Heparin-coated Circuits Research Articles

Increased cerebral blood flow velocities assessed by transcranial Doppler examination is associated with complement activation after cardiopulmonary bypass

The role of complement activation on the cerebral vasculature after cardiopulmonary bypass (CPB) is unclear. The goal of the study was to assess whether heparin-coated CPB reduces complement activation, and influences cerebral blood flow velocities (CBFV). Twenty-four patients undergoing coronary surgery were randomly allocated to non-coated (NC-group) or heparin-coated (HC-group) CPB. Complement activation was assessed by measuring sC5b-9. Transcranial Doppler (TCD) was performed on middle cerebral arteries before and after CPB. Systolic (SV), diastolic (DV) and mean (MV) CBFV were measured. Significant increase of sC5b-9 (p=0.003) was observed in the NC-group and CBFV increased after CPB (SV by 27%, p=0.05; DV by 40%, p=0.06; MV by 33%, p=0.04) whereas no changes were detected in the HC-group. TCD values were higher in the NC-group than in the HC-group (SV, p=0.04; DV, p=0.03; MV, p=0.03) although cardiac index, systemic vascular resistance, haematocrit and pCO(2) were similar. Postoperative SV, DV and MV were significantly correlated with sC5b-9 (r=0.583, p=0.009; r=0.581, p=0.009; r=0.598, p=0.007, respectively). Increased CBFV after CPB are correlated to the level of complement activation and may be controlled by heparin-coated circuits.

Heparinized cardiopulmonary bypass circuits and low systemic anticoagulation: An analysis of nearly 6000 patients undergoing coronary artery bypass grafting

Heparin coating of cardiopulmonary bypass circuits reduces the inflammatory response and increases the thromboresistance during extracorporeal circulation. These properties enables a lower systemic heparin dose, which has been shown to reduce the need for blood transfusions. Experience with this technique accumulated over 11 years has been analyzed. All patients underwent on-pump coronary artery bypass grafting with heparin-coated circuits. Apart from some patients receiving a high intraoperative dose of aprotinin, the systemic heparin dose was reduced, with a lower level of an activated clotting time of 250 seconds during extracorporeal circulation. The overall strategy aimed at a fast-track regimen, with early extubation, minimal use of blood transfusions, and rapid postoperative recovery. Altogether, 5954 patients were included; 1131 (19.0%) were female (median age, 70 years), and 4823 were male (median age, 65 years). The median additive EuroSCORE was 3 (range, 0-14; mean 3.5 ± 2.5). No significant signs of clotting were seen in any part of the extracorporeal circuit. Bank blood products were given to 427 (7.2%) patients. Median extubation time was 1.7 hours. The stroke rate was 1.0%, transient neurologic deficits occurred in 0.7%, and perioperative myocardial infarction occurred in 1.2%. On the fifth day, 88.1% of the patients were physically rehabilitated and ready for discharge. Thirty-day mortality was 0.9% (54 patients). The experience with this patient cohort including mostly low- to medium-risk patients with a relatively short cardiopulmonary bypass time indicates that coronary artery bypass grafting performed with heparin-coated circuits and reduced level of systemic heparinization is safe and results in a very satisfactory clinical course. No signs of clotting or other technical incidents were recorded.

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

In High-Risk Patients, Combination of Antiinflammatory Procedures During Cardiopulmonary Bypass Can Reduce Incidences of Inflammation and Oxidative Stress

Previous studies showed that cardiopulmonary bypass (CPB) was directly associated with a global activation of the inflammatory response, production of oxygen free radicals, and signs of myocardial injury. We therefore evaluated, in the weakest patients, the biological and clinical benefits of a therapeutic optimization of CPB through the combination of several antiinflammatory procedures. High-risk patients undergoing cardiac surgery under CPB were included in this prospective randomized study. Control patients (n = 14) underwent conventional CPB, and treated patients (n = 13) underwent a CPB with Baxter Duraflo II heparin-coated circuits, high doses of aprotinin, and pre-CPB hemofiltration. Usual clinical hemodynamic and biological criteria, inflammation, and oxidative stress markers were measured before, during, and to the second postoperative day. Free radicals were quantified using electronic spin resonance spectroscopy with a spin trap. Significantly lower concentrations of C-reactive protein, interleukin-6, creatine kinase-MB, I-troponin, lactic acid, and systemic free radicals were observed in the plasma of treated patients. These patients had a reduction of postoperative complications and of the length of stay in the intensive care unit. Therefore, pre-CPB therapeutic optimization can reduce the inflammatory response, lower the level of oxidative stress, and help to ameliorate clinical outcome in high-risk patients.

