Biomedical subjects

Xavier M Mueller

Publications and source records attributed to Xavier M Mueller.

17 recordsLinked to original sources

PubMed2004

Drug immunosuppression therapy for adult heart transplantation. Part 1: immune response to allograft and mechanism of action of immunosuppressants.

In the early days of transplantation, immunosuppression therapy was rather broad and nonspecific, mainly using high-dose corticosteroids and azathioprine. Thereafter we progressively narrowed the target of immunosuppressive strategy starting with polyclonal antibodies. The introduction of cyclosporine, OKT3, and tacrolimus further narrowed the target on the T-cell pathways. More recently mycophenolate mofetil progressively took the place of azathioprine with its higher lymphocyte specificity and sirolimus and interleukin-2 receptor antibodies were introduced. In this field in constant movement the aim is to find a drug or a regimen that provides optimal immunosuppression therapy with minimal side effects, in other words to find the right balance between overimmunosuppression and underimmunosuppression therapy. This review is divided into two parts. The first part will provide a basic understanding of the immunologic response to allograft and explain how conventional and recently introduced immunosuppressive agents work. The second part will describe the clinical application of immunosuppressive drugs to provide practical information for those in charge of heart transplant recipients.

Adrenal Cortex Hormones↗

PubMed2004

Drug immunosuppression therapy for adult heart transplantation. Part 2: clinical applications and results.

This review describes the clinical application of classical immunosuppressive drugs as well as that of more recent drugs. All current immunosuppressive drugs target T-cell activation, and cytokine production and clonal expansion, or both. Immunosuppressive protocols can be broadly divided into induction therapy, maintenance immunosuppression, and treatment of acute rejection episodes.

Acute Disease↗

PubMed2004

High prevalence of unsuspected abdominal aortic aneurysms in patients hospitalised for surgical coronary revascularisation.

OBJECTIVES: Prevalence of abdominal aortic aneurysms (AAA) is not exactly known among patients with coronary artery disease (CAD) who are considered for surgical revascularisation. We evaluated the value of screening AAA among coronary patients admitted in our cardiovascular surgery unit. METHODS: Over a 24-month period, an abdominal echography was proposed to male patients aged 60 or more while hospitalised for surgical coronary revascularisation. Patients with previous investigation of the aorta were excluded. The aorta was considered aneurysmal when the anterior-posterior diameter was of 30 mm or more. RESULTS: Three hundred and ninety-five consecutive patients all accepted a proposed abdominal echographic screening for AAA. Forty unsuspected AAA were detected (10.1%). The mean diameter was 38.9 +/- 1.3 mm. Four AAA were larger than 50 mm and considered for surgery after the CABG procedure. Surveillance was proposed to the other 36, especially the 10 patients with an AAA larger than 40 mm. Patients with AAA were significantly older than those without AAA (71.3 +/- 0.8 vs. 69.4 +/- 0.3 years, P<0.05). Smoking history (P<0.05) and hypertension (P<0.05) were also associated more frequently with AAA. More than 16% of the patients being smokers and suffering hypertension presented with unsuspected AAA. CONCLUSIONS: In-hospital screening of AAA is very efficient among patients with coronary artery disease. Therefore, patients with CAD may be considered for routine AAA screening.

Aged↗

PubMed2003

A new equine pericardial stentless valve.

