Microdialysis in early detection of temporary pancreatic ischemia in a porcine model.

BACKGROUND: Ischemic injury to the pancreas occurs in various clinical conditions. A method for online monitoring of pathophysiological events in pancreatic parenchyma is missing. AIMS: To assess the timing of microdialysis (MD) technique response on temporary changes in pancreatic perfusion, and to evaluate the relationship between MD data and systemic markers of anaerobic metabolism and inflammation. METHODS: In anaesthetized normoventilated pigs, MD probes were placed in right (control) and left (ischemic) pancreatic lobes, respectively. Following the clamping of the vessels, ischemia was verified by tissue oxygen tension (P(ti)O(2)) measurements. RESULTS: P(ti)O(2) decreased within 20 min after the clamping of the vessels, already returning to baseline levels at the first sampling point after the removal of the clamp. MD lactate levels increased, whereas pyruvate and glucose levels decreased at 20 min after the induction of ischemia. These trends continued until the end of ischemia and returned to baseline following reperfusion. Serum lactate, amylase and tumor necrosis factor-alpha levels decreased throughout the protocol time. CONCLUSION: MD data were in concordance with changes in P(ti)O(2), which is indicative of local anaerobic metabolism. MD allowed the detection of pathophysiological processes within the ischemic pancreas at a stage when no elevations of systemic markers of ischemia or inflammation were observed.

Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients.

BACKGROUND: Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi-centric, double-blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation. METHODS: Patients (n=413) given nutrition by an enteral and/or a parenteral route with the aim of providing full nutrition were included within 72 h after ICU admission. Glutamine was supplemented as i.v. l-alanyl-l-glutamine, 0.283 g glutamine/kg body weight/24 h for the entire ICU stay. Placebo was saline in identical bottles. All included patients were considered as intention-to-treat patients. Patients given supplementation for >3 days were considered as predetermined per protocol (PP) patients. RESULTS: There was a lower ICU mortality in the treatment arm as compared with the controls in the PP group, but not at 6 months. For change in the SOFA scores, no differences were seen, 1 (0,3) vs. 2 (0.4), P=0.792, for the glutamine group and the controls, respectively. CONCLUSION: In summary, a reduced ICU mortality was observed during i.v. glutamine supplementation in the PP group. The pragmatic design of the study makes the results representative for a broad range of ICU patients.

Assessment of the Surgical Apgar Score in a Swedish setting.

BACKGROUND: Predicting major post-operative complications is an important task for which simple and reliable methods are lacking. A simple scoring system based on intraoperative heart rate, blood pressure and blood loss was recently developed to fill this gap. This system, the Surgical Apgar Score, shows promising results both in terms of validity and in terms of usefulness. The goal of this study was to study both these components in a Scandinavian setting. METHODS: Pre-operative patient characteristics and intraoperative variables were recorded for 224 patients undergoing general and vascular surgery between 26 October and 17 December 2009. Major complications were evaluated during a 30-day follow-up. The relationship between Surgical Apgar Score and major complication was analysed using χ(2)-tests and the relative risk between different scoring patient groups was analysed. RESULTS: The study showed a strong correlation between the Surgical Apgar Score and major complication (P<0.001). 61.5% of the lowest-scoring patients sustained a major complication compared with only 6.4% in the highest-scoring group. This is equivalent to a relative risk of 7.14 (95% CI: 2.88-17.5, P<0.001). CONCLUSIONS: The Surgical Apgar Score is valid in a Scandinavian setting. We also note that there were no practical issues in collecting the score. Together with patient pre-operative risk, the score has great potential to guide clinicians when making post-operative decisions and give immediate feedback about the surgical procedure. The next step should be to educate surgical staff about the score.

Physiological responses to touch massage in healthy volunteers.

OBJECTIVES: To evaluate effects of touch massage (TM) on stress responses in healthy volunteers. METHODS: A crossover design including twenty-two (mean age=28.2) healthy volunteers (11 male and 11 female) cardiac autonomic tone was measured by heart rate (HR) and heart rate variability (HRV). Stress hormone levels (cortisol) were followed in saliva. We also measured blood glucose and serum insulin. Extracellular (ECV) levels of glucose, lactate, pyruvate and glycerol were followed using the microdialysis technique (MD). TM was performed on hands and feet for 80 min, during control, participants rested in the same setting. Data were collected before, during, and after TM and at rest. Saliva cortisol, serum glucose, and serum insulin were collected before, immediately following, and 1 h after intervention or control, respectively. RESULTS: After 5 min TM, HR decreased significantly, indicating a reduced stress response. Total HRV and all HRV components decreased during intervention. Saliva cortisol and insulin levels decreased significantly after intervention, while serum glucose levels remained stable. A similar, though less prominent, pattern was seen during the control situation. Only minor changes were observed in ECV levels of glucose (a decrease) and lactate (an increase). No significant alterations were observed in glycerol or pyruvate levels throughout the study. There were no significant differences between groups in ECV concentrations of analyzed substances. CONCLUSIONS: In healthy volunteers, TM decreased sympathetic nervous activity, leading to decreased overall autonomic activity where parasympathetic nervous activity also decreased, thereby maintaining the autonomic balance.

