Ischemic preconditioning improves preservation with cold blood cardioplegia in valve replacement patients.

OBJECTIVE: The purpose of this study was to test the hypothesis that ischemic preconditioning improves myocardial protection in valve replacement patients undergoing cold-blood cardioplegic arrest and to study the mechanisms of human myocardial ischemic preconditioning initially. METHODS: Forty patients who required double valve replacement were studied. After the institution of cardiopulmonary bypass, 20 patients were preconditioned with two cycles of 3 min of aortic cross-clamping and 2 min of reperfusion before cardioplegic arrest (group IP). Twenty patients were not preconditioned as controls (group C). All hearts were arrested with 4 degrees C cold-blood cardioplegic solution. During perioperation, the blood samples were collected from coronary sinus and radial artery, which were used to measure calcitonin gene-related peptide (CGRP) and creatine kinase-MB (CK-MB). The right atrial myocardial tissue was collected to measure superoxide dismutase/malondialdehyde (T-SOD/MDA) and to observe myocardial ultrastructure. Hemodynamic date were measured. RESULTS: After reperfusion for 30 min, myocardial MDA was significantly lower in group IP than in group C (2.6+/-0.2 vs. 3.8+/-0.3 nM/mg) and T-SOD was significantly higher in group IP than in group C (13.1+/-12.1 vs. 9.2+/-1.2 IU/mg). Ischemic preconditioning significantly increased the production of myocardial CGRP just after preconditioning (92.0+/-4.1 vs. 52.3+/-4.5 pg/ml) and the begin of reperfusion (95.3+/-3.8 vs. 61.2+/-4.9 pg/ml), and deduced the release of CK-MB at 12 h post-reperfusion (77.5+/-9.2 vs. 136.5+/-8.9 IU/l). Preconditioning also improved cardiac function at 30 min and 12 h after reperfusion (cardiac index 2.8+/-0.3 vs. 2.3+/-0.2 l/min per m2 and 2.9+/-0.1 vs. 2.4+/-0.2 l/min per m2). CONCLUSIONS: Ischemic preconditioning enhance cardioplegic protection in valve replacement patients. The possible protective mechanism was that ischemic preconditioning decreased the production of oxygen free radicals.     

钙网蛋白在不同预处理心肌细胞缺血再灌注的保护作用

目的 观察3种不同预处理对在体缺血再灌注心肌的保护作用,探讨钙网蛋白(CRT)在预处理心肌细胞缺血再灌注损伤的作用.方法 将30只成年SD大鼠随机分成5组(n=6),分别为缺血再灌注组、缺血预处理组、腺苷预处理组、远程预处理组和假手术组.建立大鼠在体缺血冉灌注损伤模型,观察各组缺血再灌注前后心功能变化,并检测再灌注末血清肌钙蛋白T(cTnT)、丙二醛(MDA)、超氧化物歧化酶(SOD)的变化以及心肌组织CRT的表达.结果 缺血预处理组、远程预处理组与缺血再灌注组比较(±dp/dt max)有明显提高(P<0.05).缺血预处理组、腺苷预处理组、远程预处理组cTnT、MDA值均低于缺血再灌注组,SOD值高于缺血再灌注组(P<0.05);腺苷预处理组SOD值高于缺血预处理组和远程预处理组,cTnT值则低于后2组(P<0.05);缺血预处理组、腺苷预处理组、远程组与缺血再灌注组比较,CRT表达灰度值均显著降低(P<0.05).结论 腺苷预处理、远程预处理均可以模拟缺血预处理的心肌保护作用;预处理可能通过下调钙网蛋白高表达减轻在体大鼠心肌细胞缺血再灌注损伤.     

Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers

We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.     

