Acute Kidney Injury in Patients Undergoing Open Abdominal Aortic Aneurysm Repair: A Pilot Observational Trial.

OBJECTIVES: Acute kidney injury (AKI) is a frequent complication after open repair of abdominal aortic aneurysms (AAA). Little research has been done to determine whether intraoperative hemodynamic events may precipitate AKI. Novel biomarkers also may aid in the earlier diagnosis of AKI. DESIGN: A pilot prospective observational trial. SETTING: A single tertiary academic medical center. PARTICIPANTS: Participants were 40 adult patients undergoing open repair of infrarenal AAA. INTERVENTIONS: Intraoperative hemodynamic monitoring of heart rate, mean arterial pressure, central venous pressure, and cardiac index was performed on a continuous basis. Blood samples were obtained at baseline and at 24 hours postoperatively for inflammatory biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL). MEASUREMENTS AND MAIN RESULTS: AKI occurred in 20% of patients (8 of 40). Hypotension, including duration (defined as the length of time mean arterial pressure was<65 mmHg) and magnitude (the area under the curve of a mean arterial pressure<65 mmHg), was the only factor associated with postoperative AKI. Urinary NGAL at the conclusion of surgery had excellent ability to predict the development of AKI (area under the curve 0.84, 95% confidence interval = 0.70-0.97). The cytokines pentraxin 3 (PTX3), interleukin-1 receptor antagonist (IL1-RA), macrophage chemotactic protein (MCP), suppressor of tumorigenicity 2 (ST-2), and interleukin-10 (IL-10) also had good ability to predict the development of AKI in the immediate postoperative period. CONCLUSIONS: AKI occurs frequently in patients undergoing open repair of AAA. Intraoperative hypotension was the only factor that predicted the development of subsequent AKI. Urinary NGAL and several novel inflammatory biomarkers demonstrated good ability to predict its development. Novel biomarkers also may aid in the early diagnosis of AKI.

Extracellular pH changes during spreading depression and cerebral ischemia: mechanisms of brain pH regulation.

We have examined the extracellular pH (pHe) during spreading depression and complete cerebral ischemia in rat parietal cortex utilizing double-barrelled H+ liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial PCO2 of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ve). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ve, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ve. A prolonged acidic shift of 0.42 pH units then occurred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased from baseline 1.2 mM to 7.0 mM (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in Ve, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazolamide), Na+/H+ counter transport (amiloride), and Cl-/HCO-3 countertransport (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.

Cerebral pressure-flow relationship during cardiopulmonary bypass in the dog at normothermia and moderate hypothermia.

We studied cerebral autoregulation by analyzing cerebral pressure-flow curves during cardiopulmonary bypass (CPB) with alpha-stat (alpha-stat) acid-base management at 28 (n = 9) and 37 degrees C (n = 9) in two groups of dogs. Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were determined multiple times in each animal over an extensive range of cerebral perfusion pressure (CPP). The CPP was altered by changing perfusion flow rate. The dependence of CBF on CPP during normothermic and moderate hypothermic CPB was assessed using a block design analysis of covariance with CPP as the covariate. We anticipated maximal statistical power with this analysis to define if cerebral autoregulation was intact. This method of statistical analysis was compared with the conventional interpretation by linear regression analysis. Animals were administered sodium thiopental until an isoelectric electroencephalogram was obtained to assure stable depth of anesthesia independently of temperature effects. The animals were randomly assigned to either temperature group. The CBF was determined by injection of radioactive microspheres at each of five target CPPs randomly allocated (50, 60, 70, 80, and 90 mm Hg). The brain oxygen content difference was defined as arterial minus superior sagittal sinus (SSS) oxygen content. No difference in CPP, hemoglobin, arterial carbon dioxide tension, or pH was seen between groups at any time period. In both groups, total CBF (tCBF) increased significantly with increasing CPP (p = 0.012 and 0.017 for normothermic and hypothermic CPB, respectively; CPP as covariate). The between-group difference in slopes (CPP x temperature effect) approached statistical significance (p = 0.059).(ABSTRACT TRUNCATED AT 250 WORDS)

Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass.

