Efficacy of prostacyclin analogue (OP-2507) in viable hepatic grafts from pigs with non-beating hearts

Abstract We investigated whether the stable prostacyclin analogue (OP-2507; OP) would ameliorate warm ischemia-related injury of the liver graft under conditions of a nonbeating heart. Thirty-ix mongrel pigs were arranged into 3 groups of 6 pairs. Group 1 pigs underwent orthotopic liver transplantation from heart-beating donors (HBD). In group 2, animals received liver grafts from nonheart-beating donors (NHBD), defined as 30 min of cardiac arrest. Group 3 pigs received grafts from NHBD, but the donor had been pretreated with OP by intraportal infusion (2 μg/kg min for 30 min immediately before the induction of cardiac arrest). The grafts were preserved at 4 °C in Euro-Collins solution in which OP was dissolved at 200 4μg/l. Five-day survival rates after transplantation improved significantly in OP-treated animals (3/6, for group 3), compared with 0/6 for group 2 ( P < 0.05, generalized Wilcoxon test). Five of 6 animals survived more than 5 days in the HBD group (group 1). Although the serum transaminase activities and bile production did not differ in the early phase of recirculation among the groups, there was a significant improvement in the hepatic microcirculatory environment in the surviving groups (groups 1 and 3). Analysis of arterial prostanoid levels showed a substantial suppression of PGE, release by OP treatment following reperfusion. Our data indicate that a stable prostacyclin analogue can be clinically useful for expanding the donor pool by improving the quality of the liver graft.     

Attenuation of ischemia reperfusion-induced lung edema by prostaglandin I2 analogue OP-2507 in the isolated perfused rat lung

Using the physiological salt solution (PSS)/Ficollperfused rat lung, we studied the effect of prostaglandin I₂ (PGI₂) analogue, OP-2507, on ischemia-reperfusion lung injury. Ischemia was induced by stopping perfusion and ventilation. Reperfusion after 90 min of normothermic ischemia increased mean pulmonary artery perfusion pressure (Ppa) and produced significant lung edema. Pretreatment with OP-2507 (200 ng·ml⁻¹ and 1000 ng·ml⁻¹) equally attenuated the increase in Ppa and lung edema after reperfusion. Lactate dehydrogenase release from the OP-2507-treated lungs of both doses were significantly lower than the untreated lungs. Thus, OP-2507 seems to be a useful agent for preventing ischemia-reperfusion lung injury.     

The beneficial effect of prostacyclin analogue (OP 2507) on rat liver transplantation subjected to an extended anhepatic phase

We investigated the effect of a prostacyclin analogue (OP 2507) on PVG (RT1^c) recipients subjected to an extended anhepatic phase (AH) and transplanted orthotopically with PVG livers. All of the animals that underwent orthotopic liver transplantation (OLT) with a 20-min AH survived for 1 week with or without OP 2507 (OP) treatment (10/10, 100%). When the AH was lengthened to 45 min, the 1-week survival rate of recipients was poor in OP-untreated groups (1/10, 10%). Treatment of the recipient with OP 2507, 0.15 g/kg per minute for 30 min, prior to the 45-min AH substantially improved 1-week survival (5/6, 83.3%, P<0.05). The serum TNF- level at day 1 in OP-treated animals that underwent OLT with a 45-min AH was significantly lower than that in animals with 45-min AH OLT without OP treatment. We conclude that OP 2507 treatment has potential usefulness as a perioperative treatment when the AH is extended during OLT.     

Nitrous oxide does not depress left ventricular contractility in ischemic rat heart

The direct effects of nitrous oxide on left ventricular contractility and myocardial oxygen consumption (MVO₂) in the ischemic isolated rat heart were studied. The rat heart was isolated and perfused by a Langendorf technique. The aortic stump was cannulated and the heart was perfused with Kumpeis solution bubbled with 95% O₂ and 5% CO₂ (control phase). A latex balloon was inserted into the left ventricle (LV) to measure LV pressures and dP/dt. Coronary flow was measured and MVO₂ was calculated. After the control phase, perfusion pressure was decreased to induce global ischemia (ischemic phase). There were four groups of eight hearts each: control, nitrogen, nitrous oxide, and halothane groups. After 15 min of ischemic phase, the perfusion pressure was increased and the gas mixture was changed to the standard gas mixture (reperfusion phase). Nitrous oxide did not further depress myocardial contractility compared with nitrogen in the ischemic phase, and did not alter MVO₂ in the ischemic phase compared with nitrogen. Halothane significantly depressed myocardial contractility and decreased MVO₂ in the ischemic phase compared with the control.     