内源性一氧化氮在非创伤性缺血预处理中对兔肺的保护作用

目的探讨内源性一氧化氮（NO）在非创伤性缺血预处理（N—WIP）中对兔肺缺血／再灌注（I／R）损伤的保护作用及可能机制。方法采用N-WIP及经典缺血预处理（C-IP）的动物模型，比较两种缺血预处理方法中内源性NO对兔肺在缺血／再灌注损伤中的保护效应。将40只大白兔随机平均分为4组：对照组、I／R组、C—IP组和NWIP组。对比观察各组血清及肺组织中NO2^-／NO3^-、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性以及肺湿／干重比。结果N—WIP组和C-IP组的兔肺再灌注后NO2^-／NO3^-含量均高于I／R组（P〈0．01），甚至高于对照组（P〈0．05）。两种缺血预处理组SOD活性均高于I／R组（P〈0．01），肺湿／干重比和MDA含量均低于I／R组（P〈0．05，P〈0．01）。结论N-WIP与C-IP对移植肺在缺血／再灌注损伤中具有同等强度的保护作用。其机制可能是通过诱发内源性一氧化氮（NO）舒张血管，从而起到保护血管内皮的效应。     

缺血预处理通过抑制炎症反应保护心肌细胞的研究

目的 探讨缺血预处理(IP)对心肌细胞的保护作用及其机制.方法 2004年4月至2004年12月期间在我科行瓣膜置换手术的患者36例,根据是否采取缺血预处理分为预处理组(20例)和对照组(16例),比较两组炎症因子白细胞介素(IL)-8、IL-10、肿瘤坏死因子-α(TNF-α)和心肌细胞转录因子NF.KB p65蛋白的变化情况,分析IP对机体炎症反应的影响.结果 两组患者细胞因子IL-8、IL-10、TNF-α均在主动脉开放6 h时达到高峰,术后5 d均恢复到术前水平.预处理组开放后6 h、术后1 d、术后2 d IL-8和TNF-a水平明显低于对照组(P<0.05),IL-10水平显著高于对照组(P<0.05).复灌后两组心肌细胞中NF-KB p65蛋白表达明显增多,预处理组表达量明显低于对照组(P<0.05),与术后1 d TNF-α呈正相关.结论 缺血预处理可能通过降低机体的炎症反应途径达到心肌细胞保护的效果.     

Oxygen-derived free radical scavengers for amelioration of reperfusion damage in heart transplantation

In this study we tried to define the possible benefits of the oxygen-derived free radical scavengers after 3 hours of cold myocardial global ischemia, as required in the setting of cardiac transplantation. Twenty-one pig hearts were harvested after preservation with a cold cardioplegic solution (St. Thomas' Hospital solution) and topical cooling. Normothermic reperfusion with blood was achieved with a special heart-lung machine preparation, which allows the heart to beat in a working or nonworking mode. Twelve hearts served as control hearts (group I), and nine (group II) were subjected to superoxide dismutase and catalase. Superoxide dismutase was applied at a dose of 40 U/ml of cardioplegic solution and 1500 U/kg body weight with the start of reperfusion. Catalase was added to the cardioplegic solution in a dose of 100 U/kg and 3500 U/kg body weight with the start of reperfusion. After 15 minutes of retrograde reperfusion, both left ventricular developed pressure and its first derivative were significantly higher in group II (137 +/- 7.6 mm Hg, 2467 +/- 162 mm Hg/sec) than in group I (105 +/- 6 mm Hg, 1676 +/- 231 mm Hg/sec, p less than 0.05 for each). In addition, a considerably higher coronary blood flow was observed in group II throughout the 180-minute period of reperfusion (p = 0.047). We therefore conclude that the combined administration of superoxide dismutase and catalase during the initial period of cardioplegic arrest and during early reperfusion of donor hearts submitted to 3 hours of cold ischemia has a beneficial effect on myocardial performance.     

Lower torso ischemia-induced lung injury is leukocyte dependent.

