高渗盐右旋糖酐溶液复苏烧伤

既往研究提示,烧伤后心脏功能受损即使给予足量的等渗液复苏也未能改善。大量晶体复苏可导致水肿,使冠状血管受压和阻力增加,心肌缺血的加重将进一步抑制心脏功能。本实验则在烧伤后首次投用高渗盐右旋糖酐溶液(HSD),其渗透压为2400mOsm,含有分子量为7万,浓度为6％的右旋糖酐,按4ml/kg计算用量,在伤后30分钟内输完以预防心肌功能失常及减少等渗液需要量。后续的复苏液为乳酸林格液(LR),并设计成不同剂量组。为排除     

小量高渗盐液复苏出血性休克

出血性休克的初期治疗,输大量等渗盐水是有效的,并已被广泛应用.高渗溶液作为一种复苏液在实验动物和人同样有效。等渗或高渗液虽在休克中可有效地恢复血容量,但高渗溶液在复苏中对心血管系统有更多益处。输入高渗盐液可增加心肌收缩力,并直接扩张毛细血管前阻力血管,减少周围总阻力,增加肠系膜血流和     

肠内输入高渗电解质葡萄糖液对犬35%总体表面积烧伤复苏效果的研究

目的 探讨肠内输入高渗电解质葡萄糖液(HEGS)对犬35%总体表面积(TBSA)烧伤复苏效果的影响.方法 Beagle犬18只,随机分为对照组(N组)、高渗液组(H组)和等渗液组(Ⅰ组),每组6只,采用凝固汽油燃烧法制作35%TBSA Ⅲ°烧伤模型.高渗液组于伤后0.5 h通过肠道给予HEGS(1.8%NaCl的5%葡萄糖液),24 h补液总量按2 ml/(kg·1%TBSA)计算;等渗液组烧伤后0.5 h通过肠道补充IEGS(即0.9%NaCl的5%葡萄糖液),24 h补液总量按4 ml/(kg·1%TBSA)计算;对照组烧伤后不予补液.测定各组犬烧伤前及烧伤后0.5、2.0、4.0、6.0、8.0、24.0 h的心排血指数、全心舒张末期容积指数、血容量、血浆渗透浓度、肠黏膜血流量、肠道对复苏液中水分和钠离子的吸收速率,数据进行双因素方差分析.结果 烧伤后各组心排血指数、全心舒张末期容积指数、血容量和肠黏膜血流量均明显下降,两补液组于伤后2 h逐渐回升,明显高于对照组(P<0.05),两补液组之间差异无统计学意义(P>0.05);高渗液组补液后血浆渗透浓度明显升高,显著高于其他两组(P<0.05);烧伤后两补液组肠道对复苏液中的水分和钠离子的吸收速率均逐渐增加,高渗液组肠道对水分吸收速率低于等渗液组(P<0.05),钠离子吸收速率则高于等渗液组(P<0.05).结论 35%TBSA烧伤后0.5 h通过肠内补充HEGS可以被肠道有效吸收,并在减少1/2补液量的前提下,基本维持有效血容量,达到肠内补充等渗液体复苏相似的血流动力学效果.     

严重烧伤早期心肌收缩性与钙转运功能变化

目的研究烧伤早期心肌肌浆网(SR)钙转运功能变化,探讨其在烧伤后心肌收缩功能下降发病中的作用。方法采用30％TBSAⅢ度烧伤大鼠模型,离体心脏灌流,测定伤前及伤后心肌室内压最大变化速率(±dp/dtmax)变化,制备心肌肌浆网,应用微孔滤膜过滤技术测定心肌SR~(45)Ca~(2 )转运功能改变。结果与对照组相比,烧伤组左心室±dp/dtmax明显降低(P<0.01),心肌SRCa~(2 )-ATPase活性及SR~(45)Ca~(2 )摄取初速度、摄取容量均明显降低(P<0.01),偶联率比对照值大幅度下降。结论烧伤后早期心肌肌浆网Ca(2 )转运功能严重障碍,其是烧伤后心肌收缩功能降低的重要因素之一。     

