of bowel wall energy metabolism. The type of anesthesia, however, had no further statistically significant effect. Short-term inhalation of Xe or N2O seems to have no deleterious effects on the metabolic balance of the gut wall during intestinal obstruction.