Lower torso ischemia leads on reperfusion to sequestration of polymorphonuclear leukocytes (PMN) in the lungs and increased permeability. This study tests the role of circulating leukocytes (WBC) in mediating this lung injury. Anesthetized sheep prepared with chronic lung lymph fistulae underwent 2 hours of bilateral hind limb tourniquet ischemia. In untreated controls (n = 7), 1 minute after reperfusion there were transient increases in mean pulmonary arterial pressure (MPAP) from 13 to 38 mmHg (p less than 0.05) and pulmonary microvascular pressure (Pmv) from 7 to 18 mmHg (p less than 0.05), changes temporally related to a rise in plasma thromboxane (Tx) B2 levels from 211 to 735 pg/ml (p less than 0.05). Lung lymph TxB2 levels rose from 400 to 1005 pg/ml at 30 minutes (p less than 0.05), and remained elevated longer than plasma levels. Lung lymph flow (QL) rose from 4.3 to 8.3 ml/30 minutes (p less than 0.05) after 30 minutes of reperfusion and remained elevated for 2 hours. The lymph/plasma (L/P) protein ratio was unchanged from 0.6, while the lymph protein clearance increased from 2.6 to 4.6 ml/30 minutes (p less than 0.05), suggesting increased microvascular permeability. WBC counts decreased within the first hour of reperfusion from 6853 to 3796/mm3 (p less than 0.05), and lung histology after 2 hours showed proteinaceous exudates and leukosequestration of 62 PMN/10 high-powered fields (HPF), higher than the 22 PMN/10 HPF (p less than 0.05) in sham animals (n = 3). Recruitment of the pulmonary vasculature by left atrial balloon inflation (n = 3) resulted in a rise in MPAP to 20 mmHg. After 3 hours of balloon inflation, QL stabilized at 9.8 ml/15 minutes, and a pressure-independent L/P protein ratio of 0.3 was achieved. During reperfusion, QL increased further to 11.2 ml/15 minutes, the L/P ratio rose to 0.56 and the calculated osmotic reflection coefficient decreased from 0.70 to 0.44, documenting an increase in lung microvascular permeability. In contrast to these untreated ischemic controls, sheep (n = 7) rendered leukopenic with hydroxyurea or nitrogen mustard and having a total WBC count of 760/mm3 and PMN count of 150/mm3 did not manifest reperfusion-induced increases in MPAP, Pmv, QL, lymph protein clearance, or lung lymph. TxB2 level (p less than 0.05). Plasma TxB2 levels rose slightly at 30 minutes from 199 to 288 pg/ml (p less than 0.05). Lung histology was normal. These data indicate that WBC mediate the ischemia-induced increase in pulmonary microvascular permeability.     

Ischemic preconditioning attenuates the lipid peroxidation and remote lung injury in the rat model of unilateral lower limb ischemia reperfusion

BACKGROUND: Ischemia and reperfusion of the skeletal muscle tissue may cause remote lung injury. We aimed to evaluate the protective effect of ischemic preconditioning (IP) on the lung during unilateral lower limb ischemia reperfusion (IR). METHODS: Four groups of rats were used in this study: (i) the sham group (sham, n = 6) served as time controls, they remained anesthetized for the whole duration of the study; (ii) the ischemia and reperfusion group (IR, n = 10) underwent 4 h of left lower limb ischemia followed by 2 h of reperfusion; (iii) the ischemic preconditioning group (IP, n = 10), the left lower limbs of rats were exposed to three cycles of IP (10 min of ischemia followed by 10 min of reperfusion); and (iv) the ischemic preconditioning plus ischemia reperfusion group (IP/IR, n = 10) underwent IP followed by IR as in the IP and IR groups. Plasma and tissue samples were taken at the end of the study period for determination of lung tissue myeloperoxidase activity (MPO) and polymorphonuclear leukocyte count (PMNL), histological lung injury score and plasma thiobarbituric acid reactive substances (TBARS) level. RESULTS: PMNL count and MPO activity in the lung tissue, and plasma TBARS level were higher in the IR group compared with other groups while there were no differences between the sham and the IP and between the sham and the IP/IR groups. Histological lung injury score was higher in the IR group than in the IP/IR and sham groups. The plasma TBARS level in the IP group was significantly lower than in the IP/IR group. CONCLUSION: IP pretreatment reduces lipid peroxidation and lung injury caused by lower limb IR.     

Superior protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium. Clinical study in comparison with St. Thomas' Hospital solution

The protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium has been assessed in adult patients undergoing heart operations. Postreperfusion recovery of cardiac function and electrical activity was evaluated in 34 patients; 16 received low-calcium, magnesium-free potassium cardioplegic solution (group I) and 18 received St. Thomas' Hospital solution, which is enriched with calcium and magnesium (group II). There were no significant differences between the two groups in age, sex, body weight, and New York Heart Association functional class. Aortic occlusion time (107.3 +/- 46.8 minutes versus 113.6 +/- 44.3 minutes), highest myocardial temperature during elective global ischemia (11.5 degrees C +/- 3.1 degrees C versus 9.3 degrees C +/- 3.2 degrees C), and total volume of cardioplegic solution (44.2 +/- 20.5 ml/kg versus 43.4 +/- 17.6 ml/kg) were also similar in the two groups. On reperfusion, electrical defibrillation was required in four cases (25.5%) in group I and in 15 cases (83.3%) in group II (p less than 0.005), and bradyarrhythmias were significantly more prevalent in group II (6.3% versus 44.4%; p less than 0.05). Serum creatine kinase MB activity at 15 minutes of reperfusion (12.3 +/- 17.0 IU/L versus 42.6 +/- 46.1 IU/L; p less than 0.05) and the dose of dopamine or dobutamine required during the early phase of reperfusion (1.8 +/- 2.5 micrograms/kg/min versus 6.1 +/- 3.3 micrograms/kg/min; p less than 0.0002) were both significantly greater in group II. Postischemic left ventricular function, as assessed by percent recovery of the left ventricular end-systolic pressure-volume relationship in patients who underwent aortic valve replacement alone, was significantly better in group I (160.4% +/- 45.5% versus 47.8% +/- 12.9%; p less than 0.05). Serum level of calcium and magnesium ions was significantly lower in group I. Thus low-calcium, magnesium-free potassium cardioplegic solution provided excellent protection of the ischemic heart, whereas St. Thomas' Hospital solution with calcium and magnesium enabled relatively poor functional and electrical recovery of the heart during the early reperfusion period. These results might be related to differing levels of extracellular calcium and magnesium on reperfusion.     

Successful extended hypothermic cardiopulmonary preservation for heart-lung transplantation

The inability to obtain sufficiently extended hypothermic organ preservation is a major restriction on clinical heart-lung transplantation. We used core cooling, nonrecirculating retrograde heart perfusion, and lung immersion with liposomal recombinant human superoxide dismutase in an attempt to provide effective 12-hour cardiopulmonary preservation. Donor dogs supported by cardiopulmonary bypass were rapidly cooled to 15 degrees C with cardioplegic arrest, and heterotopic heart and unilateral left lung transplantations were performed. In control dogs (n = 7), hearts and lungs, harvested after core cooling and cardioplegic arrest, were transplanted with a total mean ischemic time of 88 +/- 5 minutes. In group II (n = 7), heart-lung blocks were similarly excised but preserved at 4 degrees C for 12 hours (756 +/- 30 minutes) and then transplanted. During preservation, the lungs were immersed in hyperosmolar extracellular solution. For the heart, retrograde coronary sinus perfusion was performed with intracellular solution containing perfluorochemicals at a temperature of 4 degrees C and a rate of 30 ml/hr for 12 hours. In group III (n = 7), donor organs were similarly excised and preserved for 12 hours (726 +/- 39 minutes), except that liposomal recombinant human superoxide dismutase was administered during harvest, preservation, and reperfusion. Myocardial function, assessed by the ratio of end-systolic pressure to end-systolic dimension, after the 12-hour preservation period in both experimental groups was similar to that of the control group 4 and 6 hours after transplantation. The mean arterial oxygen capacity of the transplanted left lung during ventilation with an inspired oxygen concentration of 40% was also similar in each group. In contrast, the 12-hour preservation of pulmonary function assessed by pulmonary vascular resistance, the accumulation of extravascular lung water, and histologic evidence of alveolar wall injury, interstitial edema, and perivascular hemorrhage were significantly impaired in the absence of liposal recombinant human superoxide dismutase. These findings suggest that successful extended cardiopulmonary preservation for heart-lung transplantation is possible with core cooling, nonrecirculating retrograde heart perfusion, and hypothermic lung immersion incorporating liposomal recombinant human superoxide dismutase.     

The effect of superoxide dismutase and catalase on myocardial reperfusion injury in the isolated rat heart

This study was designed to evaluate the efficacy of superoxide dismutase (SOD) and catalase on ischemic and reperfusion injury in the isolated working rat heart. The temperature and duration of ischemia varied under three conditions: 1) at 37 degrees C for 35 minutes, 2) at 28 degrees C for 120 minutes and 3) at 20 degrees C for 120 minutes. SOD (100 mg/L) and catalase 10 mg/L) were either added to St. Thomas' Hospital cardioplegic solution during ischemia (CP group) or to the reperfusion solution for 10 minutes after reflow (RS group). They were compared with a control group which received no free radical scavengers. The postischemic recovery ratio of cardiac functions were markedly superior to the values of the control group with a significant difference being noted in the CP and RS groups under ischemia at 37 degrees C and 28 degrees C. In the series done at 20 degrees C, a significant improvement was seen in the RS group, and the CP group also showed better functional recovery rates compared with the control group, although the differences were not statistically significant. Thus, SOD and catalase added to the cardioplegic solution or reperfusion fluid demonstrated an excellent protective effect on the myocardium against ischemic or reperfusion injury in both hypothermic ischemia and normothermia.     

