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.

Plasma levels of endothelin-1 after a pulmonary embolism of bone marrow fat.

BACKGROUND: During orthopedic surgery, embolization of bone marrow fat can lead to potentially fatal, intra-operative cardiovascular deterioration. Vasoactive mediators may also be released from the bone marrow and contribute to these changes. Increased plasma levels of endothelin-1 (ET-1) have been observed after pulmonary air and thrombo-embolism. The role of ET-1 in the development of acute cardiovascular deterioration as a result of bone marrow fat embolization during vertebroplasty was therefore investigated. METHODS: Bone cement was injected into three lumbar vertebrae of six sheep in order to force bone marrow fat into the circulation. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output, arterial and mixed venous blood gas parameters and plasma ET-1 concentrations were measured at selected time points. Post-mortem, lung biopsies were taken for analysis of intravascular fat. RESULTS: Cement injections resulted in a sudden (within 1 min) and severe increase in pulmonary arterial pressure (>100%). Plasma concentrations of ET-1 started to increase after the second injection, but no significant changes were observed. Intravascular fat and bone marrow cells were present in all lung lobes. CONCLUSION: Cement injections into vertebral bodies elicited fat embolism resulting in subsequent cardiovascular changes that were characterized by an increase in pulmonary arterial pressure. Cardiovascular complications as a result of bone marrow fat embolism should thus be considered in patients undergoing vertebroplasty. No significant changes in ET-1 plasma values were observed. Thus, ET-1 did not contribute to the acute cardiovascular changes after fat embolism.

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.

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.

Contribution of cervical smooth muscle activity to the duration of latent and active phases of labour.

OBJECTIVE: To identify the effect of cervical muscle activity as an additional factor influencing the duration of the latent and active phase of labour. DESIGN: Prospective observational study. SETTING: The Ljubljana Maternity Hospital. PARTICIPANTS: Fifty healthy nulliparous women requiring induction of labour having relatively unripe cervices. METHODS: At the onset of labour an open-ended catheter was inserted to measure intrauterine pressure during the latent and active phase of labour. Electromyographic activity of the cervix was registered by two bipolar spiral needle electrodes placed in the transverse direction on the proximal part of the cervix in the vagina. The mean intensity of distinctive peaks in an electromyographic spectrogram were calculated in the time/frequency domain. Multiple linear regression was used to find factors affecting the duration of the latent and active phase of labour. MAIN OUTCOME MEASURES: Duration of the latent and active phase of labour. RESULTS: Eleven independent variables explained 64% of the variance of the latent phase duration, the most important being the effacement and consistency of the cervix, and intensity of electromyographic signals. For the duration of the active phase the same variables explained 36% of the variance; the most important variables were mean duration of uterine contractions, mean maximum intensity of uterine contractions and the newborn's head circumference. CONCLUSIONS: The cervical smooth muscle activity, expressed as an electromyographic signal, contributes to the duration of the latent phase but not to the duration of the active phase. However, frequent cervical contractions are not associated with a longer latent phase.

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.

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.

Affinity pump system: a new peristaltic blood pump for cardiopulmonary bypass.

An in vitro study has been carried out to assess the pump performance of a new peristaltic, extracorporeal displacement pump (Affinity) for cardiopulmonary bypass. The pump system consists of a pump rotor (0-110 rpm), a pump chamber, a venous reservoir with a 5/8" connecting tube and the Affinity console. The polyurethane chamber is connected to the venous reservoir by a 5/8" tube and fills passively due to the hydrostatic pressure exhibited by the fluid height in the venous reservoir. The implementation of an occlusive segment in the pump chamber, which collapses in low filling states, should prevent significant negative pressures. An in vitro circuit was filled with bovine blood (37 degrees C, hematocrit 35%) and the pump flow was measured by an ultrasonic transit time flow probe with respect to pre-load, diameter and length of attached tubing in the venous line, pump speed (rpm) and size of the connecting tube (3/8" and 5/8"). At 108 rpm and a preload equal to 10 mmHg, the flow was 8.6 +/- 0.42 l/min for an afterload of 80 mmHg. The reduction of the inlet connector to 3/8" diminished the pump flow significantly to 5.2 +/- 0.31 l/min (p < 0.0001). The pump flow decreased linearly with respect to the length of the attached tube in the venous line and for a 2 m long 5/8" silicon tube, the rpm-optimized flow was still 6.0 +/- 0.28 l/min at a preload of 10 mmHg. In case of low filling state or too high rpm, the occlusive segment collapsed and no cavitation bubbles could be detected. Our in vitro measurements yield a nomogram for rpm-optimized blood flow with respect to the pre-load in the venous reservoir. The delivered 5/8"connecting tube facilitates optimum filling of the pump chamber for high blood flow, but limits the use of venous reservoirs to Affinity products. The pump yields a high blood flow even when long tubing in the venous line is used. This makes the pump a candidate for a ventricular assist device. In hypovolemia or high rpm, the occlusive segment collapses and no negative pressure is generated at the inflow site of the pump chamber.

Flow measurements through aortocoronary and intraluminal coronary shunts.

