Cardiopulmonary bypass with low systemic heparinization: an experimental study.
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Animals↗
Biomedical subjects
B Leskosek
Publications and source records attributed to B Leskosek.
Performance characteristics of a disposable ventricle assist device.
A disposable ventricle assist device (VAD) including atrium, ventricle and trileaflet valves (all polyurethane) can be driven either a) by its original self adjusting drive unit (ABIOMED BVS 5000) or b) by a standard intra-aortic balloon pump console (DATASCOPE). Maximum flow in vitro was 4.3 l/min with the original drive console versus 9.2 l/min for activation with the intra-aortic balloon pump console. Performance characteristics of the VAD were evaluated in 11 bovine experiments. In vivo left ventricular assist for up to 24 hours with VAD and either original drive console or standard intra-aortic balloon pump console showed superior flow on activation with the intra-aortic balloon pump console (5.3 +/- 1.7 l/min) versus original drive console (3.5 +/- 0.5 l/min). After 6 hours of assist (before any transfusions) there was no significant difference in classic parameters for evaluation of blood trauma such as plasma hemoglobin production, LDH production and platelet depletion. We conclude that VAD is extremely simple to use. Activation by an intra-aortic balloon pump console enables significant increase of VAD-output without detectable increase of blood trauma. Successful weaning of VAD activated with standard intra-aortic balloon pump console was possible in a first clinical application.
Aortic Valve Insufficiency↗
Left ventricular volume determination in dogs: a comparison between conductance technique and angiocardiography.
Left ventricular (LV) volume was determined simultaneously by monoplane cineangiocardiography and conductivity using a multielectrode conductance catheter at rest and during pressure loading in seven mongrel dogs (mean body weight 22 kg). LV volumes were calculated frame-by-frame (75 frames s-1) by angiocardiography and matched with instantaneous volumes obtained by conductivity. There was an excellent correlation between the two techniques at rest (correlation coefficient, r = 0.96) and during pressure loading (r = 0.92) when the data of each dog were pooled. The standard error of estimate of the mean angiographic volume was 4%. The slope of the regression analysis showed a small but significant (P less than 0.01) decrease from 0.365 at rest to 0.289 during pressure loading, whereas the intercept remained unchanged (24 versus 26 ml). Since no calibration for parallel conductivity of the surrounding tissue was performed, LV end-systolic volume was significantly over- and LV ejection fraction significantly underestimated whereas LV end-diastolic volume was estimated correctly by the conductance technique. It is concluded that LV end-diastolic volume can be determined accurately by the conductance technique in dogs. However, LV end-systolic volume is significantly over- and ejection fraction significantly underestimated. Since there is a good correlation between angiocardiography and conductivity, exact determination of LV volumes and ejection fraction is feasible using a correction factor. The change in slope of the regression equation between angiocardiography and conductivity suggests a change in conductivity of the surrounding tissue during pressure loading which limits the application of the conductance catheter to stable haemodynamic situations or calls for repeated calibrations by an independent technique during acute interventions.
Angiocardiography↗
[Pulsatile versus non-pulsatile mechanical circulatory assistance].
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Animals↗
Is there a relationship between gastric mucosal blood flow and stress lesions in hemorrhagic shock?
The relationship between gastric mucosal blood flow and stress lesion formation during hemorrhagic shock was studied in anesthetized dogs. Shock was induced by graded arterial bleeding. Blood flow was measured by means of the radioactive microsphere technique. Mapping of blood flow was achieved by measuring the microsphere accumulation in mucosal and muscle segments of 1-2 cm side length of the entire stomach. To produce a varying incidence of lesions the metabolic acidosis of shock was either fully corrected by intravenous sodium bicarbonate (n = 5), partially corrected (n = 4) or left uncorrected (n = 3). Mucosal lesions developed more frequently in dogs without correction than in dogs with partial correction or full correction. In 4 dogs not subjected to shock, no mucosal lesions were observed at the end of the experiments. Mucosal blood flow varied from segment to segment by a factor of up to 20, but individual segments tended to maintain their relative flow values during shock. Correction of metabolic acidosis did not significantly affect blood flow. Likewise, flow was similar in segments with and without lesions. Therefore, low regional blood flow did not predispose to the development of lesions and high flow did not prevent them. We conclude that focal mucosal ischemia alone does not lead to stress lesion formation during hemorrhagic shock.
Animals↗
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).
Animals↗
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.
Animals↗
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.
Animals↗
Ventricular assist with heparin surface coated devices.
Heparin surface coated ventricular assist devices (VADs) were evaluated without systemic heparinization and compared with uncoated control VADs with systemic heparinization (bovine experiments, n = 8; bodyweight, 75 +/- 6 kg). No heparin was given in the study group, whereas heparin (300 IU/kg) was given before cannulation in the control group. Mean activated clotting time (ACT) was 127 +/- 12 sec before and 122 +/- 17 sec after 6 hours of left ventricular assist for coated (NS) versus 184 +/- 114 sec before and 650 +/- 240 sec after for uncoated (p less than 0.05) VADs. No difference was observed in platelet depletion, plasma hemoglobin, lactic dehydrogenase (LDH) production, mixed venous oxygen saturation, and VAD clot score. No VAD occlusions occurred. Ventricular assist can be achieved without systemic heparinization if VADs are improved.
Animals↗
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)
Animals↗
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.
Animals↗
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.
Animals↗