The effect of hydroxyethyl starch 6% 130/0.4 compared with gelatin on microvascular reactivity.

We compared the effects on microvascular reactivity of hydroxyethylstarch (Volulyte(®) ) and gelatin (Geloplasma(®) ) during acute haemodilution. The hypothesis was that Volulyte would provide better microvascular reactivity than Geloplasma. Forty patients undergoing elective cardiac surgery were randomly assigned to receive either Volulyte or Geloplasma as the exclusive priming solution of the cardiopulmonary bypass. To evaluate microvascular reactivity, postocclusive reactive hyperaemia was examined before and after cardiopulmonary bypass. Microvascular reactivity assessments included the rate of the occlusion and reperfusion slopes and reperfusion times. After cardiopulmonary bypass, increases in reperfusion time were significantly smaller in the Volulyte group (3 (-27 to 9 [-35 to 33]%) vs 29 (-17 to 76 [-34 to 137]%) in the Geloplasma group, p = 0.02 between groups). Rate of reperfusion increased in the Volulyte group (26 (-17 to 43 [-59 to 357])%), whereas it decreased in the Geloplasma group (-22 (-47 to 16 [-84 to 113])%), p = 0.02 between groups. The shorter reperfusion times and increased reperfusion rate suggest that Volulyte maintains better microvascular reactivity than Geloplasma.

Postmortem pump-driven reperfusion of the vascular system of porcine lungs: towards a new model for surgical training.

PURPOSE: The objective of this experiment is to establish a continuous postmortem circulation in the vascular system of porcine lungs and to evaluate the pulmonary distribution of the perfusate. This research is performed in the bigger scope of a revascularization project of Thiel embalmed specimens. This technique enables teaching anatomy, practicing surgical procedures and doing research under lifelike circumstances. METHODS: After cannulation of the pulmonary trunk and the left atrium, the vascular system was flushed with paraffinum perliquidum (PP) through a heart-lung machine. A continuous circulation was then established using red PP, during which perfusion parameters were measured. The distribution of contrast-containing PP in the pulmonary circulation was visualized on computed tomography. Finally, the amount of leak from the vascular system was calculated. RESULTS: A reperfusion of the vascular system was initiated for 37 min. The flow rate ranged between 80 and 130 ml/min throughout the experiment with acceptable perfusion pressures (range: 37-78 mm Hg). Computed tomography imaging and 3D reconstruction revealed a diffuse vascular distribution of PP and a decreasing vascularization ratio in cranial direction. A self-limiting leak (i.e. 66.8% of the circulating volume) towards the tracheobronchial tree due to vessel rupture was also measured. CONCLUSIONS: PP enables circulation in an isolated porcine lung model with an acceptable pressure-flow relationship resulting in an excellent recruitment of the vascular system. Despite these promising results, rupture of vessel walls may cause leaks. Further exploration of the perfusion capacities of PP in other organs is necessary. Eventually, this could lead to the development of reperfused Thiel embalmed human bodies, which have several applications.

Evaluation of the use of a heparin dose-response test in dogs to determine the optimal heparin dose during intravascular procedures and assessment of the in vitro heparin response in healthy dogs.

BACKGROUND: No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. OBJECTIVES: To evaluate an activated clotting time (ACT)-based heparin dose-response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin - ACT and in vitro heparin - factor anti-Xa activity (anti-Xa) relationships in dogs. METHODS: Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0-0.5-1-2-4 international unit (IU)/mL) was prepared and ACT and anti-Xa were determined using whole blood and frozen plasma, respectively. RESULTS: The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti-Xa increased significantly with increasing blood heparin concentration. Heparin - ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin - anti-Xa remained linear throughout the tested range. CONCLUSIONS: The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin - ACT relationship, as observed in vitro. Anti-Xa is a promising alternative for ACT; however, unavailability as a point-of-care test and lack of in vivo target values restrict its current use.

Influence of variations in systemic blood flow and pressure on cerebral and systemic oxygen saturation in cardiopulmonary bypass patients.

