Quality of diabetes care, diabetes knowledge and risk of severe hypoglycaemia one and four years after participation in a 5-day structured treatment and teaching programme for intensified insulin therapy

PURPOSE: Cardiopulmonary bypass (CPB) is characterized by translocation of intestinal endotoxin and subsequent endogenous production of the pro-inflammatory cytokine interleukin-6 (IL-6). Plasma lipid fractions, especially high density lipoproteins, bind and neutralize endotoxin and, therefore, inhibit endotoxin-induced macrophage cytokine production, including IL-6. Increased IL-6 plasma levels have been implicated in adverse consequences associated with CPB. Previous studies demonstrated large interpatient variability in IL-6 plasma levels after CPB. The purpose of this study was to evaluate the relationship between plasma lipid concentrations and the concentrations of IL-6 following CPB in humans. METHODS: In a prospective study, a group of 15 patients selected to exclude variables known to influence post-CPB plasma levels of IL-6 (preoperative left ventricular ejection fraction > 45%, similar durations of aortic cross clamping and total CPB time, similar temperature control during CPB, and avoidance of platelet transfusion and shed mediastinal blood re-infusion), IL-6 was measured at baseline, one and 24 hr post-CPB. RESULTS: Interleukin-6 plasma concentrations (mean +/- SD) increased at one (142 +/- 89 pg.ml-1, P < 0.05) and 24 (129 +/- 82 pg.ml-1, P < 0.05) hr post-CPB compared with baseline (1.5 +/- 1 pg.ml-1) concentrations. An inverse correlation was found between IL-6 plasma concentrations at one hour post-CPB and plasma cholesterol concentrations (r = -0.592, P = 0.02), high density lipoprotein (r = -0.595, P = 0.02), and low density lipoprotein (r = -0.656, P = 0.01). CONCLUSIONS: These results suggest that plasma lipids attenuate the production of IL-6 during CPB and may partly explain the variability of interpatient levels of IL-6 reported post-CPB by others.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

Thyroid function in a population with an extra iodine intake]

Polymorphonuclear leukocyte (PMN) superoxide (.O2-) production has been implicated in the pathogenesis of cardiopulmonary bypass (CPB)-related end organ injury. PMN "priming" has been described as an event which enhances the release of .O2- following a second, activating insult. We hypothesized that PMN priming occurs during CBP and is temporally related to the plasma level of complement (C3a), interleukin (IL)-6, and IL-8. PMNs were isolated from 10 CPB patients pre-bypass (preCPB), 5 min after protamine administration (PROT), and at 6 and 24 h post-CPB. PMN .O2- production was measured by a cytochrome c reduction assay in the presence or absence of either phorbol 12-myristate-13-acetate (PMA, 0.4 microgram/ml) or N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM) and also after priming with 2000 nM platelet-activating factor (PAF) followed by activation with either PMA or FMLP. Plasma levels of C3a, IL-6, and IL-8 were determined by enzyme-linked immunosorbent assay. PMA-activated PMN .O2- production was significantly elevated at 6 h post-CPB compared to pre-CPB levels (11.04 +/- 0.9 vs 7.62 +/- 0.57, P = 0.009), indicating that CPB is associated with in vivo PMN priming. When PMNs were primed in vitro with PAF and then activated with PMA or FMLP, .O2- release at 6 h post-CPB was also significantly greater than pre-CPB levels (16.04 +/- 0.74 vs 12.2 +/- 0.92, P = 0.038; and 17.33 +/- 1.38 vs 13.33 +/- 1.35, P < 0.05), indicating that CPB acts synergistically with PAF to prime PMNs. Levels of C3a rose significantly over pre-CPB levels at PROT (P = 0.001), and IL-6 and IL-8 rose over pre-CPB levels at 6 h post-CPB (P = 0.01 and P = 0.006, respectively). These findings demonstrate that CPB not only directly primes PMNs, but also potentiates priming of PMNs by PAF. This "primed" PMN state, which coincided with the increased plasma levels of inflammatory mediators, may suggest a mechanism of predisposition to organ dysfunction following CPB.     