Comparison of polymethoxyethylacrylate-coated circuits with leukocyte filtration and reduced heparinization protocol on heparin-bonded circuits in different risk cohorts

The relative benefits of strategic leukofiltration on polymer-coated and low-dose heparin protocol on heparin-coated circuits were studied across EuroSCORE patient risk strata for three different cohorts. In a prospective, randomized study, 270 patients undergoing coronary artery bypass grafting were allocated into three groups (n = 90): Group 1 - polymethoxyethylacrylate-coated circuits + leukocyte filters; Group 2 - polypeptide-based heparin-bonded circuits with reduced heparinization; and Group 3--CONTROL: uncoated circuits. Each group was further divided into three subgroups (n = 30), with respect to low- (EuroSCORE 0-2), medium- (3-5), and high- (6+) risk patients. Blood samples were collected at T1: following induction of anesthesia; T2: following heparin administration; T3: 15 min after CPB; T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: ICU. In high-risk cohorts, leukocyte counts demonstrated significant differences at T4 and T5 in Group 1, and at T4 in Group 2. Platelet counts were preserved significantly better at T4 and T5 in both groups (p < 0.05 versus control). Serum IL-2 and C3a levels were significantly lower at T3, T4 and T5 in Group 1, and T4 and T5 in Group 2 (p < 0.05). Postoperative bleeding, respiratory support time and incidence of atrial fibrillation were lower in the study groups versus control. Cell counts on filter mesh and heparin-coated fibers/ circuits were significantly higher in the high-risk cohorts versus uncoated fibers. Phagocytic capacity increased on filter mesh, especially in high-risk specimens. SEM evaluation demonstrated better preserved coated circuits. Leukofiltration and coating reduced platelet adhesion, protein adsorption, atrial fibrillation and reduced heparinization acted via modulation of systemic inflammatory response in high-risk groups.

Recent developments in the perioperative management of the paediatric cardiac patient

Survival of infants born with complex cardiac anomalies has dramatically improved, and the growing population of patients with congenital heart disease reaching adulthood has resulted in an increased incidence of long-term complications related to the perioperative period. This review focuses on recent advances in strategies to prevent, detect, treat, or predict early and late complications arising from open heart surgery for congenital heart disease. Aprotinine and recombinant factor VIIa may effectively reduce the risk of excessive perioperative bleeding, and the use of steroids, complement component C4A, heparin-coated circuits, and modified ultrafiltration may play a role in the control of the postoperative inflammatory response. Milrinone is becoming increasingly popular in the prevention and treatment of the reduced postoperative cardiac output, and extracorporeal life support has become a well established and successful form of support for postoperative myocardial dysfunction, even in the functionally univentricular heart. In recent years interest increased in optimizing myocardial protection using contents-differentiated and temperature-differentiated blood cardioplegia and in optimizing cerebral protection using a higher haematocrit during bypass and by using selective regional perfusion in favour of circulatory arrest. Hearts can be mended, but salvation of hearts and brains needs further rigorous attention.

Does the Additional Use of Heparin-Coated Extracorporeal Circuits (ECC) Optimize the Effect of Modified Ultrafiltration (MUF) in Pediatric Perfusion?