BACKGROUND: Although both pressure and flow are considered important determinants of regional organ perfusion, the relative importance of each is less established. The aim of the present study was to evaluate the impact of variations in flow, pressure, or both on cerebral and whole-body oxygen saturation. METHODS: Thirty-four consenting patients undergoing elective cardiac surgery on cardiopulmonary bypass were included. Using a randomized cross-over design, four different haemodynamic states were simulated: (i) 20% flow decrease, (ii) 20% flow decrease with phenylephrine to restore baseline pressure, (iii) 20% pressure decrease with sodium nitroprusside (SNP) under baseline flow, and (iv) increased flow with baseline pressure. The effect of these changes was evaluated on cerebral (Sc(O2)) and systemic (Sv(O2)) oxygen saturation, and on systemic oxygen extraction ratio (OER). Data were assessed by within- and between-group comparisons. RESULTS: Decrease in flow was associated with a decrease in [from 63.5 (7.4) to 62.0 (8.5) %, P<0.001]. When arterial pressure was restored with phenylephrine during low flow, Sc(O2) further decreased from 61.0 (9.7) to 59.2 (10.2) %, P<0.001. Increase in flow was associated with an increase in Sc(O2) from 62.6 (7.7) to 63.6 (8.9) %, P=0.03, while decreases in pressure with the use of SNP did not affect Sc(O2). Sv(O2) was significantly lower (P<0.001) and OER was significantly higher (P<0.001) in the low flow arms. CONCLUSIONS: In the present elective cardiac surgery population, Sc(O2) and Sv(O2) were significantly lower with lower flow, regardless of systemic arterial pressure. Moreover, phenylephrine administration was associated with a reduced cerebral and systemic oxygen saturation.

Does contemporary oxygenator design influence haemolysis?

Based on their design, all membrane oxygenators generate a certain resistance to flow. In clinical practice, this resistance is calculated by measuring both blood flow and the pressure drop over the oxygenator. Historically, some designs, such as the Kolobow spiral coil oxygenator and the Cobe flat sheet oxygenator, had quite a high pressure drop, but were, nevertheless, considered very haemocompatible. Today, both medium and low pressure drop oxygenators are commercially available. Based on physics and the existing literature, this review aims to investigate whether pressure drop by itself can be considered an independent factor of haemolysis.

Surgical correction of an infundibular pulmonic stenosis and ventricular septal defect in a Shetland Sheepdog.

A four-month-old male Shetland Sheepdog presented with exercise intolerance. Physical examination revealed an IV/VI left cranial systolic heart murmur. Echocardiography showed a severe infundibular pulmonic stenosis and a concomitant restrictive ventricular septal defect. As clinical signs of congestive right-sided heart failure worsened and were refractory to medical treatment, surgical correction was advised. Via sternotomy, with cardiopulmonary bypass and cardioplegic cardiac arrest, ventricular septal defect closure and resection of the stenotic infundibular band were performed through right ventriculotomy, followed by patch enlargement. Postoperative recovery was uneventful and echocardiography showed complete resolution of the stenosis and successful closure of the ventricular septal defect. Follow-up echocardiography revealed restenosis after seven weeks and recurrence of right-sided heart failure three months postoperatively. Stenting of the restenosis was attempted via a hybrid procedure with sternotomy and direct transventricular approach. The dog developed fatal ventricular fibrillation during stent deployment. This is the first dog in which surgical right ventricular patch enlargement under cardiopulmonary bypass is reported for the treatment of a primary infundibular pulmonic stenosis.

Venous drainage--gravity or assisted?

Since the early start of cardiopulmonary bypass, vascular access has been recognized as a main variable for obtaining optimal blood flow during cardiopulmonary bypass. In particular, venous drainage can limit the maximum flow as the wide, low-resistance, collapsible veins are connected with smaller stiff cannulas and tubing. Due to the introduction of long venous cannulas for minimally invasive cardiac surgery and the desire to limit hemodilution during cardiopulmonary bypass, more and more centers have started using assisted venous drainage techniques. This article gives an overview of these techniques, with their respective advantages and disadvantages.

Active or passive bio-coating: does it matters in extracorporeal circulation?