Hypothermia eliminates isoflurane requirements at 20 degrees C

BACKGROUND: Hypothermia decreases anesthetic requirements, but the temperature that completely eliminates anesthetic needs has not been previously determined. METHODS: Eight female goats were anesthetized with isoflurane and catheters were placed in the femoral artery and cranial vena cava, after which the right carotid artery and external jugular vein were dissected free. Peripheral temperature was monitored in the rectum and core temperature in the vena cava. A thermistor was placed in the epidural space via a small burr hole to monitor brain temperature. Minimum alveolar concentration (MAC) for isoflurane was determined by eliciting gross, purposeful movement with a tail clamp. Cardiopulmonary bypass (CPB) was established using bubble oxygenators with venous blood drained from a jugular vein and arterial blood infused with a roller pump into the carotid artery. The animals were cooled to approximately 29 degrees C, and MAC redetermined, after which further cooling to 20 degrees C was accomplished. Isoflurane was eliminated, core and brain temperature adjusted in 2-3 degrees C increments, and the tail clamp applied until two temperatures were found that just permitted and just prevented movement. The animals were rewarmed, isoflurane added, and post-CPB MAC determined. RESULTS: At 38.5 degrees C, pre-CPB MAC was 1.3 +/- 0.1% (mean +/- SEM). At 29.0 degrees C, MAC was 0.7 +/- 0.1%, and the anesthetizing temperature was 20.1 +/- 0.6 degrees C. At 37.3 degrees C, post-CPB MAC was 1.0 +/- 0.1% (P < 0.05 vs. pre-CPB). CONCLUSIONS: These results confirm the rectilinear decrease in MAC seen in previous studies and establishes the anesthetizing temperature at 20 degrees C.     

Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.     

Ethane: a marker of lipid peroxidation during cardiopulmonary bypass in humans

The goals of this study were to (1) determine the utility of quantification of ethane as a marker of ischemia-reperfusion during human cardiopulmonary bypass (CPB); and (2) determine, using an animal model for this surgical procedure, whether the mode of surgical approach produced increases the quantity of exhaled ethane. Human CPB was initiated following standard anesthetic and monitoring regimens. Samples of gas were collected at baseline and at multiple defined time points throughout the studies. Ethane was determined using cryogenic concentration and gas chromatography. Sternotomy increased exhaled ethane compared to baseline (p < .007; 5.8 +/- 1.7 vs. 3.0 +/- 0.7 nmol/m2 x min); ethane returned to baseline levels prior to the initiation of CPB. Aortic unclamping produced ethane elevation (p < .05; 2.3 +/- 0.8 vs. 1.5 +/- 0.4 nmol/m2 x min) with the levels being related to a lower cardiac index and a higher systemic vascular resistance post aortic unclamping. Termination of CPB significantly increased ethane levels compared to baseline (p < .002; 4.8 +/- 1.7 vs. 3.0 +/- 0.7 nmol/m2 x min). Independent variables that correlated with increased ethane measurements included a higher arterial blood pH on bypass and the change in hemoglobin pre- and post-CPB. Electrocautery, but not scalpel, incision of the porcine abdominal wall increased ethane levels significantly (p < .02). These results indicate that exhaled ethane may be a valuable marker of lipid peroxidation during and following CPB.     

Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs

BACKGROUND: The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28 degrees C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia. METHODS: Sagittal sinus and cortical microdialysis catheters were inserted into anesthetized pigs. Animals were placed on CPB and randomly assigned to 37 degrees C (n = 10), 34 degrees C (n = 10), 31 degrees C (n = 11), or 28 degrees C (n = 10) management. Next 20 min of global cerebral ischemia was produced by temporarily ligating the innominate and left subclavian arteries, followed by reperfusion, rewarming, and termination of CPB. Cerebral oxygen metabolism (CMRO2) was calculated by cerebral blood flow (radioactive microspheres) and arteriovenous oxygen content gradient. Cortical excitatory amino acids (EAA) by microdialysis were measured using high-performance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebrospinal fluid was sampled to test for S-100 protein and the cerebral cortex was biopsied. RESULTS: Cerebral oxygen metabolism increased after rewarming from 28 degrees C, 31 degrees C, and 34 degrees C CPB but not in the 37 degrees animals; CMRO2 remained lower with 37 degrees C (1.8 +/- 0.2 ml x min[-1] x 100 g[-1]) than with 28 degrees C (3.1 +/- 0.1 ml x min[-1] x 100 g[-1]; P < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37 degrees C animals. With 28 degrees C and 31 degrees C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37 degrees C and remained significantly greater during reperfusion in the 34 degrees C and 37 degrees C groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degrees C animals. S-100 protein in cerebrospinal fluid was greater in the 37 degrees C (6 +/- 0.9 microg/l) and 34 degrees C (3.5 +/- 0.5 microg/l) groups than the 31 degrees C (1.9 +/- 0.1 microg/l) and 28 degrees C (1.7 +/- 0.2 microg/l) animals. CONCLUSIONS: Hypothermia to 28 degrees C and 31 degrees C provides significant cerebral recovery from 20 min of global ischemia during CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 28 degrees C compared with 31 degrees C. In contrast, ischemia during 34 degrees C and particularly 37 degrees C CPB showed greater EAA release and evidence of neurologic morbidity. Cooling to 31 degrees C was necessary to improve acute recovery during global cerebral ischemia on CPB.     

