Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis.

BACKGROUND: Hypoxia-inducible factor (HIF)1 alpha is considered to play a key role in the adaptation of cells to hypoxia by stimulating angiogenesis via regulation of vascular endothelial growth factor and by metabolic adaptation to O(2) deprivation. METHODS: Expression of HIF-1 alpha protein and p53 was investigated by immunohistochemistry in 51 specimens of supratentorial pure oligodendrogliomas. Microvessels density (MVD) was determined by anti-CD34 immunostaining. The influence of HIF-1 alpha expression on survival was investigated using univariate and multivariate analysis. RESULTS: Strong expression of HIF-1 alpha was observed in 12 (23.5%) specimens, moderate in 21 (41.2%) specimens, and weak in 8 (15.7%) cases, and no expression was found in 10 samples (19.6%). There was no correlation of HIF-1 alpha expression with histologic grading (P = 0.428, Mann-Whitney test). Hypoxia-inducible factor-1 alpha expression and MVD showed a strong correlation (P < 0.001, r = 0.735, Spearman coefficient of correlation). Overexpression of p53 was observed in only two cases. Patients with strong or moderate expression of HIF-1 alpha had a significantly shorter overall survival rate compared with those with low or no expression in univariate (P = 0.0434; log-rank test) and multivariate analysis (P = 0.0187). CONCLUSIONS: Overexpression of HIF-1 alpha indicates a diminished prognosis in oligodendrogliomas, independent of p53 status. This finding may be explained by the strong vascularization of these tumors that prevents hypoxia and allows O(2) diffusion and henceforth tumor progression.

Effect of stationary guiding vanes on improvement of the washout behind the rotor in centrifugal blood pumps.

In centrifugal pumps, there always exists an area of stagnation between the rear of the rotor and the rear housing wall that promotes thrombus formation around the axle. Some current devices overcome the problem by using holes in the rotor plane, leading to increased hydrodynamic losses and shear stress. In this study, a simple apparatus was developed to overcome this problem. Guiding vanes were fixed to the rear housing wall. These vanes decrease the tangential velocity of the fluid and thus the centrifugal force, leading to an increased secondary flow toward the axle. The effect of such vanes was studied in videographic and ultrasound studies. An increase of washout and mixing between the flow layers could be demonstrated (stay time < 200 msec versus several seconds without vanes). In the first animal experiment using nonoptimized vanes, there was no thrombus at the back plane or the seal, and only a small thrombus at the transition between axle and rotor. Hemolysis was slightly elevated (3.2 mg/dl versus 2.5 mg/dl in control experiments). In conclusion, it is highly likely that this simple system will improve the flow characteristics in centrifugal pumps.

Mechanical bridge to transplantation with the Vienna heart in TAH and LVAD configuration.

The Vienna heart uses a vacuum formed, pellethane pulsatile ventricle and is available in left ventricular assist (LVAD) and total artificial heart (TAH) configurations. This device was used as mechanical support of the failing heart in nine patients intended for heart transplantation. In two patients with cardiomyopathy an orthotopic TAH was implanted; one survived despite severe preoperative ischemic liver damage, and the other died of sepsis. In seven patients an atrio-aortic LVAD was implanted; six had suffered an acute myocardial infarction with cardiogenic shock, and one could not be weaned off bypass. Three patients survived. These included one 65-year-old with incipient ARDS at operation, and a 40-year-old with preoperative liver and kidney insufficiency who was transplanted in septicemia. In this patient the septic focus, natural and artificial heart, were removed at transplantation. Four patients died. In one we were unable to establish satisfactory circulation, one died after failure of the transplanted heart, one suffered a lethal cerebral embolism and one developed multi-organ failure after repeated attacks of ventricular fibrillation. With the Vienna heart sufficient circulatory support could be established with cardiac outputs between 6 and 8 l/min for the TAH and 3.5 to 4.5 l/min for the LVAD. With this type of support an overall survival rate of 44% could be achieved. Mechanical hemolysis was not a clinical problem and no device failure occurred.

Timing for implantation and transplantation in mechanical bridge to transplantation.