Immediate and 5-year cumulative outcome after paediatric intensive care in Sweden.

BACKGROUND: Little has been reported about intensive care of children in Sweden. The aims of this study are to (I) assess the number of admissions, types of diagnoses and length-of-stay (LOS) for all Swedish children admitted to intensive care during the years 1998-2001, and compare paediatric intensive care units (PICUs) with other intensive care units (adult ICUs) (II) assess immediate (ICU) and cumulative 5-year mortality and (III) determine the actual consumption of paediatric intensive care for the defined age group in Sweden. METHODS: Children between 6 months and 16 years of age admitted to intensive care in Sweden were included in a national multicentre, ambidirectional cohort study. In PICUs, data were also collected for infants aged 1-6 months. Survival data were retrieved from the National Files of Registration, 5 years after admission. RESULTS: Eight-thousand sixty-three admissions for a total of 6661 patients were identified, corresponding to an admission rate of 1.59/1000 children per year. Median LOS was 1 day. ICU mortality was 2.1% and cumulative 5-year mortality rate was 5.6%. Forty-four per cent of all admissions were to a PICU. CONCLUSIONS: This study has shown that Sweden has a low immediate ICU mortality, similar in adult ICU and PICU. Patients discharged alive from an ICU had a 20-fold increased mortality risk, compared with a control cohort for the 5-year period. Less than half of the paediatric patients admitted for intensive care in Sweden were cared for in a PICU. Studies are needed to evaluate whether a centralization of paediatric intensive care in Sweden would be beneficial to the paediatric population.

Dopamine or norepinephrine infusion during thoracic epidural anesthesia? Differences in hemodynamic effects and plasma catecholamine levels.

BACKGROUND: During thoracic epidural anesthesia, an intravenous dopamine infusion augments the systemic pressure response and modifies plasma catecholamine levels. If such an altered response occurs when norepinephrine is infused is not clear. Therefore, dopamine and norepinephrine induced circulatory and catecholamine responses were studied before and during thoracic epidural anesthesia. METHODS: Nine chloralose-anesthetized dogs were equipped with thoracic epidural catheters. Dopamine (5, 10, and 20 microg kg(-1) min(-1)), and norepinephrine (0.1, 0.25, and 0.5 microg kg(-1) min(-1)) were infused before and during epidural anesthesia, while cardiovascular performance and plasma catecholamine changes were studied. RESULTS: Thoracic epidural anesthesia decreased arterial pressure, and cardiac contractility. The systemic pressure response induced by dopamine was augmented during epidural anesthesia. Norepinephrine did not increase arterial pressure and myocardial contractility as markedly as dopamine, and cardiac output was not altered. Thoracic epidural anesthesia attenuated the plasma norepinephrine level. Plasma dopamine levels were augmented by the dopamine infusion during epidural anesthesia, while plasma norepinephrine levels were attenuated. In contrast, norepinephrine augmented the plasma norepinephrine levels during epidural anesthesia. In general, plasma norepinephrine levels were three to six times higher during a norepinephrine infusion compared to a dopamine infusion. CONCLUSION: The cardiovascular response to a graded dopamine infusion is augmented during thoracic epidural anesthesia, while norepinephrine-induced effects are unaltered. The modified plasma catecholamine levels may contribute to the hemodynamic differences between dopamine and norepinephrine infusions during thoracic epidural anesthesia.

Survey of routines for sedation of patients on controlled ventilation in Nordic intensive care units.