Early evaluation of results from systemic thrombolysis in acute myocardial infarct: the value of troponin I

STUDY OBJECTIVES: This paper compares the performance of an experimental nasal positive airway pressure device that automatically adjusts the level of applied pressure (APAP) with the performance of a conventional continuous positive airway pressure (CPAP) in a sleep laboratory study. DESIGN: In a randomized sequence, conventional CPAP therapy was applied for 1 night (CPAP night) and APAP therapy the following night (APAP night). SETTING: The study was conducted in an accredited sleep disorders center. PATIENTS OR PARTICIPANTS: Twenty-six men and 5 women between the ages of 35 to 73 (51 +/- 9.6) years with body mass index 35.82 +/- 8.35 (kg/m2) who were diagnosed (using standard nocturnal polysomnography [NPSG] methods) as having OSA syndrome were studied. The subjects were treated with conventional CPAP for approximately 8 (7.79 +/- 3.16) weeks at home prior to their participation in this study. MEASUREMENTS AND RESULTS: All standard polysomnography data and nasal mask pressures were recorded using a computer-based data acquisition system. Sleep and respiratory data were scored by a registered polysomnographer. The mean apnea-hypopnea index (AHI) for subjects for the NPSG night was 55.2 +/- 33.7. It dropped to 4.2 +/- 3.8 for the CPAP night and to 5.4 +/- 5.4 for the APAP night. There was no significant (p = 0.05) difference between mean AHI indices, sleep stages, sleep stage shifts, and snore arousals for CPAP night and APAP night. However, all the measures showed significant (p = 0.05) improvement over NPSG night. The mean of APAP applied pressure (8.4 +/- 3.3 cm H2O) was significantly (p = 0.05) lower than the prescribed pressure (11.5 +/- 3.1 cm H2O), but there was no significant (p = 0.05) difference between the maximum APAP applied pressure (12.8 +/- 4.3 cm H2O) and the prescribed pressure (11.5 +/- 3.1 cm H2O). All mean comparison tests were carried out using two-tailed statistics. CONCLUSIONS: APAP appears to be as effective as CPAP in treating OSA patients. APAP delivers the same level of therapy as CPAP, but it reduces the average airway pressure while providing needed peak pressures.     

Emboli from an extraluminal blood flow hollow fiber oxygenator with and without an arterial filter during cardiopulmonary bypass in a pig model