异氟醚对高血压大鼠缺血心肌收缩功能和ATP含量的影响

目的：研究异氟醚对高血压大鼠（ＳＨＲ）缺血心肌收缩功能和ＡＴＰ含量的影响。方法：应用离体心脏Ｌａｎｇｅｎｄｏｒｆ逆行灌注模型，研究异氟醚对心肌缺血前后ＬＶＥＤＰ、ＬＶＤＰ、＋ｄｐ／ｄｔ、－ｄｐ／ｄｔ和ＣＦ的影响，并用Ｌｕｃｉｆｅｒｉｎ／Ｌｕｃｉｆｅｒａｓｅ法测定再灌注末心肌ＡＴＰ含量。结果：１．５ＭＡＣ的异氟醚能显著增加正常血压（ＮＴＲ）和ＳＨＲ离体心脏的ＣＦ。在缺血期间，异氟醚显著抑制了ＮＴＲ和ＨＲ心肌缺血性挛缩的发生时间和幅度。再灌注期间，异氟醚促进了ＮＴＲ和ＨＴＲ心脏收缩功能和心肌ＡＴＰ含量的恢复，但是异氟醚促进ＳＨＲ缺血心肌收缩功能恢复和心肌ＡＴＰ再合成的作用显著低于ＮＴＲ。结论：异氟醚对ＨＴＲ心肌缺血再灌注损伤的保护作用显著低于ＮＴＲ心肌。     

Sevoflurane reduces dysrhythmias during reperfusion in the working rat heart

Purpose. The effects of sevoflurane on myocardial reperfusion injury have not been well studied. The purpose of this study was to determine the effects of sevoflurane on myocardial function, arrhythmia, and metabolism during reperfusion in an isolated working rat heart model. Methods. Thirty-two hearts were divided into four groups according to the timing of 2.5% sevoflurane administration: group I, control, no sevoflurane; group II, sevoflurane administered only before ischemia; group III, sevoflurane only during reperfusion; group IV, sevoflurane during the whole study period. Myocardial contractility, myocardial ATP, lactate, and glycogen levels were assessed in the reperfusion period following global heart ischemia of 15 min duration. The incidence and duration of ventricular fibrillation were also observed in the reperfusion period. Results. There was no difference in cardiac output and left ventricular dP/dt max among the four groups at 10, 15, and 20 min after reperfusion. There was no difference in myocardial ATP, lactate and glycogen contents between the groups. The incidences of ventricular fibrillation during reperfusion were 100%, 63%, 100%, and 25% (P < 0.05 vs control), and the durations of ventricular fibrillation during reperfusion were 375 ± 269, 104 ± 98 (P < 0.05 vs control), 303 ± 189, and 93 ± 245 (P < 0.05 vs control) in groups I, II, III, and IV, respectively (mean ± SD). Conclusion. The administration of sevoflurane prior to reperfusion appears to provide myocardial protection, as assessed by reduced dysrhythmias during reperfusion. Received: December 14, 1999 / Accepted: July 25, 2000     

Effects of sevoflurane on myocardial metabolism during postischemic reperfusion in the rat

In experiments on isolated rat heart lung preparation, the effects of sevoflurane on myocardial metabolism during postischemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate and glycogen. Hearts were perfused for 10min initially and made globally ischemic for 8min. Afterwards, they were reperfused for 12min. Sevoflurane was administered from 5min after the start of perfusion to the end of reperfusion. There was no significant difference in myocardial lactate levels between the sevoflurane (S) and control groups. However, the myocardial ATP level in Group S was significantly higher than that in control (17.45 ± 1.51 vs 15.50 ± 0.87:P < 0.01). The administration of sevoflurane to the isolated rat heart during pre- and post-ischemia enhanced metabolic recovery in the postischemic state.(Kashimoto S, Oguchi T, Kume M et al.: Effects of sevoflurane on myocardial metabolism during postischemic reperfusion in the rat. J Anesth 2: 23–26, 1989)     

Effect of prostacycline analogue OP-41483 and perfusate on liver preservation by simple hypothermia in rats

