Percutaneous heart valves; past, present and future.

Percutaneous heart valves provide a promising future for patients refused surgery on the grounds of significant technical challenges or high risk for complications. Since the first human intervention more than 10 years ago, over 50 different types of valves have been developed. The CoreValve and Edwards SAPIEN valves have both experienced clinical trials and the latter has gained FDA approval for implantation in patients considered inoperable. Current complications, such as major vascular bleeding and stroke, prevent these valves from being commonly deployed in patients considered operable in conventional surgery. This review focuses on the past and present achievements of these valves and highlights the design considerations required to progress development further. It is envisaged that, with continued improvement in valve design and with increased clinical and engineering experience, percutaneous heart valve replacement may one day be a viable option for lower-risk operable patients.

The aortic valve: structure, complications and implications for transcatheter aortic valve replacement.

The aortic valve operates in a complex haemodynamic environment, opening and closing over 100,000 times a day. When complications arise, such as aortic stenosis, prognosis can be very poor, leading to death within the first few years. Surgical valve replacement is currently the standard treatment for aortic stenosis. A thorough understanding of the anatomy and function of the native valve is imperative when developing a prosthetic replacement that can withstand the complex demands of the heart. This review focuses on the anatomy, structure and disease of the aortic valve and the implications for a transcatheter aortic valve replacement (TAVR). Current complications with TAVR, such as major vascular bleeding, conduction disturbances and patient-prosthesis mismatch (PPM), can be overcome by reducing the delivery profile and through the use of more accurate imaging technologies to work towards a fully functional and durable prosthesis.

Cytokines in the systemic inflammatory response syndrome: a review.

INTRODUCTION: Patients subject to major surgery, suffering sepsis, major trauma, or following cardiopulmonary bypass exhibit a systemic inflammatory response. This inflammatory response involves a complex array of inflammatory polypeptide molecules known as cytokines. It is well accepted that the loss of local control of the release of these cytokines leads to systemic inflammation and potentially deleterious consequences including the Systemic Inflammatory Response Syndrome, Multi-Organ Dysfunction Syndrome, shock and death. METHODS: The Medline database was searched for literature on mechanisms involved in the development of SIRS and potential targets for modifying the inflammatory response. We focus on the novel therapy of cytokine adsorption as a promising removal technology. RESULTS: Accumulating data from human studies and experimental animal models suggests that both pro- and anti- inflammatory cytokines are released following a variety of initiating stimuli including endotoxin release, complement activation, ischaemia reperfusion injury and others. DISCUSSION: Pro-and anti-inflammatory cytokines interact in a complex and unpredictable manner to influence the immune system and eventually cause multiple end organ effects. Cytokine adsorption therapy provides a potential solution to improving outcomes following Systemic Inflammatory Response Syndrome.

Surgical treatment of renal cell carcinoma with right atrial thrombus: early experience and description of a simplified technique.

Operative management of patients presenting renal cell carcinoma's (RCC) with right atrial tumor thrombus extension is a technical challenge. It requires the use of cardiopulmonary bypass (CPB). The aim of this study was to report our early experience and to describe a simplified CPB technique. 5 consecutive patients underwent surgical resection by a joint cardiovascular and urological team. The ascending aorta was canulated. The venous drainage was achieved using a proximal canula inserted in the superior vena cava and a distal canula inserted in the IVC below the renal veins. Right atrium thrombus extension was extracted under normothermic CPB without cross clamping or cardioplegic arrest. A cavotomy was performed at the ostium of the renal vein and an endoluminal occlusion catheter was introduced. The thrombectomy and the radical nephrectomy were then performed. The occurrence of gaseous or tumor embolism, operative time, perioperative bleeding, and post-operative complications were assessed. Mean patients age was 62.9 years. Atrial and caval thrombectomy were achieved successfully in all patients. Mean operative time was 206 min. Mean CPB time was 62 min. Mean hospital stay was 18.8 days. One death occurred, due to respiratory failure. An asymptomatic early thrombosis of the IVC was diagnosed by CT scan in 1 patient. The four remaining patients were alive 6 months after the surgical procedure. Minimally invasive CPB technique can be used to treat intra atrial thrombus tumor extension arising from renal cell carcinoma. It can be performed safely with acceptable complications rate.

A recovery model of minimally invasive cardiopulmonary bypass in the rat.