OBJECTIVE: Small aortic valve replacement remains a challenging hemodynamic problem. A new bioprosthesis (3F Therapeutics, Lake Forest, Calif) was designed to further improve the hemodynamic performance currently achieved with stentless bioprostheses. This valve consists of a tubular structure assembled from 3 equal sections of equine pericardial material, with virtually no foreign material except for a thin polyester ring. Its hemodynamic performance was compared with that of a commercially available stentless prosthesis in a bovine model. PATIENTS AND METHODS: Twelve calves (55 +/- 2.8 kg) received a 19-mm 3F valve (3F group, n = 6) or a 19-mm stentless control valve (control group, n = 6). The animals were fully equipped for hemodynamic monitoring and transvalvular gradient measurements. After implantation, dopamine was infused in increasing doses, and the hemodynamic values were recorded at each step of 100-microg/min increase. Linear regression analysis was applied for group comparison of each variable. RESULTS: The mean transvalvular gradient at 4.5 L/min was 3.48 +/- 0.14 mm Hg (95% confidence interval) in the 3F group and 5.72 +/- 0.28 mm Hg in the control group (P <.0001) and at 6.5 L/min, 7.4 +/- 1.55 mm Hg, and 11.13 +/- 0.18 mm Hg, respectively (P <.0001). The effective orifice area at 4.5 L/min was 2.4 +/- 0.03 cm(2) in the 3F group and 1.86 +/- 0.02 cm(2) in the control group (P <.0001) and at 6.5 L/min, 2.41 +/- 0.04 cm(2), and 1.96 +/- 0.02 cm(2), respectively (P <.0001). CONCLUSIONS: This new bioprosthesis without a stent and without a supporting wall that has its commissures fixed directly to the aorta outperforms in vivo standard stentless prostheses in the immediate postimplant period.

Animals↗

PubMed2003

Limitations using the vacuum-assist venous drainage technique during cardiopulmonary bypass procedures.

Vacuum-assist venous drainage (VAVD) can increase venous blood return during cardiopulmonary bypass (CPB) procedures. However, the negative pressure created in the closed cardiotomy reservoir can be transmitted to the oxygenator if a nonocclusive or centrifugal arterial pump is used, resulting in bubble transgression (BT) from the gas to blood compartment of the oxygenator. We analyzed the vacuum pressure required to produce BT using an in vitro circuit including successively a closed reservoir, a pump (centrifugal or roller), and an oxygenator. A constant hydrostatic pressure was maintained onto the oxygenator. Vacuum was applied on the cardiotomy reservoir, progressively increasing negative pressure from 0 to -80 mmHg and monitoring BT with a bubble detector. Six different oxygenators were compared. A partially occlusive roller pump and a centrifugal pump were compared to a control, which was without any pump. A mean negative pressure of -53 +/- 7 mmHg was necessary to produce BT in all the oxygenators in the absence of a pump. The presence of a centrifugal pump between the reservoir and the oxygenator significantly increased the negative pressure required to produce BT compared to the control (-67 +/- 7 mmHg, p < .05). No bubbles were detected using the roller pump (> -80 mmHg needed for BT), thus statistically significant when compared to the centrifugal pump (p < .05). The centrifugal pump offers significant resistance to BT but not as much compared to the roller pump, though BT cannot be prevented if the pump is turned off while the vacuum remains on the reservoir. Therefore, VAVD is a safe technique as long as the perfusionist stops the vacuum when the arterial pump is no longer in use.

Adult↗

PubMed2002

Atrial fibrillation and minimally invasive coronary artery bypass grafting: risk factor analysis.

Atrial fibrillation (AF) is a frequent arrhythmia after conventional coronary artery bypass grafting. With the advent of minimally invasive technique for left internal mammary artery-left anterior descending coronary artery (LIMA-LAD) grafting, we analyzed the incidence and the risk factors of postoperative AF in this patient population. This prospective study involves all patients undergoing isolated LIMA-LAD grafting with minimally invasive technique between January 1994 and June 2000. Twenty-four possible risk factors for postoperative AF were entered into univariate and multivariate logistic regression analyses. Postoperative AF occurred in 21 of the 90 patients (23.3%) analyzed. Double- or triple-vessel disease was present in 12/90 patients (13.3%). On univariate analysis, right coronary artery disease (p <0.01), age (p = 0.01), and diabetes (p = 0.04) were found to be risk factors for AF. On multivariate analysis, right coronary artery disease was identified as the sole significant risk factor (p = 0.02). In this patient population, the incidence of AF after minimally invasive coronary artery bypass is in the range of that reported for conventional coronary artery bypass grafting. Right coronary artery disease was found to be an independent predictor, and this may be related to the fact that in this patient population the diseased right coronary artery was not revascularized at the time of the surgical procedure. For the same reason, this risk factor may find a broader application to noncardiac thoracic surgery.

Aged↗

PubMed2002

A new expandable venous cannula for minimal access heart surgery.

