Risk factors for HR- and HER2-defined breast cancer in Slovenian postmenopausal women.

OBJECTIVE: The study aimed to investigate the influence of some generally recognized risk factors for hormone receptor (HR)- and human epidermal growth factor receptor 2 (HER2)-defined breast cancer among Slovenian postmenopausal women. METHOD: Eligible women diagnosed with breast cancer were compared with 709 controls of the same age and ethnicity. Immunohistochemistry and FISH analyses were used to classify cases into molecular subtypes: 454 HR(+), 106 HR(-), 81 HER2(+) and 603 HER2(-). Adjusted odds ratios and 95% confidence intervals were estimated using multivariate logistic regression analysis. RESULTS: Overweight and obese women were at increased risk of HR(+), HER2(-) and of HR(+), HR(-), HER2(-) tumors, respectively. Women who started menstruating at the age of 11 years or earlier were at decreased risk of ER(-)PR(-) tumors. Users of hormone replacement therapy (HRT) were negatively associated with HR(+) and HER2(-) tumors. The inverse effect was most pronounced with the use of estrogen-only HRT, and longer duration of HRT use did not result in a significant change in risk. In contrast, combined HRT decreased the risk of HER2(+) tumors. Having a first-degree relative with breast and/or ovarian cancer increased the risk of HR(+) and HER2(-) tumors. CONCLUSION: We conclude that certain breast cancer risk factors may vary by molecular subtypes. According to our results, HRT use may have a greater influence on HR (+) and HER2(-) breast cancers and the risk of HER2-defined breast cancer may differ with respect to the regimen of HRT.

Hormone replacement therapy and some risk factors for breast cancer among Slovenian postmenopausal women.

OBJECTIVE: The aim of the study was to examine the influence of the use of hormone replacement therapy (HRT) and of some generally recognized risk factors on breast cancer risk among Slovenian postmenopausal women. METHODS: Eligible women diagnosed with breast cancer and a control group of women of the same age and ethnicity were invited to participate in the case-control study via a personal letter and asked to complete a written questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated using multivariate logistic regression analysis. RESULTS: A total of 784 cases and 709 controls aged 50-69 years were enrolled. HRT use was inversely associated with breast cancer risk. The effect was most pronounced with the use of estrogen-only replacement therapy (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.30-0.87). Longer duration of HRT use did not result in a significant change in risk (1 to <5 years of HRT use: OR 0.44, 95% CI 0.26-0.73; ≥ 5 years of HRT use: OR 0.51, 95% CI 0.30-0.87). Obesity (25 ≤ body mass index <30 kg/m(2): OR 1.34, 95% CI 1.04-1.73; body mass index ≥ 30 kg/m(2): OR 1.89, 95% CI 1.36-2.63), smoking ≥ 10 cigarettes per day (OR 1.70, 95% CI 1.20-2.43), and any first-degree relative with breast or ovarian cancer (OR 1.52, 95% CI 1.11-2.08) were positively associated with breast cancer risk. CONCLUSIONS: Our analysis revealed some differences from the previously published literature, which might reflect underlying demographic changes. Comprehensive medical care in HRT users without pre-existing breast abnormalities probably reduces the incidence of new breast cancer cases in Slovenia.

Stent coating with titanium-nitride-oxide for reduction of neointimal hyperplasia.