AIMS: Temporary insertion of shunts during coronary artery bypass grafting (CABG) on the beating heart may provide the minimal flow required for adequate myocardial protection (40 to 60 ml/min). We investigated the flow as a function of the pressure head over three aortocoronary shunts and one intraluminal coronary shunt. METHODS: The aortocoronary shunts (VS-01590 with bulb size 2, 3 and 4 mm) and the intraluminal shunt (IVS-4030, bulb size 4 mm) were perfused with 47% glycerin solution at 37 degrees C. The preload was raised in 5 mmHg steps from 35 to 80 mmHg. The afterload was set at 12 mmHg. A regression analysis of the flow on the pressure head was performed. RESULTS: For maximal preload the flow through the aortocoronary shunts was 15.9 +/- 1.3, 46.2 +/- 2.2 and 75.4 +/- 3.3 ml/min, for the intraluminal shunt it was 76.1 +/- 3.4 ml/min. To provide a flow of 40 ml/min a preload of 70, 50 and 45 mmHg was necessary for the 3 mm and 4 mm aortocoronary shunt and the intraluminal shunt respectively. For the aortocoronary and the intraluminal shunts the beta-coefficients were 0.27, 0.66, 1.13 and 1.02 ml/(min*mmHg) respectively with all p < 0.0001. CONCLUSIONS: For adequate pressure head the 3 mm and 4 mm aortocoronary shunt and the intraluminal shunt provide myocardial protection. In case of severe proximal coronary stenosis the intraluminal shunt will not guarantee myocardial protection and main benefit reduces to working in a bloodless field. The insertion of shunts is a cheap and simple method to optimize CABG on the beating heart.

Electromyographic activity of the uterus above the placental implantation site.

The aim of this study was to evaluate the electromyographic (EMG) activity of the uterus concerning the placental implantation site. In a clinical trial, 55 pregnant women in the last trimester of pregnancy were enrolled. They were divided into two major groups: 25 women had placental implantation site on the anterior and 30 women on the posterior uterine wall. With regard to the presence/nonpresence of contractions, each group was further divided into two subgroups. Uterine EMG activity was recorded by electrodes placed on the abdominal wall. All signals were transferred through a series of amplifiers. Amplified and filtered EMG signals were digitized and written on a hard disk, simultaneously with the signals of external tocodynamometry. From the 30-min EMG recording, we calculated the average root mean square (RMS) and the average median frequency (MF) of the signal. A significant difference of the abdominal EMG activity concerning the placental implantation site was found only in pregnant women with contractions. The RMS was significantly lower in the placental implantation site on the anterior uterine wall, whereas the MF was significantly higher. It can be concluded that the placental implantation site influences the uterine EMG activity registered through the abdominal wall, especially when registered above the placental implantation site.

Hemodynamic properties of the hemopump HP14.

BACKGROUND: The Hemopump HP14 is a catheter-mounted, transvalvular, left ventricular assist device intended for femoral percutaneous insertion. The pump was developed for patients with postoperative or postinterventional low cardiac output and for CABG surgery on the beating heart. Little is known about the effect of afterload and hematocrit on the pump performance. METHODS: The influence of hematocrit and afterload on the pump flow was tested using an in vitro model filled with heparinized bovine blood. Regression analysis of the pump flow with respect to three hematocrit values (20%, 30%, 40%) and ten afterload levels (30 mmHg-120 mmHg in 10 mmHg increments) was performed for all pump speed levels (n = 7). RESULTS: At all pump speed levels reduction of afterload and hematocrit were significant predictors for increasing pump flow (p<0.001). For hematocrit values between 40% and 20% and highest pump speed, mean pump flow at lowest afterload ranged between 2.34 and 2.53 L/min; and at highest afterload between 1.31 and 1.53 L/min. For speed level 1, afterload of 120 mmHg and hematocrit of 40% there was a maximal retrograde flow of 230+/-35 ml/min. CONCLUSIONS: Pump performance is significantly improved by both afterload and hematocrit reduction. In the weaning phase and during the removal of the device, the pump should run at a speed level of at least three to prevent retrograde flow in the pump. Estimates for pump flow in vivo can be extrapolated from our diagrams. Our results show that the Hemopump HP14 is a valuable alternative to intra-aortic balloon counterpulsation.

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.

Optimized performance of the Abiomed BVS 5000: adjustment of the pump height based on Doppler control of the flow pattern.