OBJECTIVE: To determine whether myocardial protection is improved by restoring physiologic variability to the cardioplegia pressure signal during cardiopulmonary bypass, we compared cardiac function in pigs in the first hour after either conventional cold-blood cardioplegia (group CC) or computer-controlled biologically variable pulsatile cardioplegia (group BVC). METHODS: Invasive monitors and sonomicrometry crystals were placed, and cardiopulmonary bypass was initiated. The aorta was crossclamped, and cold blood cardioplegic solution was infused intermittently through the aortic root with either conventional cardioplegia (n = 8) or biologically variable pulsatile cardioplegia (n = 8; mean pressure, 75 mm Hg for 85 minutes). The crossclamp was released, cardiac function was restored, and separation from cardiopulmonary bypass was completed. With stable temperature and arterial blood gases, hemodynamics and systolic and diastolic indices were compared at 15, 30, and 60 minutes after cardiopulmonary bypass. RESULTS: Diastolic stiffness doubled from 0.027 +/- 0.016 mm Hg/mm (mean +/- SD) at baseline to 0.055 +/- 0.036 mm Hg/mm (P =.003) at 1 hour after bypass in group CC, associated with increased left ventricular end-diastolic pressure from 9 +/- 2 to 11 +/- 2 mm Hg (P =.001), mean pulmonary artery pressure from 14 +/- 2 to 20 +/- 3 mm Hg (P =.003), and serum lactate levels from 2.0 +/- 0.5 to 5.6 +/- 2.3 mmol/L (P =.008). Systolic function was not affected. In group BVC diastolic stiffness, left ventricular end-diastolic pressure, and pulmonary artery pressure values were not different from control values at any time after bypass, and serum lactate levels were significantly less than with conventional cold blood cardioplegia. Peak pressure variability with biologically variable pulsatile cardioplegia fit a power-law equation (exponent = -3.0; R(2) = 0.97), indicating fractal behavior. CONCLUSION: Diastolic cardiac function is better preserved after cardiopulmonary bypass with biologically variable pulsatile cardioplegia and fractal perfusion. This may be attributed to enhanced microcirculatory perfusion with improved myocardial protection. A model supporting these results is presented.

Computer-controlled cardiopulmonary bypass increases jugular venous oxygen saturation during rewarming.

BACKGROUND: Conventional roller pump apulsatile cardiopulmonary bypass (CPB) was compared with computer-controlled pulsatile bypass, which was designed to recreate biological variability (return of beat-to-beat variability in rate and pressure with superimposed respiratory rhythms). The degree of jugular venous oxygen saturation (SjvO2) less than 50% during rewarming from hypothermic CPB was compared for the two bypass techniques. An SjvO2 less than 50% during rewarming from hypothermic CPB is correlated with cognitive dysfunction in humans. METHODS: Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid-base management and arterial filtration. After baseline measurements and normothermic CPB, the animals were randomized to apulsatile CPB (n = 12) or computer-controlled pulsatile CPB (roller pump speed adjusted by an average of 2.9 voltage output modulations/s; n = 12). The animals were then cooled to a nasopharyngeal temperature of 28 degrees C. During rewarming to stable normothermic temperatures, SjvO2 was measured at 5-minute intervals. The mean and cumulative areas for an SjvO2 less than 50% were determined for all animals. RESULTS: No between-group differences in temperature were noted during hypothermic CPB or during rewarming. The rate of rewarming was not different between groups. Mean arterial pressure, partial pressure of oxygen in arterial blood, and partial pressure of carbon dioxide in arterial blood also did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. Mean pulse pressure was 10.0 +/- 4.8 mm Hg in the apulsatile CPB group and 20.7 +/- 5.2 mm Hg in the pulsatile CPB group (p = 0.0002; unpaired t test). Markedly greater mean and cumulative areas under the curve for SjvO2 less than 50% were seen with apulsatile CPB (164 +/- 209 versus 1.9 +/- 3.6% x min, p = 0.021; and 1,796 +/- 2,263 versus 23 +/- 45% x min, p = 0.020, respectively). CONCLUSIONS: Computer-controlled pulsatile CPB was associated with significantly greater SjvO2 during rewarming from hypothermic CPB. Both the mean and cumulative areas under the curve for SjvO2 less than 50% exceeded a ratio of 75:1 for apulsatile versus computer-controlled pulsatile CPB. These experiments suggest that cerebral oxygenation was better preserved during rewarming from moderate hypothermia with computer-controlled pulsatile CPB, which returned biologic variability to the flow pattern.