This study was undertaken to develop a rodent (rat) model of cardiopulmonary bypass (CPB) that has been designed to mimic functionally the minimally invasive clinical setting. The circuit is similar to the clinical model in terms of its construction, configuration, material surface area to blood volume ratio, and priming volume to blood ratio. The overall priming volume was 10 mL. Thirty-six male Sprague-Dawley rats (422 +/- 32 g) were anaesthetized while maintaining spontaneous ventilation. Anticoagulation was achieved with heparin (500 IU/kg). Blood arterial pressure was monitored continuously. Normal central temperature was maintained throughout. Intermittent arterial blood gas levels also were monitored. All animals were cannulated in preparation for CPB; however, CPB, utilizing a double roller pump and a flow rate of 100 mL/kg/minute for 60 min, was initiated in only 18 animals, the remaining 18 animals acting as non-CPB controls (Sham). The animals were haemodynamically stable. After the operative procedure, the animals were allowed to recover from the anaesthesia and, after transfer to a recovery facility, were monitored for a period of 1 week. There were no differences between the groups in terms of blood gas analysis and blood pressure data; all animals survived the procedure and had an uneventful follow-up. Differences were found between the CPB animals and the Sham group in terms of TNFalpha used as a marker of inflammatory processes. This trend tends to support this model as an analogue for the clinical scenario for future studies of CPB-related inflammation. Overall, the CPB procedure was easy to perform and was associated with excellent survival. This recovery model is an effective tool to perform pathophysiological studies associated with minimally invasive CPB.

Does cardiopulmonary bypass still represent a good investment? The biomaterials perspective.

Cardiopulmonary (CPB) bypass is 50 years old this year, and has undergone considerable change in that time, particularly with regard to developing technology. However, in recent years the routine application of CPB, as the treatment of choice for patients undergoing reparative heart surgery, has been challenged by new, evolving techniques, particularly Off-Pump Coronary Artery Bypass (OPCAB) and stenting. This paper considers whether CPB still represents a sound investment prospect, with particular emphasis on the biomaterial developments currently taking place. Whilst we accept that routine application of CPB is shrinking under pressure from less invasive techniques, we suggest that this may represent an opportunity to deliever a more highly evolved perfusion to the core of very sick and complex patients who may not be suitable candidates for OPCAB or stenting. These patients will benefit from the application of new technologies currently under development, such as smaller perfusion circuits, improved biomaterial surfaces, smart membranes, and biosensor technology, all aimed at making clinical perfusion a safer and more predictable procedure for the patient. All things considered, we feel that CPB, although shrinking in absolute size, still represents a good investment.

Biomaterial development for cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is dependent on materials foreign to the patient for its successful application. When blood comes into contact with these so-called biomaterials, an inappropriate inflammatory response, which can be life-threatening in some patients, may develop. The reason for this inappropriate activation of host defence mechanisms is not entirely clear, however a number of strategies have evolved over the years to minimize this unwanted sequelae of CPB. These strategies include surface coating of the materials of the circuit, using new materials thought to improve biocompatibility, and using a number of pharmacological interventions designed to suppress the inflammatory response. Recently, there has been some evidence which indicates that the plasticizer employed in the polyvinyl chloride (PVC) tubing of the CPB circuit may play a part in the development of the inflammatory response. The work described in this paper tends to support this thesis. These studies showed that by washing the plasticizer from the surface of the PVC tubing, the biocompatibility, as reflected in the upregulation of CD11b on the surface of neutrophils, was enhanced. Furthermore, the use of non-plasticized substitutes for PVC had a similar effect. The benefit from removing the plasticizer was similar to that gained from surface coating with heparin, one of the conventional approaches to reducing the inflammatory response to CPB.

The effect of circuit surface area on CD11b(mac-1) expression in a rat recirculation model.

The aim of the study was to assess the effect of exposed surface area of diethylhexylphthalate plasticized polyvinylchloride (PVC) on the expression of the adhesion molecule CD11b(mac-1) on neutrophils and to determine whether there is any apparent advantage in the current trend in reducing circuit surface area in terms of neutrophil activation. The study was carried out using a parallel plate rodent recirculation biomaterial testing model on 4 groups of 10 adult male Sprague Dawley rats weighing between 350 and 450 g. One group comprised the control group in which there was no biomaterial exposure. In the remaining 3 groups, the animals were subjected to either high (48 cm2), intermediate (24 cm2), or low (12 cm2) biomaterial surface area exposure. The parallel plate test cell was connected to the right femoral circulation and recirculation initiated at a flow rate of 1.5 ml/min for a period of 60 min. Blood samples were taken at 0, 30, and 60 min for the assessment of CD11b expression. Cd11b was assessed using flow cytometric analysis on neutrophils. The results demonstrated that there was a surface area related effect in the upregulation of CD11b. The difference at the terminal sample point between the highest surface area group (293.95 +/- 18.57%) and the low surface area group (133.80 +/- 49.31%) was highly statistically significant (p < 0.001). These results demonstrate that there may be some gain in terms of reduced inflammatory response from reducing the exposed surface area of PVC in extracorporeal perfusion circuits.

Leucodepletion during cardiopulmonary bypass reduces blood transfusion and crystalloid requirements.

