Images in cardiology: kidney cancer with cardiac extension.
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Aged↗
Biomedical subjects
D Tixier
Publications and source records attributed to D Tixier.
Intestinal tissue oxygenation and tumor necrosis factor-alpha release during systemic blood flow changes in pigs with left ventricular assist devices.
We previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) increased following a reduction in systemic blood flow to 60% or less of the original cardiac output using a left ventricular assist device (LVAD). The aim of this study was to investigate the effect of reducing systemic blood flow on tissue oxygenation in the gastrointestinal tract (GIT) and the consequences of this on TNF-alpha release. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha of the superior mesenteric vein was measured at baseline and during systemic blood flow changes. Simultaneously, pH, lactate, oxygen delivery index (DO(2)I), oxygen consumption index (VO(2)I), and oxygen extraction (O(2)ER) in the GIT were measured. The pH decreased and the lactate level increased significantly (p < 0.05) at a systemic blood flow of 50% or less. The VO(2)I was positively correlated with DO(2)I. The O(2)ER increased significantly (p < 0.05) with reductions in systemic blood flow to 30% or less. There was a significant (p < 0.01) correlation between TNF-alpha and O(2)ER at levels higher than 55%. These data demonstrate that the GIT oxygenation is inadequate with a reduction in systemic blood flow to 50% and that GIT oxygenation becomes critical at a reduction of 30%. During LVAD weaning, careful attention must be given to the GIT. The pH and lactate may be good markers of the adequacy of tissue oxygenation in the GIT.
Animals↗
Effect of variation in systemic blood flow on plasma TNF-alpha in a pig model with left ventricular assist device.
Tumor necrosis factor-alpha (TNF-alpha) release has been implicated in a sepsis-like syndrome following cardiopulmonary bypass (CPB). This also may be important in patients who have had a left ventricular assist device (LVAD) implanted. This report investigates the effect of reducing systemic blood flow on hemodynamic response, mixed venous oxygen saturation (SvO(2)), and the release of TNF-alpha. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha in the femoral artery (FA) and superior mesenteric vein (SMV) was measured at baseline and following systemic blood flow changes. Simultaneously, hemodynamic parameters and oxygen saturation in the pulmonary artery (SvO(2)) were measured. Following reductions in systemic blood flow, plasma TNF-alpha increased gradually to a maximum level at a systemic blood flow of 20%. There was no significant difference between TNF-alpha levels in the SMV and the FA. There was a significant (p < 0.05) correlation between cardiac index, stroke volume index, and TNF-alpha. The SvO(2) decreased significantly (p < 0.05) at a systemic blood flow of 30 and 20%. A rise in TNF-alpha occurred when the SvO(2) was less than 75%. The data demonstrate that a reduction in systemic blood flow causes an increase in plasma TNF-alpha. This can lead to the development of a sepsis-like syndrome in a group of patients who already are hemodynamically compromised. While weaning short-term LVAD support, rapid diminution of the cardiac output and the pump flow must be avoided.
Analysis of Variance↗
The target antigens of naturally occurring human anti-beta-galactose IgG are cryptic on porcine aortic endothelial cells.
The identification of the xeno-antigens/xeno-antibodies combinations involved in pig-to-human xenograft rejection is an essential step for understanding this process and for the development of procedures to prevent it. Although it is widely accepted that the terminal disaccharide Galalpha1,3Gal-R is by far the major epitope recognized by human natural antibodies reactive with pig tissues, there is also evidence that other carbohydrate epitopes might be important in xenograft rejection. In an attempt to further improve our knowledge of the repertoire of human natural antibodies with anti-pig specificity we sought to determine whether naturally occurring human anti-beta-galactose IgG could interact with porcine aortic endothelial cells (PAEC). Histochemical analysis of porcine aorta sections revealed that the carbohydrate structures recognized by the anti-beta-galactose IgG are present on endothelial cells but in a cryptic form that can be unmasked by sialidase treatment. These structures were also found to be cryptic in cultured PAEC. In addition we demonstrated that PAEC may adsorb fetal calf serum (FCS) glycoproteins when cultured in FCS-supplemented medium, a process susceptible to generating artifactual observations in carbohydrate antigens analysis. In conclusion, despite their abundance, human anti-beta-galactose IgG do not represent a primary concern in pig-to-human xenotransplantation as the carbohydrate structures to which they bind are normally masked by sialic acid residues on porcine endothelial cells. However, whether these cryptic epitopes might be exposed on endothelial cells from genetically engineered animals should be further investigated because, if so, additional approaches will be needed to suppress their interaction with human anti-beta-galactose IgG.