Biologically variable pulsation improves jugular venous oxygen saturation during rewarming.

BACKGROUND: Conventional pulsatile (CP) roller pump cardiopulmonary bypass (CPB) was compared to computer controlled biologically variable pulsatile (BVP) bypass designed to return beat-to-beat variability in rate and pressure with superimposed respiratory rhythms. Jugular venous O2 saturation (SjvO2) below 50% during rewarming from hypothermia was compared for the two bypass techniques. A SjvO2 less than 50% during rewarming is correlated with cognitive dysfunction in humans. METHODS: Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid base management and arterial filtration. After apulsatile normothermic CPB was initiated, animals were randomized to CP (n = 8) or BVP (roller pump speed adjusted by an average of 2.9 voltage output modulations/second; n = 8), then cooled to a nasopharyngeal temperature of 28 degrees C. During rewarming to stable normothermia, SjvO2 was measured at 5 minute intervals. The mean and cumulative area for SjvO2 less than 50% was determined. RESULTS: No between group difference in temperature existed during hypothermic CPB or during rewarming. Mean arterial pressure, arterial partial pressure O2, and arterial partial pressure CO2 did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. The range of systolic pressure was greater with BVP (41 +/- 18 mm Hg) than with CP (12 +/- 4 mm Hg). A greater mean and cumulative area under the curve for SjvO2 less than 50% was seen with CP (82 +/- 96 versus 3.6% +/- 7.3% x min, p = 0.004; and 983 +/- 1158 versus 42% +/- 87% x min; p = 0.004, Wilcoxon 2-sample test). CONCLUSIONS: Computer-controlled BVP resulted in significantly greater SjvO2 during rewarming from hypothermic CPB. Both mean and cumulative area under the curve for SjvO2 less than 50% exceeded a ratio of 20 to 1 for CP versus BVP. Cerebral oxygenation is better preserved during rewarming from moderate hypothermia with bypass that returns biological variability to the flow pattern.

Cerebral hypoxia during cardiopulmonary bypass: a magnetic resonance imaging study.