BACKGROUND: During percutaneous cannulation, the diameter of the venous cannula is determined by the size of the access site. To limit this restriction, the Smart cannula (Cardiosmart Ltd., Fribourg, Switzerland) has been developed. Because its design allows self-expansion within the recipient vein, diameter restriction is limited to the access site. METHODS: In 6 calves (78 +/- 4.3 kg), the jugular vein and the carotid artery were cannulated through a cervicotomy. The Smart cannula was tested against three percutaneous cannulas with a diameter of 27, 25, and 21F, respectively. Stenotic percutaneous access to the vein was simulated by 1-cm wide tape encircling the vein that could be adjusted to a diameter of 27, 25, and 21F, respectively. The maximal flow rate, reached with stable reservoir level and a negative pressure of 44 mm Hg, was determined three times for each access size with the Smart cannula (one size fits all) and the corresponding percutaneous cannula successively. RESULTS: For an access size of 27F, the flow of the Smart cannula was 5.7 +/- 0.4 L/min and that of the percutaneous cannula was 4.3 +/- 0.2 L/min (p < 0.0001); for 25F, flow rates were 5.6 +/- 0.5 and 3.9 +/- 0.2 L/min, respectively (p < 0.0001); and for 21F, the flow rates were 4.3 +/- 0.4 and 2.7 +/- 0.3 L/min, respectively (p < 0.0001). The percentage increase of flow for the 27, 25, and 21F sizes were 34% +/- 9%, 42% +/- 16%, and 53% +/- 18%, respectively (one-way analysis of variance, p = 0.014). CONCLUSIONS: For the present set-up, the Smart cannula outperforms commercially available percutaneous cannulas. The smaller the size of the insertion site, we observed a higher gain of flow with the Smart cannula.

Animals↗

PubMed2002

A new concept of integrated cardiopulmonary bypass circuit.

OBJECTIVE: Standard cardiopulmonary bypass (CPB) circuits with their large surface area and volume contribute to postoperative systemic inflammatory reaction and hemodilution. In order to minimize these problems a new approach has been developed resulting in a single disposable, compact arterio-venous loop, which has integral kinetic-assist pumping, oxygenating, air removal, and gross filtration capabilities (CardioVention Inc., Santa Clara, CA, USA). The impact of this system on gas exchange capacity, blood elements and hemolysis is compared to that of a conventional circuit in a model of prolonged perfusion. METHODS: Twelve calves (mean body weight: 72.2+/-3.7 kg) were placed on cardiopulmonary bypass for 6 h with a flow of 5 l/min, and randomly assigned to the CardioVention system (n=6) or a standard CPB circuit (n=6). A standard battery of blood samples was taken before bypass and throughout bypass. Analysis of variance was used for comparison. RESULTS: The hematocrit remained stable throughout the experiment in the CardioVention group, whereas it dropped in the standard group in the early phase of perfusion. When normalized for prebypass values, both profiles differed significantly (P<0.01). Both O2 and CO2 transfers were significantly improved in the CardioVention group (P=0.04 and P<0.001, respectively). There was a slightly higher pressure drop in the CardioVention group but no single value exceeded 112 mmHg. No hemolysis could be detected in either group with all free plasma Hb values below 15 mg/l. Thrombocyte count, when corrected by hematocrit and normalized by prebypass values, exhibited an increased drop in the standard group (P=0.03). CONCLUSION: The CardioVention system with its concept of limited priming volume and exposed foreign surface area, improves gas exchange probably because of the absence of detectable hemodilution, and appears to limit the decrease in the thrombocyte count which may be ascribed to the reduced surface. Despite the volume and surface constraints, no hemolysis could be detected throughout the 6 h full-flow perfusion period.

Animals↗

PubMed2002

Hemodynamics optimization during off-pump coronary artery bypass: the 'no compression' technique.