BACKGROUND: Sedation strategies and practice for patients on controlled ventilation is variable from place to place as well as over time. Less sedation results in shorter ventilation time and new ventilatory modes permit more awake patients. Previous works estimated sedative and analgesic use in Nordic ICUs some years ago, but current practice is not known. We therefore designed this study to describe pharmacological and practical routines for sedation of patients on controlled ventilation. MATERIAL AND METHODS: We used an electronic questionnaire about characteristics of the participating ICUs and the routines for sedation of ventilator-treated patients, and secondly, an Internet-based 5-day registration on the use of drugs for sedation and analgesia. RESULTS: Eighty-eight of 220 ICUs (36%) responded to the questionnaire and 47 out of these 88 units (53%) used a sedation scale. Written guidelines for sedation were used in 41% of the units. Both daily interruption of sedation infusions and guidelines for weaning from the ventilator were used in 15% of the units. Data on 202 patients (633 patient days) from 55 ICUs were reported. Among analgesics, fentanyl predominated (240/633 days), followed by ketobemidon (160/633 days) and morphine (115/633 days). Propofol and midazolam were the most commonly used agents for sedation (345 and 238/633 days, respectively). CONCLUSION: Most units used a sedation scale, although other strategies to reduce the sedation level had not yet been fully introduced. Differences in pharmacological strategies were found between the Nordic countries, and some favourite drugs could be identified.

Primary sepsis in a university hospital in northern Sweden: a retrospective study.

BACKGROUND: Severe sepsis and septic shock are associated with high mortality rates. Data on sepsis outcome from Scandinavian countries are sparse. The aim of this study was to examine the length of stay (LOS) in the ICU, ICU mortality and costs of care for adult patients with primary sepsis in a university hospital in northern Sweden. METHODS: We performed a retrospective data analysis of records of 92 patients admitted over a 3-year period, under the diagnosis of sepsis or urosepsis. Demographic data, admission category, APACHE II score, aetiology and severity of sepsis, ICU LOS, mortality and TISS were analyzed. RESULTS: Eighty-one adult patients were identified by standard definitions as suffering from sepsis. The median ICU length of stay was 4.2 days, 6 days for survivors and 2.1 days for non-survivors. Thirteen out of 20 deaths occurred within the first 3 days after admission. Overall ICU mortality rate was 24.7% while the ICU mortality for patients with septic shock was 57.7%. The mean costs of care for patients with sepsis were 3139 Euros day(-1) and the cost of care per patient surviving sepsis was 38,494 Euros. CONCLUSION: The incidence of primary sepsis in our ICU was low. Previous reports on high mortality in association with severe sepsis and septic shock are valid also at our hospital. The ICU-LOS was shorter than previously reported, while our costs of care were in the same range as stated by others. This retrospective analysis is valid for interpretation of the applicability of currently available sepsis therapies.

Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.

OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.

Do lung recruitment maneuvers decrease gastric mucosal perfusion?

OBJECTIVE: To evaluate effects of lung recruitment maneuvers on gastric mucosal perfusion, systemic circulation, and lung mechanics in patients with acute lung injury. DESIGN: Prospective observational clinical study. SETTING. General intensive care unit of university hospital. PATIENTS AND PARTICIPANTS: Fourteen patients with acute lung injury (ten in the main study group and four in a validation group). INTERVENTIONS. Three 2-min-long recruitment maneuvers (RM) with transient increases in mean airway pressure to 35 cmH(2)O (RM1 and RM2) and 44 cmH(2)O (RM3). MEASUREMENTS AND RESULTS: Measurements of systemic hemodynamics, gastric mucosal perfusion (laser Doppler flowmetry), and lung mechanics were performed immediately before, at the end of, and 3 min after each RM. Cardiac index decreased during all RMs while mean arterial pressure decreased only during RM3. Gastric mucosal perfusion was not significantly changed during any of the RMs. When comparing values obtained before the first RM with values after the third RM there was a significant decrease in cardiac index ( P=0.043) and a non-significant ( P=0.051) decrease in gastric mucosal perfusion. There were no significant changes in systemic oxygenation or lung mechanics after three RMs, even though four patients showed marked transient increases in systemic oxygenation during RMs. CONCLUSIONS: In this study of ten patients there were no significant changes in gastric mucosal perfusion during lung recruitment maneuvers. There was, however, a trend towards gradual decreases in gastric mucosal perfusion.

Does dopexamine influence regional vascular tone and oxygenation during intestinal hypotension?