The effect of an arterial filter on visceral emboli was quantified with autologous indium-111 labeled platelets (INPLT) during cardiopulmonary bypass (CPB) in Yorkshire pigs. Biodistribution of INPLT was determined in 12 control pigs (30-35 kg, unoperated control [n = 6] and sham operated control [n = 6]). CPB was carried out with (n = 6) and without (n = 6) an arterial filter in 12 pigs at a flow rate of 2.5-3.5 L/min. Platelets labeled with In-111 tropolone (650-780 microCi) were injected intravenously 24 hr before CPB. All pigs were systemically heparinized (activated coagulation time > 400 sec); CPB was instituted with a roller pump, an extraluminal blood flow oxygenator (Bentley Univox, 1.8 m2), and an arterial filter (0.25 m2) and continued for 3 hr. Platelet kinetics, pooling, and counts were monitored by a Geiger probe and a Coulter counter. The thrombi in the oxygenator and arterial filter and emboli in viscera and brain were imaged with a gamma camera and measured with an ion chamber and gamma counter. Percentage of INPLT (mean +/- SD) in organs, tissues, and components of the circuit in four groups of pigs was calculated. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140: control) of porcine platelets was carried out with blood samples taken before, during, and after CPB for estimation of circulating platelet aggregates and platelet microparticles. Pulmonary, renal, cardiac, and cerebral emboli in pigs undergoing CPB with and without a filter were similar (p < 0.1). The amount of filter adherent thrombi was small (0.04 +/- 0.01%); oxygenator adherent thrombus in both groups was similar (p < 0.1). Emboli were found in the cerebral medulla, hippocampus, and posterior cerebral cortex in both groups. During CPB, the arterial filter functioned minimally as a trap for platelet thrombi detached from the oxygenator and circulating emboli. Flow cytometry of blood demonstrated the shift of equilibria from single platelets to platelet aggregates and microparticles during CPB and their gradual reversal to single platelets after CPB; the loosely adherent emboli disaggregated and further shifted these equilibria to single platelets and smaller aggregates, probably through the action of endogenous nitric oxide and prostacyclin. The emboli were trapped in organs and tissues and microparticles were sequestered by the reticuloendothelial system.     

Auto-CPAP treatment in obstructive sleep apnea syndrome: a prospective randomized study during initiation of treatment

OBJECTIVE: The efficacy and acceptance of self-regulated continuous positive airway pressure (auto-CPAP) ventilation was compared with conventional CPAP administration in the treatment of patients with obstructive sleep apnoea. PATIENTS AND METHODS: Using a cross-over design, under polysomnographic monitoring in a sleep laboratory, 25 patients with obstructive sleep apnoea underwent conventional CPAP or auto-CPAP treatment. Using a questionnaire, patients gave their assessment of its acceptability and efficacy after each treatment session. RESULTS: The mean pressure during treatment was the same in the two groups (7.2 +/- 1.9 versus 7.1 +/- 1.9 mbar; no significant difference). Maximal pressure during auto-CPAP averaged 3.7 +/- 2.1 mbar higher than during conventional CPAP ventilation. The mean apnoea-hypopnoea index (AHI) during auto-CPAP, 4.4 +/- 4.3 mbar, during auto-CPAP was significantly higher than during conventional CPAP treatment (2.8 +/- 2.8 mbar; P = 0.044). In eight patients on auto-CPAP an AHI of 5 or less could not be reached, while an AHI of 5 or less was obtained in all but three patients under conventional CPAP. In a subgroup of 17 patients, in whom a reduction of AHI to at most 5 was achieved with both conventional and auto-CPAP, analysis of sleep pattern and of arousals was similar with the two forms of ventilation. Several patients reported that with auto-CPAP falling in sleep was more difficult and they slept less well. None of the patients preferred auto-CPAP. CONCLUSION: By means of the auto-CPAP neither a pressure reduction nor an improvement in compliance could be achieved. Therapeutic effectiveness was significantly less as with conventional CPAP therapy.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin removal device--an alternative to protamine

OBJECTIVES: To evaluate the therapeutic efficacy and applicability of a heparin removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity adsorption as an alternative to protamine in reversing systemic heparinization following cardiopulmonary bypass (CPB). DESIGN: A prospective study. SETTING: University research laboratory. SUBJECTS: Adult female swine (n=7). INTERVENTIONS: Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected to 60 mins of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual-lumen cannula which was connected to an HRD via extracorporeal circulation. Blood flow was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the plasma separation chamber of the HRD (where heparin was bound to PLL), and reinfused into the right atrium. The HRD run time was determined by a previously established mathematical model of first-order exponential depletion. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, kaolin and celite activated clotting time (ACT), activated partial thromboplastin time (APTT), heparin concentration, and plasma free hemoglobin were obtained before, during, and after the use of the HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove 90% total body heparin. Use of the HRD was not associated with any adverse hemodynamic reactions or increases in plasma free hemoglobin. The heparin concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000 secs and APTT >150 secs in all animals. During heparin removal, total body heparin content followed first-order exponential depletion kinetics. At the end of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables). CONCLUSIONS: The HRD is capable of reversal of anticoagulation following CPB without significant blood cell damage or changes in hemodynamics. The HRD, therefore, can serve as an alternative to achieve heparin clearance in clinical situations where use of protamine may be contraindicated.     