BACKGROUND: Coronary stents prevent constrictive arterial remodeling but stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body reaction, which is absent for titanium. The hypothesis of the present study was that titanium renders the stent surface biologically inert, with reduced platelet and fibrinogen binding. METHODS AND RESULTS: Twelve pigs were instrumented with a stainless steel and 2 titanium-nitride-oxide-coated stents (TiNOX 1, ceramic; TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens of stented segments were analyzed by digital morphometry. Platelet adhesion and fibrinogen binding studies were performed in the perfusion chamber. Under in vitro conditions, TiNOX 1 showed reduced platelet adhesion (65+/-3%) compared with TiNOX 2 (72+/-5%; P<0.05) and stainless steel (71+/-4%; P<0.05). Platelet adhesion 48 hours after incubation with human plasma, however, was not different between TiNOX 1 (17+/-3%) and 2 (15+/-3%) but was significantly higher with stainless steel (23+/-2%; P<0.05). Fibrinogen binding was significantly reduced with TiNOX 2 (54+/-3%) compared with TiNOX 1 (82+/-4%, P<0.05) or stainless steel (100%, P<0.05). Histomorphometry revealed a significantly larger neointimal area in stainless steel (2.61+/-1.12 mm(2)) than in TiNOX 1-coated (1.47+/-0.84 mm(2), P<0.02) or TiNOX 2-coated (1.39+/-0.93 mm(2), P<0.02) stents. The reductions were 44% and 47%, respectively. CONCLUSIONS: TiNOX coating significantly reduces neointimal hyperplasia in stainless steel stents. The antiproliferative effect was similar for both TiNOX coatings, suggesting that the electrochemical properties are more important for attenuation of neointimal proliferation than the observed differences in platelet adhesion and fibrinogen binding.

Regional diastolic dysfunction in postischaemic myocardium in calf: effect of nisoldipine.

OBJECTIVE: The aim was to assess the effect of nisoldipine on left ventricular systolic and diastolic function during prolonged myocardial ischaemia. METHODS: The left circumflex coronary artery was ligated for 2 h and reperfused for 4 h in 12 calves. The animals were randomised to a control group (n = 6) or to treatment with 1.25 mg.h-1 intravenous nisoldipine (n = 6) during 2 h of ischaemia. Circulatory support by a ventricular assist device was performed throughout the experiment except for the time of haemodynamic measurements. Regional wall thickening of a normal and an ischaemic left ventricular region was determined using pairs of ultrasonic crystals. Left ventricular pressure was measured by micromanometry. Left ventricular wall thickness and regional wall stiffness at a common preload of 10 mm Hg were calculated using an elastic model with shifting asymptote. RESULTS: Ten animals survived after 6 h. No difference was observed in systolic function between controls and nisoldipine treated animals. Systolic thickening of the ischaemic wall remained depressed 4 h after reperfusion and showed some recovery after dopamine infusion. Ischaemic wall stiffness at a common preload was lower after nisoldipine during ischaemia and reperfusion than in controls. Control wall stiffness remained unchanged during the whole experiment with and without nisoldipine. Diastolic thinning of the ischaemic wall was prevented by nisoldipine during ischaemia and after reperfusion. CONCLUSIONS: Prolonged myocardial ischaemia is associated with increased myocardial stiffness of the ischaemic wall. Mechanical unloading can help to bridge the acute phase but cannot prevent postischaemic diastolic dysfunction of the ischaemic wall. Nisoldipine has a beneficial effect on regional diastolic function during ischaemia and reperfusion by decreasing regional wall stiffness and preventing diastolic thinning of the ischaemic wall.

Quantitative gas transfer of an intravascular oxygenator.

The intravascular oxygenator is a newly developed device for intracaval gas exchange in critically ill patients with respiratory failure. In an experimental ex vivo model, performance characteristics of the intravascular oxygenator/carbon dioxide removal device were studied. With a mean hemoglobin concentration of 6.2 +/- 1.9 g/dL (mean +/- standard deviation), total O2 transfer was 21.8 +/- 4.8 mL/min at a blood flow of 1 L/min, 37.0 +/- 12.6 mL/min at 2 L/min, at 2 L/min, and 47.5 +/- 16.7 mL/min at 3 L/min. Total CO2 transfer was 27.3 +/- 6.6 mL/min at a blood flow of 1 L/min, 38.6 +/- 8.9 mL/min at 2 L/min, and 40.4 +/- 9.3 mL/min at 3 L/min. In contrast to total gas transfer, O2/CO2 transfer rates (mL/L) diminished significantly with increasing blood flow. In addition, there was a negative correlation between O2 transfer rate and venous O2 partial pressure (r = -0.73; p < 0.0001), a positive correlation between CO2 transfer rate and venous CO2 partial pressure (r = 0.65; p < 0.0001), and a positive correlation between O2 and CO2 transfer rates and blood hemoglobin level (r = 0.57 [p < 0.01] and r = 0.70 [p < 0.01], respectively). These results demonstrate that the behavior of the intravascular hollow-fiber oxygenator is similar to that of the classic membrane oxygenator used for cardiopulmonary bypass: total gas transfer correlates directly with blood flow and venous CO2 partial pressure and indirectly with venous O2 partial pressure. The O2 and CO2 transfer rates increase significantly with increasing hemoglobin content of the blood.