Changes in rat livers preserved by simple cooling immersion in modified Sacks' solution, Ross' solution and Ross' solution with OP-41483, a PGI₂ analogue, were compared after 12, 24, 36, and 48 hours. The viability of the preserved livers was assessed by measuring the tissue ATP concentrations and quantifying morphologic changes in the mitochondria observed by transmission electron microscopy using a 4-point scale, the mitochondrial score. A general trend towards progressive mitochondrial degeneration was observed in all groups. After 12 hrs of preservation, there was no significant difference between the groups. From 24 to 48 hours, the mitochondrial scores for livers preserved with OP-41483 were significantly higher than in the two other groups. No difference among the groups in tissue ATP concentration was observed at any time. Thus, OP-41483 was considered to retard mitochondrial degeneration in liver preservation by simple hypothermic immersion and does so by a mechanism not directly related to intracellular energy stores. The possibility that OP-41483 acts by stabilizing the lysosomal membrane is discussed.     

缺血后适应对糖尿病大鼠再灌注心肌的保护作用及其与P-Akt的关系

目的 探讨缺血后适应对糖尿病大鼠离体心脏缺血再灌注损伤的影响及其信号机制.方法 2周龄健康SD大鼠60只,雌雄不拘,体重250～300 g,随机分为6组:空白对照组(N组);缺血再灌注组(IR组);缺血后适应组(Post组);糖尿病大鼠后适应组(Dpost组);糖尿病大鼠缺血再灌注组(DIR组);糖尿病大鼠空白组(DN组).将链脲酶素(STZ,美围Sigma公司)按65 mg/kg经大鼠腹腔注射,48 h后断尾法连续两次测血糖≥16.65 mmol/L,并出现多饮、多食、多尿、体重减轻,脱毛等表现确定糖尿病模型成功.糖尿病模型制作成功后建立离体心脏Langendorff灌注模型,观测心脏冠状动脉灌流量、心肌梗死范围,免疫印迹(western blot)对P-Akt测定、电镜下观察心肌和线粒体改变.结果 糖尿病大鼠血糖浓度平均为(23.15±2.16)mmol/L,非糖尿病大鼠为(4.16±0.31)mmol/L.两组大鼠血糖浓度差异有统计学意义(P<0.01).缺血后适应组(Post组、DPost组)较缺血再灌注组(IR组、DIR组)冠状动脉流量(ml/min)明显增加(6.5±1.2、5.6±1.0对3.4±1.0、2.0±1.3),心肌梗死范围(%)明显减少(25.2±2.1、34.2±3.6对47.5±3.5、65.2±4.5),P-Akt的表达明显增强,心肌纤维和线粒体的完整程度明显较好.结论 缺血后适应在糖尿病大鼠离体心脏具有显著的保护作用,这一作用可能与Akt激活有关.     

缺血预处理对大鼠离体心脏心肌线粒体功能的影响

目的研究缺血预处理（IPC）对大鼠离体心脏心肌线粒体功能的影响。方法SD大鼠72只，随机分为4组（n=18）：对照组（CON组）、缺血再灌注组（IR组）、缺血预处理组（IPC组）和5-羟葵酸（5-HD）拮抗IPC组（5-HD＋IPC组）。采用Langendorff装置建立大鼠离体心脏缺血再灌注模型，IPC组在全心停灌前，给予2次缺血预处理，每次缺血5min，间隔5min；5-HD＋IPC组预处理前灌注5-HD 10min。各组于平衡末、缺血前、再灌注30min各取6个心脏，分离心肌线粒体并测定线粒体呼吸控制率（RCR）、磷氧比（ADP／O2）、NADH氧化酶（NADH-OX）、琥珀酸氧化酶（SUC-OX）、细胞色素C氧化酶（CYTC-OX）的活性。结果与CON组比较，IR组、IPC组和5-HD＋IPC组再灌注30min RCR、ADP／O2、NADH-OX、SUC-OX和CYTC＋OX的活性降低（P〈0．05）；与IR组比较，IPC组和5-HD＋IPC组再灌注30min上述各指标升高（P〈0．05）；与IPC组比较，5-HD＋IPC组再灌注30min上述各指标降低（P〈0．05）。结论缺血预处理可改善大鼠离体心脏缺血再灌注时心肌线粒体的功能，其机制与mitoKATP的激活有关。     