The implantation of a mechanical blood pump in a deteriorating candidate for heart transplantation is indicated in general if the cardiac index is less than 1.9 L/min/m2 despite maximal inotropic support. Deterioration of end organ function may be taken as a second factor indicating the need for mechanical support as patients with acute onset of shock may react differently from patients with chronic deterioration. Preoperative need for dialysis largely reduces the chances of long-term survival. The time on support should be long enough to normalize or at least improve secondarily damaged organ systems, but with time infectious and thromboembolic complications will increase. So optimal periods for artificial heart support range between two days and four weeks. Age less than 40 years is a positive predictor for outcome in TAH bridging. The general guidelines, however, do not preclude a favourable outcome in complicated cases, as we show in our own series.

The new small Viennese total artificial heart: experimental and first clinical experiences.

For bridging to transplantation, a new small total artificial heart (TAH) design has been developed. Function of the two membrane pumps (filling volume left: 87 ml, and right: 75 ml; four mechanical disc valves and screwed connectors) for orthotopic implantation were studied in calf experiments. A calf survival up to 180 days was achieved without problems by pumping with a rate of 117 +/- 2.4 beats/min and a cardiac output of 7.4 +/- 0.7 L/min. For bridging to transplantation, the New Small Viennese TAH was implanted into a small 45-year-old patient (height 160 cm, weight 75 kg) with end-stage coronary heart disease. The patient deteriorated suddenly [mean aortic pressure: 38 mm Hg; cardiac output (CO): 1.8-2.1 L/min; anuria and multiple organ failure] while waiting for a donor heart. Even though his pericardial space was not enlarged, no fitting problems appeared. By using pumping rates of 104.3 +/- 8.7 beats/min, a cardiac output of 5.8 +/- 0.63 L/min was achieved (free hemoglobin was 4.1 +/- 0.48 mg/dl). Even though blood circulation was reestablished, after a TAH duration of 12 days, multiple organ failure persisted, and TAH bridging had to be stopped. In November 1989, a 50-year-old deteriorating transplant candidate with idiopathic cardiomyopathy was bridged for 6 days. Adjusting the heart rate to 86.5 +/- 11.2 beats/min, a CO of 6.84 +/- 0.46 L/min was achieved (free hemoglobin was 5.9 +/- 1.7 mg/dl). Because of chronic liver dysfunction, the patient developed severe icterus while on the TAH, and it took 2 months after heart transplantation to achieve physiological bilirubin concentrations. The patient recovered fully and remains in excellent condition.

[Successful bridge transplantation with the Vienna artificial heart]. / Erfolgreiche Bridge-Transplantation mit dem Wiener Kunstherzen.

The Vienna Heart, a pulsatile artificial ventricle, vacuum-formed from Pellethane has been used successfully as total artificial heart (TAH) and left ventricular assist device (LVAD) to bridge over patients in terminal heart failure. A 50 year-old patient with cardiomyopathy had to be resuscitated and was transferred in cardiogenic shock, with impaired renal and liver function. 6 days after orthotopic implantation of a Vienna TAH a suitable donor organ was found and the patient was transplanted. 7 weeks later he was discharged and is alive and well now. A 40-year-old patient was transferred in cardiogenic shock 22 days after recurrent anterior infarction. Due to renal failure he was on haemofiltration. Congestive liver failure caused a severe coagulation disorder so a Vienna LVAD was implanted without the use of extracorporeal circulation. Despite development of septicaemia he was transplanted 24 days later. It was thought that either the ventricular thrombus or the LVAD was the septic focus. All consecutive blood cultures have been negative and he was discharged 6 weeks later. To our knowledge, case 1 represents the first successful bridging with a non-Jarvic TAH. The second case shows that sepsis is not necessarily a contraindication to heart transplantation.

Testing of biomaterials, accelerated ageing.

The residual elongation is a critical property of materials used for manufacturing diaphragms of artificial hearts. It is therefore important to check goods received or to control manufactured diaphragms, whether their creep properties are within the required limits. Ordinary creep tests take at least several months, while the release of goods received or diaphragms manufactured should be possible within a few days. Acceleration of the creep test by increasing the test temperature permits an estimation whether the creep properties of a material are within the required limits within a week.