BACKGROUND: Neurocognitive deficits after open heart operations have been correlated to jugular venous oxygen desaturation on rewarming from hypothermic cardiopulmonary bypass (CPB). Using a porcine model, we looked for evidence of cerebral hypoxia by magnetic resonance imaging during CPB. Brain oxygenation was assessed by T2*-weighted imaging, based on the blood oxygenation level-dependent effect (decreased T2*-weighted signal intensity with increased tissue concentrations of deoxyhemoglobin). METHODS: Pigs were placed on normothermic CPB, then cooled to 28 degrees C for 2 hours of hypothermic CPB, then rewarmed to baseline temperature. T2*-weighted, imaging was undertaken before CPB, during normothermic CPB, at 30-minute intervals during hypothermic CPB, after rewarming, and then 15 minutes after death. Imaging was with a Bruker 7.0 Tesla, 40-cm bore magnetic resonance scanner with actively shielded gradient coils. Regions of interest from the magnetic resonance images were analyzed to identify parenchymal hypoxia and correlated with jugular venous oxygen saturation. Post-hoc fuzzy clustering analysis was used to examine spatially distributed regions of interest whose pixels followed similar time courses. Attention was paid to pixels showing decreased T2* signal intensity over time. RESULTS: T2* signal intensity decreased with rewarming and in five of seven experiments correlated with the decrease in jugular venous oxygen saturation. T2* imaging with fuzzy clustering analysis revealed two diffusely distributed pixel groups during CPB. One large group of pixels (50% +/- 13% of total pixel count) showed increased T2* signal intensity (well-oxygenated tissue) during hypothermia, with decreased intensity on rewarming. Changes in a second group of pixels (34% +/- 8% of total pixel count) showed a progressive decrease in T2* signal intensity, independent of temperature, suggestive of increased brain hypoxia during CPB. CONCLUSIONS: Decreased T2* signal intensity in a diffuse spatial distribution indicates that a large proportion of cerebral parenchyma is hypoxic (evidenced by an increased proportion of tissue deoxyhemoglobin) during CPB in this porcine model. Neuronal damage secondary to parenchymal hypoxia may explain the postoperative neuropsychological dysfunction after cardiac operations.

Regional cerebral blood flow and response to carbon dioxide during controlled hypotension with isoflurane anesthesia in the rat.

Regional (frontal, parietal, occipital, cortical, and basal ganglia) cerebral blood flow (rCBF) was examined at 1.5 and 3.5 MAC inspired isoflurane/O2 anesthesia in the rat using the radioactive microsphere technique to determine the effects of controlled hypotension with deep isoflurane anesthesia on rCBF and the response of rCBF to changes in PaCO2 when mean blood pressure (BP) was decreased to levels below the lower limit of the autoregulatory threshold. Four groups of six rats were studied with rCBF 1 determined at 1.5 MAC (mean BP 80-90 mm Hg) followed by two rCBF determinations at 3.5 MAC (mean BP 46-48 mm Hg). For CBF 1 the regional CO2 response was a 3.1-3.9% increase in rCBF/mm Hg increase in CO2. Regional cerebral blood flow (ml/g/min) ranged from 0.64 +/- 0.05-0.83 +/- 0.15 at PaCO2 of 19 mm Hg to 1.34 +/- 0.11-1.80 +/- 0.33 at PaCO2 of 41 mm Hg to 2.61 +/- 0.26-3.72 +/- 0.37 at PaCO2 of 59 mm Hg (mean +/- SEM). With controlled hypotension (CBF 2) rCBF was unchanged during normocarbia, increased 100% during hypocarbia, P less than 0.01 vs CBF 1 and decreased 30% during hypercarbia, P less than 0.01 vs CBF 1. For rCBF 3 measurements, the BP and inspired concentration of isoflurane were kept constant, while PaCO2 was increased in two and decreased in two of the four groups. Within-group comparisons between rCBF 2 and rCBF 3 results demonstrated loss of CO2 responsiveness of the rat cerebrovasculature in every region during controlled hypotension to below the autoregulatory threshold at 3.5 MAC isoflurane/O2 anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

The cerebral pressure-flow relationship during 1.0 MAC isoflurane anesthesia in the rabbit: the effect of different vasopressors.