The effect of oxygen free radical scavengers on the recovery of regional myocardial function after acute coronary occlusion and surgical reperfusion

This study investigated the effects of the oxygen free radical scavengers superoxide dismutase and catalase, the peroxide ion inhibitor, in crystalloid potassium cardioplegic solution on infarct size and global and regional myocardial function after occlusion of the left anterior descending artery and surgical reperfusion in young sheep on cardiopulmonary bypass. After 1 hour of occlusion, the animals were randomized to receive either routine potassium cardioplegia or cardioplegia with superoxide dismutase and catalase. Global hemodynamics measured by maximum rate of pressure rise showed significant improvement after 5 hours of reperfusion in the group treated with superoxide dismutase and catalase (1843 +/- 163 versus 979 +/- 191, p less than 0.001). Regional myocardial function was measured by ultrasonic crystals implanted in the ischemic area and in a nonischemic control segment. The percent systolic shortening or bulging was calculated. At end of reperfusion in the animals treated with superoxide dismutase and catalase, there was active shortening in the ischemic area after reperfusion of +9.2% +/- 0.4% versus 2.1% +/- 0.8% in untreated animals (p less than 0.001). Infarct size measured by triphenyltetrazolium chloride staining showed significant difference (p less than 0.001) between animals treated with superoxide dismutase and catalase (0.9% +/- 0.1%) and control animals (61% +/- 70%). Superoxide dismutase and catalase given in the cardioplegic solution before reperfusion of an acutely ischemic area of myocardium enhances recovery of contractile function and results in a significant reduction in infarct size, which suggests improved salvage of the ischemic myocardium.     

腺苷预处理对体外循环术后心肌肌钙蛋白变化的影响

目的 探讨腺苷预处理对心脏直视手术的心肌保护效果。方法 ３０例择期心瓣膜置换术患者随机分成实验组和对照组，每组１５例。实验组在术前行腺苷预处理。分别于转流前、主动脉阻断３０分钟和６０分钟、主动脉开放后３０分钟及术后２４小时采血测定心肌肌钙蛋白Ｔ（ｃＴｎＴ）、心肌酶谱和丙二醛。结果 腺苷预处理ｃＴｎＴ和心肌酶外漏明显减少，丙二醛生成减少。结论 腺苷预处理能减轻心肌肌缺血再灌注损伤。     

The effect of superoxide dismutase and catalase on myocardial reperfusion injury in the isolated rat heart

This study was designed to evaluate the efficacy of superoxide dismutase (SOD) and catalase on ischemic and reperfusion injury in the isolated working rat heart. The temperature and duration of ischemia varied under three conditions: 1) at 37°C for 35 minutes, 2) at 28°C for 120 minutes and 3) at 20°C for 120 minutes. SOD (100 mg/L) and catalase (10 mg/L) were either added to St. Thomas' Hospital cardioplegic solution during ischemia (CP group) or to the reperfusion solution for 10 minutes after reflow (RS group). They were compared with a control group which received no free radical scavengers. The postischemic recovery ratio of cardiac functions were markedly superior to the values of the control group with a significant difference being noted in the CP and RS groups under ischemia at 37°C and 28°C. In the series done at 20°C, a significant improvement was seen in the RS group, and the CP group also showed better functional recovery rates compared with the control group, although the differences were not statistically significant. Thus, SOD and catalase added to the cardioplegic solution or reperfusion fluid demonstrated an excellent protective effect on the myocardium against ischemic or reperfusion injury in both hypothermic ischemia and normothermia.     