Influence of hemodynamics on the performances of intravascular gas exchangers.

BACKGROUND: The intravascular gas exchanger is a lung assist device for augmentation of gas exchange in critically ill patients with severe acute respiratory failure. These patients often require inotropic support therapy due to the cardiovascular instability that almost inevitably accompanies severe respiratory failure. METHODS: We investigated the interaction of vasoactive medication (dopamine, nitroglycerin, and noradrenaline) with the gas exchange performances of the intravascular gas exchanger in a bovine experimental model. RESULTS: Dopamine administration highly increased cardiac output, caval flow rates, and diameter of vena cava inferior. These effects resulted in a significant increase in oxygen transfer (baseline, 35 +/- 6 mL/min versus 153 +/- 27 mL/min at 20 micrograms.kg-1.min-1 of dopamine, p < 0.001) and carbon dioxide elimination (baseline, 35 +/- 2 mL/min versus 47 +/- 4 mL/min at 20 micrograms.kg-1.min-1 of dopamine, p < 0.001). Administration of nitroglycerin did not cause significant changes of the hemodynamic parameters nor did it affect the oxygen transfer or carbon dioxide elimination. Noradrenaline caused a moderate increase in cardiac output and caval flow, but no changes of caval diameter. hemodynamic changes were accompanied by an increase in oxygen transfer from 38 +/- 5 mL/min to 68 +/- 7 mL/min (p < 0.01) and carbon dioxide elimination from 33 +/- 1 mL/min to 40 +/- 1 mL/min (p = 0.03). The multiple regression analysis showed significant influence of changes in cardiac output on oxygen transfer (p < 0.001) and carbon dioxide elimination (p = 0.004). The administration of vasoactive drugs induced slight changes in caval diameter that did not significantly affect the gas transfer. CONCLUSIONS: The results from our study reveal the major influence of cardiac output on efficiency of gas transfer of the intravascular oxygenator.

Treatment of acute pulmonary hypertension with inhaled nitric oxide.

We examined the effectiveness of inhaled nitric oxide (NO) as a selective pulmonary vasodilator in acute pulmonary hypertension in an in vivo canine model with fixed cardiac output. In 5 dogs, total right heart bypass was instituted, and pulmonary hypertension was induced by infusion of the thromboxane analogue U-46619. During U-46619 infusion, NO was administered at 10 and 40 ppm for 5 minutes followed by breathing of the oxygen mixture without NO. Pump flow was held constant during the experiment. Infusion of the thromboxane analogue resulted in an increase in pulmonary vascular resistance and systemic vascular resistance from 147 +/- 83 to 740 +/- 126 dyne.s.cm-5 and from 1,720 +/- 113 to 2,407 +/- 232 dyne.s.cm-5, respectively. During inhalation of 10 ppm NO, pulmonary vascular resistance significantly decreased to 613 +/- 55 dyne.s.cm-5 (p < 0.05) and further decreased to 527 +/- 163 dyne.s.cm-5 with 40 ppm NO inhalation (p < 0.05). Systemic vascular resistance did not change during NO treatment (2,300 +/- 70 dyne.s.cm-5 during 40 ppm NO). There was no increase in intrapulmonary shunting or methemoglobin levels during NO inhalation. In this setting, with a constant cardiac output throughout the experiment, NO acted as a selective pulmonary vasodilator without altering systemic vascular resistance. However, induced pulmonary vasoconstriction was only partially reversed by NO inhalation.

Effect of intermittent warm blood cardioplegia on functional recovery after prolonged cardiac arrest.

