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.

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.

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.

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.

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.

Effect of perfusion temperature on glucose and electrolyte transport during hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin.

INTRODUCTION: Hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin is increasingly used in patients with carcinomatosis from colorectal cancer. For reasons of chemical stability, oxaliplatin can only be administered in a dextrose (D5%) solution, and this causes peroperative glucose and electrolyte shifts. Here, we examined the influence of perfusion temperature on glucose and electrolyte transport, metabolic shifts, and surgical morbidity. METHODS: Patients with carcinomatosis underwent cytoreduction and HIPEC using oxaliplatin (460 mg/m(2) in D5%, open abdomen) during 30 min at 39°-41 °C. Intraperitoneal (IP) temperature was measured at three locations using thermocouple probes. The area under the temperature versus time curve (AUCt) was calculated using the trapezoid rule. The influence of perfusion temperature on surgical outcome was assessed using linear regression models and the Mann Whitney U test where appropriate. RESULTS: From July 2005 until March 2011, 145 procedures were performed in 139 patients with a diagnosis of CRC (70%), pseudomyxoma peritonei (11%), ovarian cancer (10%), or miscellaneous peritoneal malignancies (9%). Postoperative mortality and major morbidity were 1.4% and 26%, respectively. Higher perfusion temperature was related to more pronounced changes in serum glucose (P = 0.058), sodium (P = 0.017), and lactate (P < 0.001). The median duration of nasogastric drainage was 5 days, and this was unrelated to perfusion temperature (P = 0.76). The GI fistula rate and reoperation rate were 12.4% and 16.5% respectively; neither was related to perfusion temperature. CONCLUSIONS: In patients undergoing HIPEC with oxaliplatin, perfusion temperature exacerbates peroperative metabolic shifts but does not affect surgical outcome.

End-organ protection in cardiac surgery.

Mortality and morbidity postcardiac surgery with cardiopulmonary bypass (CPB) remain relative stable over the last decades, while the number of patients with increased comorbidity and more complex cardiac disease increases. Nevertheless, end-organ dysfunction and/or failure remain an issue. Multiple perioperative variables, such as non-optimal oxygen delivery, manipulation of the aorta, hyperlactatemia, type of anesthesia, surgical procedure and myocardial protection can be hold responsible for end-organ failure postcardiac surgery. However, it becomes more and more evident that also pre-existing factors, such as metabolic syndrome, renal insufficiency, hypertension, stroke and infection exacerbate mortality and morbidity. Unfortunately, these predisposing risk factors cannot be influenced perioperatively. Therefore, therapy should focus on controlling perioperative variables that, in combination with the predisposing factors, will further exacerbate organ dysfunction. In order to achieve this, more emphasis should be given to a patient-specific, goal-directed perfusion approach. This review will mainly focus on the impact of perioperative variables.

Platelet gel supernatant as a potential tool to repopulate acellular heart valves.

OBJECTIVE: The aim of this study was to repopulate decellularized heart valve matrices with ovine mesenchymal stem cells (oMSCs) by the use of platelet gel (PG) supernatant, a storage vehicle for growth factors. METHODS: oMSCs were exposed to different concentrations of PG-released supernatant and cell proliferation was evaluated using the MTS assay. oMSC motility and invasiveness were assayed using a Boyden chamber. A quantitative sandwich enzyme immunoassay was used to examine amounts of bFGF and TGF-ß1 in the PG supernatant. Repopulation of acellular heart valve matrices was stimulated by seeding matrices with oMSCs supplemented with the PG supernatant. RESULTS: The most significant increase in proliferation induced by PG supernatant appeared at 1 × 10(5) plts/ml concentration. Higher concentrations evoked reduction of the stimulatory process. oMSC motility was most significantly stimulated at 1 × 10(6) plts/ml. Stimulating invasiveness of oMSCs needed the much higher concentration of 2 × 10(6) plts/ml. Immunoassays revealed that sheep PG supernatant contains 184.8 pg/ml bFGF and 60.5 ng/ml TGF-ß1. Moreover, repopulation of acellular heart valve matrices was significantly enhanced by PG supernatant addition and resulted in upregulation of the myofibroblast marker alpha-smooth muscle actin. CONCLUSIONS: Growth factors released from platelets had the potential to induce cell repopulation in a heart valve tissue engineering procedure, through stimulation of mesenchymal stem-cell migration and invasion.

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.

