Severe hypoxaemia with a left ventricular assist device in a minipig model with an undiagnosed congenital cardiac disease.

We describe the placement of a left ventricular assist device (LVAD) in a pig with spontaneously occurring atrial septal defect (ASD) (incidental finding) that created a right-left cardiac shunt, with subsequent severe hypoxaemia. Early diagnosis was critical in order to prevent end-organ damage due to hypoxaemia. Adequate monitoring alerted us to the deterioration in oxygenation, haemodynamics and cerebral oxygen metabolism. This forced us to change the level of assistance provided by the pump, and thus dramatically correct this impairment. Necropsy revealed an ostium secundum ASD. In conclusion, if hypoxaemia presents after implementation of an LVAD, the presence of a right-left shunt must be ruled out. The first step must be a judicious reduction in assist device flow to minimize intracardiac shunting. Subsequently, atrial septal closure of the defect should be considered. We report an experimental model of severe hypoxaemia after placement of an LVAD as part of a larger research project.

Role of elastic fibers in cooling-induced relaxation.

The objective of this work was to confirm the main role of elastic fibers in differing responses of certain vessels during cooling from 37 to 8 degrees C. Previous results have shown that the nature of the vessel (conduit vessel vs muscular vessel) determines the different behavior (dilatation vs contraction) of isolated vessel segments when temperature decreases from 37 to 8 degrees C. In this work, it has been demonstrated that vessels with a great amount of elastic fibers show a dilatation when cooling. On the other hand, muscular vessels with fewer elastic fibers, such as the renal artery, undergo a contraction. The output of calcium from intracellular stores causes contraction of the renal artery during cooling. In this vessel, vasodilatation occurs only when mechanisms of smooth muscle contraction are inactive, as is the case with vessels that have undergone a cold storage period of 48 h. The results presented in this work confirm that there are two main effects, which directly depend on the vessel origin. In conduit arteries, the decrease of temperature induces a vascular relaxation, dependent on the elastic component of the vessel wall. In muscular vessels, the predominant effect is cooling-induced contraction due to an increase of intracellular calcium. This cooling-induced contraction needs the vessel to be in optimal conditions with an active metabolism of the muscular cells. These results are a crucial issue in the sense of explaining several biomedical mechanisms where hypothermia is implicated. The type of vessel implicated in procedures, such as isolated organ perfusion, extracorporeal circulation, and bypass surgery, must be taken into account.

Perfusate lactate dehydrogenase level and intrarenal resistance could not be adequate markers of perfusion quality during isolated kidney perfusion.

The main goal of this work was to study the influence of perfusion pressure and flow waveform during kidney perfusion, and the relationship between renal vascular resistance (RVR) and lactate dehydrogenase (LDH) concentration in the perfusate. Simultaneous constant pressure kidney perfusions were performed with either pulsatile or continuous flow at either 30 or 80 mm Hg of constant perfusion pressure. Mean flow, pressure, and RVR were displayed online during perfusion. Perfusate samples for LDH, creatine phosphatase kinase (CPK), and alkaline phosphatase (AP) determinations were taken. At the end of the perfusion, 2 ml of Evans blue was injected into the circuit to obtain images of perfusate distribution, and the kidneys were weighed. Also, hematoxylin/eosine studies were performed, showing more Bowman's space and tubular dilation in kidneys perfused with high pressure. We did not find differences in RVR between kidneys perfused at 30 and 80 mm Hg; nevertheless, perfusate distribution was better in the 80 mm Hg perfusions. We did not find any correlation between enzyme release and RVR in kidneys perfused with different mean pressures. These findings suggest that vascular resistance and LDH concentration cannot be independently considered as adequate markers of perfusate distribution.

Paradoxical effects of temperature on vascular tone.

Temperature may have significant influence on vascular tone in such cases as organ preservation, coronary bypass surgery, and extracorporeal circulation. The aim of this research was to study the direct effect of temperature variation on vascular tone in an attempt to elucidate the mechanisms involved. In a first series of experiments, the isometric tension of two different vessels (rat thoracic aorta and pig renal branch artery) was studied at different temperatures. To study the role of calcium in this response, a second series of experiments was performed. In this the vessels were incubated with the intracellular chelator BAPTA/AM. Further experiments were performed to test the effect of cold storage. Our results show that changes in temperature lead to different results in pig renal artery and rat aorta. A decrease in temperature induced a highly reproducible relaxation in rat aorta, whereas pig renal artery presented cooling-induced contraction. Moreover, whereas calcium depletion failed to inhibit cooling-induced relaxation in rat aorta, it did not provoke cooling-induced contraction in pig renal artery. Similar responses were obtained with cold storage and calcium depletion. We intend to demonstrate that, just as the effect of temperature variation on pig renal artery is due to a metabolic mechanism, its effect on rat aorta may be due to structural factors. This hypothesis is supported by the result of histological studies which demonstrate a higher proportion of elastin fibres in rat aorta than in pig renal artery.