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.     

Characteristics of vascular wall cells subjected to dynamic cyclic strain and fluid shear conditions in vitro

Surfactant bolus instillation may be associated with a drop in blood pressure. Platelet-activating factor (PAF) has been found in surfactant preparations. The aim of this study was to evaluate rapid tracheal infusion of surfactant during 5 min as an alternative to bolus instillation and to examine whether a PAF receptor antagonist is able to prevent the decrease in blood pressure. METHODS: Surfactant deficiency was induced in 16 adult rabbits by lung lavages with saline. Six animals received a bolus of a porcine surfactant preparation (Curosurf (CS); 200 mg/kg), labeled with red microspheres to assess pulmonary distribution. In another 5 rabbits, the same amount of labelled CS was instilled by tracheal infusion within 5 min. A third group of 5 animals received 3 mg/kg body weight of the PAF antagonist WEB 2170 before CS bolus instillation. RESULTS: After CS bolus administration, mean PaO2 increased by 44.7 +/- 8.3 kPa (mean +/- SD) within 2 min and remained at this level. Mean arterial blood pressure dropped transiently by 2.3 +/- 2 kPa within 5 min. Pulmonary distribution of surfactant was even. After infusion, mean PaO2 rose by 22.4 +/- 16.3 kPa within 15 min. Blood pressure dropped by 1.8 +/- 1.1 kPa within 15 min. The distribution was extremely uneven. Blood pressure decreases also occurred after pretreatment with PAF receptor antagonist. CONCLUSION: Rapid tracheal infusion of surfactant results in poorer oxygenation, an inhomogeneous distribution and a similar decrease in blood pressure compared to the bolus instillation method. Blood pressure changes could not be prevented by a PAF receptor-specific antagonist.     

A new method for quantitation of platelet microthrombi and microemboli from cardiopulmonary bypass in organs using 111In labeled platelets

During cardiopulmonary bypass (CPB), showers of microemboli (ME) distribute among the organs and connective tissues according to regional blood flow. Post CPB, ME were quantified by subtracting residual platelets (RP) in the organs of a group of unoperated control Yorkshire pigs (n = 6) from those of operated pigs. The RP level was minimized by heparinization (300 IU/kg) before death and exsanguination. The number of adherent microthrombi (MT) and ME from the oxygenator (OX), arterial filter (AF), and thoracotomy site were determined using 111In labeled autologous platelets (INPLT) (525-585 microCi administered 24 hr before CPB) in two CPB groups (ACT > 400 sec) of 12 pigs (30-35 kg). CPB was carried out at a flow of 2.5-3.5 L/min at 28 degrees C with a roller or a centrifugal pump, OX (Bentley Univox 1.8 m2), AF (0.25 m2), and cardiotomy reservoir (CR) (Bentley BR: 3,500), for 90 (n = 6) and 180 (CPB 180, n = 6) min. Six pigs underwent thoracotomy without CPB. L-Arginine was infused at a dose of 2 mg/ kg/min during CPB (n = 6). Flow cytometry was used to estimate the circulating ME in blood. MT and organ trapped ME were imaged with a gamma camera and measured with an ion chamber and a gamma counter. ME values (percent of injected INPLT dose) in six organs and four connective tissues were calculated for all five groups. INPLT distribution indicated a uniform distribution of low level platelet MT in the CR and AF. Circulating ME amounted to 2.5% of total platelets. In the CPB circuit, ME generation in AF was the rate-limiting step (n = 4 x 10(5)). Similar studies in organs and tissues suggested the presence of a uniform distribution of the total events of ME (n = 500 x 10(6)). ME increase in brain, lung, liver, and skeletal muscle following thoracotomy and CPB was significant. The low level of ME in ischemia sensitive organs also indicated the presence of a thrombolytic threshold for cumulative ME. ME disaggregation was activated at an early stage to prevent ischemic damage, specifically in the brain. Measurement of trapped ME provided a novel, reliable, and one step method of evaluation of thrombogenicity of a CPB device and drugs.     