Left ventricular diverticulum: incidental finding on dual source cardiac CT.

The purpose of this retrospective study is to describe the prevalence, size and location of left ventricular (LV) diverticulum-diverticuli on cardiac dual source CT. Dual source computed tomography cardiac angiography (DS CTCA) was performed in 482 patients. Where literature states their rare occurrence, this retrospective study demonstrates the fairly common finding of incidental LV diverticulum on DS CTCA examinations. LV diverticuli were found incidentally in 20 out of 482 patients (4.1%), a substantially higher incidence than previously reported. Although diverticuli were most common along the inferoseptal wall (45%) they also occurred in all parts of the left ventricular wall. Multiple diverticuli were found in 30% of patients. Dimensions of the LV diverticuli varied enormously. LV diverticuli are reported to be frequently associated with other congenital anomalies. Complications ranging from sudden death and heart failure to embolic events have been described in literature. No relevant associated anomaly or complication was present in the studied 20 patients. Our data support the hypothesis that LV diverticuli, incidentally found in adulthood, follow a benign course and can be managed conservatively. More knowledge is however required to understand history and prognosis about this condition.

Haemostasis monitoring during sequential aortic valve replacement and liver transplantation.

Despite advances in anaesthesiological and surgical techniques, cardiac surgery in cirrhotic patients remains hazardous. This report outlines our experience with haemostasis monitoring in two consecutive cases of sequential aortic valve replacement and liver transplantation. Clotting disturbances proved to have fatal consequences since one of these patients died following massive lung embolism. The second patient underwent successfully this combined procedure and is in good clinical state 14 months postoperatively. Evaluation and discussion of the coagulation monitoring by the Sonoclot Analyzer in both patients and related therapeutic suggestions for the prevention of thrombotic events are discussed.

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.

Interaction of plasma proteins with commercial protein repellent polyvinyl chloride (PVC): a word of caution.

Protein adsorption onto polymers remains a problem. In recent years, several protein-repellent PVC tubings have been developed. Although several studies report the interaction between plasma coagulation proteins and PVC, few address the interaction with other plasma proteins. Two commercial brands of untreated medical grade PVC tubing, phosphorylcholine-coated PVC tubing, triblock-copolymer (polycaprolactone-polydimethylsiloxane-polycaprolactone)-treated PVC tubing and poly-2-methoxyethylacrylate (PMEA)-coated tubing were exposed for 60 minutes to human plasma. A broad spectrum of plasma proteins was found on all tubing. The adsorbed albumin to total protein ratio is lower than the similar ratio in plasma while alpha1 and alpha2 globulins are over-represented in the protein spectrum. On PMEA tubing, not only alpha globulins, but also beta and gamma globulins, are found in high concentrations in the adsorbed protein. PMEA tubing and uncoated PVC tubing of brand B had a higher amount of protein adsorbed compared against all other tubing (p < 0.05). There were no statistical differences in protein adsorption between the triblock-copolymer-treated tubing, the phosphorylcholine-coated tubing and the uncoated PVC tubing of brand A. The average thickness of the protein layer was 23 nm. Plasma protein adsorption still exists on uncoated and protein-repellent tubing and can initiate a systemic inflammatory reaction.

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.

Evaluation of different paediatric venous cannulae using gravity drainage and VAVD: an in vitro study.

Six different commercially available paediatric venous cannulae, together with a specially constructed cannula, were tested in vitro for their pressure-flow relationship. With the cannulae placed in an open reservoir, flow increased with larger diameters and higher pressures. At a pressure of 30 cm H2O, flows were 219 +/- 20, 285 +/- 13, 422 +/- 11 and 728 +/- 4 ml/min for the 12, 13.2, 14 and 16 French, respectively. No differences were found between angled and straight cannulae. When the cannulae were tested in a latex model simulating the right atrium and vena cavae, the highest flow obtained by gravity was 164 ml/min using an angled 14-French cannula. When vacuum was applied to augment venous return, a maximum flow of 179 ml/min was measured using an angled 14-French cannula. Collapse can occur when the pressure difference becomes too high in the test system. This is important, since most children are selectively cannulated in both major veins. Monitoring of the intravascular pressure might help to prevent collapse. A larger-diameter venous cannula does not always produce the highest flow when placed in a vein. This is most obvious when augmenting venous return. The design of the cannula tip, in combination with VAVD, can affect the venous return.