异丙酚对大鼠离体心脏左右心室功能的影响

目的 研究三种浓度的异丙酚对离体大鼠左右心室收缩功能的影响。方法 雄性SD大鼠10只,经Langendorff离体心脏恒压灌注,依次梯度输入含有异丙酚1、3和10ug/ml的灌注液。通过心室内的乳胶水囊经换能器连于MacLab Instruments和Macintosh微机系统,观察给药前后以及不同浓度丙酚对左右心室等容收缩时压力和速度指标的影响。结果 10ug/ml的异丙酚提高了左右心室的发展压,降低了舒张末期压;同时回忆了左右心室收缩和舒张的速度;增加了冠脉灌流量。结论 异 保护心肌舒缩功能的作用,不直接抑制左右心室的内在收缩性,高浓度时有扩张冠脉的作用。     

伤后立即切痂对30%Ⅲ度烧伤大鼠心肌力学的影响

目的研究伤后立即切痂对大鼠心肌力学特别是左心室舒缩功能的影响。方法采用大鼠30％TBSAⅢ度烧伤模型,随机分为烧伤组、烧伤补液组和切痂组。切痂组伤后按 Parkland 公式补液并立即切痂植以正常大鼠皮肤。颈动脉插管至左心室测量心肌力学参数。结果烧伤组心肌力学参数下降非常显著,烧伤补液组各点参数大多降低,但明显高于烧伤组,除左心室舒张末压(LVEDP)外,切痂组心肌力学参数与烧伤补液组相近。伤后24小时烧伤补液组心肌收缩功能显著低于切痂组。结论在有效复苏下,30％Ⅲ度烧伤大鼠伤后立即实施切痂是可行且有益的。     

伤后立即切痂对30% Ⅲ度烧伤大鼠心肌力学的影响

目的研究伤后立即切痂对大鼠心肌力学特别是左心室舒缩功能的影响。方法采用大鼠３０％ＴＢＳＡⅢ度烧伤模型，随机分为烧伤组、烧伤补液组和切痂组。切痂组伤后按Ｐａｒｋｌａｎｄ公式补液并立即切痂植以正常大鼠皮肤。颈动脉插管至左心室测量心肌力学参数。结果烧伤组心肌力学参数下降非常显著，烧伤补液组各点参数大多降低，但明显高于烧伤组，除左心室舒张末压（ＬＶＥＤＰ）外，切痂组心肌力学参数与烧伤补液组相近。伤后２４小时烧伤补液组心肌收缩功能显著低于切痂组。结论在有效复苏下，３０％Ⅲ度烧伤大鼠伤后立即实施切痂是可行且有益的     

严重烧伤早期心肌收缩性与钙转运动能变化

研究烧伤早期心肌肌浆网钙转运动能变化，探讨其在烧伤后心肌收缩功能下降发病中的作用。方法 采用３０％ＴＢＳＡⅢ度烧伤大鼠模型，离体心脏灌流，测定伤前及伤后心肌室内压最大变化速度变化，制备心肌肌浆网，应用微孔滤膜过滤技术测定心肌ＳＲ＾４５Ｃａ＾２＋转运活性及ＳＲ＾５Ｃａ６２＋摄取初速度，摄取容量均明显降低，偶联率比对照值大幅度下降。     

严重烧伤早期心肌收缩性与钙转运功能变化

目的研究烧伤早期心肌肌浆网（ＳＲ）钙转运功能变化，探讨其在烧伤后心肌收缩功能下降发病中的作用。方法采用３０％ＴＢＳＡⅢ度烧伤大鼠模型，离体心脏灌流，测定伤前及伤后心肌室内压最大变化速率（±ｄｐ／ｄｔｍａｘ）变化，制备心肌肌浆网，应用微孔滤膜过滤技术测定心肌ＳＲ４５Ｃａ２＋转运功能改变。结果与对照组相比，烧伤组左心室±ｄｐ／ｄｔｍａｘ明显降低（Ｐ＜０．０１），心肌ＳＲＣａ２＋－ＡＴＰａｓｅ活性及ＳＲ４５Ｃａ２＋摄取初速度、摄取容量均明显降低（Ｐ＜０．０１），偶联率比对照值大幅度下降。结论烧伤后早期心肌肌浆网Ｃａ２＋转运功能严重障碍，其是烧伤后心肌收缩功能降低的重要因素之一。     

大鼠严重烧伤早期心肌局部肾素-血管紧张素系统的变化

心脏存在有独立的肾素一血管紧张素系统(RAS),心脏可自身合成、释放肾素、血管紧张素。与循环RAS不同,心脏局部RAS只作用于心脏局部,主要参与心肌局部血流量和血管紧张性的调节,也参与心肌收缩力的调节。心脏局部RAS在维持心血管正常功能活动及参与心血管疾病的发生、发展过程中起着不容忽视的作用。我们动态观察了大鼠烧伤后心肌局部RAS的变化,并对其病理生理意义进行了探讨。     