OBJECTIVE: Heart manipulation during OPCAB may cause hemodynamical instability in particular for access to the posterior and lateral walls. The 'no compression' technique involves enucleation of the heart without any compression on the cavities, and stabilization of the target area with a suction device. The impact of this technique on hemodynamics is assessed. METHODS: In order to analyze a homogeneous group, 26 consecutive patients with triple grafts, one to each side of the heart in the same sequential order (posterior, lateral and anterior wall successively) were selected. Heart rate (HR), mean pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), mean arterial pressure (MAP, mmHg), cardiac output index (COI, l/min per m(2)), and central venous saturation (SvO(2),%) were monitored. A coronary shunt was used for all the anastomoses. RESULTS: HR was stable with baseline value of 60+/-10 and the highest value for the anterior wall, 63.6+/-8 (P=0.23). PAP and PCWP exhibited their highest increase, when compared with baseline, for the lateral wall, 23.9+/-4.7 vs. 20.7+/-6.2 (P=0.06), and 17.2+/-4.7 vs. 14.9+/-5.6 (P=0.16), respectively. MAP, COI and SvO(2), exhibited their largest drop, when compared with baseline, for the lateral wall too, 73.1+/-9.1 vs. 77.1+/-7.5 (P=0.12), 1.99+/-0.47 vs. 2.26+/-0.55 (P=0.09), and 70.5+/-8.4 vs. 74.8+/-9.3 (P=0.12), respectively. CONCLUSIONS: None of the hemodynamical parameter differed significantly from baseline value for all three territories. While hemodynamics was perfectly maintained during the posterior and anterior walls revascularization, exposure of the lateral wall led to marginal changes only.

Aged↗

PubMed2002

An alternative to left ventricular volume reduction.

BACKGROUND: Left ventricular (LV) remodeling leading to ventricular dilatation is ultimately a maladaptative process according to the law of Laplace. To counteract the wall stress increase, a new concept of reducing the LV cavity radius by changing the LV globular shape to a bilobular one through the insertion of transventricular splints has emerged. This procedure is tested in a model of congestive heart failure. METHODS: A bovine model was used (n = 9). Following splint insertion through a sternotomy, boluses of 2 liters of crystalloid were injected. After every bolus, hemodynamic measurements were performed without and with the splints tightened to a 10% and 20% stress level reduction, respectively. Comparisons between the 3 measurements were performed with analysis of variance test (p < 0.05). RESULTS: Splint tightening significantly reduced right and left heart pressures for central venous pressure (CVP) >10 mm Hg (CVP: 14.7 +/- 5.2, 12.1 +/- 5, 10.6 +/- 4.7 mm Hg, p < 0.001 for baseline, 10% and 20% stress level reduction, respectively; mean pulmonary artery pressure: 33.5 +/- 4.7, 31 +/- 4.4, 29.4 +/- 5.1 mm Hg, p < 0.001; pulmonary capillary wedge pressure: 20.5 +/- 2.8, 18.9 +/- 3.3, 17.5 +/- 3.1 mm Hg, p < 0.001). The same holds true for cardiac output (6.5 +/- 1.6, 6.7 +/- 1.4, 6.8 +/- 1.7 liter/minute, p < 0.001), whereas heart rate and mean arterial pressure were not affected. The systemic and pulmonary resistances did not vary significantly throughout the procedure. Importantly, none of the hemodynamic parameters worsened at any stage with the splints. CONCLUSIONS: In this model, hemodynamic parameters are improved with the splints for higher values of CVP, supporting the concept of reshaping the remodeled LV. This technique has the potential to improve patients with congestive heart failure.

Animals↗

PubMed2002

Flow dynamic comparison of peripheral venous cannulas used with centrifugal pump assistance in vitro.

Because of the risk of vein collapse, the benefits of using a centrifugal pump to assist venous drainage for cardiopulmonary bypass are limited when the tips of peripheral cannulas are maintained within the vena cava. Using a mock circuit including 20 mm diameter latex tubing to mimic a vena cava, we compared the performance of 6 commercially available peripheral venous cannulas and attempted to determine potential factors influencing maximal flow drainage before vein collapse. A close correlation was observed with the total hole area of the cannula. Best performance (5.10 +/- 0.08 L/min) was obtained with an 8 mm internal diameter (ID) cannula and 343 mm2 total hole area. A larger cannula (ID 9.2 mm) with only 209 mm2 total hole area drained 5.03 +/- 0.05 L/min whereas a smaller cannula (ID 6.7 mm) with a total hole area of 586 mm2 also allowed a similar flow of 5.03 +/- 0.12 L/min. Therefore, the total hole area appears to be a critical factor in designing peripheral cannulas used in restricted chambers such as vena cavae.