Modified ultrafiltration (MUF) has been shown to exert beneficial effects on the coagulation system and the capillary leak after pediatric cardiac surgery using extracorporeal circulation (ECC). The aim of this study was to investigate whether the additional use of heparin-coated circuits is a useful option for improving biocompatibility. We randomized 28 children, using heparin-coated ECC circuits in group A (n = 14) and an uncoated equivalent set in group B (n = 14). After congenital heart surgery, MUF was performed post ECC in a standardized fashion. Blood samples were analyzed preoperatively, 10 min, 30 min, 1 h, and 48 h after ECC by flow cytometric analysis (FACSort) using surface antigens CD62/CD41b (platelets) and CD45/CD14 (monocytes). No significant difference was found with respect to mean age (20.6 months vs. 21.6 months), mean body weight (9.2 kg vs. 8.4 kg), mean ultrafiltration rate (9.1 ml/kg vs. 11.4 ml/kg), chest tube drainage, blood products, ICU stay, and 30-d survival. The percentage of CD62/CD41-positive platelets in group A (vs. B) increased up to 118 % at 60 min vs. 130 % ( P < 0.05) and declined to 98 % at 48 h postop. vs. 99 % (n. s.). The percentage of CD45/CD14-positive monocytes in group A (vs. B) increased up to 158 % at 60 min vs. 155 % (n. s.) and declined to 122 % (A) at 48 h postop. vs. 61 % (B) ( P > 0.05). Heparin coating of ECC in addition to MUF leads to a lower platelet activation. Monocyte surface markers CD45 and CD14 indicated a marked activation during ECC in both groups but additional heparin coating showed a better postoperative regeneration of monocyte markers in the late course indicating a beneficial additive effect.

Percutaneous Cardiopulmonary Support for Emergency In-Hospital Cardiac Arrest or Cardiogenic Shock

Background and Objectives:Percutaneous cardiopulmonary support (PCPS) provides hemodynamic stability for the treatment of patients suffering with cardiogenic shock or cardiac arrest, and it can be used in a wide variety of clinical settings without the need for chest exploration. In this study, we summarize a single center’s experience with performing PCPS in the patients who suffered with severe cardiopulmonary failure. Subjects and Methods: We retrospectively reviewed 30 consecutive patients with cardiac arrest or severe cardiogenic shock who received PCPS for cardiac resuscitation from November 2003 to July 2005. The self-priming, heparin-coated circuit of the Emergency Bypass System was used in all the patients. Cannulation was performed via the femoral artery and vein with using an arterial (17 to 21 French) and venous cannula (21 to 28 French), percutaneously or with a small incision. Results:The Indications for PCPS were: ischemic heart disease before coronary revascularization, myocardial disease, PCI-associated complications and post-operative hemodynamic collapse. Of the 30 patients we evaluated, 19 patients (63%) were successfully weaned off of the PCPS; 14 of these patients (47%) were later discharged from the hospital. For the survivors, the time interval from cardiac arrest or severe cardiogenic shock to the onset of PCPS was significantly shorter (p=0.01), and the urine output for the initial 24 hours was significantly higher (p=0.04). Conclusion:This retrospective analysis demonstrates the effectiveness of using PCPS for the treatment of critically unstable patients with cardiac arrest or cardiogenic shock. Larger scale studies of PCPS are now needed to confirm these findings. (Korean Circulation J 2006;36:11-16)

Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery

The complement cascade and granulocytes are activated in on-pump cardiac surgery. If activation of complement directly regulates granulocytes, granulocyte elastase (GEL) should increase significantly after protamine administration. We examined the effect of protamine on granulocytes by protamine administration and observation of the effect on GEL and C3a. Thirty patients who underwent coronary artery bypass grafting were randomly assigned to two groups. In 15 patients, protamine was administered 5 min after the termination of cardiopulmonary bypass, and was administered 35 min after cardiopulmonary bypass in the other 15 patients. All patients were perfused with heparin-coated circuits and received 300 IU/kg heparin and 3 mg/kg protamine. GEL and C3a concentrations were measured at 7 time points. GEL concentrations increased significantly just before aortic declamping and did not increase significantly after protamine administration. C3a concentrations, however, did not increase during cardiopulmonary bypass and did increase significantly after protamine administration. This study indicates that GEL does not increase after protamine administration and that complement concentration does not directly affect GEL release.