The influence of different vasopressors on the cerebral pressure-flow relationship during 1.0 MAC isoflurane anesthesia has been studied. Mean arterial pressure (MAP) was increased by one of three vasopressors [angiotensin II (AT), norepinephrine (NE), or phenylephrine (PE)] in three groups of New Zealand white rabbits (n = 11, 10, and 9, respectively). Regional cerebral blood flow (CBF) was measured at five intervals by the injection of radioactive microspheres at a stable 2.05% (1.0 MAC) end-tidal isoflurane concentration (baseline) and following elevation of mean arterial pressure (MAP) by 20%, 40%, 60%, and 80% above baseline MAP with either AT, NE, or PE. Baseline MAP was the same in all groups. No differences in MAP were seen between groups when MAP was elevated from 20% to 80% above baseline. Normocapnia (PaCO2 35.8-38.2 mmHg) was maintained throughout. Total cerebral blood flow (tCBF), hemispheric CBF (hCBF), and posterior fossa (cerebellum and brain stem) CBF (pCBF) were determined. Baseline tCBF, hCBF, and pCBF was similar in all groups. For each experiment a pressure-flow curve was generated by curvilinear regression analysis. Mean slopes and intercepts were derived for each group. For all regions examined, the slope of the pressure-flow curve was significantly less steep when MAP was elevated with AT versus NE or PE (P less than 0.05 Tukey's studentized range test). There was no difference in slope between the NE and PE groups for any region. These results indicate that either NE and PE result in indirect cerebral vasodilation or that AT has intrinsic cerebral vasoconstrictive effects during 1.0 MAC isoflurane anesthesia in the rabbit.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional cerebral blood flow following hemorrhage during isoflurane anesthesia in the rabbit: comparison of techniques to support blood pressure.

The authors investigated whether the increase in cerebral blood flow (CBF) when pressure passive following hemorrhage was dependent on the technique used to increase cerebral perfusion pressure (CPP). Twenty-one New Zealand white rabbits anesthetized with isoflurane in oxygen were studied with four regional blood flow determinations in each. Blood flow was determined by injection of radioactive microspheres during the following experimental conditions: Injection 1: 1 h after 1.0% inspired isoflurane; injection 2: 25 min after hypotension (MAP 50 mmHg) was induced by isoflurane; injection 3: 10-15 min after superimposed hemorrhagic hypotension to a MAP of 30 mmHg; injection 4: 25 min after restoring MAP to 50 mmHg by one of three techniques: decreasing inspired isoflurane concentration (group 1); restoration of blood volume (group 2); and phenylephrine infusion (group 3). Normocapnia was maintained throughout (35.8-38.4 mmHg). There was no group X time interaction (treatment effect) for total CBF (tCBF) (P = 0.309) or for any supratentorial region (frontal, parietal, occipital cortex P = 0.821, 0.413 and 0.342 respectively) for the three techniques used to increase CPP. A significant group X time interaction was seen for infratentorial structures (P = 0.002 for cerebellum and P = 0.035 for brain stem). When MAP was increased by decreasing the inspired isoflurane concentration significantly lower rCBF to infratentorial structures was seen compared with that following the other two techniques. A significant group X time interaction was seen for cardiac output following hemorrhage (P = 0.052) being significantly higher with blood volume expansion versus phenylephrine infusion. A group X time interaction was not seen for renal blood flow (P = 0.0306).

Epidural anesthesia and acutely increased intracranial pressure. Lumbar epidural space hydrodynamics in a porcine model.