BACKGROUND: There is some evidence that continuous warm blood cardioplegia offers good myocardial protection; however, the effects of interrupting cardioplegia remain controversial. To study this, we compared the effects of continuous and intermittent antegrade warm (37 degrees C) blood cardioplegia on functional recovery after prolonged cardiac arrest (180 minutes). METHODS: Twenty-four juvenile pigs were randomly assigned into four groups. Group 1 received continuous cardioplegia, group 2 underwent several periods of 15 minutes of cardioplegia interrupted by 5 minutes of normothermic ischemia, and group 3 underwent several periods of 10 minutes of cardioplegia interrupted by episodes of 10 minutes. The hearts of group 4 received no cardioplegia. Left ventricular systolic function was assessed from fractional left ventricular shortening and percentage left ventricular wall thickening, and left ventricular diastolic function was determined from the time constant of relaxation and the constant of myocardial stiffness. RESULTS: Systolic and diastolic functions were slightly depressed 1 and 2 hours after cross-clamp removal in all four groups, without significant differences among the groups. CONCLUSIONS: These data suggest that antegrade warm blood cardioplegia can be interrupted for up to 10 minutes without obvious negative effects on left ventricular function in the normal myocardium, provided that the intermittent doses of cardioplegia are sufficient to restore the metabolic demands of the arrested myocardium.

Superior hemodynamics in left heart bypass without systemic heparinization.

Open-chest left heart bypass was performed in 10 canine experiments (30 +/- 9 kg) by a servo controlled roller pump for 6 h at a pump flow of 50 ml/min per kg bodyweight. The surfaces of the tubing sets were either standard (with systemic heparinization) or with end-point attached heparin (no systemic heparin). Besides continuous monitoring of hemodynamics, a standard battery of blood samples was taken before bypass, after 10 min and every hour thereafter. There is no evidence of increased fibrin production in the group with end-point attached heparin surfaces perfused without systemic heparinization. Superior hemodynamics in left heart bypass performed without systemic heparinization appear to be due to improved hemostasis, reduced blood loss and therefore reduced transfusion requirements. Left heart bypass with heparin-coated equipment has been successfully used for resection of a thoracoabdominal aneurysm in six patients.

Optimization of venous return tubing diameter for cardiopulmonary bypass.

OBJECTIVE: To determine the optimal venous tubing diameter for adult cardiopulmonary bypass (CPB) to improve gravity drainage and to reduce priming volume. METHODS: (A) Maximum bovine blood flow rates by gravity drainage were assessed in vitro for four different tubing diameters (1/2, 3/8, 5/16,1/4 inch) with three different lengths and various pre- and afterloads. Based on the results of (A) and multiple regression analyses, we developed equations to predict tubing sizes as a function of target flows. (C) The equations obtained in (B) were validated by ex vivo bovine experiments. (D) The clinically required maximal flows were determined retrospectively by reviewing 119 perfusion records at Zurich University. (E) Based on our model (B), the clinical patient and hardware requirements, the optimal venous tubing diameter was calculated. (F) The optimized venous tubing was evaluated in a prospective clinical trial involving 312 patients in Hangzhou. RESULTS: For a mean body surface area of 1.83+/-0.2 m(2), the maximal perfusion flow rate (D) achieved with 1/2-inch (=1.27 cm(2)) venous tubing was 4.62+/-0.57 l/min (range: 2.50-6.24 l/min). Our validated model (B,C) predicted 1.0 cm(2) as optimal cross-sectional area for the venous line. New tubing packs developed accordingly were used routinely thereafter. The maximal flow rate was 4.93+/-0.58 l/min (range: 3.9-7.0) in patients with a mean body surface area of 1.62+/-0.21 m(2). CONCLUSION: The new venous tubing with 1.0-cm(2) cross-sectional area improves the drainage in the vast majority of adult patients undergoing CPB and reduces the priming volume (-27 ml/m). Reduced hemodilution can prevent homologous transfusions if a predefined transfusion trigger level is not reached.

Uterine electrical activity as predictor of preterm birth in women with preterm contractions.

