Changes in cardiac output in the acute period of closed chest injury

Experiments on dogs showed that a combination of external blood loss (20 ml/kg) and injury to the thoracic cage causes a clear decrease in pumping function of the heart, terminating in some cases in acute cardiac failure and death of the animals. If the adaptive reactions of the heart and of the body as a whole are maintained, after a period of temporary depression of the myocardium, gradual normalization of the pumping function took place with restoration of homeostasis, even without any special treatment.Laboratory of Experimental Pathology, N. V. Sklifosovskii Emergency Aid Institute, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 274–276, March, 1980.     

滚压泵离体长时间转流对红细胞损伤的研究

目的 :探讨滚压泵长时间转流对红细胞的损伤。方法 :采用两种滚压泵Polystan小儿泵 (A组 )和COBE泵 (B组 )分两组 ,作 5对 16h离体转流实验。测定项目 :FHb、PLT、红细胞脆性度、红细胞电镜扫描观察。血标本为转前、转中 4h后每隔 2h抽血标本 ;电镜标本为转前、转中每隔 4h抽一次。结果 :1.FHb随转流时间延长而呈线性增加 ,两组溶血指数分别为 0 .2 96mg/L/h和 0 .3993mg/L/h。两组没有差异 ;2 .PLT同FHb一样呈线性增加 ,直线回归分析提示 ,二者有明显的相关性 ;3.两组红细胞脆性度转中无明显改变 ;4 .电镜观察显示 ,转中标本可见到各种变形红细胞膜 ,棘球红细胞计数表明 ,转流时间越长 ,棘球红细胞数越多。结果 1.滚压泵长时间转流不但使部分红细胞直接破损 ,引起即时溶血 ,而且还造成大量红细胞亚损伤 ,导致术后的延迟性溶血 ;2 .红细胞形态学的改变是导致术后延迟性溶血的基础。     

Detection of nucleoside triphosphate hydrolase as a circulating antigen in sera of mice infected with Toxoplasma gondii.

The nucleoside triphosphate hydrolase, which is present in the tachyzoite form of Toxoplasma gondii, was detected as a circulating antigen in sera of mice infected with a virulent (RH) or an avirulent (Beverly) strain of T. gondii. The enzyme was detected with a monoclonal antibody incorporated into an enzyme-linked immunosorbent assay. The lower limit of sensitivity of the assay was about 0.3 ng/ml, and standard assays provided a linear plot of nucleoside triphosphate hydrolase concentration over a range of 0.3 to 12 ng/ml. In mice inoculated intraperitoneally with tachyzoites of the RH strain, nucleoside triphosphate hydrolase emerged in the serum 1 day after injection, and then the concentration increased and reached a value of 30 micrograms/ml on day 5. In mice inoculated intraperitoneally with cysts of the Beverly strain, nucleoside triphosphate hydrolase was detected at day 3 after injection, and a peak concentration of 89 ng/ml was seen on day 10. The concentration of enzyme decreased thereafter, and the enzyme disappeared from the circulation on day 56.     

In vitro performance testing of a pediatric oxygenator with an integrated pulsatile pump

For different lung and heart diseases (e.g., acute respiratory distress syndrome, congenital heart failure, and cardiomyopathy) extracorporeal membrane oxygenation is a well-established therapy, particularly in the field of neonatal and pediatric medicine. To reduce the priming volume of the extracorporeal circuit, different components can be combined. In this study, an oval-shaped oxygenator (called ExMeTrA) with integrated pulsatile pump was tested in vitro using porcine blood. A feasibility study regarding the performance of collapsing and expanding silicone tubes within an oxygenator fiber bundle as a pulsatile pump was previously completed with successful results. The findings of this study improve upon the previous feasibility results, particularly in terms of gas exchange and filling volume. Five modules were manufactured in sizes of 20 ± 2.2 ml (priming volume) with fiber surface areas of 0.24 ± 0.027 m(2) and an analytically calculated volume pumping capacity of 692 ± 75 ml/min. The modules were made of polymethylpentene fibers with dense outer layer to permit long-term applications. The gas exchange rates at a gas/blood flow ratio of 2:1 were between 64 and 72.7 ml(O)(2)/l(blood) and between 62.5 and 81.5 ml/l(blood), depending on the blood flow. The individual module's pumping capacity ranged from 200-500 ml/min thus providing room for further improvements. In order to enhance the pumping capacity while maintaining sufficient gas exchange rates future optimization, adjustments will be made to the inlet and outlet geometries.     