BACKGROUND: The effects of epidural injection on intracranial pressure (ICP), lumbar epidural pressure, cerebral blood flow (CBF), and spinal cord blood flow (SCBF) were studied after acutely increased ICP in swine. METHODS: Twenty pigs, anesthetized with isoflurane and mechanically ventilated to maintain normocarbia, had two Tuohy needles placed in the lumbar epidural space. The ICP, lumbar epidural pressure, heart rate, mean arterial pressure, and central venous pressure were monitored. All animals had a Fogarty catheter placed in the parietal epidural space. Six pigs were randomized to a normal ICP group (group N) and eight pigs to an increased ICP group by inflation of the Fogarty catheter balloon (group R). Each pig had 0.33 ml.kg-1 of 2.0% carbonated lidocaine injected over 20 s via an epidural needle placed at L3. The ICP and lumbar epidural pressure were then monitored continuously for 30 min. Pressure-time data were fit to traditional compartmental models. Epidural elastance and resistance were calculated using a derivation of the Windkessel theory. An additional six pigs had ICP elevated as in group R and CBF and SCBF measured using radioactive microspheres at five time periods: baseline, 0-60 s, 100-160 s, 200-260 s, and at 30 min after epidural injection. RESULTS: The animals did not differ with respect to heart rate, central venous pressure, or mean arterial pressure at baseline. The ICP was 10 +/- 2 mmHg in group N, and 24 +/- 2 mmHg after balloon inflation in group R. After epidural injection, peak ICP was significantly greater in group R (76 +/- 22 vs. 54 +/- 17 mmHg) but not different by 30 min (17 +/- 5 vs. 11 +/- 1 mmHg). Epidural elastance in group N was 8.3 +/- 3.1 mmHg.ml-1 and 12.8 +/- 3.0 mmHg.ml-1 in group R (P = 0.045). Epidural resistance was 1,330 +/- 590 mmHg.s.ml-1 in group N and 2,220 +/- 600 mmHg.s.ml-1 in group R (P = 0.038). The CBF and SCBF were less than 10% of baseline during the 0- to 60-s time period after epidural injection. Thereafter, CBF and SCBF did not differ from baseline values. CONCLUSIONS: In this porcine model, epidural injection increased ICP. With increased ICP at baseline, more pronounced increases in ICP followed epidural injection. With increased baseline ICP, both epidural elastance and resistance increased compared with controls. The CBF and SCBF were markedly reduced immediately after local anesthetic injection into the epidural space.

A comparison of the cerebral pressure-flow relationship for halothane and isoflurane at haemodynamically equivalent end-tidal concentrations in the rabbit.

The cerebral pressure-flow relationship for halothane and isoflurance was studied at end-tidal concentrations which resulted in similar baseline mean arterial pressure (MAP). Two groups of New Zealand white rabbits (n = 8; each group) were studied with five regional blood flow determinations in each animal. Blood flow was determined by injecting radioactive microspheres during the following conditions: injection 1: after stable 2.05 per cent end-tidal isoflurane (1.0 MAC) Group I; or after stable 0.74 +/- 0.04 per cent end-tidal halothane (0.53 MAC) Group H. Injections 2-5: after MAP was increased 20, 40, 60, and 80 per cent respectively above baseline MAP by phenylephrine infusion. Baseline MAP was the same for both groups (64.3 +/- 3.1 vs 67.2 +/- 2.0 mmHg; mean +/- SEM; Group I and H respectively). Baseline total CBF (tCBF; 0.68 +/- 0.03 vs 0.86 +/- 0.05) and hemispheric CBF (hCBF; 0.64 +/- 0.03 vs 0.96 +/- 0.06) were significantly greater in Group H; no significant difference between groups was seen for baseline posterior fossa CBF (pCBF; 0.79 +/- 0.06 vs 0.75 +/- 0.04). For each experiment a pressure-flow curve was generated by curvilinear regression analysis. Significantly greater phenylephrine concentrations were required for injections 2-5 in Group H. Mean slopes and intercepts were derived for each group. Within each group comparison of the pressure-flow curves for hCBF vs MAP and pCBF vs MAP showed autoregulation was less impaired in posterior fossa structures (cerebellum and brain stem) for both anaesthetic agents (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of hypocarbia on the resolution of transient increases in brain extracellular potassium.