OBJECTIVE: To estimate the risk of preterm birth in women admitted to the tertiary maternity hospital for preterm contractions by measuring electrical uterine activity. STUDY DESIGN: The study included 47 patients with contractions between the 25th and 35th week of gestation and additional risk factors for preterm delivery. Uterine electrical activity was recorded using bipolar electrodes placed on the abdominal surface. A logistic model with the electromyographic and obstetric data was built, preterm delivery before 37th week of gestation being the outcome measure. RESULTS: Seventeen patients (36%) delivered before term. Logistic regression model suggested only the intensity of electrical uterine activity and woman's body weight to be significant predictors of preterm delivery, with high values related to preterm birth. They predict preterm delivery with the sensitivity of 47% and specificity of 90%. CONCLUSION: We propose uterine EMG as a simple, non-invasive means to estimate the risk of preterm birth in a high-risk population with multiple risk factors present.

Activity of smooth muscles in human cervix and uterus.

OBJECTIVE: To find the similarities and dissimilarities between the activity of the human smooth muscles in the cervix and in the uterine corpus at the onset of induced labour. STUDY DESIGN: Electromyographic activity was measured in 14 primiparous women after amniotomy. The data were sampled and stored digitally in real time. For statistical analysis, the first 20 min of recordings following amniotomy were analyzed. The ratio between the mean activity at a given time and the mean activity over the whole 20 min was used for the comparison between the cervical and uterine activity. RESULTS: The analysis of correlation showed that the electromyographic activity in the cervix differed from that in the uterine corpus in the majority of the enrolled cases. CONCLUSIONS: The muscular activity in the cervix is independent of that in the uterine corpus at the onset of induced labour.

Coagulation patterns in bovine left heart bypass with phospholipid versus heparin surface coating.

The current study was designed to evaluate tubing sets with either polymeric phospholipids or ionically bound heparin in six bovine experiments (body weight, 70 +/- 5 kg). No heparin was given systemically. Left heart bypass was started with 300 ml of clear priming solution and maintained over 6 hours (50 ml/kg/min). Coagulation studies included platelet counts, activated coagulation time (ACT), thrombin time (TT), fibrinogen (Factor I), antithrombin III (AT III), and fibrinopeptide A (FPA). Normalized platelet levels dropped from 100 +/- 12% before to 86 +/- 13% after 6 hours of left heart bypass for heparin, compared with 100 +/- 46% to 90 +/- 44% for phospholipid coating (NS). The ACT increased from 146 +/- 7 sec at 10 min to 159 +/- 16 sec after 6 hours for heparin, compared with 122 +/- 4 to 126 +/- 5 sec for phospholipid (p < 0.05). Thrombin time changed from 18 +/- 0 sec before to 19 +/- 1 sec after 6 hours for heparin, as compared with 16 +/- 1 sec to 18 +/- 1 sec for phospholipid (NS). Factor I levels decreased from 1.5 +/- 0.3 g/L to 1.3 +/- 0.1 g/L for heparin, compared with 1.5 +/- 0.2 g/L to 1.4 +/- 0.3 g/L for phospholipid. Antithrombin III levels changed from 102 +/- 26% to 91 +/- 7% for heparin, compared with 123 +/- 12% to 118 +/- 12% for phospholipid. Fibrinopeptide A levels changed from 100 +/- 60% to 130 +/- 13% for heparin, compared with 100 +/- 11% to 99 +/- 6% for phospholipid (P < 0.05). No macroscopic red clots were found in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravascular oxygenation. Influence of the host vessel diameter on oxygen transfer.