Effect of lidocaine on ischaemic preconditioning in isolated rat heart

Background. Lidocaine is frequently used as an agent to treatventricular arrhythmias associated with acute myocardial ischaemia.Lidocaine is a potent blocker not only of sodium channels, butalso of ATP-sensitive potassium channels. The opening of thesechannels is a key mechanism of ischaemic preconditioning. Weinvestigated the hypothesis that lidocaine blocks the cardioprotectioninduced by ischaemic preconditioning. Methods. Isolated rat hearts (n=60) were subjected to 30 minof no-flow ischaemia and 60 min of reperfusion. Control hearts(CON) underwent no further intervention. Preconditioned hearts(PC) received two 5-min periods of ischaemia separated by 10min of reflow before the 30 min ischaemia. In three groups,lidocaine was infused at concentrations of 2, 10 or 20 µgml^–1 for 5 min before the preconditioning ischaemia. Leftventricular developed pressure (LVDP) and infarct size (IS)(triphenyltetrazolium choride staining) were measured as variablesof ventricular function and cellular injury, respectively. Results. PC reduced IS from 24.8 (SEM 4.1) % to 4.0 (0.7) %of the area at risk (P<0.05). Adding 2 or 10 µg ml^–1lidocaine had no effect on IS compared with PC alone (3.7 (0.7)%, 6.9 (1.8) %). Adding 20 µg ml^–1 lidocaine increasedIS to 14.1 (2.5) % compared with PC (P<0.05). Baseline LVDPwas similar in all groups (111.4 (2.1) mm Hg). Compared withCON, PC improved functional recovery (after 60 min of reperfusion;52.3 (5.9) mm Hg vs 16.0 (4.0) mm Hg, P<0.01). The improvedventricular function was not influenced by addition of 2 or10 µg ml^–1 lidocaine (47.3 (5.7) mm Hg, not significant;45.3 (7.3) mm Hg, not significant), but was blocked by the infusionof 20 µg ml^–1 lidocaine (22.5 (8.0) mm Hg, P<0.01vs PC). Conclusions. Lidocaine blocks the cardioprotection induced byischaemic preconditioning only at supratherapeutic concentrations.     

Protective effects of halothane but not isoflurane against global ischaemic injury in the isolated working rat heart

The effects of equi-anaesthetic concentrations of halothane (HAL) and isoflurane (ISO) on myocardial performance, perfusion, oxygenation and lactate release were studied before, during and after a low-flow, global ischaemic insult in isolated, paced rat left heart preparations. An antegrade perfusion technique was used, where left atrial pressure (LAP) and mean aortic pressure (MAP) could be altered independently of each other. Aortic flow, coronary flow (CF) and PO₂ in venous coronary effluent were continuously recorded and stroke volume, myocardial oxygen consumption (MVO₂) and myocardial oxygen extraction as well as lactate release were calculated. The hearts were exposed for at least ten minutes to the perfusate without (control, n=10) or with HAL (n=10) or ISO (n= 10) at a MAP of 80 mmHg (10.4 kPa) and a LAP of 7.5 mmHg (1.0 kPa). After baseline measurements, MAP was reduced to 25 mmHg (3,2 kPa) for a total of nine minutes. Thereafter MAP was increased to 80 mmHg (10.4 kPa) for another nine minute period. During the whole experimental procedure, LAP was maintained at 7.5 mmHg (1.0 kPa) and heart rate at 325 beats per minute. In the pre-ischaemic control period, MVO₂ was lower with HAL compared to ISO (P<0.05) and control (P<0.05). Stroke volume was also lower with HAL compared to control (P<0.05). During hypoperfusion, lactate release was twice as high in the control group (P<0.0I) and with ISO (P<0.01) compared to HAL. This was accompanied by a lower oxygen extraction with HAL compared to control (P<0.05) and ISO (P<0.05). In the post-ischaemic periods, MVO₂ and stroke volume were lower with HAL compared to ISO and control. There were no significant differences in CF between the groups. We conclude that HAL, but not ISO, exerts a direct protective effect against a glycon'c anaerobic metabolism during low-flow global myocardial ischaemia.     

缺血后处理对大鼠离体心脏缺血再灌注损伤的作用

目的探讨缺血后处理对大鼠离体心脏缺血再灌注损伤的作用。方法24只Wistar大鼠,随机分为3组(n=8):正常对照组(C组)、缺血再灌注组(I/R组)、缺血后处理组(IPC组)。采用大鼠离体心脏Langendorff灌流模型,C组用K-H液灌注160min;I/R组全心缺血40 min,再灌注120 min; IPC组全心缺血40 min后,再灌注10 s,缺血10 s,反复6次,然后持续再灌注118 min。测定再灌注15、30、120 min时冠脉流量(CF)及冠脉流出液心肌肌钙蛋白I(cTnI)浓度,再灌注120 min时,取心肌组织,测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,电镜下观察心肌细胞超微结构。结果缺血再灌注可导致CF降低,冠脉流出液cTnI浓度升高,心肌SOD活性下降,MDA含量升高,心肌细胞超微结构产生病理学改变,缺血后处理可减弱上述改变。结论缺血后处理减轻脂质过氧化反应,对大鼠离体缺血再灌注心脏产生保护作用。     

