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S Novak

Publications and source records attributed to S Novak.

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Quantitation of platelet loss with indium-111 labeled platelets in a hollow-fiber membrane oxygenator and arterial filter during extracorporeal circulation in a pig model.

Platelet consumption in a hollow-fiber membrane oxygenator (HFMO) and arterial filter (AF) during cardiopulmonary bypass (CPB) was quantified in five pigs using Indium-111 labeled autologous platelets. Platelet labeling was performed 20-24 hours before CPB. After general endotracheal anesthesia, the pigs were systemically heparinized and were placed on CPB via a median sternotomy. After 3 hours of CPB, radioactivity was quantified with a gamma camera and an ionization chamber. The percent of injected dose (mean +/- SD) was 0.79 +/- 0.45 in the HFMO, 2.52 +/- 0.93 in AF, 4.3 +/- 1.2 in blood loss during CPB. Platelet consumption in HFMO during CPB was lower than in bubble oxygenators (19%) or silicone membrane oxygenators (12%) as observed in previous studies.

Animals↗

Rate constants of embolization and quantitation of emboli from the hollow-fiber oxygenator and arterial filter during cardiopulmonary bypass.

A direct technique was developed to estimate parameters related to half life (T1/2) and rate constants of embolization (RCE) and to quantitate emboli of three sizes (small, medium, and large) shed from the oxygenator and arterial filter during cardiopulmonary bypass (CPB). Cardiopulmonary bypass was performed in 16 Yorkshire pigs divided as follows: systemic heparin group (SHG:6), systemic heparin/heparinized circuit group (SH/HCG:5), and Iloprost (Bentley) (2 ng/kg/min)/heparinized circuit group (IHCG:5) with In-111 labeled autologous platelets. The anesthetized pigs (20-25 kg) underwent CPB at 2.5-3.0 L/min for 3 hours. Pigs were injected with In-111 platelets (300-420 microCi) 24 hours before CPB. Cardiopulmonary bypass was instituted with a roller pump and hollow-fiber oxygenator, and thrombosis and embolization on the oxygenator and filter were monitored by a calibrated Geiger probe (WMB Johnson Associates, Montvale, NJ). The radioactivity in the oxygenator and filter reached peak values at 25-45 min after CPB; the radioactivity then declined in the oxygenator but remained at a steady state in the filter, suggesting continuous embolization at the same rate of trapping. The curve stripping technique of the normalized radioactivity time curve of the oxygenator was used for RCE estimation of different sized emboli shed from the oxygenator; 42% of thrombus embolized from the oxygenator in SHG with three rate constants, with T1/2s of 12 min, 42 min, and 13 hr; the SH/HCG embolized 35% with T1/2 of 78 min, and the IHCG embolized 30%, with a T1/2 of 22 min. This indicates that there is less embolization in the IHCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neutrophil dynamics and retention in lung, oxygenator, and arterial filter during cardiopulmonary bypass in a pig model.

Interactions of neutrophils with adsorbed proteins in components of the cardiopulmonary bypass (CPB) circuit and expression of leukocyte adhesion molecules on activated neutrophils affect neutrophil kinetics and margination. Lung and skeletal muscle along with oxygenator (OX) and arterial filter (AF) in the extracorporeal circuit provide the major areas of neutrophil (N) interaction. The dynamics of N-interaction and N-retention during 3 hr CPB was quantified with autologous In-111 labeled neutrophils (INN) in 4 groups of 20 Yorkshire pigs (28-35 kg, 5 sham; 5 CPB, 1 hr; 5 CPB, 3 hr and 5 CPB with heparinized circuit, 3 hr); anesthetized pigs were injected with INN (500-650 microCi), 30 min before CPB and heparinized, and underwent CPB with a roller pump, a hollow fiber OX (Bentley CM 50, 5.0 m2) and AF (Bentley AF 025, 0.25 m2) at 2.5-3.6 l/min for 3 hr. N-dynamics on OX and AF was monitored by a calibrated Geiger probe. Neutrophil deposition, like that of plasma proteins on OX, reached a steady state almost instantly, but increased on filter with CPB time. INN distribution was viewed with a gamma camera; total INN was measured with an ion chamber and INN in samples of fibers and tissues was quantified with a gamma counter. INN in lung did not change significantly during CPB and increased in liver. The percentage of injected INN in lung, liver, and brain changed with CPB time and showed significant increase over sham-operated animals. Heparin coating of components decreased INN retention. INN/meter2 of lung, OX, and AF at 3 hr were 0.26 +/- 0.07%, 0.06 +/- 0.02%, and 6.17 +/- 3.94%, and significantly lower on a heparin coated filter (2.14 +/- 1.30%). Capillary surface areas of viscera and connective tissues (lung, 100; liver, 134; spleen, 20; heart, 7; skeletal muscle, 92; fat, 12; bone, 3; bone marrow, 5; brain, 0.1 meter2) were estimated from distribution of activated INN in pigs. Lung INN retention was much higher than that of the polymer surfaces of OX/AF, indicating the role of cell adhesion molecules on INN retention on endothelial cells of lung and viscera. By direct continuous monitoring and quantitation of INN at the end of CPB, a sensitive technique for quantitation of neutrophil kinetics, margination, and retention during CPB was developed.