A new hypothesis on the mechanism of calcification formed on a blood-contacted polymer surface

Calcification on a blood-contacting polymer surface in an artificial heart is one of the most serious problems. Recently, we maintained a goat with a total artificial heart (AH) for 532 days without systemic anticoagulation. Sactype blood pumps coated with segmented polyurethane and incorporating jellyfish valves, thin polymer membrane valves, were used in the experiment. The pump was exchanged for a new one on the 312th day on the left side and the 414th day on the right side. They were analyzed with a scanning electron microscope (SEM) and an X-ray microanalyzer. The valve membrane after 312 days of pumping revealed plastic deformation expanding toward upstream between the spokes by creep fatigue with blood pressure difference when the valve closed. Calcification on the membrane was concentrated in the limited portions that received a strong stretching force: the upstream side of the membrane between the spokes and downstream side of the membrane on the spokes. Slight or no calcification was observed on the opposite side of the membrane that received a compression force, and no calcification was found on nonmoving parts such as the center of the membrane and spokes. A new hypothesis on the mechanism of calcification at the portion that received repeated stretching force was raised. The repeated stretching force would extend the polymer membrane, causing some loosening between polymer molecules and generating microgaps. The blood protein and phospholipid would invade into these microgaps, which would then attract Ca ions followed by phosphate ions to make their complexation. The hypothesis could well explain the calcification phenomena on a blood-contacting polymer surface, and gave a good clue on how to protect from calcification.     

Responses of vasopressin release in patients with cardiopulmonary bypass anesthetized with enflurane and morphine.

Changes in plasma level of arginine vasopressin (AVP), arterial pressure, and urine flow were studied before, during and after cardiopulmonary bypass (CPB) in 11 patients with congenital heart disease. Anesthesia was induced with thiopental sodium (3-5 mg/kg) and was maintained with enflurane (1.0-1.5%), 50% N2O in O2 and morphine (0.5 mg/kg). Concentration of plasma AVP increased slightly from 3.8 +/- 1.5 pg/ml after induction and increased 3-fold after sternotomy. Plasma AVP level increased to 132 +/- 26 pg/ml and 218 +/- 54 pg/ml after 5 and 60 min on CPB, respectively. When the circulation returned to normal, plasma AVP level decreased gradually but was still significantly higher at 24 hr (13.4 +/- 2.5 pg/ml). Marked osmolar diuresis was induced with mannitol in the priming solution used during the CPB: increases in urine flow, Na excretion and osmolar clearance. Possible mechanisms of marked increase in AVP release and differences of AVP responses during CPB reported by other investigators are discussed.     

The effects of pulsatile flow upon renal tissue perfusion during cardiopulmonary bypass: a comparative study of pulsatile and nonpulsatile flow

This study was conducted to directly compare the effects of pulsatile and nonpulsatile blood flow in the extracorporeal circulation upon renal tissue perfusion by using a tissue perfusion measurement system. A total cardiopulmonary bypass circuit was constructed to accommodate twelve Yorkshire swine, weighing 20 approximately 30 kg. Animals were randomly assigned to group 1 (n = 6, nonpulsatile centrifugal pump) or group 2 (n = 6, pulsatile T-PLS pump). A tissue perfusion measurement probe (Q-Flow 500) was inserted into the renal parenchymal tissue, and the extracorporeal circulation was maintained for an hour at a pump flow rate of 2 L/min after aortic cross-clamping. Tissue perfusion flow in the kidney was measured before bypass and every 10 minutes after bypass. Renal tissue perfusion flow was substantially higher in the pulsatile group throughout bypass (ranging 48.5-64.1 ml/min/100 g in group 1 vs. 51.0-88.1 ml/min/100 g in group 2). The intergroup difference was significant at 30 minutes (47.5 +/- 18.3 ml/min/100 g in group 1 vs. 83.4 +/- 28.5 ml/min/100 g in group 2; p = 0.026). Pulsatile flow achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation. A further study is required to observe the effects of pulsatile flow upon other vital organs and its long-term significance.     