An extra corporeal venovenous bypass circuit (right atrium to pulmonary artery), including an intravascular gas exchanger in a blood chamber with a variable inner diameter, was developed for ex vivo evaluation of the host vessel diameter/intravascular oxygen transfer relationship. Three host vessel diameters mimicking different configurations of the caval axis were studied in three bovine experiments (body weight 82 +/- 3 kg). Blood flow was 3,000 ml/min and device oxygen inflow was 2,300 ml/min. Serial blood samples were taken for 26 mm, 23 mm, and 20 mm inner blood chamber diameters after hemodynamic stabilization before and after exposure of the circulating blood to the intravascular gas exchanger (sampling ports at blood chamber inlet and outlet). Measured oxygen saturation at the blood chamber inlet was 25.0 +/- 11.7% for the 26 mm diameter as compared to 31.7 +/- 12.6% for 23 mm, and 28.7 +/- 9.2% for 20 mm. At the outlet, the corresponding O2 saturations were 34.5 +/- 11.5% for 26 mm, 42.9 +/- 8.8% for 23 mm, and 43.2 +/- 6.2 for 20 mm. Total O2 transfer was 24.9 +/- 11.5 ml/min for 26 mm, 31.9 +/- 7.4 ml/min for 23 mm, and 35.9 +/- 12.2 ml/min for 20 mm (p < 0.05). Likewise, O2 transfer rate was 8.3 +/- 3.8 ml/L, 10.6 +/- 2.4 ml/L, and 12.0 +/- 4.0 ml/L (p < 0.05). Parallel analyses of total CO2 transfer and CO2 transfer rates provided less consistent findings. At 3 L/min, the pressure drop between the inlet and outlet of the blood chamber was 12 +/- 3 mmHg for 26 mm, 26 +/- 1 mmHg for 23 mm, and 38 +/- 2 mmHg for 20 mm diameters (p < 0.001). The authors conclude that oxygen transfer of a given intravascular gas exchanger appears to be indirectly proportional to the host vessel diameter. Increasing blood pressure gradient as a function of decreasing diameter has to be considered in clinical application.

Coagulation patterns during deheparinization with immobilized polycation.

Reversal of systemic heparinization with protamine is problematic during perfusion with heparin surface coated devices because protamine reacts with both circulating and surface bound heparin. Hence, the development of a deheparinization device allowing for ex vivo heparin absorption by the means of an immobilized polycation is of prime interest for a number of indications. To assess the coagulation patterns during ex vivo deheparinization, a heparin surface coated venovenous pump loop including a plasma separator with immobilized polycation was studied in a bovine model (n = 6, body weight 71 +/- 5 kg). After systemic heparinization with 300 IU of heparin/kg body weight, spontaneous evolution (control) of coagulation parameters was compared to ex vivo deheparinization with a mean pump flow of 500 ml/min. No device failure occurred during the procedures and all plasma separators remained patent. These baseline levels were measured for control versus ex vivo deheparinization: activated coagulation time 158 +/- 6 sec (161 +/- 4 sec: NS), antithrombin III 101 +/- 5% (108 +/- 8%: NS), fibrinopeptide A 3.4 +/- 1.7 ng/ml (4 +/- 1.7 ng/ml: NS). After heparin application mean activated coagulation time was longer than 1000 sec in both groups. Sixty minutes later, the activated coagulation time was 757 +/- 43 sec (184 +/- 5 sec: P < 0.05), antithrombin III was 96 +/- 12% (99 +/- 2%: NS), and fibrinopeptide A was 2.7 +/- 0.7 ng/ml (9.5 +/- 3.5 ng/ml: P < 0.05). It is concluded that ex vivo deheparinization resulted in significant acceleration of activated coagulation time normalization. Fibrinopeptide A production in the group with ex vivo deheparinization appeared to be higher. As antithrombin III levels were close to normal in both groups, allowing for adequate function of circulating as well as surface bound heparin, and the coagulation process was blocked by significant heparin levels in the control group, the difference for FPA may be due to activation of the coagulation process in the surgical field (sternotomy).

Intravascular gas transfer. Membrane surface area and sweeping gas flows are of prime importance.