Prevention of free radical-induced myocardial reperfusion injury with allopurinol

Growing evidence supports the concept that oxygen free radicals are an important cause of myocardial ischemic and reperfusion injury. This study was designed to determine if toxic oxygen metabolites may exacerbate ischemic injury upon reoxygenation. Left ventricular function was studied in a group of seven dogs receiving intermittent, 4 degrees C, hyperosmolar, hyperkalemic (KCI 25 mEq/L) saline cardioplegic solution. This group was compared to a group (n = 7) receiving a hyperkalemic (KCI 25 mEq/L) cardioplegic solution designed to scavenge superoxide anion and hydroxyl radical: superoxide dismutase (3,000 U/ml) and mannitol (325 mOsm/L). A third group of five animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours and hyperkalemic saline cardioplegic solution. After 60 minutes of ischemia (10 degrees to 15 degrees C) and 45 minutes of reperfusion, left ventricular mechanical function was better in the groups receiving free radical scavengers and allopurinol pretreatment than in the group receiving only hyperkalemic saline cardioplegic solution. Free radical scavengers preserved myocardial function in this model of hypothermic global ischemia and reperfusion. Our data support the concept that injury occurs primarily during reperfusion with the generation of oxygen free radicals via the hypoxanthine-xanthine oxidase reaction. Allopurinol has potential clinical application in the prevention of reperfusion injury.     

Calcitonin Gene-Related Peptide-Induced Preconditioning Improves Preservation With Cardioplegia

Background. Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts.

Methods. Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All hearts were arrested using St. Thomas Hospital cardioplegia, and then reperfused with normothermic Krebs-Henseleit solution for 60 minutes after the 4- or 8-hour hypothermic ischemic period. Hearts were subjected to two cycles of 5-minute ischemia and 10-minute reperfusion in the ischemic preconditioning group. In the CGRP-pretreated group, Krebs-Henseleit solution containing CGRP (5 × 10⁻⁹ mol/L) was substituted for the ischemic period.

Results. At 30 minutes of reperfusion after 4-hour storage, left ventricular pressure (mm Hg) and its first derivative (dp/dt_max, mm Hg/s) in the control, ischemic preconditioning, and CGRP groups were 65.2 ± 5.93 and 1,170 ± 119, 94.13 ± 4.93 and 1,825 ± 145.83, and 85.47 ± 4.17 and 1,900 ± 123.13, respectively (p < 0.01). After 8-hour storage, left ventricular pressure (mm Hg) and dp/dt_max (mm Hg/s) in the same groups were 51.07 ± 5.83 and 815 ± 107.17, 83.47 ± 6.54 and 1,480 ± 120.91, and 84.8 ± 8.49 and 1,396 ± 126.16 (p < 0.01). Ischemic preconditioning and CGRP-induced preconditioning also significantly reduced the release of myocardial enzymes.

Conclusions. The present studies suggest that ischemic preconditioning protects against ischemia-reperfusion injury even after 8 hours of hypothermic preservation in isolated rat hearts, and that CGRP exerts preconditioning-like cardioprotection.     

Protective effects of glutamate and aspartate on the ischemic and reperfused myocardium of hearts from starved rats

To determine the protective effects of amino acids on the ischemic and reperfused myocardium, an experimental study was carried out. Rats were starved for 20 days, then separated into the following three groups: group I: control, group II: glutamate and aspartate were administered before aortic cross clamping for 5 minutes, and added to the cardioplegic solution, group III: glutamate and aspartate were given during the initial 15 minutes of reperfusion. After 25 minutes of equilibration, the hearts were made ischemic at 35.5 degrees C for 45 minutes, and arrested with high potassium cardioplegic solution immediately after aortic cross clamping. The recovery of cardiac output in group II was significantly (p less than 0.05 vs group I & III) better than that in groups I and III, with no difference between groups I and III. Tissue analysis for high energy phosphate compounds revealed that the levels of ATP and total adenine nucleotides were significantly (p less than 0.05 vs group I & III) higher in group II. Lactate output during the initial three minutes of reperfusion was decreased to the greatest extent in group II. Metabolic studies involving the examination of oxygen utilization also revealed no differences between groups I and III. Thus, addition of glutamate and aspartate before and during aortic cross clamping is effective for reducing ischemic damage, however, the administration of these amino acids during the reperfusion is without significant effects.     