Intraoperative Interventions: American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery

A comprehensive evidence review was conducted of the medical literature regarding the relationship between intraoperative interventions and the incidence of postoperative atrial arrhythmias, including, most commonly, atrial fibrillation (AF). Fifteen randomized, controlled studies and one large-scale concurrent cohort study were identified that reported on the following issues: systemic temperature during surgery (one report); "beating heart" surgery vs conventional bypass surgery (three reports); type of myocardial protection (five reports); the use of adjunctive posterior pericardiotomy (one report); the use of thoracic epidural anesthesia (TEA) [two reports]; the use of glucose-insulin-potassium (GIK) solutions (two reports); and the use of heparin-coated circuits for cardiopulmonary bypass (CPB) [two reports]. Based on a systematic review of the reported data and an analysis of the quality of the reported data, we recommend the following: (1) that mild hypothermia, rather than moderate hypothermia, may be effective in reducing the frequency of postoperative AF; (2) the use of posterior pericardiotomy may be a useful adjunct to reduce the frequency of postoperative AF; and (3) the use of heparin-coated CPB circuits is associated with less postoperative AF. Because of conflicting or inadequate data, we cannot conclude that the frequency of postoperative AF is affected by (1) the use of beating-heart techniques, (2) the type of myocardial protection strategy used, (3) the use of TEA, or (4) the use of GIK solutions perioperatively.

PMEA Polymer-Coated PVC Tubing Maintains Anti-Thrombogenic Properties during in vitro Whole Blood Circulation

Poly(2-methoxyethylacrylate) (PMEA) is a new coating material that appears to reduce protein and platelet adsorption. However, the exact performance of PMEA coated circuit remains to be revealed in well-controlled experiments. Therefore, we compared its hemocompatibility with covalent-bound heparin-, and non-coated circuits during 6 hours of in vitro circulation, using donor blood from six volunteers. In our model, simple tubing circuits containing one-way ball valve were placed on the rotary table, which moved alternatively to generate pulsatile recirculation of heparinized human blood inside the tubing. Using this model, we expected fine assessment of the material surface, because we could reduce blood damage by avoiding air and a blood pump. Moreover, the small capacity of circuit allowed us to compare three kinds of circuits using a single unit of donor blood, eliminating effects by possible variations between blood donors. The anti-thrombin capacity of the PMEA-coated circuits was maintained even after six hours blood circulation, whereas surface thrombin generation increased markedly after use in non-coated circuits (P<0.05). Deposition of fibrin onto PMEA circuits was reduced more than 30% compared with heparin and non-coated circuits (P<0.05). However, the increase of plasma Factor XIIa was similar in all circuits. Increase of CD11b expression on circulating leukocytes and of plasma C3a was ameliorated in the heparin- and PMEA-coated circuits (P<0.05). PMEA-coated circuits appear to maintain their anti-thrombogenicity during use, otherwise PMEA-coated and heparin-coated circuits showed a similar character in hemocompatibility. This long-standing anti-thrombogenicity might be attributable to less adsorption of activated blood components onto the surface.

Strategies to reduce hemostatic activation during cardiopulmonary bypass

Introduction We evaluated whether a modified protocol for cardiopulmonary bypass (CPB) could reduced the systemic hemostatic activation associated with this procedure. Materials and methods The in vivo rates of thrombin, fibrin, plasmin and D-dimer generation were determined in each subject during CPB using measured levels of hemostatic factors combined with a computer model of the cardiovascular and hemostatic systems. A standard CPB group using uncoated circuits, standard heparin levels and direct shed blood reinfusion ( n = 9) was compared to a modified CPB group using heparin-coated circuits, shed blood collection, washing and reinfusion post-operatively, lower heparin levels and epsilon-amino-caproic acid ( n = 10). Results and conclusions Standard CPB increased average thrombin generation 9-fold, decreased fibrin generation 2-fold, increased plasmin generation 11-fold and increased fibrin degradation and D-dimer generation 19-fold. During CPB in the modified group thrombin generation was not increased beyond surgical levels, lower heparin concentrations allowed each thrombin to make more fibrin prior to inhibition, while fibrin degradation was suppressed by epsilon-amino-caproic acid. At baseline for every 100 fibrins formed only 1–2 were degraded to D-dimer. During standard CPB for every 100 fibrins generated on average 34 fibrins were degraded with some subjects showing a net fibrin loss. In contrast, in the modified CPB group for every 100 fibrins formed only 4 fibrins were degraded ( p < 0.0001 vs. standard group). Kinetic modeling of hemostasis in individual patients showed that a modified CPB protocol could reduce excessive thrombin generation during CPB and suppress fibrin degradation moving hemostatic regulation back towards normal.