Animals↗

Reduction of neutrophil margination by L-arginine during hypothermic cardiopulmonary bypass in a pig model.

Nitric oxide generation by L-arginine (2 mg/kg/min) infusion during cardiopulmonary bypass (CPB) increases blood flow to all organs and reduces cytokine induced organ damage by reducing the level of marginating neutrophils (Ns). The N-trapping in the oxygenator (OX), arterial filter (AF), cardiotomy reservoir (CR), and N-margination were quantified with indium 111 labeled autologous neutrophils (INN) in nine groups of 40 Yorkshire pigs (30-35 kg). Cardiopulmonary bypass (180 min or 90 min CPB, 90 min reperfusion) was carried out at 2.5-3.5 L/min and at two temperatures (18 degrees C, 28 degrees C). The INN (650-780 microCi) was administered intravenously 15 mins before CPB. All pigs received heparin systemically (activated coagulation time > 400 secs); CPB was instituted with a roller pump, OX (Univox 1.8 m2), AF (0.25 m2), and CR (BCR-3500, Bentley Lab, Irvine, CA). The INN distribution in the device (OX, AF, CR) and organs was imaged with a gamma camera and measured with an ion chamber and a gamma counter. The LA infusion decreased N-trapping, estimated as the percent of injected INN (mean +/- standard deviation), in OX from control (2.7 +/- 2.02)% to (0.94 +/- 0.29)%, and margination in lung from control (48 +/- 4)% to minimal levels (23 +/- 2)% (p < 0.01). In the CPB reperfusion group, a beneficial effect was observed at LA low dose and toxicity of higher N-margination at 15 mg/ kg/min. Neither CPB temperature nor Leumedin affected N-margination significantly.

Animals↗

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.

Animals↗

Donor cardiectomy for other transplantation centers.

Inadequate supply of donor hearts is the greatest limitation to wider utilization of heart transplantation. We performed donor cardiectomy for other transplantation centers in three cases. The donor heart functioned well in all cases, and the recipients were all discharged. Donor cardiectomy for other transplantation centers allows utilization of hearts that might otherwise be lost for transplantation.

Adult↗

Platelet preservation during cardiopulmonary bypass with iloprost and Duraflo-II heparin-coated surfaces.

To test the hypothesis that temporary platelet inhibition during cardiopulmonary bypass (CPB) with surface heparinized systems may result in platelet preservation, nine Yorkshire pigs were placed on CPB for 3 hours. Platelet labeling was done in all pigs with Indium-111 tropolone. CPB was instituted with a roller pump, a hollow fiber membrane oxygenator (Bentley CM-50 [Baxter-Bentley Laboratories, Irvine, CA]), and an arterial filter. The extracorporeal perfusion systems were surface-coated with the Duraflo-II heparin complex. Group A pigs (n = 5) were systemically heparinized (activated coagulation time longer than 400 sec). Group B pigs (n = 4) were placed on CPB without systematic heparinization, but have received the stable prostacyclin-analog Iloprost (ZK36374) at 1 ng/kg/min i.v. from 30 min before and during CPB. Platelet counts declined in group A pigs at 5 min, 1 hr, 2 hr, and 3 hr of CPB to 79.8% (mean), 66.5%, 71.3%, and 69.0% of pre-CPB values, respectively (p less than 0.05). In group B pigs, mean platelet count during CPB was higher than 90% of control value. Percentage of injected radioactivity detected in the oxygenator was 2.82% in group A pigs versus 0.73% in group B pigs (p = 0.0541). Surface heparinization with the Duraflo II heparin coating complex in combination with Iloprost-induced temporary platelet inhibition resulted in platelet count preservation during CPB in the pig model.