Effect of hypertonic saline solution on the left ventricular functions of isolated hearts from burned rats

Objective: To study the effect of hypertonic saline solution on the left ventricular functions of isolated hearts from Imrned rats. Methods: Thirty-six Wistar rats were used and divided into 4 groups: (1) normal hearts perfused with isotonic Krebs-Henseleit solution; ( 2 ) normal hearts perfused with Krebs-Henseleit solution which contained 215 mmoVL Na^ ; (3) hearts of rats suffered from 25% TBSA third degree burn and perfnsed with isotonic Krebs-Hensekit solution; (4) hearts of the burned rats perfused with Krebs-Henseleit solution which contained 215 mmol/L Na^ . The systolic and diastolic functions of the left ventricle were observed. Results: During perfusion, there were very short periods of decrease in heart systolic and diastolic functions at first, but they recovered very soon and even became stronger than normal both in the normal and burned rats.The systolic and diastolic functions of the hearts increased very siLmificantly when the perfusion solution was changed to isotonic solution from the hypertonic solutions. The effect of the hypertonic s.gline solution on the ventricular systolic and diastolic improvements was stronger in the hearts of the burned rats than that in the normal hearts. Conclusions: Hypertonic saline solution can directly affect myocardium and significantly improve the ventricular systolic and diastolic functions, especially in the hearts of the burned rats.     

The mechanism of myocardial damage following potassium citrate (Melrose) cardioplegia.

To determine the reasons for clinical failure of Melrose solution, potassium arrest was studied in isolated working rat hearts. Eight control hearts were stable for 2-1/2 hours. After 1/2 hour of work, 42 experimental hearts were subjected to 1 hour of ischemis by aortic cross-clamping with unmodified ischemia in eight hearts and ischemia with simultaneous intracoronary injection of 5 ml. of 4 degrees C. (1)Krebs-Henseleit buffer in seven hearts (2)potassium chloride buffer in six hearts, (3)potassium citrate buffer in eight hearts (both 26 mEq. per liter of K, approximately 300 mOsm. per liter), (4)Melrose solution in seven hearts (greater than 200 mEq. per liter of K, greater than 400 mOsm. per liter), (5)hypertonic potassium citrate buffer in six hearts (26 mEq. per liter of K, greater than 400 mOsm. per liter). The pH of all solutions was 7.8 plus or minus 0.1. After recovery isotonic potassium citrate- and potassium chloride-arrested hearts and time-matched control hearts showed no significant differences in cardiac output, coronary flow, systolic pressure, or heart rate. Hypertonic potassium citrate decreased the recovery of cardiac function after arrest and Melrose arrest was not significantly different from unmodified ischemia. Intracoronary cold isotonic Krebs-Henseleit buffer was better than Melrose arrest but inferior to 26 mEq. er liter of potassium arrest. Arrest with 26 mEq. per liter of potassium augments perfusion hypothermia and prevents significant functional and histologic myocardial damage during 1 hour of ischemis. Previous authors assumed that hypertonicity and citrate were responsible for poor results with Melrose solution, but high potassium concentration is the major deleterious factor with hypertonicity playing a contributory role.     

Ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels or Na/H exchange inhibition: which is the best protective strategy for heart transplants?

OBJECTIVE: This study was designed to compare ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels and Na(+)/H(+) exchange inhibition in an isolated heart model of cold storage, simulating the situation of cardiac allografts. METHODS: Sixty-seven isolated isovolumic buffer-perfused rat hearts were arrested with and stored in Celsior solution (Imtix-Sangstat) at 4 degrees C for 4 hours before a 2-hour reperfusion. Group I hearts served as controls and were arrested with and stored in Celsior solution. In group II, hearts were preconditioned by two 5-minute episodes of global ischemia, each separated by 5 minutes of reperfusion before arrest with Celsior solution. Group III hearts were arrested with and stored in Celsior solution supplemented with 100 micromol/L of the mitochondrial adenosine triphosphate-sensitive potassium channel opener diazoxide. In group IV, hearts received an infusion of diazoxide (30 micromol/L) during the first 15 minutes of reperfusion. Group V hearts underwent a protocol combining both interventions used in groups III and IV. In group VI, hearts were arrested with and stored in Celsior solution supplemented with 1 micromol/L of the Na(+)/H(+) exchange inhibitor cariporide. Group VII hearts received an infusion of cariporide (1 micromol/L) during the first 15 minutes of reperfusion. In group VIII, hearts underwent a protocol combining both interventions used in groups VI and VII. Group IX hearts were ischemically preconditioned as in group II, and sustained Na(+)/H(+) exchange inhibition during both storage and early reperfusion was used as in group VIII. RESULTS: On the basis of comparisons of postischemic left ventricular contractility and diastolic function, coronary flow, total creatine kinase leakage, and myocardial water content, values indicative of improved protection were obtained by combining ischemic preconditioning with Na(+)/H(+) exchange inhibition by cariporide given during storage and initial reperfusion. The endothelium-dependent vasodilatory postischemic responses to 5-hydroxytryptamine or acetylcholine and endothelium-independent responses to papaverine were not affected by these interventions. CONCLUSIONS: These data suggest that cardioprotection conferred by the Na(+)/H(+) exchange inhibitor cariporide is additive to that of ischemic preconditioning and might effectively contribute to improve donor heart preservation during cardiac transplantation.     