Cardiopulmonary Bypass↗

PubMed2002

Hemocompatibility of a coaxial pump catheter for less invasive heart surgery.

Off-pump coronary artery bypass (OPCAB) requires heart manipulation during exposure of the lateral and posterior walls of the heart, which may cause hemodynamic instability, mainly through right ventricular dysfunction. A coaxial atrial cannula connected to a minicentrifugal pump was developed to bypass the right heart. This study was designed to test the hemocompatibility of this pump ongoing for 6 h. In five calves (bodyweight, 70.3+/-4.2 kg), the pump was inserted and set to its maximal motor speed of 7000 rpm. Blood samples were taken for blood gas analyses, hematology and chemistry on an hourly basis. ANOVA was used for statistical analysis. During the 6-h run, hematocrit and red blood cell count were stable (p=0.77 and 0.87, respectively). Platelet count was not significantly altered (p=0.55). LDH was stable (p=0.61) and plasma free hemoglobin remained below 100 mg/l throughout the experiment. Adequate tissue perfusion was maintained as reflected by the stable mixed venous oxygen saturation (baseline, 72.5+/-2%, and 6 h, 65.6+/-3.4%) and no defect of any pump system was detected during this 6-h testing. This right heart minipump appears to have a minimal impact on red cells and platelets when set at its maximal speed for 6 h, underlining the hematological safety of the system.

Animals↗

PubMed2002

Circulatory support for OPCAB procedures.

During off-pump coronary artery bypass grafting (OPCAB) which allows complete revascularization through a median sternotomy, revascularization of the lateral and posterior walls requires the verticalization of the heart, which may cause haemodynamic disturbance. This concern has stimulated the development of circulatory support with mini-pumps. Initially, these pumps were designed for the right side of the heart, which was found to be the main contributor to haemodynamic instability under experimental conditions. The three types of mini-pumps that have been developed so far - two for the right side of the heart and one for both sides - are reviewed as well as a new concept of integrated cardiopulmonary bypass (CPB) circuit with reduced surface and priming volume. However, with increasing experience and improved methods of exposition, OPCAB has become a procedure that can be performed without support in the majority of the cases. Nevertheless, the concept of miniaturization and the possibility to insert these devices through a peripheral access has opened the way to new indications, mainly short-term circulatory support for acute heart failure. This development is welcome in a field where available devices are invasive and plagued with a heavy morbidity.

Assisted Circulation↗

PubMed2002

[ECMO and cardiopulmonary support].

ECMO (extracorporeal membrane oxygenation) may be viewed as a prolonged cardiopulmonary bypass allowing for a prolonged cardio-respiratory support. Since its introduction in the 60's, its indication has expanded from acute respiratory failure to acute cardiac failure refractory to conventional treatments. The target group involves mainly those patients presenting with a cardiogenic shock following cardiac surgery or acute myocardial infarction. The advantages of this form of circulatory support, when compared with long-term ventricular assist devices, are its less invasive aspect, its ease of implantation and its reduced cost. However, its main limitation lies in its limited duration of 7 to 10 days, in particular because of hemorrhage complications. Currently, ECMO provides a temporary hemodynamical stability in order to perform an invasive cardiac treatment (coronary bypass or percutaneous dilatation), or to assess the eligibility of the patient for a long-term ventricular assist device, which will enable to wait for the availability of an allograft. The latter scenario is crucial nowadays because of the severe lack of organ donors, which is the leading cause of death among patients waiting for a heart transplant.

Cardiac Output, Low↗

PubMedDate not supplied

Antithrombotic properties of trillium coated connectors.

