Influence of the Compliance of the Pump Housing and Cannulas of a Paracorporeal Pneumatic Ventricular Assist Device on Transient Pressure Characteristics

Abstract: The dependence of transient pressure characteristics of a ventricular assist device (VAD) on the compliance of its housing and cannulas was investigated in a mock circulation. The peak rate of change of pressure ( dP/dt _max) values was greater in the cannulas than other compartments and was associated with valve closure-induced pressure oscillations. When cannula compliance was increased from 0.0057 to 0.0129 cm³/mm Hg, these values decreased by ˜20%, and outflow cannula pressure oscillation frequency decreased from 17.5 Hz by 35%. This trend was also apparent in the inflow. A VAD housing compliance increase from 0.0162 to 0.0483 cm³/mm Hg caused a dP/dt _max decrease of 30% in both the blood chamber and the outflow cannula. The effect of this change on the inflow was weaker implying that housing absorbs the energy associated with outflow deceleration more effectively than the inflow. These findings suggest that increasing VAD housing and cannulas compliance can improve hydrodynamic performance.     

Selection for donor-specific cytotoxic T lymphocytes within the allografted human heart.

Lymphocytes were cultured from cardiac biopsies following heart transplantation using interleukin-2-conditioned medium. Using the technique of limiting dilution analysis the frequency of donor specific cytotoxic T lymphocytes was measured in cells cultured from biopsies and compared with that in peripheral blood lymphocytes taken at the same time as the biopsy. The graft cell population showed a considerably higher frequency of donor-specific CTL when compared with the PBL. CTL frequencies in the graft cells were always higher against the donor than against third-party cells. These data demonstrate that there was either selective sequestration or selective expansion of donor-reactive T cells in the heart following cardiac transplantation. These results emphasize the need to investigate more closely the events occurring in the heart, and may explain the lack of specificity and sensitivity in immune monitoring (IM) or cytoimmune monitoring (CIM) seen in many centers.     

A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients

Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, C_max, C_min and t_max) showed that there were no significant differences between the two formulations except for the t_max, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London     

RASER: a new ultrafast magnetic resonance imaging method.

A new MRI method is described to acquire a T(2)-weighted image from a single slice in a single shot. The technique is based on rapid acquisition by sequential excitation and refocusing (RASER). RASER avoids relaxation-related blurring because the magnetization is sequentially refocused in a manner that effectively creates a series of spin echoes with a constant echo time. RASER uses the quadratic phase produced by a frequency-swept chirp pulse to time-encode one dimension of the image. In another implementation the pulse can be used to excite multiple slices with phase-encoding and frequency-encoding in the other two dimensions. The RASER imaging sequence is presented along with single-shot and multislice images, and is compared to conventional spin-echo and echo-planar imaging sequences. A theoretical and empirical analysis of the spatial resolution is presented, and factors in choosing the spatial resolution for different applications are discussed. RASER produces high-quality single-shot images that are expected to be advantageous for a wide range of applications.     

Reproducible model of post-infarction left ventricular dysfunction: haemodynamic characterization by conductance catheter.

OBJECTIVE: The understanding of pathophysiology and cellular mechanisms of chronic heart failure requires the creation of appropriate and accurately characterized animal models, thus enabling meaningful evaluation of evolving medical and surgical therapies. METHODS: The left anterior descending and its diagonal branch were ligated in 12 sheep to induce left ventricular dysfunction. RESULTS: Study of left ventricular pressure-volume loops 3 months post-operatively showed a significant deterioration of both systolic and diastolic indexes of left ventricular function. The left ventricular end-diastolic pressure increased from 3+/-1 to 7+/-1 mmHg (P<0.001) along with a substantial increase in end-diastolic volume from 78+/-8 to 121+/-6 ml (P=0.002) and a significant decrease in cardiac output from 2+/-0.2 to 1.5+/-0.2 l/min (P=0.001). The left ventricular end-systolic pressure-volume relationship deteriorated from 2.7+/-0.37 to 0.7+/-0.16 mmHg/ml (P=0.0002) along with a significant reduction in the pre-load recruitable stroke work (P=0.001). The ejection fraction decreased from 34+/-2% to 16+/-4% (P<0.001) with a significant decrease in +dp/dt and -dp/dt (P=0.009). The mean systemic blood pressure, however, was maintained due to a substantial increase in the systemic vascular resistance (P=0.007). CONCLUSION: This study describes a reproducible large animal model of left ventricular dysfunction. This model is potentially useful to study the pathogenesis of remodelling, surgical management of heart failure and development of novel treatment strategies.     

Transplantation using hearts from primary pulmonary hypertensive donors for recipients with a high pulmonary vascular resistance

BACKGROUND: Transplantation for patients with a high pulmonary vascular resistance (PVR) carries an increased risk of mortality and right heart failure following heart transplantation and continues to be a major problem. We evaluated the use of hearts from patients who underwent heart and lung transplantation for primary pulmonary hypertension (PPH) as part of a domino procedure because these hearts have hypertrophied right ventricles used to increased pulmonary pressures, but could have a compromised left ventricle or irreversible damage of the right ventricle. METHODS: We reviewed 12 patients with PVR >4 Wood units who underwent orthotopic heart transplantation between 1989 and 1998 using hearts from donors with PPH as part of a domino procedure. RESULTS: We studied 10 men and 2 women, mean age 42.9 years. Mean PVR was 5.3 (range, 4-9) Wood units. Mean ischemia time was 85.3 minutes, and mean donor age was 32 years. Actuarial survival was 75% at 1 year and 75% at 5 years. In the early post-operative period, 3 patients had temporary arrhythmias, 2 required permanent pacemaker implantation, 1 had atrial fibrillation, and 1 had ventricular tachycardia that required defibrillator implantation. At a mean follow-up of 7.8 years, 2 patients had developed asymptomatic transplant coronary disease (both at 8.5 years after transplantation), 1 moderate and 1 very mild; the rest had none. Mean left ventricular ejection fraction at latest follow-up was 70.1% (range, 63%-78%). Right ventricular function assessed clinically and by echocardiography was adequate in the short and long term. CONCLUSIONS: Our results suggest that heart and lung recipients with PPH can provide useful donor hearts to patients with increased PVR and that these hearts function well in the intermediate and long term.     

Canavan disease or N-acetyl aspartic aciduria: a case report]

Canavan disease or N-acetyl aspartic aciduria, is an autosomal recessive leukodystrophy characterized by spongy degeneration of brain. The disease is an inborn error of metabolism caused by aspartoacylase deficiency resulting from accumulation of N-acetyl aspartic acid in the brain. The authors report a case in a 10-month-old boy who presented with developmental delay and megalencephaly noticeable after 4 months of age. Magnetic resonance imaging of the brain showed diffuse white matter degeneration. The diagnosis of Canavan disease was confirmed by nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry.