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.     

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     

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.     

In Vivo Effects of TRH, T3 and cGH on Antibody Production and T- and B-Lymphocytes Proliferation in Immature Male Chickens

Newly hatched White Leghorn male chicks were used in this study. Different doses of T₃ (O.1 or 1 ppm) or TRH (1 or 5 ppm) were administered in the feed for an 8-week period. Chicken growth hormone (cGH) (10 μg/kg BW) was injected (i.v.) into a different group of chicks twice daily for 1 week starting at 7 weeks of age. A different group received both T₃ (0.1 and 1 ppm) and cGH. Serum concentrations of T₄, T₃ and GH, antibody production against sheep red blood cells (SRBC) and Brucella Abortus (BA), and in vitro proliferative response of both T- and B-lymphocytes to mitogenic stimulation were measured. Supplementation of T₃ (1 ppm) significantly lowered T₄ and increased T₃ concentrations. No effect of any hormone treatment on antibody production was observed. T₃ supplementation and cGH injection alone or with T₃ (0.1 ppm) significantly increased blastogenic response of lymphocytes to either Con-A or LPS mitogenic stimulation. It was concluded that T₃ and GH are involved in lymphocyte activity of chickens.     

PCR analysis of egyptian respiratory adenovirus isolates, including identification of species, serotypes, and coinfections

Eighty-eight adenovirus (Ad) isolates and associated clinical data were collected from walk-in patients with influenza-like illness in Egypt during routine influenza surveillance from 1999 through 2002. Respiratory Ad distributions are geographically variable, and serotype prevalence has not been previously characterized in this region. Serotype identity is clinically relevant because it predicts vaccine efficacy and correlates strongly with both clinical presentation and epidemiological pattern. Species and serotype identities were determined using several well-validated multiplex PCR protocols culled from the literature and supplemented with a few novel primer sets designed to identify rare types. The isolates included common species B1 serotypes (Ad3 and Ad7), common species C serotypes (Ad1, Ad2, and Ad5), the less common species B2 serotype Ad11, and three isolates of the rare species B1 serotype Ad16. Two isolates that appear to be variant Ad16 were also identified. Fifteen coinfections of multiple adenoviral types, primarily AdB/AdC and Ad3/Ad7 dual infections, were detected. The majority of these were verified using redundant PCR tests targeted at multiple genes. PCR is able to resolve coinfections, in contrast to traditional serum neutralization tests. PCR is also comparatively rapid and requires very little equipment. Application of the method allowed an inclusive determination of the serotypes found in the Egyptian respiratory sample set and demonstrated that coinfections are common and may play a previously unrecognized role in adenovirus pathogenesis, evolution, and epidemiology. In particular, coinfections may influence adenoviral evolution, as interserotypic recombination has been identified as a source of emerging strains.     

Role of nimodipine in the therapy of subarachnoid and intracerebral hemorrhage

Syndromes of intracranial hemorrhage, and particularly subarachnoidal, i.e., intracerebral hemorrhage (SAH and IH) present clinical entities that are the most severe conditions in neurology. Timely recognition, diagnosis and adequate therapy are imperative. The most important factor that aggravates an already difficult prognosis of those entities is cerebral vasospasm. Upon the presented facts, the aim of this investigation was to establish the value and role of administration of selective calcium channel blocker--nimodipine in patients with SAH and IH compared to the degree of neurological and functional impairment, as well as the recovery of the function of consciousness compared to the patients with those syndromes from an earlier period, who were not treated with this medicament. Investigation comprised 30 patients who received nimodipine and 20 patients without this agent in therapeutic program. Results of the investigation confirmed significant difference concerning the neurological recovery, improvement of functional capability and recovery or consciousness disturbances, respectively, in patients who received nimodipine compared to the group without this agent. It can be concluded that nimodipine as calcium channel blocker with multitopic pharmacological effects on mechanism of SAH or IH development, respectively, as well as on the development of complications of those syndromes, particularly to the development of vasospasm and reactive ischemia, with the improvement of hemorrheologic disorders deserves to be included as the unavoidable segment of therapeutic program of SAH and IH syndrome immediately after clinical phenomenology is revealed.     

Prognostic value of certain enzymatic and hormonal assays in threatened abortion

The following biochemical indices were evaluated comparatively as predictors of the course of threatened abortion: serum oxytocinase, heat stable alkaline phosphatase, leucine aminopeptidase, urinary pregnanediol, and urinary estriol. 36 cases, grouped into controls and pathological cases, were studied. In normal pregnancy, there was a progressive rise in the levels of the serum oxytocinase, leucine aminopeptidase, urinary estriol, and pregnanediol. Serum heat stable alkaline phosphatase showed an undifferentiated range of results in nonthreatened pregnancies. In the group of threatened abortion cases, results were, therefore, considered abnormal if 2 or more successive determinations showed progressive reduction in enzyme or hormonal levels, and abnormality was also diagnosed if the results were below the normal range (published tabularly, per gestational week). The prognostic value of these biochemical indices was as follows: of 16 cases with normal serum oxytocinase values, 31.2% aborted, whereas of 10 with abnormal values, 70% aborted. Of 16 cases with serum leucine normal values, 37.5% aborted, whereas Of 10 abnormal cases, 60% aborted. Of 18 cases with normal heat stable alkaline phosphatase values, 55.5% aborted, whereas of 8 cases with abnormal values, 25% aborted. Of 17 cases with normal urinary estriol determinations, 45% aborted, whereas of 9 cases with abnormal values, 44.5% aborted. And of 17 cases with normal pregnanediol levels, 41% aborted, whereas of 9 cases with abnormal values, 55.5% aborted. These results show that combined estimation of serum oxytocinase and urinary pregnanediol is a reliable parameter in anticipating pregnancy outcome in cases of threatened abortion.