The effect of acute hypocarbia on baseline extracellular K+ concentration [( K+]e) and its effect on the ability of the cerebral microenvironment to recover from transient increases in [K+]e has been assessed in rats. Spreading depression of cortical activity was used to present a reproducible K+ load to the extracellular space. Baseline [K+]e and the half-time for resolution of the [K+]e changes seen with spreading depression waves were measured for the hypocarbic and normocarbic states by means of double-barrelled K+ microelectrodes placed approximately 400 micron below the cortical surface. Three spreading depression waves were initiated in each animal for the two CO2 states. In group 1 (n = 10), the rats were initially normocarbic (PaCO2 41.6 +/- 3.0 mmHg; mean +/- SD), then hypocarbic (PaCO2 19.0 +/- 2.5 mmHg) for the second series of measurements. The baseline [K+]e was significantly higher in the normocarbic state 3.4 +/- 0.4 versus 3.0 +/- 0.4 mM l-1, P less than 0.01 (paired t test). During normocarbia, the K+ load (delta[K+]e) presented to the extracellular space following spreading depression was 49.4 +/- 7.5 mM l-1, n = 10 (peak [K+]e - baseline [K+]e). The half-time for resolution of the presented [K+]e load was 24.3 +/- 6.1 s. Following hypocarbia of 1.4 +/- 0.6 h, there was no change in delta[K+]e (49.0 +/- 6.0 mM l-1) but resolution t1/2 had increased to 35.8 +/- 11.2 s, P less than 0.01 paired t test.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenylephrine increases regional cerebral blood flow following hemorrhage during isoflurane-oxygen anesthesia.

Using the radioactive microsphere technique regional cerebral blood flow (rCBF) and total CBF (tCBF) were examined in rats at three time periods: baseline (CBF1) during 1.5 MAC inspired isoflurane-oxygen anesthesia, CBF2; during 1.5 MAC inspired isoflurane anesthesia combined with hypotension induced by hemorrhage and CBF3; during isoflurane and hemorrhage plus phenylephrine infused to restore mean arterial pressure (MAP) to baseline. For CBF1 MAP was 89 +/- 3 mmHg (mean +/- SEM, n = 9) with PaCO2 44 +/- 1 mmHg. For CBF2 following graded hemorrhage MAP was 48 +/- 2 mmHg and PaCO2 43 +/- 1 mmHg. For CBF3 MAP was 93 +/- 2 and PaCO2 45 +/- 1 mmHg, following infusion of phenylephrine (PE) at 13.9 +/- 4.0 micrograms.kg-1.min-1. Total CBF1 was 1.84 +/- 0.18 ml.g-1.min-1, tCBF2 1.32 +/- 0.09 ml.g-1.min-1 (P less than 0.05 vs. tCBF1) and tCBF3 2.60 +/- 0.18 (P less than 0.05 vs. tCBF1 and 2). For tCBF3 hemoglobin concentration had decreased 23% from 14.2 +/- 0.2 g.100 ml-1 to 11.0 +/- 0.5 g.100 ml-1 (P less than 0.05). Regional CBF decreased significantly in seven of 12 regions examined from CBF1 to CBF2 and was significantly higher in all regions for CBF3. For CBF1-3 infratentorial blood flows (cerebellar and brain stem) were significantly higher than flows to the supratentorial structures (cerebral cortical and basal ganglia). During isoflurane anesthesia, phenylephrine infused to support MAP following hemorrhagic hypotension effectively maintains rCBF and tCBF. There is no indication that phenylephrine infused to increase MAP following hemorrhage results in cerebral vasoconstriction in rats anesthetized with isoflurane.

Isoflurane and halothane impair both systolic and diastolic function in the newborn pig.