Animals↗
Effects of the 14F hemopump on coronary hemodynamics in patients undergoing high-risk coronary angioplasty.
BACKGROUND: The influence of the 14F Hemopump on coronary hemodynamics in patients with coronary artery disease remains unknown. METHODS: Systemic and coronary hemodynamic measurements were obtained in eight patients among 13 who underwent high-risk coronary angioplasty in our institution with the support of the Hemopump. Coronary blood flow velocity was measured with a 0.014-inch Doppler-tipped guide wire both proximal and distal to the target lesion. RESULTS: Angioplasty decreases the diameter coronary stenosis from 76% +/- 21% to 22% +/- 11%. Hemopump support did not change systemic hemodynamics either before or after angioplasty. During angioplasty Hemopump support decreased the pulmonary capillary wedge pressure from 23.5 +/- 8.5 mm Hg to 18.6 +/- 7 mm Hg (p = 0.013). No changes in either heart rate, mean and systolic aortic pressures, and cardiac index were observed throughout the procedure. After successful angioplasty was performed, the ratio of proximal to distal flow velocity decreased from 2.11 +/- 1 to 1.65 +/- 0.2 (p = 0.05). However, Hemopump did not affect absolute coronary blood flow velocities or the phasic pattern of flow velocities (diastolic systolic velocity ratio, diastolic and systolic velocity integrals) either in proximal or distal locations either before or after angioplasty. CONCLUSIONS: This study shows that although the 14F Hemopump produces unloading of the left ventricle, it does not importantly alter coronary hemodynamics when systemic hemodynamics are stable. Whether the Hemopump would maintain or improve coronary blood flow in compromised patients remains to be determined.
Aged↗
[Wearable Baxter-Novacor mechanical ventricular assistance].
Progressive technological developments have permitted clinical use of the wearable Baxter-Novacor left ventricular assist system. The system allows total bypass of the left ventricular function, and recovery of and adequate circulation in patients in cardiogenic shock. Since the first clinical use, in March 1993, eight patients about to die have been supported with a cardiac transplantation. This experience suggests that an an acceptable answer to the problem of organ shortage is now available.
Adolescent↗
Mechanical circulatory support towards the permanent implantation.
Experience on wearable LVAS Novacor support accumulated since the first implantation in March 1993, includes in November 1995, seven cases (six male, one female, mean age 34) of cardiogenic shock, unresponsive to optimal medical management referred for urgent transplantation. Post-implantation period was free of any major incident in all but one, allowing transplantation in five, on an elective basis, and prolongation of the waiting period, at home in two. This experience suggests that a major breakthrough in the technology of mechanical support has been achieved: patients awaiting transplantation can be discharged home, which is both the result and an contributing factor of a satisfactory quality of life. This improvement allows speculations on coming studies on permanent implantation of the wearable LVAS Novacor, as an alternative therapy to cardiac transplantation.
Adult↗
[Wearable mechanical ventricular support].
Progressive technological developments have permitted clinical use of the wearable Baxter-Novacor left ventricular assist system. The system allows total bypass of the left ventricular function, and recovery of an adequate circulation in patients about in cardiogenic shock. Since the first clinical use, in March 1993, six patients about to die have been supported with a cardiac transplantation. This experience suggests that an acceptable answer to the problem of organ shortage is non available.
Assisted Circulation↗
[Mechanical circulatory assistance using the Novacor implanted device. A postoperative follow-up].