The Impact of Heparin-Coated Cardiopulmonary Bypass Circuits on Pulmonary Function and the Release of Inflammatory Mediators

The Impact of Heparin-Coated Cardiopulmonary Bypass Circuits on Pulmonary Function and the Release of Inflammatory Mediators

Descending Thoracic Aortic Aneurysm Repair With the Aid of Partial Cardiopulmonary Bypass: Heparin‐coated Circuits Versus Nonheparin‐coated Circuits

We have performed descending thoracic aortic aneurysm repairs with partial cardiopulmonary bypass, including heparin-coated circuits. The aim of this study was to evaluate (i) the impact of partial cardiopulmonary bypass on distal organ function and surgical outcomes; and (ii) the effectiveness of using heparin-coated circuits for preventing bleeding complications. From July 1980 to June 2004, 309 patients underwent descending thoracic aortic aneurysm repairs using partial cardiopulmonary bypass. Their mean age was 61 years (range 19-81 years). One hundred of the 309 patients underwent repair of descending thoracic aortic aneurysm with heparin-coated circuits. Blood data for renal and hepatic function were collected on the day before the operation and postoperative days. The in-hospital mortality was 15%. Distal organ dysfunction included spinal cord dysfunction in 2 patients (0.7%) and renal failure necessitating hemodialysis in 15 patients (5%, 15/297: excluded 12 dialysis patients). Multivariate analyses showed that preoperative hemodialysis and emergency operation were risk factors for operative mortality and that emergency operation was a risk factor for requiring hemodialysis. Renal and hepatic function normalized by 2 weeks after surgery. There were no significant differences between the heparin-coated group and nonheparin-coated group in amounts of packed red cells, fresh frozen plasma, and platelets transfused during the procedures. Our data showed that partial cardiopulmonary bypass is a safe and effective method for distal perfusion. Using this technique, descending thoracic aortic aneurysm repair can be performed with acceptable mortality and morbidity. However, the superiority of heparin-coated circuits over nonheparin-coated ones was not proved.

Bluntly traumatic tracheal transection: usefulness of percutaneous cardiopulmonary support for maintenance of gas exchange

Respiratory management of tracheal injuries is a crucial key to successful treatment. We present herein a patient with a traumatic tracheal transection in whom we confronted difficulty in airway management after false intratracheal intubation. No associated injuries were seen in the patient, then, primary repair of the trachea was carried out under ventilatory support via percutaneous cardiopulmonary support system (PCPS). For a short period in the application of PCPS, the use of a heparin-coated circuit made systemic heparinization unnecessary during and after operation, and the outcome was satisfactory. In a carefully selected patient, ventilatory support via PCPS is useful.

Does the additional use of heparin-coated extracorporeal circuits (ECC) optimize the effect of Modified Ultrafiltration (MUF) in pediatric perfusion?

Objectives: Modified ultrafiltration (MUF) has been shown to exert beneficial effects on the coagulation system and the capillary leak after pediatric cardiac surgery using extracorporeal circulation (ECC). Aim of this study was to investigate if the additional use of heparin-coated circuits is a useful option for improving biocompatibility.

A Closed Perfusion System With Heparin Coating and Centrifugal Pump Improves Cardiopulmonary Bypass Biocompatibility in Elderly Patients

Cardiopulmonary bypass induces a systemic inflammatory and hemostatic activation, which may contribute to postoperative complications. Our aim was to compare the inflammatory response, coagulation, and fibrinolytic activation between two different perfusion systems: one theoretically more biocompatible with a closed-circuit, complete heparin coating, and a centrifugal pump, and one conventional system with uncoated circuit, roller pump, and a hard-shell venous reservoir. Forty-one elderly patients (mean age, 73 +/- 1 years, 66% men) undergoing coronary artery bypass grafting or aortic valve replacement were included in a prospective, randomized study. Plasma concentrations of complement factors (C3a, C4d, Bb, and sC5b-9), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-8), granulocyte degradation products (polymorphonuclear elastase), and markers of coagulation (thrombin-antithrombin) and fibrinolysis (D-dimer, tissue plasminogen activator antigen and tissue plasminogen activator-plasminogen activator inhibitor-1 complex) were measured preoperatively, at bypass during rewarming (35 degrees C), 60 minutes after bypass, and on day 1 after surgery. The mean concentrations of C3a (-39%; p = 0.008), Bb (-38%; p < 0.001), sC5b-9 (-70%; p < 0.001), interleukin-8 (-60%; p = 0.009), polymorphonuclear-elastase (-55%; p < 0.003), and tissue plasminogen activator antigen (-51%; p = 0.012) were all significantly lower in the biocompatible group during rewarming. Sixty minutes after bypass, the mean concentrations of sC5b-9 (-39%; p = 0.006) and polymorphonuclear-elastase (-55%; p < 0.001) were lower in the biocompatible group. The results suggest that a closed perfusion system with a heparin-coated circuit and a centrifugal pump may improve cardiopulmonary bypass biocompatibility in elderly cardiac surgery patients in comparison with a conventional system.

New strategies to control the inflammatory response in cardiac surgery

To present and interpret data from recent clinical studies (July 2002-August 2003) of strategies to control the inflammatory response after cardiac surgery. Off-pump coronary artery bypass techniques, which avoid the need for extracorporeal circulation, attenuate the inflammatory response and appear to confer clinical benefit. Concerns regarding the quality of the revascularization after off-pump coronary artery bypass appear to have been allayed. At present, ventricular assist devices do not enhance the efficacy of off-pump coronary artery bypass. In patients undergoing cardiopulmonary bypass, heparin-coated circuits, hypothermic pulmonary perfusion, normoxic reperfusion after aortic unclamping, and modified ultrafiltration hold promise. Strategies to maintain perioperative haemodynamic stability, such as enoximone therapy, may be beneficial, particularly in elderly patients. Aprotinin may have important beneficial anti-inflammatory actions in higher-risk adult and paediatric patients. The therapeutic potential of corticosteroids, particularly when administered in multiple dosages is increasingly clear. Direct anti-mediator therapies that focus upon key effector molecules and pathways of the inflammatory response offer future therapeutic options. The potential for strategies that inhibit the inflammatory response to improve outcome after cardiac surgery is clear. Large-scale multicentre trials investigating the most promising strategies, including off-pump coronary artery bypass, heparin-coated circuits, and perioperative corticosteroid and aprotinin therapy, are urgently needed. These trials need to be restricted to the high-risk patient groups most likely to experience benefit. In the interim, the optimal strategy to minimize the inflammatory response to cardiac surgery will remain elusive.

The inflammatory response to cardiopulmonary bypass: a therapeutic overview.

The demographic of cardiac surgery patients continues to evolve to include older, sicker candidates, all the while maintaining an expectation of excellent outcomes. These latter results can only be achieved by the parallel advancement and re-examination of the technology of cardiopulmonary bypass (CPB); the key tool used daily by surgical teams worldwide. In this review, we will provide an overview of integrated therapeutic strategies that can be utilized to minimize the complex and myriad changes related to inflammation after CPB with the understanding that this may abrogate the detrimental end-organ and systemic effects of blood activation. Therapeutic strategies specifically related to the technology can be classified into those targeting biomaterial dependent or independent processes. The former can be addressed by the utilization of currently available biocompatible surfaces such as with heparin-coated circuits, phosphorylcholine-coated circuits ('biomembrane mimicry') and circuits composed of copolymers containing surface-modifying additives. The most important strategies related to biomaterial independent activation include the modification of techniques related to cardiotomy blood management and blood filtration. Finally, all of these strategies must be integrated and tailored with complementary pharmacologic agents such as aprotinin and steroids to optimize anti-inflammatory synergism. Only if we are armed with a comprehensive knowledge of the molecular and cellular basis for these strategies will we be able to continue to evolve our treatment in parallel with our patients to achieve these goals.

Improving Cardiopulmonary Bypass: Heparin-Coated Circuits

Heparin-coated circuits have been repeatedly proven to reduce the inflammatory response and foreign surface activation triggered upon initiation of cardiopulmonary bypass (CPB). In recent years, increasing numbers of studies are proving significant reductions in postoperative blood loss and transfusion requirements and improvements in clinical outcomes as a result of heparin-coated circuits. These results are promising steps in our efforts to improve CPB, as our patient population gets older and more complicated.