PURPOSE: Volatile anaesthetics have considerable effects on diastolic relaxation in the adult myocardium. We hypothesized that isoflurane (1) and halothane (H) may have even greater effects on diastolic function in the newborn, as the newborn heart has increased passive stiffness and altered calcium handling relative to the adult. Using a newborn pig model, we compared I and H at three clinically relevant concentrations with respect to both systolic and diastolic function. METHODS: Sixteen newborn pigs were randomized for study at control (background fentanyl 100 micrograms.kg-1.hr-1 and 0.5, 1.0 and 1.5 MAC of I (n = 8) or H (n = 8). Temperature, arterial blood gases, and LVEDP were controlled. Left ventricular pressure (LVP) was monitored continuously and LV anterior-posterior dimension was determined by using sonomicrometry crystals. Systolic function was assessed by peak positive dP/dT (dP/dTmax) and the slope of the end-systolic pressure-dimension (ESP-D) relationship. Diastolic relaxation was given by peak negative dP/dT (-dP/dTmax) and the time constant for ventricular relaxation (tau). Left ventricular stiffness was calculated from the slope of the end-diastolic pressure-dimension (EDP-D) relationship. RESULTS: At equal MAC concentrations, I and H were identical in effect for every variable studied. Systolic function was depressed at all anaesthetic concentrations. Control dP/dTmax (I:1815 +/- 561 (SD) mmHg.sec-1, H:1841 +/- 509) decreased to 832 +/- 341 with 1.5 MAC I and 691 +/- 127 with 1.5 MAC H (P < 0.05 vs control). ESP-D slope decreased from 62 +/- 31 mmHg.mm-1 at control to 15 +/- 11 with 1.5 MAC I and from 79 +/- 16 to 37 +/- 15 with 1.5 MAC H (P < 0.05 vs control). Diastolic function was affected only at higher MAC anaesthesia. Control tau increased from 18.0 +/- 6 msec to 29.1 +/- 7.5 with 1.5 MAC I and from 20.8 +/- 5.9 to 30.0 +/- 11.3 with 1.5 MAC H (P < 0.05). EDP-D slope was increased at both 1 and 1.5 MAC anaesthesia. EDP-D slope increased from 0.16 +/- 0.24 mmHg.mm-1 at control to 0.58 +/- 0.46 with I MAC I and from 0.16 +/- 11 to 0.50 +/- 0.35 with 1 MAC H. The -dP/dTmax decreased at every MAC level of anaesthesia. CONCLUSION: These combined systolic and diastolic effects help to explain the increased sensitivity of the newborn myocardium to volatile anaesthetics.

Left ventricular systolic and diastolic function is unaltered during propofol infusion in newborn swine.

UNLABELLED: Propofol is a cardiac depressant with minimal diastolic effects in the adult myocardium. Cardiac effects of propofol in the newborn are unknown. We examined hemodynamic variables and systolic and diastolic left ventricular function in 12 newborn pigs exposed to propofol at three different infusion rates (7.5, 15, and 30 mg x kg(-1) x h(-1)) in random order with a background of fentanyl (100 microg x kg(-1) x h(-1)). Left ventricular (LV) pressure (Plv) and LV anterior-posterior dimension, determined by sonomicrometry, were continuously monitored. Mean arterial pressure (MAP), heart rate (HR), and LV end-diastolic pressure (LVEDP) were determined at every infusion. Systolic function was assessed by the maximal pressure-time derivative (dP/dt(max)), the slope of the end-systolic pressure-dimension relationship (ESP-D), and by the preload recruitable stroke work index (PRSWI). Diastolic function was assessed by relaxation indices, the minimal pressure-time derivative (dP/dt(min)) and the relaxation time constant (tau), and by a stiffness index, the slope of the EDP-D relationship. MAP decreased approximately 25%, from 75.9 +/- 15.6 to 56.3 +/- 14.8 mm Hg (P < 0.05) with propofol, with no dose effect. HR and LVEDP were unchanged from control. Both dP/dt(max) and dP/dt(min) decreased with propofol infusion, but load-independent indices of systolic function (ESP-D slope and PRSWI) and tau were unchanged. Diastolic stiffness was not affected with either 7.5- or 30-mg x kg(-1) x h(-1) infusions but decreased significantly from 0.27 +/- 0.18 mm Hg/mm at control to 0.18 +/- 0.18 mm Hg/mm (P < 0.05) with propofol 15 mg x kg(-1) x h(-1). With this profile, propofol may be useful for the newborn requiring anesthesia. IMPLICATIONS: Most anesthetics depress heart function in the newborn. We examined both heart contraction and relaxation during anesthesia with propofol in newborn pigs. Propofol had minimal influence on heart function in this model at the doses studied. This may therefore be a useful anesthetic to test in the newborn human.