The postoperative follow-up of 8 patients on the waiting list for cardiac transplantation, with implanted left ventricular assist devices of the Novacor type, was marked by right ventricular failure in the first week, controlled by positive inotropic agents and the maintenance of high right ventricular preload. The outcome later on showed that an ambulatory life was possible for 6 of the 8 patients, allowing the wait for cardiac transplantation under excellent conditions. Three major complications were observed: a case of aspergillosis endocarditis, one vertebrobasilar cerebrovascular accident and one low output state by progressive degradation of right ventricular function: after a period of circulatory assistance of 52 to 201 days. 6 out of the 8 patients underwent cardiac transplantation, 5 of which were successful.
Adolescent↗
Characterization of antiendothelial cell and antiheart antibodies following heart transplantation.
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Aorta↗
Use of brequinar sodium for preventing cardiac allograft rejection in primates.
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Animals↗
[Discordant heart xenografts. Experimental study in pigs conditioned by total lymphoid irradiation and cyclosporine A].
The use of discordant xenografts may solve some of donor shortage problems. The beneficial effects of treatment with total lymphoid irradiation (TLI) and classical drugs on this discordant model of transplantation rejection was evaluated. Twenty-four lamb hearts were transplanted heterotopically in the abdomen of 24 pigs. Group I received no treatment (control). Group II received continuous intravenous medical treatment cyclosporin A (CyA) (5 mg/kg) and azathioprine (3 mg/kg) 3 days prior to transplantation. Group III received the same medical treatment and simultaneously 12 grays of irradiation in 5 equal fractions with a high rate (100 cGy/min) or a low rate (1.6 cGy/min) prior to transplantation. Group IV also received 12 grays in 5 fractions at a high rate followed by the medical treatment started 5 days after TLI and continued until the day of transplantation. Antibody and serum cyclosporine levels were monitored. Histology specimen were analyzed at the end of the experiment. Mean GST (graft survival time) in group I and II was 140 +/- 35 min and 117 +/- 27.4 min respectively. The histological features of these hearts suggested acute humoral rejection (hemorrhage, thrombosis, and edema) without cellular infiltration. In group III, one heart functioned 4.5 days with pathological features of cellular rejection and a second animal died at 6 hours with a functioning graft with no evidence of an acute rejection. Both had been treated with the low rate TLI protocol (1.6 cGy/min). The mean GST in this group was 1080 +/- 794 min. In Group IV, one graft functioned for 6.5 days and another for 3.25 days. Mean GST was significantly increased in this group to 4800 +/- 2647 min (p < 0.05). A cellular infiltration was seen in this two grafts. The remaining graft was rejected in 6 hours with histological lesions typical of acute humoral rejection. Antibodies levels at the time of transplantation were lowest (40%) in group IV and in the low rate irradiation group. The ability of TLI to induce tolerance and to prolong survival in a discordant xenograft model depends upon cumulative dose, rate of irradiation, delay between TLI and graft placement, and combined treatment with immunosuppressive drugs. A high rate of TLI and graft placement is delayed. Low rates of irradiation may be beneficial when there is a very short period between treatment and transplantation. These findings highlight the potential usefulness of TLI in combination with immunosuppressive drug therapy when antibody-mediated rejection occurs, such as with xenograft and in sensitized patient.
Animals↗
Preoperative total lymphoid irradiation with intravenous cyclosporine dramatically enhances discordant xenograft survival.
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Animals↗
Donor hearts with impaired hemodynamics. Benefit of warm substrate-enriched blood cardioplegic solution for induction of cardioplegia during cardiac harvesting.