Isolated kidney controlled perfusion with true physiological pulsatile waveform.

A computer controlled perfusion system has been developed to study the behavior of perfused kidneys in several conditions. The system is designed to perform kidney perfusions at constant pressure and low temperature (about 4 degrees C). We compared 2 types of perfusion pumps, a classical roller pump widely used in hemodialysis circuits and a vacuum powered tubular pump with active valves developed by our group and able to produce a flow pattern very similar to the pulse wave in the human circulatory system. In this preliminary study, we show the hydrodynamics obtained with both pumps in isolated hypothermic kidneys perfused with this system. The different flow patterns with both pumps seem to determine differences in the preservation conditions of the kidney.

Tubular vacuum-powered blood-pumping device with active valves.

We propose a new vacuum-driven blood pump having a tubular shape with active valves. This design avoids any possible problems caused by membrane breakage, thereby minimizing the risk of gas embolic events and stagnation regions. By using active valves, it is possible to ensure better flow control and minimize pressure gradients inside and outside the pump. The low cost of the pump's disposable parts enables it to be used for such applications as a ventricular assist device, a pulsatile pump device in extracorporeal circulation, a pump in hemodialysis and apheresis circuits, and a pump in extracorporeal membrane oxygenator systems.

Hydrodynamic response of a VAD with a compliant cannula: results of in vitro tests.

We report on comparative in vitro tests of two ventricular assist devices (VAD) one with a rigid input cannula and the other with a collapsible (compliant) inlet cannula. We show how this compliant cannula yields significant improvements in the hydrodynamic performance of the system.

Development and clinical assay of the BCM ventricular assist device.

The development of a ventricular assist device is depicted. The seven subprograms that make up the project are described briefly. Results obtained during the clinical assay showed that the new design of the input cannula working as a false auricle provides better efficiency, as well as a certain level of autoregulation for the device.

Improvement of the hydrodynamic response of a ventricular assist device: a false auricle solution.

We propose a new design of the auricular cannula in ventricular assist devices (VADs), consisting of a collapsible large cannula with a capacity approximately equal to the ejection volume of the VAD. The device works as a false auricle and filters the negative pressure that occurs during diastole. We show that the use of this type of cannula improves the hydrodynamic efficiency and the stability of the working conditions. Moreover, during chronic implantation in sheep, hemolysis stays well below pathological levels. These improvements result in much better controllability of the whole VAD.

First clinical implantation of the BCM 3.5 ventricular assist device (VAD).

We report on the first human implantation of the BCM 3.5 ventricular assist device in a 46-year-old man suffering from terminal stage cardiomyopathy. The circulatory support was used as a bridge to heart transplantation. The patient was in cardiogenic shock and was on assisted circulation for 18 days after which he underwent cardiac transplantation. While receiving support from the ventricular assist device, the patient's condition improved remarkably and 50 days after transplantation he was discharged from hospital. We give a detailed description of the surgical technique, with special emphasis on the procedures for air extraction. We describe the evolution of the hemodynamic status before and after implantation. Final inspection of the device and cannulae after removal showed no thrombi and only small fibrin deposits in the membrane-wall junction.

Blood biochemistry values of sheep (Ovis aries ligeriensis).

1. Analysis of biochemical parameters were carried out on material pooled from 30 female sheep (Ovis aries ligeriensis). 2. The values determined were for the common metabolites and enzymes utilized for specific studies in general metabolism (urea, glucose, cholesterol, lipids, bilirubin, uric acid, creatinine, alkaline phosphatase, GOT, GPT, LDH, LAP, CGT, CK and amylase). 3. Results of these studies were compared with values from normal human adults. 4. The differences obtained in human and sheep ranges can be explained by the different physiology of the two species. 5. This study gives values for the sheep as an experimental animal in biomedical research.