地氟醚预处理对缺血/再灌注心肌的保护作用

目的　探讨地氟醚预处理抗心肌缺血／再灌注损伤作用及其可能机制。方法 ２０例心脏瓣膜置换术病人随机分为地氟醚观察组与芬太尼对照组,观察血浆过氧化脂质（ＬＰＯ）水平、红细胞超氧化物歧化酶（ＳＯＤ）活性、心脏指数（ＣＩ）、每搏指数（ＳＩ）、肌酸激酶同工酶（ＣＫ－ＭＢ）、心肌细胞形态变化及开放主动脉后心脏复跳情况。结果观察组再灌注后血浆ＬＰＯ与ＣＫ－ＭＢ浓度显著低于对照组,红细胞ＳＯＤ活性相对大于对照组,电镜下心肌细胞损害明显轻于对照组,ＣＩ、ＳＩ、心脏自动复跳率高于对照组。结论　地氟醚通过诱导预适应具有心肌保护作用。     

Hyperoxygenated solution preconditioning attenuates lung injury induced by intestinal ischemia reperfusion in rabbits

BACKGROUND: The current study was undertaken to elucidate the possible therapeutic effects of hyperoxygenated solution (HOS) preconditioning on lung injury induced by intestinal ischemia/reperfusion (I/R) in rabbits. MATERIALS AND METHODS: Eighty rabbits were randomly divided into four groups (n = 20 each) as follows: (1) control group in which sham operation was performed (sham group), (2) HOS pretreatment group and sham operation (HOS + sham group), (3) ischemia/reperfusion group (I/R group), (4) HOS pretreatment and ischemia/reperfusion group (HOS + I/R group). Intestinal I/R model was produced by clamping superior mesenteric artery with an atraumatic vascular clamp for 1 h, and followed by reperfusion for 2 h. Animals in HOS + sham group and HOS + I/R group received intravenous HOS infusion (20 mL/kg, 10 mL/kg.h for 2 h) every day for 5 d before operation, and animals in sham group and I/R group received the same amount of normal saline in the same way. At the end of reperfusion, 8 animals from every group were sacrificed and histopathological changes of lung were observed; pulmonary edema, lung myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels in lung tissues were also detected. The rest 12 animals in every group underwent 60 min of intestinal ischemia followed by 72 h of reperfusion, and effects of HOS pretreatment on survival in rabbits with lung injury induced by intestinal I/R was observed. RESULTS: When rabbits were subjected to 60 min of intestinal ischemia, a high incidence of mortality was observed within 24 h. In this situation, HOS preconditioning before the start of ischemia/reperfusion significantly reduced the mortality. HOS preconditioning also decreased lung wet/dry ratio, neutrophil infiltration, lipid membrane peroxidation, and increased superoxide dismutase activity in the lungs after intestinal I/R compared with the I/R-treated rabbit lungs without HOS treatment. Histopathological analysis also indicated the effectiveness of HOS pretreatment. CONCLUSIONS: HOS preconditioning could preserve superoxide dismutase activity, decrease lipid membrane peroxidation and neutrophil infiltration in the lungs, then ameliorate the deleterious changes in pulmonary injury induced by intestinal I/R.     

Experimental studies on the effects of superoxide dismutase on warm ischemic-reperfusion injury of the lung]

Transient impairment of the transplanted lung in early postoperative period is one of difficult problems in lung transplantation. It is likely that reperfusion injury of the warm ischemic lung is contributory. The purpose of this study is to evaluate the effects of superoxide dismutase (SOD) on reperfusion injury of warm ischemic lung. Thirty mongrel dogs were divided into four groups. In group I (n = 6), the left lung with complete hilar stripping was placed in warm ischemic state under deflation for 1 hour. In group II (n = 9), the left lung with complete hilar stripping was kept in warm ischemic condition under inflation. Group III (n = 6) animals with same manipulation as group I received superoxide dismutase (SOD 20 mg/kg) before reperfusion. Group IV (n = 9) animals underwent same manipulation as group II and received SOD (20 mg/kg) before reperfusion. Before warm ischemia, immediately after reperfusion, and 1 and 2 hours, blood gases, left pulmonary vascular resistance were measured under the occlusion of right pulmonary artery. Extra vascular lung water content (EVLW) was measured at autopsy and lung was processed for histology. In group II, III and IV, blood gases and EVLW showed significantly better values than group I. In group I and III, left pulmonary vascular resistance increased prominently after reperfusion, however did not change in group II and IV. From these results, we concluded that inflated lung reduced the extent of pulmonary edema after reperfusion and SOD was effective in preventing warm ischemic damage even in deflated lung.