The Abiomed BVS 5000 is an automatic volume-driven paracorporeal pulsatile assist device providing left, right or biventricular support. The paracorporeal position allows optical adjustment of filling volumes of the device, which determines the output of the system. A procedure to adjust for maximal stable flow has not yet been established. In vitro measurements have been performed to assess the flow and pressure characteristics of the Abiomed BVS 5000 by raising the preload in 5 mmHg steps before running the system. Doppler probes were placed at the inflow and outflow lines of the pump. After setting the afterload at 80 mmHg the assist device was started. Two measurements were performed to find optimal flow (based on Doppler control and optical adjustment). (1) By Doppler control a stable flow pattern was found at a preload of 25 mmHg with a mean atrial pressure of 5 mmHg and a mean flow of 5.3 +/- 0.7 l/min (mean +/- standard deviation) at the inflow and outflow sites (the console flow was 4.8 +/- 0.4 l/min with a frequency of 61.8 +/- 2.0 l/min). (2) Optical adjustment of the pump height gave rise to a preload of 35 mmHg where we recorded a maximal atrial pressure of 107 +/- 5.8 mmHg, a maximal retrograde flow of -4.3 +/- 1.2 l/min at the inflow and -1.2 +/- 0.4 l/min at the outflow site. The mean flow at the inflow and outflow sites was 5.1 +/- 0.5 l/min (the console flow was 4.6 +/- 0.3 l/min with a frequency of 59.6 +/- 2.6 Hz). At an initial afterload of 60 and 40 mmHg the system showed the same qualitative behaviour, but the results were less accurate. Optical adjustment of the pump height may result in an atrioventricular valve insufficiency with undetected retrograde flow and high atrial pressures. We conclude that a Doppler flow probe must be placed at the inflow site to guarantee maximal stable flow.

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.

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.

Biventricular assist using a portable driver in combination with implanted devices: preliminary experience.

Left ventricular assist systems with portable drive units are increasingly used in the clinical setting. However, such systems usually are not suitable for right ventricular support, and therefore, in the case of biventricular heart failure, they must be combined with other support devices that require additional drive consoles. As a result, most of the benefits of the wearable drive units (early mobilization and outpatient care) are lost. This present study was performed to evaluate biventricular support with implanted assist devices and a portable DC/battery-powered driver (Thoratec TLC-II). Electronic control by nonvolatile RAM accessible via RS232 interface, internal backup emergency battery, and optional manual activation are additional features of this 6 kg biventricular drive unit. In 3 bovine experiments (body weight 70 +/- 5 kg) partial cardiopulmonary bypass (CPB) was established, and two ventricular assist devices were implanted into a preperitoneal pocket on each side after connection to the right atrium and the pulmonary artery and to the left atrium and aorta, respectively. After weaning the patient from CPB, activated coagulation time (ACT) was kept at greater than 180 s, and biventricular support with the portable driver was activated. After 10 min, mean device flow stabilized at 3.5 +/- 0 L/min and remained at that level throughout the ensuing 6 h (3.5 +/- 0.3 L/min; NS). The heart rate moved from 130 +/- 13 beats per minute (bpm) at the end of CPB to 116 +/- 13 bpm after 10 min of assist (p < 0.05). Right atrial pressure moved from 11 +/- 2 mm Hg at the end of CPB to 13 +/- 3 mm Hg after 10 min of assist (not significant [NS]). Mean pulmonary artery pressure was 18 +/- mm Hg at the end of CPB and 17 +/- 5 mm Hg after 10 min of assist (NS). Left atrial pressure was 10 +/- 1 mm Hg at the end of CPB and 13 +/- 3 mm Hg after 10 min of assist (NS). Mean aortic pressure was 73 +/- 11 mm Hg at the end of CPB and 77 +/- 3 mm Hg after 10 min of assist (NS). Mixed venous oxygen saturation increased from 49 +/- 9% at the end of CPB to 58 +/- 10% after 10 min of assist (p < 0.05). The portable drive unit that was tested provides adequate power to maintain significant biventricular support with implanted right and left assist devices. The configuration of batteries tested driving two ventricles provides independence for 60 min.

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.

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.

[Thrombosis-resistant heparin-coated diffusion membrane oxygenators: an experimental study]. / Die Thromboseresistenz heparinbeschichteter Diffusionsmembranoxygenatoren: eine experimentelle Untersuchung.

In the present study the thromboresistance of heparin-coated diffusion membrane oxygenators (Jostra, M 30) combined with heparin-coated venous reservoirs, tubing sets and arterial filters was investigated in six bovine experiments (70 +/- 5 kg). The perfusion with reduced systemic heparin dose (100 IE/kg) body weight) was performed with activated clotting time over 180 seconds. The perfusion began with a blood flow of 31/min and was maintained during six hours. Clotting studies including blood platelet count, activated clotting time, fibrinogen (factor I), antithrombin III and fibrinopeptid A were performed before the operation and ten minutes, two hours and five and six hours after beginning of bypass. The venous and arterial saturation remained stable during the whole investigation. After ten minutes activated clotting time dropped from 619 +/- 114s to 203 +/- 15s after six hours (p < 0.05). The antithrombin III level changed significantly from 109 +/- 11% to 95 +/- 16%. Factor 1 and fibrinopeptid A changes were not significant: from 1.6 +/- 0.3 g/1 to 1.5 +/- 0.3 g/1, and 3.0 +/- 1.4 ng/mL to 3.5 +/- 1.2 ng/mL, accordingly. There were no mechanical defects and especially no plasma leakage. Slight sediments were found only in areas of stagnant blood flow. The investigated bypass circuit with reduced systemic heparinization seems therefore particularly appropriate for long-term perfusions.