BACKGROUND: Local effects of dopexamine on intestinal vascular tone and oxygenation were investigated during intestinal hypotension. To this end, we employed an experimental model, in which the superior mesenteric arterial pressure (PSMA) was controlled by an adjustable perivascular clamp. This approach enabled us to keep the intestinal perfusion pressure (IPP) constant in the face of any systemic circulatory alterations. METHODS: In 11 barbiturate-anesthetized pigs, we instrumented the superior mesenteric circulation for assessments of vascular resistance (RMES), IPP, jejunal mucosal perfusion (Laser Doppler) and intestinal tissue oxygenation (microoximetry). Measurements were carried out before and during dopexamine infusions (0.5 and 1.0 micro g.kg-1.min-1) at a freely variable PSMA (i.e. the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. RESULTS: At a constant PSMA of 50 mmHg, dopexamine had no significant intestinal vascular effects. However, at a constant PSMA of 30 mmHg, both doses of dopexamine were associated with decreases in RMES. Effects of dopexamine on intestinal oxygen delivery and extraction were minimal during these procedures, while a minor decrease in intestinal tissue oxygen tension was observed during dopexamine administration at the lowest IPP level. CONCLUSION: At very low intestinal perfusion pressures (approximately 30 mmHg) dopexamine produces intestinal vasodilation in excess of what is produced by intrinsic autoregulation. This suggests that there is a vasodilatory reserve in the intestine under such conditions and that a pharmacological vasodilator like dopexamine may improve intestinal circulation during regional severe hypotension.

Splanchnic vasoconstriction by angiotensin II is arterial pressure dependent.

BACKGROUND: Our hypothesis was that splanchnic vasoconstriction by exogenous angiotensin II (Ang II) is significantly potentiated by local mechanisms increasing vasomotor tone and that splanchnic tissue oxygenation during administration of Ang II is perfusion pressure dependent. The aim was to study local splanchnic circulatory effects and tissue oxygenation during intravenous infusion of Ang II at different levels of regional arterial driving pressure in a whole-body large animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h-1) in anaesthetised instrumented pigs (n=8). Mean superior mesenteric arterial pressure (PSMA) was adjusted by a local variable perivascular occluder. Perivascular ultrasound and laser-Doppler flowmetry were used for measurements of mesenteric venous blood flow and superficial intestinal blood flow, respectively. Intestinal oxygenation was evaluated by oxygen tissue tension (PtiO2) and lactate fluxes. RESULTS: Ang II produced prominent and dose-dependent increases in mesenteric vascular resistance (RSMA) when the intestine was exposed to systemic arterial pressure, but Ang II increased RSMA only minimally when PSMA was artificially kept constant at a lower level (50 mmHg) by the occluder. Although Ang II decreased PtiO2 at a PSMA of 50 mmHg, splanchnic lactate production was not observed. CONCLUSION: We demonstrate that splanchnic vasoconstriction by exogenous Ang II is dependent on arterial driving pressure, suggesting significant potentiation through autoregulatory increases in vasomotor tone. Intestinal hypoxaemia does not seem to occur during short-term infusion of Ang II in doses that significantly increases systemic arterial pressure.

Effects of positive end-expiratory pressure on intestinal circulation during graded mesenteric artery occlusion.

BACKGROUND: Reduced gut perfusion is associated with multiple organ failure. Positive end-expiratory pressure (PEEP) reduces cardiac output (CO) and portal blood flow, and might be detrimental in a situation of already compromised intestinal circulation. The aim of this study was to investigate regional circulatory and metabolic effects of PEEP during graded regional hypoperfusion. METHODS: In 12 barbiturate-anesthetized pigs, we measured systemic and regional blood flows (superior mesenteric arterial, QSMA and portal venous, QPORT), jejunal mucosal perfusion (LDF), tissue oxygenation (PO2TISSUE) and metabolic parameters at PEEP (0, 4, 8 and 12 cm H2O) in a randomized order. Measurements were performed at unrestricted intestinal perfusion pressures (IPP) and at IPP levels of 50 and 30 mmHg. RESULTS: During unrestricted IPP, PEEP decreased MAP, CO, QSMA and QPORT, while systemic, and preportal (RPORT) vascular resistances and jejunal mucosal perfusion were not significantly changed. Preportal tissue oxygen delivery and PO2TISSUE decreased, while preportal tissue oxygen uptake was unaltered. During restricted IPP, PEEP produced the same pattern of hemodynamic alterations as when IPP was not restricted. QPORT and QSMA were lowered by the reductions in IPP, and QPORT was further reduced during PEEP. At an IPP of 30 mmHg, this reduction in QPORT decreased preportal tissue oxygen uptake. Consequently, intestinal ischemia, as indicated by increased net lactate production, occurred. Simultaneously, jejunal mucosal perfusion and PO2TISSUE declined. CONCLUSION: At IPP levels below 50 mmHg, even moderate levels of PEEP impaired local blood flow enough to cause intestinal ischemia. Our data underscore the importance of considering regional circulatory adaptations during PEEP ventilation.

Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block.

BACKGROUND: Although signs of sympathetic blockade following interscalene brachial plexus block include Horner's syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block. METHODS: Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg(-1)) followed by a continuous infusion (0.25 mg kg(-1) h(-1)). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end-inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation. RESULTS: Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp-induced cutaneous vasoconstrictor and heat-induced vasodilator responses were attenuated. CONCLUSIONS: Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.

Effects of desflurane on the pig intestinal circulation during hypotension.

BACKGROUND: The aim of the present study was to analyze the perfusion pressure dependency for the splanchnic vascular effects of desflurane (DES). METHODS: We measured portal blood flow (QPORT, perivascular ultrasound) and jejunal mucosal perfusion (JMP; laser Doppler) in pentobarbital-anesthetized pigs (n=10). Experimentally, decreases in mean arterial pressure (MAP) were produced by pericardial infusions of dextran. The protocol included sets of measurements at incremental doses of DES (1, 2, 4 and 6%) prior to and during pericardial infusions. RESULTS: Although QPORT and JMP decreased significantly during pericardial infusions, DES, irrespective of dose, did not reduce QPORT until MAP had decreased below 65-70 mm Hg. In higher MAP ranges, vasodilation in pre-portal tissues was powerful enough to maintain QPORT in spite of concurrent decreases in driving arterial pressure, as produced by either DES or pericardial infusion, or by a combination of both. We found no effects of DES on JMP even at very low MAP (about 40 mm Hg during pericardial infusion), indicating that the normal physiological response of the small intestine to redistribute blood flow from deeper to more superficial layers during hypotension was unimpaired by DES. CONCLUSIONS: Our data suggest a wide dose-tolerability of DES as regards the splanchnic circulation during hypotensive states.

Systemic levels and preportal organ release of tissue-type plasminogen activator are enhanced by PEEP in the pig.

BACKGROUND: Endothelium-derived tissue-type plasminogen activator, t-PA, is the key enzyme in the initiation of endogenous thrombolysis. Plasma levels of t-PA increase in response to sympatho-adrenergic activation. In the mesenteric vascular bed an increased norepinephrine spillover has been observed during positive end-expiratory pressure ventilation, PEEP. This experimental study examines the effects of PEEP-induced alterations on regional release rates and systemic levels of t-PA in vivo. METHODS: The protocol included measurements of arterio-venous concentration gradients of t-PA and the respective plasma flow across the pulmonary, coronary, hepatic and preportal vascular beds, in pigs, during zero-PEEP and at 2, 4 and 10 min after the application of a PEEP of 10 cm H2O. Both total plasma t-PA antigen (ELISA with a porcine t-PA standard) and active t-PA (spectrophotometric functional assay) were determined. RESULTS: During zero-PEEP, a high preportal basal net release and hepatic net uptake of total t-PA was observed. With PEEP, the magnitude of the preportal net release of t-PA was markedly enhanced (+24+/-5%), as was hepatic net uptake (+21+/-8%), simultaneously to a significant decrease in liver plasma flow (-30+/-2%). PEEP-induced alterations in active t-PA mirrored those observed in total t-PA. No significant net fluxes of total or active t-PA were observed across the coronary or the pulmonary vascular beds. CONCLUSIONS: Clinically used levels of PEEP induce increases in net release of endothelially derived t-PA within preportal organs. The application of PEEP is associated with increased systemic levels of total and active t-PA, in spite of a simultaneous increase in hepatic net uptake, indicating that the preportal vascular bed can not account for the systemic t-PA response.

The effects of desflurane on cardiac function as measured by conductance volumetry in swine.

UNLABELLED: The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. IMPLICATIONS: Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.

Aortic cross-clamping influences regional net release and uptake rates of tissue-type plasminogen activator in pigs.