Single and double hollow fiber intravascular gas exchangers were evaluated in an extracorporeal veno-venous bypass circuit (right atrium to pulmonary artery) including a tubular blood chamber (mimicking caval veins with an inner diameter of 26 mm) for evaluation of the membrane surface area/host vessel diameter gas transfer relationships. Six bovine experiments (body wt: 68 +/- 4 kg) with staged ex vivo blood flows of 1, 2, 3, and 4 L/min and a device oxygen inflow of 0, 3, and 6 L/min (0 or 3 L/min/device) were performed. Total oxygen transfer at a blood flow of 1 L/min was 33 +/- 4 ml/ min for a gas flow of 3 L/min (one device) vs 60 +/- 25 ml/ min for a gas flow of 6 L/min (two devices); at a blood flow of 2 L/min, the corresponding oxygen transfer was 46 +/- 16 ml/min for a gas flow of 3 L/min vs 95 +/- 44 ml/min for a gas flow of 6 L/min; at a blood flow of 3 L/min, the corresponding oxygen transfer was 48 +/- 24 ml/min for a gas flow of 3 L/ min vs 92 +/- 37 ml/min for a gas flow of 6 L/min (p < 0.01 for comparison of areas under the curves). Total carbon dioxide transfer at a blood flow of 1 L/min was 47 +/- 18 ml/min for a gas flow of 3 L/min vs 104 +/- 26 ml/min for a gas flow of 6 L/min; at a blood flow of 2 L/min, the corresponding carbon dioxide transfer was 59 +/- 19 ml/min for a gas flow of 3 L/ min vs 129 +/- 39 ml/min for a gas flow of 6 L/min; at a blood flow of 3 L/min, the corresponding carbon dioxide transfer was 60 +/- 22 ml/min for a gas flow of 3 L/min vs 116 +/- 49 ml/min for a gas flow of 6 L/min (p < 0.01). For the given setup, the blood flow/gas transfer relationship is non linear, and a plateau is achieved at a blood flow of 2.5 L/min for O2 and CO2. Doubling membrane surface area and consecutively sweeping gas flows result in doubling of gas transfers at all tested blood flows. However, increased membrane surface area and blood flow produce a higher pressure drop that in turn limits the fiber density that can be used clinically.

Optimized veno-venous bypass with the affinity pump.

Veno-venous bypass (VVBP) is increasingly used to avoid acute venous hypertension and low cardiac output after clamping the vena cava. Air embolism upon accidental decannulation of the inflow line and endothelial damage due to suction of the blood collecting cannula to the vessel wall are known complications specific to the currently used roller and centrifugal pumps, because they generate negative pressure at the inflow site of the pump. The Affinity pump has a unique chamber design with an occlusive segment, that collapses in low filling states preventing negative pressure at the inflow site of the pump chamber. This device was tested for VVBP in three pigs (each weighing 52.3 +/- 5.1 kg) with hepatic vascular exclusion. Blood was pumped from the femoral and portal veins to the external jugular vein and perfusion was maintained for 6 hours. The hemodynamic state of the animals was assessed by recording heart rate; systolic, mean arterial, and diastolic pressure; as well as central venous pressure. Mean pump flow during the experiment was 1,629.3 +/- 372.2 ml/min. After clamping, the inflow line of the pump mean arterial pressure significantly decreased (from 69.5 +/- 4.4 to 43.1 +/- 3.5 mm Hg), and mean pressure in the femoral vein increased significantly (from 16.1 +/- 2.6 to 26.8 +/- 5.9 mm Hg), whereas the mean pressure in the internal jugular vein did not significantly change (from 6.0 +/- 1.7 to 5.0 +/- 2.1 mm Hg). There was no suction by the blood collecting cannula on the vessel wall, and neither bubbles nor air emboli were detected and no operator intervention was needed. In conclusion, the Affinity pump eliminates device related complications due to negative pressure generated at the inlet, and guarantees stable hemodynamics. Its application is simple and safe and minimal operator intervention is needed, making the Affinity pump particularly suited for veno-venous bypass.

Biomembrane mimicry provides improved thromboresistance for total artificial hearts.

Thromboembolic events remain a significant issue in mechanical circulatory support. The aim of this study was to evaluate the potential benefit of surface modification in total artificial hearts (TAHs) using polymeric phospholipids (biomembrane mimicry). For this purpose, pneumatic TAHs (vacuum formed pellethane housing, hard double flap hinged inflow valves, soft trileaflet polyurethane outflow valves) had their blood-exposed surfaces either modified with polymeric phospholipids or unmodified before evaluation in bovine experiments. Orthotopic implantation of the TAHs was performed with cardiopulmonary bypass (CPB) using tip-to-tip heparin surface coated perfusion equipment and very low systemic heparinization (50 IU/kg bodyweight). After weaning from CPB and stabilizing hemodynamics, circulating heparin was neutralized with protamine (1:1). All animals were totally supported for 24 hours before elective sacrifice. No heparin was added at any time during support. Mean activated coagulation time (ACT) was 167+/-24 s at baseline before heparinization for CPB, 330+/-45 s at the end of CPB, 181+/-25 s after 1 hour of support, 180+/-31 s after 6 hours, and 185+/-28 s after 18 hours. After explantation, the TAHs perfused without anticoagulation were carefully analyzed. Atrial cuff coverage with red clot was 30+/-21% for artificial surfaces modified by biomembrane mimicry versus 100+/-0% for standard control surfaces (p<0.01). The number of macroscopic deposits found on the inflow valves was 1.33+/-0.47 for surfaces modified by biomembrane mimicry versus 3.83+/-1.86 for standard control surfaces (p<0.05). Likewise, on the outflow valves the number of macroscopic deposits was 0.00+/-0.00 for surfaces modified by biomembrane mimicry versus 1.00+/-0.81 for standard control surfaces (p<0.05). We conclude that presence and distribution of red clots and other macroscopic deposits are significantly different for artificial surfaces with biomembrane mimicry versus standard control surfaces. Application of the biomembrane mimicry concept has the potential to provide improved TAHs.