人工心脏电动叶轮血泵动物试验及临床试用

研制的叶轮血泵在动物小公牛身上做左心室辅助存活试验，其中三头牛存活约２个月，血液生化检测表明，动物血液成分及器官功能均未有显著改变。     

New technique of measurement of effective capacity changes of total vascular bed

A simple device was developed which can accurately measure effective changes in total vascular capacity as viewed from the site of the heart. The device consists of a funnel and a suction bottle. It is connected via a single large-bore cannula to the right atrium of an open-chest animal without opening the closed loop of the circulation. It serves to clamp the steady-state level of mean central venous pressure precisely at any desired value and to measure the volume of any displacement of blood out of or into the total vascular bed caused by changes in total vascular capacity. The device was tested in mock and animal experiments and proved to function accurately, except during a short transient phase of less than 1 min following an intervention on the total vascular capacity. Errors in clamp pressure in the steady state, which are theoretically zero, were found to be less than 0.2 mm Hg, and were practically insignificant. Errors in the volume measurement were less than 5 ml.     

A novel mechanical lung assist system sustains primary bidirectional cavopulmonary shunt circulation in pigs

Primary creation of a bidirectional cavopulmonary shunt (BCPS), which provides a stable in-series circulation, might improve survival in patients with hypoplastic left heart syndrome. However, pulmonary vascular immaturity and high pulmonary vascular resistance must be overcome to achieve a successful primary neonatal BCPS. This study tested the hypothesis that a novel mechanical lung assist (MLA) system would permit a primary BCPS in juvenile pigs. A BCPS (1(1/2) ventricle repair physiology) was created in nine 4-5-week-old pigs (mean weight 17.9 kg), followed by MLA with a miniature centrifugal pump and a hand-made double-lumen cannula for 2 hours. Systemic and cerebral hemodynamic and metabolic data were evaluated. A mean BCPS flow of 331 +/- 56 ml/min was obtained with a mean pump speed of 3899 +/- 306 rpm at 30 minutes after MLA initiation. Adequate oxygenation, ventilation, and hemodynamics were maintained. Transcranial Doppler ultrasound demonstrated consistent pre- and postoperative peak systolic and diastolic velocities of the middle cerebral artery, indicating sustained cerebral perfusion pressure. This study demonstrated that the MLA is able to sustain a high-resistance BCPS and provides a strategy or rationale for developing a primary neonatal cavopulmonary connection in appropriately selected neonates with congenital heart disease.     

血细胞碎片计数评价滚压泵溶血的意义

探讨血细胞碎片计数在血泵离体实验中的意义.分别采用POLYSTAN和COBE滚压泵,对血样本各作5次16 h离体长时间转流实验.转流前血样本作对照组、转流后4 h第1次抽取血标本,以后每隔2 h抽取1次血标本.检测指标:血细胞碎片计数、游离血红蛋白和红细胞形态学电镜观察.结果发现:分别用两种滚压泵转流后,血细胞碎片计数值均随转流时间延长而呈线性逐渐增加,各时点值与前一时点相比,有显著差异(P＜0.05).两组游离血红蛋白量也随转流时间延长而呈线性增加.血细胞碎片计数与游离血红蛋白呈直线回归相关关系.红细胞形态学电镜观察亦表明,转流时间越长,红细胞损伤越严重.实验结果提示,在滚压式血泵离体转流实验中,血细胞碎片计数可以作为一项评价血泵离体溶血性能的方便、客观指标.     

Effects of a Porphyromonas gingivalis infection on inflammatory mediator response and pregnancy outcome in hamsters.

This study examines the effects of various localized, nondissemination challenges of Porphyromonas gingivalis on inflammatory mediator production and pregnancy outcome in the golden hamster. Live or heat-killed (HK) organisms were inoculated into a previously implanted subcutaneous tissue chamber on the 8th day of gestation to determine the effects on fetal weight, viability, and resorption. In one group of animals, HK organisms were inoculated prior to mating to determine the effects of previous exposure on day-8 gestational challenges. Chamber contents were assayed at 1 and 5 days after challenge for prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-alpha). All P. gingivalis challenges caused a significant increase in chamber PGE2 and TNF-alpha at P < 0.01 in the following order of potency: HK < Live < HK+Live. For example, following the HK+Live challenge, PGE2 levels increased from 4.7 pg/ml at baseline to 362 pg/ml at day 5 and TNF-alpha increased from 26.4 pg/ml to 724 pg/ml at day 5. The same order of potency of the various challenges was maintained with regard to the toxic effects of P. gingivalis on pregnancy outcome. For the HK+Live challenge, fetal weight was decreased 24%; embryolethality increased to 26.5% and the percent fetal resorption increased to 10.6% compared with control animal levels. There was a statistically significant association between increasing levels of both PGE2 and TNF-alpha and fetal growth retardation and embryolethality at P < 0.001. These data suggest that infections with gram-negative periodontal pathogens can elicit adverse pregnancy outcomes and that the levels of PGE2 and TNF-alpha produced as a result of challenge are associated with the severity of fetal effect.     