BACKGROUND: Two types of surface coating for cardiopulmonary bypass (CPB) are used: bioactive (heparin, nitric oxide) and biopassive (albumin, polyethyleneoxide (PEO), phosphorylcholine). When haemocompatible coatings are combined with the separation of pleuro-pericardial aspiration, attenuation of both the coagulation and complement cascades, as well as better platelet preservation, has been demonstrated. This study wants to investigate if the combination of a bioactive with a biopassive coating (unfractionated heparin embedded in a phosphorylcholine matrix) combines the beneficial effects of both approaches. MATERIALS AND METHODS: Thirty patients undergoing elective CABG were prospectively randomized into two groups of 15 patients. The sole exclusion criterion was an ejection fraction of less than 40%. In the control group (PC), the whole CPB circuit was coated with phosphorylcholine (PC). In the study group (XPC), unfractionated heparin was embedded in the PC matrix of the oxygenator and arterial line filter. RESULTS: No differences were found for haemolytic index, thrombin-anti-thrombin complex (TAT), IL-6, IL-10 and blood loss. PF4 plasma concentration increased from 27.6±22.0 IU/mL to 165.7±43.9 IU/mL (p<0.001) at 15 minutes of CPB in the PC and from 16.0±9.7 IU/mL to 150.9 ± 61.3 IU/mL (p<0.001) in the XPC group. Terminal complement complex (TCC) increased over time in both groups until the end of CPB (Figure 2A). Within each group, TCC generation was statistically significantly higher after the release of the aortic cross-clamp (p<0.001) and at the end of CPB (p<0.001). Total TCC generation was statistically significantly higher in the XPC group compared to the PC group (p=0.026). The difference was statistically significant after the release of the aortic cross-clamp (p=0.005) and at the end of CPB (p=0.001). CONCLUSIONS: Based on our results, there is no additional benefit in combining phosphorylcholine with unfractionated heparin in elective patients undergoing coronary artery bypass grafting (CABG). Massive haemodilution leads to enhanced complement activation.

Optimal versus suboptimal perfusion during cardiopulmonary bypass and the inflammatory response.

Despite major improvements in perfusion techniques over the past 50 years, it is still not possible to formulate a clear definition of what is meant by optimal perfusion. In part this is due to the lack of sufficient evidence-based data and in part because of the complex pathophysiology that takes place during cardiac surgery with cardiopulmonary bypass. To find an answer we need to understand the exact mechanism of the inflammatory reaction triggered by the cardiopulmonary bypass. However, it is clear that further improvement of the cardiopulmonary bypass components alone will be sufficient. Only a combined strategy can further improve cardiopulmonary bypass-related morbidity and mortality. Such a combined strategy will embrace perfusion techniques as well as a pharmacological approach. It will also require a continuous monitoring of the microcirculation. The latter will not only allow to rapidly sense changes in the quality of perfusion but, even more important, also make it possible to intervene at the moment of deterioration. Recent research shows that such an approach has positive an impact on cardiopulmonary bypass-related morbidity postoperatively.

Use of a right ventricular continuous flow pump to validate the distensible model of the pulmonary vasculature.

In the pulmonary circulation, resistive and compliant properties overlap in the same vessels. Resistance varies nonlinearly with pressure and flow; this relationship is driven by the elastic properties of the vessels. Linehan et al. correlated the mean pulmonary arterial pressure and mean flow with resistance using an original equation incorporating the distensibility of the pulmonary arteries. The goal of this study was to validate this equation in an in vivo porcine model. In vivo measurements were acquired in 6 pigs. The distensibility coefficient (DC) was measured by placing piezo-electric crystals around the pulmonary artery (PA). In addition to experiments under pulsatile conditions, a right ventricular (RV) bypass system was used to induce a continuous pulmonary flow state. The Linehan et al. equation was then used to predict the pressure from the flow under continuous flow conditions. The diameter-derived DC was 2.4%/mmHg (+/-0.4%), whereas the surface area-based DC was 4.1 %/mmHg (+/-0.1%). An increase in continuous flow was associated with a constant decrease in resistance, which correlated with the diameter-based DC (r=-0.8407, p=0.044) and the surface area-based DC (r=-0.8986, p=0.028). In contrast to the Linehan et al. equation, our results showed constant or even decreasing pressure as flow increased. Using a model of continuous pulmonary flow induced by an RV assist system, pulmonary pressure could not be predicted based on the flow using the Linehan et al. equation. Measurements of distensibility based on the diameter of the PA were inversely correlated with the resistance.

Tissue factor as the main activator of the coagulation system during cardiopulmonary bypass.

OBJECTIVE: This study investigates the influence of foreign material and blood aspirated from nonvascular structures on activation of coagulation, hemolysis, and blood loss. METHODS: The series comprises 3 randomized groups (groups C, S, and S+P) of 10 patients undergoing routine coronary artery bypass grafting with cardiopulmonary bypass. In group C, the control group, all aspirated blood was returned into the circulation. In group S suction blood was discarded, whereas group S+P was identical to group S, with surfaces coated with phosphorylcholine. Plasma concentrations of beta-thromboglobulin, thrombin generation, haptoglobin, and free hemoglobin, as well as blood loss, were measured. RESULTS: A steady increase in free plasma hemoglobin, as well as an increased generation of thrombin, was noticed in group C. Moreover, a close correlation (r = 0.916) between the generation of thrombin and its inhibition (thrombin-antithrombin complexes) was observed. Platelets were clearly activated in group C and, to a lesser extent, in group S. In contrast, platelet activation in group S+P was negligible, resulting in a 30% decrease in blood loss (P =.05). CONCLUSIONS: Aspirated blood contaminated by tissue contact is the most important activator of the coagulation system and the principal cause of hemolysis during cardiopulmonary bypass. Contact with a foreign surface is not a main variable in the procoagulant effect of bypass. Mimicking the outer cell membrane structure resulted in decreased platelet activation and decreased blood loss.

