Stana Novak

Comparative thrombogenicity of pacemaker leads.

To evaluate the throm bogenicity of transvenous silicone and polyurethane pacemaker leads, 9 of 12 anesthetized Yorkshire pigs (27–32 kg) were implanted with silicone (n = 5) or polyurethane (n = 4) pacemaker leads via a femoral vein. The remaining three pigs served as controls. All 12 pigs were injected with autologous indium‐111 labeled platelets (300–420 μCi) 24 hours before anesthesia induction. The pigs were monitored for 3 hours under a gamma camera. Radioactivity in blood and lead segments was measured with a gamma counter. Platelet deposits were denser on silicone leads (441.58 ± 915.0 to 2.19 ± 2.07) than on polyurethane leads (1.21 ± 1.33 to 0.27 ± 0.14) (P > 0.05). Denser platelet deposits were detected at the tip of all leads. Density of platelet deposits declined from tip to distal segments in silicone leads. The percentage of injected platelet radioactivity in the lungs of pigs with either silastic leads (12.9 ± 2.3%) or polyurethane leads (10.1 ± 2.2%) was higher than in the controls (4.6 ± 0.5%) (P < 0.05). This difference indicates thrombus formation and embolization in the lungs early after lead implantation. Thrombogenicity of polyurethane leads may be lower than that of silicone leads.

Factors affecting late survival after surgical remodeling of left ventricular aneurysms

OBJECTIVES Surgical remodeling of the left ventricle has involved various techniques of volume reduction. This study evaluates factors that influence long-term survival results with 3 operative methods. METHODS From 1979 to 2000, 157 patients (134 men, mean age 61 years) underwent operations for class III or IV congestive heart failure, angina, ventricular tachyarrhythmia, and sudden death after anteroseptal myocardial infarction. The preoperative ejection fraction was 28% +/- 0.9% (mean +/- standard error), and the pulmonary artery occlusive pressure was 15 +/- 0.07 mm Hg. Cardiogenic shock was present in 26 patients (16%), and an intra-aortic balloon pump was used in 48 patients (30%). The type of procedure depended on the extent of endocardial disease and was aimed at maintaining the ellipsoid shape of the left ventricle cavity. In group I patients (n = 65), radical aneurysm resection and linear closure were performed. In group II patients (n = 70), septal dyskinesis was reinforced with a patch (septoplasty). In group III patients (n = 22), ventriculotomy closure was performed with an intracavitary oval patch. RESULTS Hospital mortality was 16% (25/157) and was similar among the groups. Actuarial survival up to 18 years was better with a preoperative ejection fraction of 26% or greater (P =.004) and a pulmonary artery occlusive pressure of 17 mm Hg or less (P =.05). Survival was worse in patients who had intra-aortic balloon pump support (P =.03). Five-year survival for all patients in group III was higher than for patients in group II (67% vs 47%, P =.04). CONCLUSIONS Factors that improved long-term survival after left ventricular surgical remodeling were intraventricular patch repair, preoperative ejection fraction of 26% or greater, and pulmonary artery occlusive pressure of 17 mm Hg or less without the need for balloon pump assist.

Comparison of Long-Term Results of Carpentier-Edwards and Hancock Bioprosthetic Valves

The long-term survival following valve replacement with Carpentier-Edwards or Hancock bioprostheses was compared between the two valve models and between the two groups totaling 407 patients who were discharged after valve replacement beginning in 1974. The two groups of patients were treated in a nonrandomized fashion. The actuarial survival for 299 patients with Carpentier-Edwards valves was 94 +/- 1.5% (+/- standard error) and 93 +/- 1.7% after 5 and 8 years of follow-up, respectively. Comparable figures for 108 patients undergoing valve replacement with Hancock valves were 89 +/- 3.0% and 83 +/- 3.7%, respectively (p = not significant [NS]). The probability of freedom from death and valve removal after 5 and 8 years of follow-up was 91 +/- 1.8% and 79 +/- 4.6%, respectively, with the Carpentier-Edwards valve and 84 +/- 3.5% and 75 +/- 4.3%, respectively, with the Hancock valve (p = NS). An accelerated rate of attrition for both valves was observed in the mitral position. There were no significant differences in actuarial survival between the two valves in the mitral or the aortic position or in the incidence of major valve-related complications.

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.

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

&NA; 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 &mgr;Ci) 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 dis‐aggregated 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. ASAIO Journal 1996;42:1010‐1018.

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)

Effect of thoracotomy and cardiopulmonary bypass on activated platelet and neutrophil dynamics and platelet emboli in a pig model

The effects of thoracotomy and components of extracorporeal circuits on dynamics of platelets and neutrophils were quantified with autologous In-111-labeled platelets (INPLT) and neutrophils (INN) during cardiopulmonary bypass (CPB) operations in Yorkshire pigs. Cardiopulmonary bypass was carried out with a hollow-fiber oxygenator and an arterial filter in 48 pigs (30–35 kg); 12 unoperated controls for platelets and neutrophils; 12 sham operated controls; 12 with 180 minutes of CPB with platelets and neutrophils; 12 with 90 minutes of CPB and 90 minutes of reperfusion at 2.5–3.5 one/min. Platelets and neutrophils were labeled with In-111 tropolone and were injected intravenously: platelets at 24 hours and neutrophils at 15 minutes before CPB. All pigs were systemically heparinized [activated coagulation time (ACT) > 400 seconds]; CPB was instituted with a roller pump, oxygenator (OX; Bentley Univox, 1.8 m2), and arterial filter (AF; 0.025 m2) for durations of 180 minutes and 90 minutes of bypass, followed by 90 minutes of reperfusion. The kinetics and pooling of platelets and neutrophils were monitored by a Geiger probe. The adherent thrombi and neutrophils in the OX, AF, viscera, and brain were imaged with a gamma camera and were measured with an ion chamber and a gamma counter. The percentile distribution of labeled platelets and neutrophils expressed as the mean ± standard deviation of injected dose in eight groups was calculated and statistical analyses were performed (ANOVA and paired t-test). Sham operation alone increased platelet retention in the lung, heart, and brain significantly (p < 0.001) over that of unoperated pigs. Neutrophil margination to lung immediately after injection was high; CPB and reperfusion altered the distribution in blood, viscera, and connective tissues. During CPB, an equilibrium among single platelets, platelet thrombi, and emboli was reached in the blood, oxygenator, arterial filter, perfused organs, and tissues. After CPB, the pulmonary neutrophil retention increased significantly (p < 0.001). Reperfusion of 90 minutes following 90 minutes of CPB decreased the level of neutrophils and increased the level of platelets in the lung. Only a small amount of platelets and neutrophils was retained in the oxygenator and arterial filter. Neutrophil retention in the OX and AF was higher than that of platelets. The small amount of retained neutrophils in the heart, kidneys, and brain suggested that cytokines, rather than marginated neutrophils alone, may play a major role in inflammatory insult to these organs during and after CPB. OX thrombi increased with the time of CPB; AF thrombus in both groups was almost similar. During CPB, AF functioned minimally as a thrombus trap with a small percent of retained thrombi; reperfusion post-CPB did not change the amount. Thoracotomy alone has a significant effect on platelet and neutrophil kinetics, and on the subsequent effect of thrombus formation, embolization, and neutrophil margination in organs during the CPB procedure.

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.

Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650–780 μCi) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30–35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/ kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT >400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m2), and an arterial filter (AF: 0.25 m2, Bentley) at a blood flow of 2.5–3.5 1/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. 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. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5–10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.

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.