Does ICSI affect early serum beta-HCG in pregnancies achieved after IVF?

This study was conducted to compare early serum human chorionic gonadotrophin (HCG) concentrations in singleton pregnancies achieved after intracytoplasmic sperm injection (ICSI), with those achieved after conventional in-vitro fertilization (IVF). Early serum HCG, 14-16 days after embryo transfer, was analysed in 99 IVF pregnancies achieved after ICSI (group A), and compared to 105 conventional IVF pregnancies (group B). All women were treated at the IVF Unit, Lis Maternity Hospital. Records were studied retrospectively. The mean +/- SE serum HCG concentration on day 14 after embryo transfer in group A was 190.5 +/- 17.4 mIU/ml, compared to 195.7 +/- 14.03 mIU/ml in group B. HCG concentration 14 days after embryo transfer in both groups A and B was higher in women with mechanical factor than in couples with male factor infertility or unexplained infertility (246 +/- 31.4, 183.3 +/- 16.4, 177.98 +/- 14.3 mIU/ml respectively). On the 16th day after embryo transfer, the HCG concentration increased, and the difference between the groups was maintained. Only in the subgroup of unexplained infertility did we find a difference in concentrations of HCG between ICSI and conventional IVF: on the 16th day following embryo transfer in this group there was a significant difference in HCG concentrations (395. 8 +/- 21 and 545.6 +/- 45.7 respectively; P = 0.04). HCG concentrations did not differ overall in the conventional IVF pregnancies compared with those achieved by ICSI. However, a statistical difference in early serum HCG concentrations was found in relation to the aetiology of infertility.     

Successful treatment of near-fatal fulminant myocarditis using bi-ventricular assist device support

Fulminant myocarditis is a rare but fatal serious disease that may cause prolonged native cardiac dysfunction with multiorgan failure despite temporary mechanical circulatory support with percutaneous venoatrial extracorporeal membrane oxygenation (VA-ECMO) or intraaortic balloon pumping (IABP). A 26-year-old man with fulminant myocarditis developed life-threatening multiorgan failure after 8 days support by VA-ECMO and IABP. He was transferred to our institution with prolonged cardiac dysfunction on hospital day 8; massive pulmonary edema developed into severe pulmonary dysfunction. Immediately after admission, VA-ECMO and IABP were switched to a paracorporeal pneumatic left ventricular assist device (LVAD) and right centrifugal ventricular assist device with an ECMO circuit shunting from the right ventricle to the pulmonary artery (RVAD-ECMO). After intensive care focusing on respiratory dysfunction, ECMO was successfully weaned, and the right ventricular assist device was switched to a durable paracorporeal pneumatic right ventricular assist device. The paracorporeal bi-ventricular assist devices were finally replaced with an implantable non-pulsatile LVAD on hospital day 181. Currently, 1 year after discharge, the patient is at home awaiting heart transplantation. Combined LVAD and RVAD-ECMO appear to be useful for resolving severe pulmonary edema due to unnecessarily long VA-ECMO support as well as kidney or liver dysfunction caused by circulatory collapse.     

Glutathione homeostasis and turnover in the totally hepatectomized rat: evidence for a high glutathione export capacity of extrahepatic tissues.

Glutathione (GSH) homeostasis and turnover were investigated in totally hepatectomized (HX) rats. A technique is described to remove the liver totally, with preservation of the hepatic portal and vena caval vasculature. Euglycemia could be maintained with hourly infusions of 50 mg 100 g-1 b.m. of glucose after bolus i.v. injection of glucose at the same dose. The efficiency of the animal model was demonstrated by examination of paraclinical blood parameters: progressive increases in total plasma bilirubin and alkaline phosphatase activity were noted after HX; the other parameters tested were predominantly in the normal range during the observation period of 6 hours. Histological examination revealed an acute but reversible impairment of intestine and kidneys. These results indicate that the surgical procedure and postoperative care were able to secure sufficient physiological conditions for the experiments over a longer period. 3 to 6 hours after HX we observed a decreased but stable plasma GSH level in anhepatic rats (about 50% of the control value). The GSH levels of brain and kidney were not changed. With increasing time period after HX the heart and lung GSH levels were depressed. A small depression of muscle GSH concentration was observed 4 and 6 hours after HX. A progressive increase in the concentration of oxidized glutathione was seen in brain and kidney. Our observations could be indicative for a high GSH export capacity of extrahepatic tissues contributing about 50% of the total GSH influx into circulation. Probably, the skeletal musculature is an important GSH origin for plasma.     