Feasibility of a pumpless extracorporeal respiratory assist device.

BACKGROUND: Our study evaluated the efficacy and feasibility of a pumpless respiratory assist device and determined its capacity for carbon dioxide removal. METHODS: In five adult pigs the left femoral vein and artery were cannulated with a 20F cannula and connected to a low-pressure hollow-fiber artificial lung. After we had obtained baseline values of mean arterial pressure, cardiac output, and blood flow across the artificial lung, the mean arterial pressure was reduced 20% and 40% relative to baseline; in a second phase, it was raised 20% and 40. Cardiac output and artificial lung flow were simultaneously recorded. We determined the carbon dioxide removal capacity of the artificial lung by gradually increasing the arterial partial carbon dioxide tension of the animal. RESULTS: An increase of 10 mm Hg in mean arterial pressure resulted in an increase of flow of 0.14 L/min. The mean pressure drop across the artificial lung was measured at 17 +/- 9 mm Hg. The shunt flow over the artificial lung varied between 14 and 25% of the cardiac output of the animal. Depending on inlet conditions, carbon dioxide removal by the artificial lung was between 62 +/- 22 mL/L/min and 104 +/- 25 mL/L/min. CONCLUSIONS: A pumpless respiratory assist device can remove a significant proportion of the metabolic carbon dioxide production. However, adequate mean arterial pressure is mandatory to maintain sufficient flow across the device. The technique seems attractive because of its simplicity and can be used in acute lung injury in conjunction of apneic oxygenation for prolonged respiratory support.

Phosphorylcholine coating of extracorporeal circuits provides natural protection against blood activation by the material surface.

OBJECTIVE: The aim of this study is to evaluate the use of a new coating, mimicking the outer cell membrane, in paediatric cardiac surgery. METHODS: Two groups of ten patients with a body weight below 8 kg, undergoing elective cardiac operations for different congenital anomalies, were prospectively enrolled in this study. In one group the whole extracorporeal circuit, including the cannulas, was coated with phosphorylcholine (PC). In the second group the same circuit was used without coating. Platelet activation (thromboxane B2 (TXB2), beta-thromboglobulin (betaTG)), activation of the coagulation system (F1+2), leukocyte activation (CD11b/CD18) and terminal complement activation (TCC) were analyzed pre-cardiopulmonary bypass (CPB), at 15, 60 min of CPB, at the end of CPB, 20 min post CPB and at postoperative day 1 and 6. RESULTS: No statistical differences were found for F1+2 and CD11b/CD18. After onset of CPB mean levels of TCC remained stable in the PC group whereas an increase was observed in the control group. During CPB betaTG values in both groups increased to a maximum at the end of CPB. Within groups the increase in betaTG levels during CPB was statistically significant (P<0.05) from baseline in the control group starting from 60 min of CPB whereas no statistical difference was observed in the PC group. After the start of CPB TXB2 mean levels increased to 405+/-249 pg/ml in the PC group vs. 535+/-224 pg/ml in the control group. After this initial increase there was a small decline in the PC group with further increase. This was in contrast to the control group were TXB2 levels further increased up to a mean of 718+/-333 pg/ml at the end of CPB (P=0.016). CONCLUSIONS: Phosphorylcholine coating had a favourable effect on blood platelets, which is most obvious after studying the changes during cardiopulmonary bypass. A steady increase of TXB2 and betaTG was observed in the control group, whereas plateau formation was observed in the phosphorylcholine group. Clinically, this effect may contribute to reduced blood loss and less thromboembolic complications. Complement activation is lower in the coated group.

Results of intravenous digital subtraction angiography (IVDSA) as a screening method for renovascular hypertension.

Since January 1982 we have combined urography in hypertensive patients with intravenous angiography of the renal arteries. In more than 80% of 163 patients the examination was of good diagnostic quality and both renal arteries were well visualised. IVDSA has a lower morbidity and cost than conventional angiography. It is more accurate than urography and therefore offers better screening of a selected group of hypertensive patients.