Brain-dead donors frequently show circulatory deterioration and often require so much inotropic support that the donor heart is of questionable value. This experimental study quantifies the cardiac metabolic consequences of brain death and the role of warm blood cardioplegic solution for induction of cardioplegia to improve the quality of potential donor hearts with impaired hemodynamics. Twelve dogs were subjected to brain death by interrupting cerebral blood flow (ligation of innominate artery, carotid arteries, and superior vena cava) and were followed up for as long as 6 hours. Each showed progressive hemodynamic deterioration, necessitating inotropic support (dopamine, calcium, and epinephrine) and large amounts of volume replacement (hetastarch; Hespan) to support the circulation (maintain mean arterial blood pressure greater than 60 mm Hg). Biopsy specimens were taken after 6 hours, or when irreversible ventricular fibrillation occurred, and were analyzed for adenosine triphosphate, creatine phosphate, glycogen, glutamate, and lactate. In six dogs the aorta was then clamped, and a 10-minute infusion of warm (37 degrees C) substrate-enriched aspartate/glutamate blood cardioplegic solution (with the dog's own blood) was given by roller pump to simulate warm induction during the harvesting process. Biopsies were then repeated. Myocardial metabolism, expressed as percent of control values, during brain death was characterized by the following: (1) moderate energy depletion (adenosine triphosphate fell 25% +/- 8%, creatine phosphate fell 55% +/- 15%; p less than 0.05 versus control: mean +/- standard error of the mean); (2) substrate depletion (tissue glutamate fell 48% +/- 9.5%, glycogen fell 66% +/- 7.5%; p less than 0.05 versus control: mean +/- standard error of the mean); and (3) evidence of anaerobic metabolism (lactate increased 374% +/- 95%; p less than 0.05 versus control: mean +/- standard error of the mean). Warm induction of blood cardioplegia in these energy- and substrate-depleted ischemic hearts showed (1) return of creatine phosphate levels to normal (113% +/- 16.8%), (2) replenishment of glutamate (201% +/- 24% of control; p less than 0.05 versus control: mean +/- standard error of the mean), and (3) 43% +/- 14% reduction in myocardial lactate content; (p less than 0.05 versus brain-dead animals). These data suggest that brain-dead donors requiring inotropic support sustain energy and substrate depletion and ischemic damage that can be reversed by a brief period of induction of cardioplegia with a warm substrate-enriched blood cardioplegic solution before harvesting.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
[Conflicting xenograft. Role of preoperative total lymphoid irradiation].
This study deals with an experimental model of discordant cardiac xenograft between 24 donor lambs of the Préalpes race and 24 recipient Camborough pigs divided up into 4 groups: I control (6) without immunosuppressive treatment; II (5) with pharmacological immunosuppression (IP); III (13) with PI and total lymphoid irradiation (TLI) and immediate graft, divided up into IIIa (5) with high-rate (HR) TLI and IIIb with low-rate (LR) TLI; IV (4) with a two-week lapse between TLI and grafting. The best graft survival rate (GSR) is obtained either after delayed LR-TLI or after LR-TLI without delay. This study seems to be the first one demonstrating that for discordant xenogenic grafts, TLI associated to PI with cyclosporin A (Cy A) significantly prolongs the survival of the graft (30 times).
Animals↗
Studies of myocardial protection in the immature heart. V. Safety of prolonged aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia.
This study tests the hypothesis that multidose, hypocalcemic aspartate/glutamate-enriched blood cardioplegia provides safe and effective protection during prolonged aortic clamping of immature hearts. Of 17 puppies (6 to 8 weeks of age, 3 to 5 kg) placed on vented cardiopulmonary bypass, five were subjected to 60 minutes of 37 degrees C global ischemia without cardioplegic protection and seven underwent 120 minutes of aortic clamping with 4 degrees C multidose aspartate/glutamate-enriched blood cardioplegia ([Ca++] = 0.2 mmol/L), preceded and followed by 37 degrees C blood cardioplegic induction and reperfusion. Five puppies underwent blood cardioplegic perfusion for 10 minutes without intervening ischemia to assess the effect of the cardioplegic solution and the delivery techniques. Left ventricular performance was assessed 30 minutes after bypass was discontinued (Starling function curves). Hearts were studied for high-energy phosphates and tissue amino acids. One hour of normothermic ischemia resulted in profound functional depression, with peak stroke work index only 43% of control (0.7 +/- 0.1 versus 1.7 +/- 0.2 gm x m/kg, p less than 0.05). There was 70% depletion of adenosine triphosphate (7.6 +/- 1 versus control 20.3 +/- 1 mumol/gm dry weight, p less than 0.05) and 75% glutamate loss (6.6 +/- 1 versus control 26.4 +/- 3 mumol/gm, p less than 0.05). In contrast, after 2 hours of aortic clamping with multidose blood cardioplegia preceded and followed by 37 degrees C blood cardioplegia, there was complete recovery of left ventricular function (peak stroke work index 1.6 +/- 0.2 gm x m/kg) and maintenance of adenosine triphosphates, glutamate, and aspartate levels at or above control levels adenosine triphosphate 18 +/- 2 mumol/gm, aspartate 21 +/- 1 versus control 2 mumol/gm, and glutamate 25.4 +/- 2 mumol/gm). Puppy hearts receiving blood cardioplegic perfusion without ischemia had complete recovery of control stroke work index. We conclude that methods of myocardial protection used in adults, with amino acid-enriched, reduced-calcium blood cardioplegia, can be applied safely to the neonatal heart and allow for complete functional and metabolic recovery after prolonged aortic clamping.