Identification of entero-aggregative Escherichia coli based on surface properties

OBJECTIVES: Afterdrop in core temperatures after discontinuation of cardiopulmonary bypass (CPB) is reported to be a sign of inadequate total body rewarming on CPB. The purpose of this study was to compare the effects of three different drug regimens on hemodynamic stability and the uniformity of rewarming during the rewarming period of CPB. DESIGN: This prospective randomized study was performed in the Anesthesiology Department of the University of Istanbul. PARTICIPANTS: Sixty-six patients undergoing uncomplicated valve replacement and aortocoronary bypass grafting surgery were studied. INTERVENTIONS: Anesthesia was maintained with isoflurane and fentanyl infusion during the prebypass and the postbypass periods. Patients were allocated into three groups by the initiation of CPB. Group 1 (n = 22): fentanyl infusion + diazepam + sodium nitroprusside (SNP) in the rewarming period), group 2 (n = 22): fentanyl infusion + isoflurane, group 3, control (n = 22): fentanyl infusion + diazepam. Rectal, esophageal, and forearm temperatures were monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: None of the durational and temperature data showed significant differences between groups 1 and 2. In the control group, afterdrop in esophageal temperature was significantly higher than groups 1 and 2 (group 1: -1.4 +/- 0.9 degrees C, group 2: -1.44 +/- 0.8 degrees C, group 3: -2.1 +/- 0.65 degrees C). In group 1, the number of patients whose mean arterial pressure (MAP) decreased below 45 mmHg was significantly higher than group 2 (p = 0.002). Mean SNP infusion rate and mean isoflurane concentration during the rewarming period were calculated as 1.55 +/- 0.8 micrograms/kg/min and 0.775 +/- 0.27%, respectively. CONCLUSIONS: Isoflurane produced more stable hemodynamic conditions than SNP during the rewarming period, improved the uniformity of rewarming, and permitted earlier extubation in the intensive care unit (ICU). It is concluded that isoflurane alone is capable of fulfilling the anesthesia needs during hypothermia and the rewarming period of CPB.     

Effect of veno-venous ultrafiltration on myocardial performance immediately after cardiac surgery in children. A prospective randomized study

OBJECTIVES: This study sought to evaluate the effects of veno-venous ultrafiltration on myocardial contractility in children undergoing cardiopulmonary bypass (CPB) for repair of congenital heart defects. BACKGROUND: Ultrafiltration (UF) is currently used to diminish postoperative fluid accumulation following CPB in children. Previous reports indicate improvement in hemodynamics immediately after UF, but the mechanism of its action is unknown. METHODS: Twenty-three patients (ages 2 months to 9.1 years; 13 males, 10 females) underwent UF for 10 min after CPB. Twelve patients underwent UF immediately after CPB (Group A). They were studied: (1) before and (2) after CPB, (3) after UF, and (4) 10 min after UF. Eleven patients underwent UF 10 min after CPB (Group B). They were studied: (1) before and (2) after CPB, (3) after a 10-min delay before UF, and (4) after UF. Contractility was determined by the difference in the observed and predicted velocity of circumferential fiber shortening for the measured wall stress, using transesophageal echocardiography. Left ventricular wall thickness was also measured. RESULTS: There was significant improvement in contractility after UF in both groups (mean+/-SD, Group A: -0.28+/-0.13 to -0.01+/-0.21 circ/s, p < 0.05; Group B: -0.26+/-0.16 to -0.11+/-0.17 circ/s, p < 0.05). Myocardial thickness to cavity dimension decreased in both groups following UF (Group A: 0.19+/-0.04 to 0.14+/-0.03, p < 0.05; Group B: 0.18+/-0.04 to 0.14+/-0.03, p < 0.05). CONCLUSIONS: UF improves hemodynamics by improving contractility and possibly by reducing myocardial edema in children following cardiac surgery. Enhanced patient outcome after ultrafiltration may in part be due to these changes.     