Trillium coating (Medtronic Inc., Minneapolis, MN) offers, in addition to the presence of heparin, endothelium-like properties of its negatively charged surface. Its thromboresistant properties on coated connectors are tested here and compared with uncoated standard connectors, as well as with the Carmeda BioActive surface (CBAS) heparin surface coating. A partial cardiopulmonary bypass bovine model (body weight 68 +/- 5 kg) was selected, and the surfaces were exposed to the blood stream (pump flow 3.5 L/min) for up to 350 minutes without systemic heparinization. Thereafter, another set of samples was exposed to stagnant blood for 20 minutes. Besides hemodynamic, hematologic, and biochemical analyses, the macroscopic appearance of 45 blood exposed surface samples were graded semiquantitatively on a scale of 0 to 10: no macroscopic deposits = grade 0, one spot (1 mm diameter) = grade 1, two spots = grade 2, five or more spots = grade 5, 10% of the surface covered with clots = grade 6, 100% covered = grade 10. When exposed to blood flow, Trillium and CBAS coatings showed a statistically significant (p = 0.03) better thromboresistance (score: 0 +/- 0 for both) than uncoated connectors (score: 0.8 +/- 1.5) in this nonheparinized model. The same holds true when the connectors were exposed to stagnant blood (score: 0 +/- 0 for both coatings vs 4.3 +/- 2.8 for controls; p = 0.03). Therefore, Trillium coating exhibits significant antithrombotic properties that outperform standards for connectors used in clinical perfusion.

Animals↗

PubMedDate not supplied

In vivo testing of a right heart mini-pump during a 24 hour period: is it safe?

A coaxial atrial cannula connected to a mini-centrifugal pump was developed to bypass the right heart during extreme exposures in off-pump coronary artery bypass surgery. This study was designed to test the effect of this pump, running during 24 hours, on blood elements to evaluate its use as a prolonged right heart support. In a calf model (body weight 68+/-5 kg), the pump was inserted and set to its maximal motor speed of 7000 rpm. Blood samples were drawn every 6 hours for blood gas analyses, as well as for hematology and chemistry. The right heart mini-pump performed perfectly at its maximal speed over the 24 hour period. Blood gas parameters and blood lactate levels reflected adequate tissue perfusion (baseline: 2.2+/-0.5 mmol/L vs. 24 h: 2+/-0.3 mmol/L; p = 0.64). Red blood cell count was stable (baseline: 9.8+/-1.4 x 10(12)/L vs. 24 h: 9.6+/-1.1 x 10(12)/L; p = 0.83). Free plasma hemoglobin remained below 100 mg/L throughout the experiment. Platelet count was stable during the first 6 hours and exhibited a tendency to drop thereafter (baseline: 749+/-104 x 10(9)/L vs. 24 h: 486+/-20 x 10(9)/L; p = 0.01). This right heart mini-pump appears to provide sufficient blood flow during a 24 hour period with minimal impact on red cell and moderate platelet damage after 6 hours. These results suggest a potential application of this system for postcardiotomy right heart support.

Animals↗

PubMedDate not supplied

Air filtering capacity of an integrated cardiopulmonary bypass unit.

To limit the morbidity of cardiopulmonary bypass (CPB), a new concept of integrating pumping, oxygenation, and air removal into a single unit has been developed (CardioVention Inc., Santa Clara, CA). The air filtration capacity of this system was tested. Three calves (73.2 +/- 2 kg) were connected to the integrated system by jugular and carotid cannulation. The integrated unit was challenged with injections of boluses of air of 5, 10, and 20 ml, three times each, and for a blood flow of 3 L/min and 5 L/min, respectively. The bubble count and size were recorded downstream of the unit with a Doppler ultrasound. At 3 L/min, bubbles were detected after injections of 20 ml only (n = 7 for the nine boluses). At 5 L/min, 1 bubble was detected with the nine injections of 5 ml, 14 bubbles were detected with nine injections of 10 ml, and 25 bubbles were detected with nine injections of 20 ml. No bubble exceeded 40 microm in diameter as determined by the Doppler ultrasound. The air filtering capacity of the CardioVention system is excellent both in terms of bubble count and of size after injection of large boluses of air. Its integrated concept offers a simplification of the circuit with fewer devices and connections, which further reduces the risk of accidental air introduction.

Air↗