Effects of isoflurane on myocardial metabolism during postischaemic reperfusion in the rat

In experiments on isolated rat heart lung preparation, the effects of isoflurane on myocardial metabolism during postischaemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate and glycogen. Hearts were perfused for 10 min initially and made globally ischaemic for 8 min in ischaemic groups. Afterwards, they were reperfused for 12 min. Isoflurane was administered from 5 min after the start of perfusion to the end of reperfusion. There was no significant difference in myocardial lactate levels between ischaemic isoflurane and control groups. However, the ATP level in the hearts in the ischaemic isoflurane group was significantly higher than that in the ischaemic control group (17.96 +/- 1.31 vs 15.50 +/- 0.87; P less than 0.005). The administration of isoflurane to the isolated rat heart during pre- and post-ischaemia enhanced metabolic recovery in the postischaemic state.     

Effect of cyclosporin A,azathioprine, and prednisolone on carbohydrate metabolism of rat hepatocytes

The effect of different immunosuppressive drugs (prednisolone, azathioprine, cyclosporin A) on liver carbohydrate metabolism in the rat was investigated. Daily administration of prednisolone (3 mg/kg body weight) and azathioprine (2 mg/kg body weight) intraperitoneally for 2 weeks caused significantly lower liver glycogen content than that in NaCl-treated controls. Liver glucose and lactate content, as well as plasma glucose, glucagon, and serum insulin concentration of these animals, remained unchanged. There were no differences in any of these parameters between cyclosporin A (15 mg/kg body weight)-treated and vehicle (olive oil/ethanol)-treated animals. Prednisolone caused significantly lower glucose production in isolated rat hepatocytes using Na-pyruvate as the substrate, whereas glucose production was unchanged in hepatocytes of azathioprine-treated rats using pyruvate or l-serine as substrates. Glucose production from pyruvate or serine was significantly inhibited by cyclosporin A compared to the vehicle, but did not differ from the effects of azathioprine and prednisolone. Lactate production was significantly lower in cyclosporin-treated animals than in those given either the vehicle or azathioprine. Cyclosporin A completely reversed the inhibition of hepatocyte glycogen consumption caused by the vehicle. However, glycogen production in the presence of cyclosporin A was comparable to the effects of prednisolone and azathioprine. Finally, hepatocyte ketone body production using pyruvate as the substrate was higher in the presence of all immunosuppressive drugs. In the presence of serine, acetoacetate production increased in rats treated with 50 mg/kg body weight cyclosporin A, and -hydroxybutyrate production in animals receiving 15 and 50 mg/kg body weight cyclosporin A.This article is dedicated to Professor K. Kochsiek, Chief of the Medical Department, University of Würzburg, FRG, on the occasion of his 60th birthday     

Effect of cyclosporin A on carbohydrate metabolism in the rat

Liver and kidney carbohydrate metabolism was investigated in rats treated with daily doses of 15 mg/kg body weight cyclosporin A (CyA) for 2 and 8 weeks or of 50 mg/kg body weight CyA for 2 weeks. The higher dosage caused significantly reduced liver glycogen and liver glycogen synthetase activity (of both active I-form and total enzyme activity), whereas the activity of the glycogen-degrading enzyme phosphorylase (active a-form and total activity) remained unchanged. Plasma glucose and glucagon levels, as well as blood ketone bodies of these animals, increased significantly and plasma insulin decreased. In contrast, kidney glycogen and glucose content were higher in rats treated with 50 mg CyA, probably due to enhanced ketone body utilization. Reduced liver glycogen synthetase activity was also found in rats treated with 15 mg CyA. Our data suggest that hypoinsulinemia, induced by CyA, might be a contributing factor to the hyperglycemia, which is mainly due to inhibition of liver glycogen synthesis. This article is dedicated to Professor Dr. August Heidland, Chief of the Division of Nephrology, University of Würzburg, FRG, on the occasion of his 60th birthday     

Functional and metabolic effects of propafenone in the rat heart-lung preparation

