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.     

Cartilage sulfation inhibitor from rat liver: partial characterization of properties and biologic action

Cartilage sulfation (somatomedin) inhibitors (CSI) from rat liver produce reversible inhibition of cartilage growth. After gel filtration Sephadex G-200, CSI appear to have MW approximately 100,000 and they are urea- and trypsin-labile factors. To explore further the mechanism of CSI action, we used the chick pelvic rudiment bioassay and studied the effect of CSI on the incorporation on 35S-sulfate (proteoglycan synthesis), 14C-leucine (protein synthesis), 3H-uridine (RNA synthesis), and 3H-thymidine (DNA synthesis). Normal rat serum (NRS) significantly stimulated the incorporation of all four isotopes, as expected. After a 24-hour incubation, CSI significantly blunted cartilage stimulation by NRS regarding total isotope uptake (1), 35S-sulfate (NRS, 96 +/- 8 mcg/100 mg cartilage dry weight; NRS + CSI, 48 +/- 4, mean +/- SEM, n = 29, P less than .05); and (2) 14C-leucine (NRS, 2,089 +/- 172 cpm/mg dry weight; NRS + CSI, 1,102 +/- 141, n = 18, P less than .05); and (3) 3H-uridine (NRS, 6,711 +/- 832 cpm/mg; NRS + CSI, 3,227 +/- 425 cpm/mg, n = 18, P less than .05); but not (4) 3H-thymidine (NRS, 3,540 +/- 620 cpm/mg; NRS + CSI 3,249 +/- 285, n = 19). The inhibition of 35S-sulfate and 14C-leucine uptake by CSI was dose-dependent and reversible. For 35S-sulfate, uptake by cartilage incubated with CSI alone for 40 hours was 13 +/- 3 micrograms/100 mg; with CSI for 16 hours then fresh medium with NRS for 24 hours uptake was 39 +/- 12, P less than .05.(ABSTRACT TRUNCATED AT 250 WORDS)