Cardiopulmonary bypass (CPB) is associated with the production of inflammatory responses, which can have significant influence on prognosis. We studied the effects of leucocyte-depletion filters on inflammatory parameters and early postoperative prognosis during coronary revascularization. Twenty patients undergoing elective coronary revascularization were randomly divided into two groups. Ten patients had leucocyte-depletion filters added to the CPB circuit (treatment group) and 10 were used as control cases (control group). Expression of CD11b on neutrophils, and production of myeloperoxidase and lactoferrin, were measured in arterial samples between induction and 3 h postbypass. In addition, clinical parameters were measured during inpatient recovery. CD11b neutrophil expression, and myeloperoxidase and lactoferrin production, were found to be upregulated during CPB and then to decline to preoperative levels by the third postoperative hour. Blood transfusion requirements were reduced in the treatment group, equalling 1.5 +/- 1.2 units, compared to 2.7 +/- 1.1 units for the control group (p value = 0.034) and so were the volumes of crystalloid infused during the first 24 h postoperatively, equalling 3.9 +/- 1.21 in the treatment group and 3.3 +/- 0.71 in the control group (p value = 0.021). Overall, the application of leucocyte depletion produced an early clinical advantage, underlining the need for an improved understanding and manipulation of the inflammatory response to CPB.

A literature review of cardiopulmonary bypass models for rats.

Cardiopulmonary bypass (CPB) has improved a great deal since its first applications in the early 1950s. If improvements are to be continued, a preclinical model of CPB for small animals is desirable, mainly because of convenience of equipment and low costs. We review the different models of CPB for rats that have been designed, discuss their characteristics and points where improvements may be made. We give suggestions and requirements for a new up-to-date model that could be a useful tool in continued research on the pathophysiology and therapeutic strategies of CPB.

Oedema, Starling and pulse reverse osmosis: towards a possible biochemical marker for oedema.

Several conflicting theories have been proposed to explain the development of oedema. Pulse reverse osmosis (PRO) suggests that oedema occurs when the mean pulse capillary pressure exceeds the osmotic gradient between the plasma and the interstitial fluid. In order to test this concept mean arterial blood pressures and colloid osmotic pressures were taken in a group of healthy volunteers, a group of patients with bilateral ankle oedema and a group of treated hypertensives. Patients with oedema were found to have colloid osmotic pressures (COP's) which were significantly less than those of the healthy volunteers (p <0.001) and the treated hypertensives (p <0.001). The results support the oedema mechanism proposed by PRO and indicate that the relationship between blood pressure and COP may be a useful biochemical marker of oedema and its treatment. Further study is required to numerically quantify this relationship.

The therapeutic significance of pulse reverse osmosis.

Pulse reverse osmosis (1) is a new theory of fluid balance and exchange which suggests that the mean blood pressure and osmotic gradient control fluid balance and that the pulse controls fluid exchange. In vitro testing has confirmed some of the physico chemical principles underlying the theory (2). The hypothesis suggests a relationship between mean capillary blood pressure and osmotic gradient. Imbalance in this relationship can be related to the development of hypertension, hypotension, oedema and shock. In an attempt to test this concept mean blood pressures and colloid osmotic pressures were measured and compared in a group of 50 healthy human volunteers. The results suggest a curvilinear correlation between the mean blood pressure and the COP.

The effects of pulsatile flow on the leukocyte depleting qualities of the Pall LG6 leukocyte depleting arterial line filter: a laboratory investigation.

The Pall LG6 arterial line filter has, in a previous publication, demonstrated its inherent leukocyte depleting qualities. This initial study was however carried out under continuous flow conditions. The present study was designed to assess the effectiveness of the LG6 filter in performing this leukocyte removal function under the more dynamic conditions of pulsatile flow. In addition to leukocyte depletion, the general blood handling and degree of energy absorption associated with the LG6 and Stat-Prime filters was also assessed. The results demonstrated that the LG6 filter was unaffected by the flow regime employed in terms of leukocyte removal and platelet depletion. There was a higher level of measured haemolysis associated with the use of pulsatile rather than nonpulsatile flow, however, this was the case with both filter types and was not found to be the case when generated values were computed. The LG6 filter absorbed more energy than the Stat-Prime filter as reflected by energy equivalent pressure (EEP) measurement, but this difference did not reach a level which was considered to be clinically significant.

Laboratory evaluation of the Pall LG6 leukocyte depleting arterial line filter.

The Pall LG6 arterial line filter has been designed to remove free circulating leukocytes from the arterial line of the extracorporeal circuit employed in openheart surgery. The filter was evaluated and compared to a control filter (Pall Stat-Prime) in terms of its general blood handling characteristics, particularly with regard to the associated level of leukocyte removal. The gross air handling characteristics of the filters were also assessed together with pressure drop. It was found that the filters differed little in terms of all factors studied other than the level of leukocyte depletion. The LG6 filter was associated with substantial levels of leukocyte depletion, particularly the depletion of neutrophils. Over the 90 minute perfusion period the LG6 filter was found to be associated with a neutrophil depletion rate of around 70% while preferentially sparing lymphocytes. This compared to a 10-20% depletion rate in the control filter. This was achieved without apparently compromising the performance of the filter in terms of the other factors studied.