Evaluation of phospholipidic surface coatings ex-vivo.

To evaluate the thromboresistant properties of phospholipidic surface coatings mimicking the lipid surface of blood cells, we studied four different types of phospholipids bound onto PVC tubings in comparison to uncoated as well as heparin bonded controls. The samples analyzed included diacetylenic phospholipid coated as a monomeric treatment (A), diacetylenic phospholipid polymerised prior to being coated (B), and two types of polymeric phospholipids made using methacrylate containing monomers (C and D). A bovine (bodyweight 67 +/- 3 kg) left heart bypass model (pump flow 3.2 +/- 0.1 l/min) was selected and the surfaces were exposed to the blood stream up to 360 min without systemic heparinization. Thereafter another set of samples was exposed to stagnant blood over 20 min. Besides hemodynamic, hematologic and biochemical analyses, the macroscopic appearance of 119 blood exposed surface samples was graded semiquantitatively on a scale of 0 to 10: no macroscopic deposits = grade 0, 1 spot (1 mm diameter) = grade 1, 2 spots = grade 2, 5 or more spots = grade 5, up to 10% of the surface covered with clots = grade 6, 100% covered = grade 10 (P < 0.05 = *): mean grade of deposits was 0.0 +/- 0.0 for segments perfused and 0.0 +/- 0.0 for segments exposed to stagnant blood with surfaces exposing to the blood either heparin, phospholipid A, or phospholipid B (NS). Phospholipids C and D were graded 0.0 +/- 0.0 if perfused and 0.7 +/- 1.2 if exposed to stagnant blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin surface coated hard shell venous reservoirs: experimental evaluation ex vivo.

The present study was designed for ex vivo evaluation of a heparin coated hard shell venous reservoir in comparison to uncoated control reservoirs. An open chest bovine right heart bypass model (n = 9, bodyweight 72 +/- 6 kg) with passive blood drainage from the right atrium into the venous reservoir and active retransfusion into the pulmonary artery (roller pump) was selected for this purpose. Clear priming was used for the open perfusion circuit. No heparin was given before or during the evaluation period which was scheduled for 6 hours. Reservoir blood flow was at the beginning 3.5 +/- 0.6 l/min for coated versus 3.4 +/- 0.3 l/min for uncoated (NS). After 6 hours, blood flow was 3.3 +/- 0.1 l/min for coated versus 2.7 +/- 0.4 l/min for uncoated (p < 0.05). Hematocrit moved from a baseline level of 30 +/- 2% for coated versus 28 +/- 3% for uncoated (NS) to 28 +/- 3% for coated versus 27 +/- 5% for uncoated (NS) after 6 hours. Prebypass platelet levels of 100% in both groups moved to 84 +/- 3% for coated versus 78 +/- 23% for uncoated (NS) after 6 hours. Activated coagulation time (ACT) before bypass was 148 +/- 12 s for coated and 153 +/- 6 s for uncoated (NS). After 6 hours, ACT was 160 +/- 9 s for coated versus 152 +/- 5 s for uncoated (NS). Thrombin time before bypass was 15 +/- 2 s for coated versus 16 +/- 2 s for uncoated (NS).(ABSTRACT TRUNCATED AT 250 WORDS)