Transluminal angioplasty: late results sustained by digital intravenous subtraction angiography.

Digital intravenous subtraction angiography (DIVSA) appears to be a technique of minimal invasiveness and high accuracy in the follow-up of patients after percutaneous angioplasty (PTA) allowing correct angiographic evaluation in more than 96% of the cases. Correlation between clinical and angiographic findings seems to be excellent. Of the controlled intravenous examinations performed in 54 successful PTA procedures 75% appeared patent after 10 to 30 months, constituting 52% of the original attempts.

Digital intravenous and intraarterial subtraction angiography. Applications to the intracranial vascular system.

Digital intravenous subtraction angiography (DIVSA) appears a promising and not highly invasive technique in the study of intracranial tumors and vascular lesions. In combination with computed tomography it should be sufficient in future for determining a preoperative tumourovascular balance. Already now it can be a valuable method in the screening for vascular malformation, in the postoperative evaluation of vascular intracranial lesions or after embolization of those lesions. In the study of the dural venous sinuses, DIVSA appears largely superior to conventional angiography. Advantages of the intravenous approach are the outpatient base, the low risk and low cost.--Low contrast dose and low pressure intraarterial subtraction technique is equivalent to conventional angiography with less risk and discomfort to the patient and resulting in considerable saving in cost.

Mass transfer characteristics of artificial lungs.

An artificial lung is used during cardiopulmonary bypass to oxygenate blood and control blood temperature. The oxygen transfer rate-flow rate characteristics of three hollow fiber membrane artificial lungs (Sarns Turbo 440, Cobe Optima, Dideco Compactflo) were determined in vitro to characterize design features. Results are presented as a unique dimensionless relationship between Sherwood number, NSh (ratio of convective to diffusive mass transfer), Schmidt number, NSc (ratio of momentum to diffusive transport), and Reynolds number, NRe (ratio of inertial to viscous forces). This relationship is a function of device porosity, epsilon, and characteristic device length, xi, defined as the ratio of the mean blood path and manifold length: Nsh/NSc(1/3) x xi(1/2) = phi x (epsilon(1/m) x NRe)(m) where phi = 0.26 and m = 1.00 for NPe < 3,200 and phi = 0.47 and m = 0.64 for NPe > 3,200 where NPe is the dimensionless Péclet number defined as NRe x NSc. We found good correspondence between the model predictions and in vitro blood oxygen transfer rates. We conclude that this dimensionless approach allows us (1) to compare artificial lungs independently, (2) to relate water tests to blood, and (3) to predict the oxygen transfer rate of a new artificial lung design.

Hydrodynamic characteristics of artificial lungs.

An artificial lung is used during cardiopulmonary bypass to oxygenate blood and to control blood temperature. The pressure drop-flow rate characteristics of the membrane compartment in three hollow fiber membrane oxygenators were determined in vitro to characterize design features. Results are presented in a unique dimensionless relationship between Euler number, N(Eu) (ratio of pressure drop to kinetic energy), and Reynolds number, N(Re) (ratio of inertial to viscous forces), and are a function of the device porosity, epsilon, and a characteristic device length, xi, defined as the ratio of the mean blood path and manifold length: [equation in text]. This dimensionless approach allows us (1) to compare oxygenators independently, and (2) to relate water tests to blood.

Hemodynamic comparison of two different pediatric aortic cannulas.

Any extracorporeal blood treatment requires an adequate and safe connection to the circulation. For cardiopulmonary bypass procedures, aortic and venous cannulas are utilized. However, the performance of these cannulas is not only dependent on their size (diameter), but also on their complete geometric design. In this paper two aortic cannula designs are evaluated hemodynamically for two different sizes (8, 10 Fr) both with aqueous fluids and with blood. Using the novel concept of equivalent diameter, a new performance parameter, and the theory of dynamic similarity the results obtained with different fluids can be compared. Data points of one cannula can be fitted to a parabolic equation. There is a significant performance difference between the two 8 Fr cannulas. The 10 Fr cannulas differ non-significantly except when water is used. Equivalent diameters obtained with water in the turbulent region are significantly higher than those obtained with fluids that have a higher viscosity (blood and aqueous glycerine mixture). The latter fluids have comparable viscosities and render an equal equivalent diameter. The coefficients of their proper parabolic fit lines can easily be recalculated into each other. This provides a simple method to quickly determine pressure drops in cannulas in the operating room.