Erythrocyte Fragment Count Predicts Hemolysis in Roller Pumps

Objective： Hemolysis in blood pumps has been measured by various in vitro test methods, in which normalized index of hemolysis （NIH） was established. As NIH is complicated and difficult to calculate, erythrocyte fragment count is proposed in the present study to predict hemolysis in roller pumps. Methods： Five paired in vitro tests were conducted using the POLYSTAN pediatric pump（group A） and COBE pump（ group B）. Ten whole blood samples （400 ml ） were circled in the roller pump for 16 h. Erythrocyte fragments count and plasma-free hemoglobin （FHb） were measured before pumping and every two hours through circulation after four-hour-pumping. The morphological changes of erythrocyte were observed by scanning electron microscope. Results： The two groups＇ EFC and FHb levels were increased linearly during a long duration of pumping and linear regression of erythrocyte fragments count and plasma-free hemoglobin were correlated. Conclusion： Erythrocyte fragments count could be used as an index in evaluating the in vitro hemolytic properties of blood pumps.     

大鼠体神经-内脏神经吻合后脑源性神经营养因子及其受体的表达变化

为了研究大鼠体神经-内脏神经吻合后脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B(TrkB)在脊髓前角神经元中的表达变化,以正常大鼠为对照,运用RT-PCR技术检测大鼠体神经-内脏神经吻合术后不同时间脊髓腰4(L4)前角神经元中BDNF及TrkB mRNA的表达变化。结果显示,在正常大鼠L4前角神经元中,BDNF及TrkB的mRNA均存在一定水平的表达;体神经-内脏神经吻合术后7d、14d、1m和2m,BDNF和TrkBm RNA的表达均升高,术后7d达到高峰,14d开始下降;2m时BD-NF mRNA的表达量仍显著高于正常组(P<0.01),而TrkB mRNA的表达量到2m时虽仍高,但与正常组相比,其差异已无统计学意义(P>0.05)。上述结果表明,大鼠体神经-内脏神经反射弧建立后,脊髓L4前角神经元的内源性BDNF及其受体TrkB的表达均增高,它们可能作为保护性因子有利于受损神经元的存活和再生。     

Predictive value of drug levels, HIV genotyping, and the genotypic inhibitory quotient (GIQ) on response to saquinavir/ritonavir in antiretroviral-experienced HIV-infected patients

Plasma levels of HIV protease inhibitors (PI) are often close to IC50 values of wild-type viruses when administered without ritonavir boosting. The impact of drug levels, resistance mutations, and the genotypic inhibitory quotient (GIQ) were examined on the response to saquinavir/ritonavir (SQV/r)-based salvage therapy. Patients with prior exposure to PI other than SQV and currently failing virologically were recruited prospectively in a multicenter trial. All patients began SQV/r 1000/100 mg bid plus another two antiretrovirals. A total of 139 patients was enrolled. At month 12, virological response (VR), defined as plasma HIV-RNA decline >1 log, was recorded in 68.2% of patients on treatment (41.7% in the intent-to-treat analysis). The median baseline number of protease resistance mutations was three. The VR was significantly lower in patients with >5 protease resistance mutations and in those with plasma SQV Cmin<0.1 microg/ml. At week 48, the VR was seen in 77.1% of patients with a GIQ>0.04 compared to 18.2% of those with a lower GIQ (P=0.001). In the multivariate analysis, 0.1 microg/ml were independently associated with VR. Interestingly, drug levels had their highest predictive value of the VR at week 12, since low SQV plasma levels often permitted ruling out poorly adherent patients. In contrast, the number of protease resistance mutations had the highest impact on the VR at week 24, suggesting that for those taking the drugs, the VR is highly dependent of the presence of resistance mutations. At any time, nevertheless, the GIQ provided the most accurate prediction of the VR.