Adenosine Triphosphate↗
Centrifugal pump or pneumatic ventricle for short-term mechanical circulatory support?
Two comparable groups of four Holstein calves were implanted with different left ventricle assist devices: the Centrimed centrifugal pump (CP) (Sarns Inc.) or the UTAH 85 VAD pneumatic ventricle (University of Utah). Operative procedure, inflow and outflow cannulae, monitoring, heparinization, were identical in both groups. No transfusion was ever required. The study was terminated after three days and autopsy was performed on the calves. Left ventricular unloading provided by both devices was complete (LVEDP less than 1 mmHg) and identical. LV bypassed flow rate was higher in CP (0.045 L/min/kg) than in UTAH 85 VAD (0.035 L/min/kg) but with no statistical difference. Blood trauma was comparable in the two groups. Daily blood samples did not show any significant changes from baseline values in creatinine, hematocrit, fibrinogen. Platelet loss from initial level was 30%; serum lactate dehydrogenase rose 150% with no significant difference in the two groups; plasma free hemoglobin never reached significant values. At autopsy, thrombotic deposits on cannuale and renal infarction rate were similar. CP housing had to be changed every day, whereas no technical failure was ever observed with the UTAH 85 VAD. Clinical response and blood damage of the two pumps used as LVAD were the same. Considering the CP has to be replaced every 24 h, the cost of three CP's would be comparable to one Utah UVAD-85 if polyurethane tricusp semi-lunar valves are used in the latter. Until the UTAH-85 VAD becomes commercially available, simple valveless low-cost CP are very attractive for short-term mechanical support.
Animals↗
Correlation between clinical and histologic patterns of degenerative mitral valve insufficiency: a histomorphometric study of 130 excised segments.
The objectives of this study were to examine quantitatively the histological changes in incompetent degenerative mitral valves obtained at surgery for mitral valve repair, and to determine whether Barlow's disease (BD) and fibroelastic deficiency (FED) can be distinguished by histology. The billowing mitral leaflet syndrome (or Barlow's disease) and FED can be distinguished on the basis of clinical patterns and gross features, but their histologic patterns have not been described. One hundred thirty patients were studied. Thirty-nine (24 males) had BD; 44 (38 males) FED; 15 (7 males) Marfan's syndrome (MS); and 32 patients (25 males) a non-determined degenerative disease. Histological changes of the resected segment of the valve were quantitatively evaluated using scores of severity. A discriminant analysis was performed. The groups defined by the computer were checked for concordance with groups defined by the surgeon. Collagen alterations were found the most severe in MS patients. BD and MS had the most myxoid infiltration. MS and FED patients had the most elastic fiber alterations. No BD in males and only one in females were misclassified by the discriminant procedure into the FED group. Overall, the percentages of correct matchings were 54% in males and 62% in females. When the age of patients and the size of ring were added to histology to determine whether this additional information provided more discrimination, the percentages of correct matchings reached 90% in males and 100% in females. BD and FED are two fairly distinct entities, which can be distinguished by quantitative histology, whereas only modest differences were found in qualitative histology.
Adolescent↗