BACKGROUND: The key regulator of intravascular fibrinolysis, tissue-type plasminogen activator (t-PA), is released from a dynamic endothelial storage pool. The aim of the study was to investigate regional t-PA net release and uptake rates in response to infra-renal aortic cross-clamping (AXC) and declamping (DC). METHODS: Anesthetized pigs were studied during 5 min of AXC, followed by a 35-min declamping (DC) period. Arterio-venous concentration gradients of total and active t-PA, as well as respective plasma flows, were simultaneously obtained across the preportal, hepatic, coronary and pulmonary vascular beds. Plasma levels of total t-PA (ELISA with purified porcine t-PA as standard), and active t-PA (spectrophotometric functional assay) were determined. RESULTS: Prior to AXC, we found a high net release rate of total t-PA across the preportal vascular bed (1700 ng.min-1 P < 0.001), and a high hepatic net uptake (4900 ng.min-1, P < 0.001), while coronary and pulmonary t-PA net fluxes were small and variable. AXC per se did not induce significant alterations in net fluxes of t-PA. Following DC, preportal and coronary net releases of total t-PA increased (to 2900 ng.min-1 and 60 ng.min-1, respectively). Despite an increase in hepatic net uptake of total t-PA (to 6100 ng.min-1) after DC, a significant increase in hepatic venous total t-PA occurred. CONCLUSIONS: The release and uptake of t-PA is indicated to be dynamic and organ-specific. DC induces an acute profibrinolytic reaction in preportal organs. The high hepatic t-PA uptake capacity restricts preportal profibrinolytic events to affect the systemic circulation.

Autoregulation and vasodilator responses by isoflurane and desflurane in the feline renal vascular bed.

BACKGROUND: Inhalational anesthetics have agent-specific effects on the renal circulation. This study investigated renal vasodilator responses produced by either autoregulation, 0.8% isoflurane (ISO) or 3.5% desflurane (DES). METHODS: We measured systemic mean arterial pressure (MAP-SYST; axillary artery), renal blood flow (QREN; perivascular ultrasound) and central venous pressure (CVP) in normoventilated cats (n = 8) during basal chloralose anesthesia (control) and after the addition of ISO and DES. Renal mean arterial pressure (MAPREN) was controlled by an aortic clamp. QREN was measured at pre-set-MAPREN levels of 50, 70 and 90 mmHg. Renal vascular resistance (RREN) was derived. RESULTS: When MAPREN was artificially restrained from 133 +/- 5 mmHg to 90 mmHg during control, RREN decreased by 35% and no significant change in QREN was observed, reflecting an intact autoregulation. RREN levels during ISO or DES at stages with unrestrained MAPREN (95 +/- 6 and 102 +/- 9 mmHg, respectively), were not significantly different from RREN at 90 mmHg during control. When MAPREN was artificially decreased below 90 mmHg, QREN decreased in a similar fashion among control and ISO/DES sequences. The autoregulatory capacity was not significantly different among these sequences. Between 90-70 mmHg, the autoregulatory capacity was reduced and not demonstrable below 70 mmHg. CONCLUSION: The renal autoregulatory capacity was not attenuated by either ISO or DES. These agents produced equipotent renal vasodilation, which was not more powerful than that produced by autoregulation alone. The renal vasorelaxant effects of ISO and DES may therefore to a substantial extent be attributable to autoregulation.

An experimental multiple-organ model for the study of regional net release/uptake rates of tissue-type plasminogen activator in the intact pig.

Experimental data indicate large between-organs variations in rates of synthesis of tissue-type plasminogen activator (t-PA), which may reflect important differences in the capacity for constitutive and stimulated t-PA release from the vascular endothelium. In this report we describe a new multiple-organ experimental in vivo model for simultaneous determinations of net release/uptake rates of t-PA across the coronary, splanchnic, pulmonary, and hepatic vascular beds. In eleven intact anesthetized pigs, blood samples were obtained simultaneously from the proximal aorta, coronary sinus, pulmonary artery, and portal and hepatic veins. Plasma flows were monitored separately for each vascular region. Total plasma t-PA was determined by ELISA with a porcine t-PA standard. Regional net release/uptake rates were defined as the product of arteriovenous concentration gradients and local plasma flows. The net release of t-PA across the splanchnic vascular bed was very high, with a mean output of 1,919 ng total t-PA x min(-1) (corresponding to 90 ng per min and 100 g tissue). The net coronary t-PA release was 68 ng x min(-1) (30 ng x min(-1) X 100 g(-1)). Pulmonary net fluxes of t-PA were variable without any significant net t-PA release. The net hepatic uptake rate was 4,855 ng x min(-1) (436 ng x min(-1) x 100 g(-1)). Net trans-organ changes of active t-PA mirrored those of total t-PA. The results demonstrate marked regional differences in net release rates of t-PA in vivo. The experimental model we present offers new possibilities for evaluation of regional secretion patterns in the intact animal.