Animals↗

Cardiopulmonary bypass with a surface-heparinized extracorporeal perfusion system.

To evaluate the effect of surface heparinization on platelet consumption during cardiopulmonary bypass (CPB) ten pigs were placed on CPB for 3 hours. All pigs were injected with autologous Indium-111 labeled platelets (300-420 uCi) 24 hours prior to CPB and were systemically heparinized prior to cannulation for CPB. CPB was established with a roller pump, a hollow fiber membrane oxygenator (HFMO, Bentley CM-50) and an arterial filter (AF, Bentley 1025). In six pigs the extracorporeal system was untreated whereas in four pigs it was surface heparinized with the Duraflo-II method. Cardiotomy suction was not used. Percent of injected radiation dose in HFMO and AF at 3 hours of CPB in the nontreated systems was 1.53 +/- 1.12 and 0.88 +/- 0.63%, whereas in the surface heparinized systems was 2.45 +/- 1.71 and 0.49 +/- 0.39% respectively (NS). (Values are mean +/- SD). Blood loss during (CPB) was 225 +/- 179 ml in the nontreated systems, and 263 +/- 103 ml in the surface heparinized systems (NS). Platelet counts were reduced by 12% or 21.8% at 3 hours of CPB in the two groups of pigs respectively (NS). No difference was observed in platelet consumption (in HFMO and in AF) or in platelet count reduction between the two groups of pigs. Surface heparinization did not improve platelet preservation in systemically heparinized pigs at 3 hours of CPB.

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Increase of intraplatelet free calcium ion during extracorporeal circulation with a hollow fiber oxygenator: arterial filter and dynamics of platelet thrombosis on oxygenator and filter in a pig model.

Intraplatelet free calcium (IPFC) ions provide a common pathway for platelet activation leading to thrombosis and embolization. IPFC levels were determined by chlorotetracycline fluorometry during extracorporeal circulation (ECC) with systemic heparin in eight Yorkshire pigs (weighing 30-40 kg; 3 control and 5 ECC); the ratio of slow phase organelle calcium sequestration to fast phase platelet-membrane binding is an index of free calcium. During 3 hr of ECC with a hollow fiber oxygenator (HFO) (Bentley CM-50) and AF (Bentley 1025), seven blood samples were collected 5 min before and during ECC. The platelet deposition (CPM/microCi) on HFO (PDHFO) was simultaneously measured with In-111-labeled autologous platelets (300-400 microCi) and a Geiger probe detector at -5, 0, 5, 30, 45, 60, 120, and 180 min. During ECC, IPFC and HFO thrombus increase significantly (p less than 0.05) at 45 min with respect to control IPFC values of 0.4 +/- 0.1, suggesting direct participation of calcium activated platelets in thrombosis on HFO. The decline of IPFC is due to extrusion and sequestration by dense granules, and decline in HFO thrombus is due to embolization. On the other hand, the embolus in the arterial filter was trapped in a linear fashion, with a consistent increase with time of ECC.

Animals↗

In moments of crisis.

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Bereavement↗

[Results of prospective cytological diagnoses of cervical intraepithelial neoplasia].

The value of prospective cytologic diagnosis in cervical intraepithelial neoplasia (CIN) is analysed by means of ROC (receiver operating characteristic) curves. Examined was a group of 160 women with subsequent cone biopsies. The result of a prospective cytologic diagnosis in moderate dysplasia, severe dysplasia and carcinoma in situ is analysed separately, taking into consideration the particular frequencies in the studied group. The most reliable prospective cytologic diagnosis is in moderate dysplasia, followed by carcinoma in situ a slightly more reliable prospective diagnosis than that in severe dysplasia.

Biopsy↗