The effects of propafenone on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Propafenone 0.3, 3 or 30µg·ml^–1 was administered 5min after the start of perfusion. Heart rate decreased in the 30µg·ml^–1 group significantly following the drug administration. The highest dose of propafenone (30µg·ml^–1) reduced cardiac output significantly, and this dose was associated with a higher incidence of arrhythmias than the other groups. Although there were no significant differences in myocardial lactate and glycogen concentrations among groups, ATP content in the 30µg·ml^–1 group was significantly less than that in the control group. As therapeutic plasma concentration of propafenone is about 0.6 (range 0.06 to 1.0) µg·ml^–1, 30µg·ml^–1 is 50 times greater than its concentration. These results suggest that the negative inotropic and chronotropic effects of propafenone are almost same with those of lidocaine which we have previously reported.(Kashimoto S, Oguchi T, Nakamura T, et al.: Functional and metabolic effects of propafenone in the rat heart-lung preparation. J Anesth 5: 392–395, 1991)     

Effects of halothane and enflurane on myocardial metabolism during postischaemic reperfusion in the rat

In experiments on isolated rat heart-lung preparation, the effects of halothane and enflurane on myocardial metabolism during postischaemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate and glycogen. Hearts were perfused for 10 min initially and made globally ischaemic for 8 min. Afterwards, they were reperfused for 12 min. Halothane or enflurane was administered from 5 min after the start of perfusion to the end of reperfusion. There were no significant differences in contents of high energy phosphates between control (C), halothane (H) and enflurane (E) groups (ATP: 15.50 +/- 0.87, 16.05 +/- 1.99 and 15.16 +/- 2.03 mumol/g dry wt, respectively). However, lactate levels in the hearts in Groups H and E were significantly higher than those in Group C (44.04 +/- 10.54, 40.63 +/- 10.34 vs 28.63 +/- 5.98). Slight deterioration in the myocardial oxidation-reduction state may be caused by inhalational anaesthetics when they are administered during the postischaemic reperfusion period.     

促红细胞生成素B螺旋结构缩氨酸对大鼠心肌缺血损伤的影响

目的探讨促红细胞生成素(rhEPO)B螺旋结构缩氨酸(pHBP)对大鼠心肌缺血损伤的影响及其机制。方法采用结扎冠状动脉前降支的方法建立大鼠急性心肌梗死(AMI)模型。90只大鼠随机分为四组:假手术组(A组,n=10)、AMI组(C组,n=20)、rhEPO组(G组,n=30)和pHBP组(E组,n=30)。建模后注射rhEPO、pHBP,24h后通过TCC染色测量MI面积。术后3、24h,Western blot法检测信号转导子与转录激活子3(STAT3)蛋白表达。8周后,通过超声心动图测量左心室舒张期末容积(LVEDV)、左心室收缩期末容积(LVESV)和左心室射血分数(EF)。结果与C组比较,E、G组MI面积明显减小(P0.05)。与A组比较,E、G组STAT3蛋白表达明显增高(P0.05)。与A组比较,E组和G组LVEDV和LVESV明显升高,EF明显降低(P0.01)。与C组比较,E组和G组LVEDV和LVESV明显降低,EF明显升高(P0.05)。结论 pHBP在大鼠心肌缺血损伤中具有心脏保护作用,其保护机制可能与其抑制心肌细胞凋亡和促进新生血管形成有关。     

Effects of reduced pulse pressure to the cerebral metabolism during prolonged nonpulsatile left heart bypass

We investigated changes in the cerebral metabolism with long-term reduced pulse pressure. Nine goats underwent pulsatile left heart bypass (LHB) for 2 weeks while awake, and nonpulsatile LHB was subsequently conducted for 4 weeks. The average pulse pressure during nonpulsatile LHB (13, 10, 11, and 11 mm Hg at the 1st, 2nd, 3rd, and 4th nonpulsatile LHB week, respectively) was significantly lower than that during pulsatile LHB (36 mm Hg). There were no significant differences in either arterio-jugular venous oxygen differences (AJDO2) and cerebral oxygen extraction ratio between the 2nd pulsatile LHB week and the 1st, 2nd, 3rd, and 4th nonpulsatile LHB weeks. The arterio-jugular venous glucose differences, jugular venous-arterial lactate differences (JAD Lactate), and lactate oxygen indexes (JAD Lactate/AJDO2) also remained unchanged during the entire course of the experiments. In conclusion, the cerebral metabolism during nonpulsatile LHB did not change compared to that during pulsatile LHB.