Activity of phosphatidylinositol-specific phospholipase C from Bacillus cereus with thiophosphate analogs of dimyristoylphosphatidylinositol

We examined the effects of nasal continuous positive airway pressure (CPAP) on exercise performance in patients with obstructive sleep apnea (OSA). Six patients were treated with nasal CPAP on seven successive days and underwent overnight sleep studies and multiple sleep latency test (MSLT) at the beginning and after the last day of the treatment. The subjects also performed incremental exercise testing using a bicycle ergometer followed by 0-w, 25-w, 50-w,--(3 minutes each) until maximum level. Arterial oxygen pressure, arterial carbon dioxide pressure at rest while awake, apnea/ hypopnea index, longest apnea duration, the lowest percutaneous oxygen saturation measured by a pulse oximeter and the value of MSLT were significantly improved after nasal CPAP. Moreover, maximal oxygen consumption was significantly increased from 1841 ml/min +/- 350 to 2125 ml/min +/- 351 (p < 0.05); however, other cardiorespiratory parameters did not change significantly. The improvement of exercise performance by short-term nasal CPAP treatment in OSA patients may correlate with the improvement of sleepiness.     

Effects of chest wall counterpressures on lung mechanics under high levels of CPAP in humans

We assessed the respective effects of thoracic (TCP) and abdominal/lower limb (ACP) counterpressures on end-expiratory volume (EEV) and respiratory muscle activity in humans breathing at 40 cmH2O of continuous positive airway pressure (CPAP). Expiratory activity was evaluated on the basis of the inspiratory drop in gastric pressure (DeltaPga) from its maximal end-expiratory level, whereas inspiratory activity was evaluated on the basis of the transdiaphragmatic pressure-time product (PTPdi). CPAP induced hyperventilation (+320%) and only a 28% increase in EEV because of a high level of expiratory activity (DeltaPga = 24 +/- 5 cmH2O), contrasting with a reduction in PTPdi from 17 +/- 2 to 9 +/- 7 cmH2O . s-1 . cycle-1 during 0 and 40 cmH2O of CPAP, respectively. When ACP, TCP, or both were added, hyperventilation decreased and PTPdi increased (19 +/- 5, 21 +/- 5, and 35 +/- 7 cmH2O . s-1 . cycle-1, respectively), whereas DeltaPga decreased (19 +/- 6, 9 +/- 4, and 2 +/- 2 cmH2O, respectively). We concluded that during high-level CPAP, TCP and ACP limit lung hyperinflation and expiratory muscle activity and restore diaphragmatic activity.     

Effect of exposure of guinea pigs to cigarette smoke on elastolytic activity of pulmonary macrophages

STUDY OBJECTIVE: To determine the effect of exposure to cigarette smoke on the elastolytic activity of guinea pigs' alveolar macrophages (AMs), and to compare elastolytic activity of AMs obtained by BAL with that of lung macrophages (LMs) obtained from minced lung tissue. METHODS: AMs were obtained by BAL from seven adult guinea pigs exposed to cigarette smoke for 5 d/wk during 6 weeks, as well as from age-matched control guinea pigs. From each animal, one lung was used to obtain LMs by mincing and teasing the lung, followed by enzymatic digestion and isolation of mononuclear cells by Hypaque-Ficoll separation. The other lung was inflated and fixed to quantitate emphysema by the destructive index (DI). Elastolytic activity (microgram of elastin degraded by 10(6) macrophages) was determined at 24, 48, and 72 h, by culturing AMs and LMs (1 x 10(6) cells in 1 mL of medium) in 3H-elastin-coated wells. RESULTS: In animals exposed to cigarette smoke, the total number of BAL cells (8.6+/-2.1 x 10(6)) and DI (21.8+/-8.1) were significantly higher than in nonexposed animals (6.4+/-1.8 x 10(6), p<0.05 for cells, and 12.1+/-4.1, p<0.01 for DI). Elastolytic activity of AMs from smoke-exposed guinea pigs was significantly higher at 24, 48, and 72 h than elastolytic activity of AMs from control animals (19.0+/-9.4 vs 10.0+/-5.3, p<0.05 at 72 h). Likewise, elastolytic activity of LMs was significantly higher in exposed than nonexposed guinea pigs (11.8+/-7.7 vs 7.4+/-5.0 at 72 h, p<0.05). Elastolytic activity of LMs was not significantly different from elastolytic activity of AMs, both in exposed guinea pigs (11.8+/-7.7 vs 19.0+/-9.4 at 72 h) and nonexposed animals (7.4+/-5.0 vs 10.0+/-5.3 at 72 h). CONCLUSIONS: These results indicate that elastolytic activity of both AMs and LMs of guinea pigs increases significantly after exposure to cigarette smoke and that AMs and LMs have similar elastolytic activities.