Long-term preservation of explanted hearts perfused with L-aspartate-enriched cardioplegic solution. Improved function, metabolism, and ultrastructure.

The effects of supplementing oxygenated St. Thomas' Hospital cardioplegic solution No. 2 with L-aspartate and/or D-glucose for the long-term preservation of excised rat hearts were determined with isolated working heart preparations. Left ventricular function was assessed at 37 degrees C with a crystalloid perfusate, before cardioplegic arrest and after 20 hours of low-flow perfusion (1.5 ml/min) with continuing arrest at 4 degrees C, and after this period, again at 37 degrees C with a crystalloid perfusate. Four groups (n = 8/group) of hearts were studied with four cardioplegic solutions: St. Thomas' Hospital solution alone, St. Thomas' Hospital solution with aspartate 20 mmol/L, St. Thomas' Hospital solution with glucose 20 mmol/L, and St. Thomas' Hospital solution plus both aspartate and glucose (20 mmol/L each). The addition of glucose to St. Thomas' Hospital solution made no significant difference in the recovery of aortic flow rates (17.7% +/- 8.6% and 21.6% +/- 7.8% of prearrest values), but when aspartate or aspartate and glucose were present, hearts showed significant improvements (89.8% +/- 5.2% and 85.0% +/- 6.2%, respectively). These improvements were associated with a reduction in the decline of myocardial high-energy phosphates during reperfusion, a reduction in cellular uptake of Na+ and Ca++, and a reduction in ultrastructural damage. These results indicate that low-flow perfusion with St. Thomas' Hospital solution plus aspartate can considerably extend the duration of safe storage of explanted hearts.     

Effect of chronic renal failure on cardiac contractile function,calcium cycling,and gene expression of proteins important for calcium homeostasis in the rat

Patients with chronic renal failure frequently develop cardiac hypertrophy and diastolic dysfunction; however, the mechanisms by which this occurs are still unclear. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy and studied for their isolated myocyte function, calcium cycling, and gene expression of proteins important in calcium homeostasis after 4 wk. Comparable rats subjected to suprarenal aortic banding for the same duration were used for comparison. Rats subjected to 5/6 nephrectomy and aortic banding developed comparable hypertension; however, rats subjected to 5/6 nephrectomy experienced a greater degree of cardiac hypertrophy and downregulation of cardiac sodium potassium ATPase (Na+/K+ -ATPase) activity than rats subjected to aortic banding. Moreover, cells isolated from the 5/6 nephrectomy rat hearts displayed impaired contractile function and altered calcium cycling compared with cells isolated from control or aortic constriction rat hearts. The 5/6 nephrectomy rat heart cells displayed a prolonged time constant for calcium recovery following stimulation, which corresponded to decreases in homogenate sarcoplasmic reticulum calcium ATPase-2a (SERCA2a) activity, protein density, and mRNA for SERCA2a. In conclusion, chronic renal failure leads to alterations in cardiac gene expression, which produces alterations in cardiac calcium cycling and contractile function. These changes cannot be explained only by the observed increases in BP.     

Role of potassium concentration in cardioplegic solutions in mediating endothelial damage

We studied the effect of potassium concentration in cardioplegic solutions on endothelial function by examining its influence on 5-hydroxytryptamine- (5-HT) and nitroglycerin-induced vasodilation in the isolated rat heart. Forty-eight rat hearts were perfused on a modified Langendorff preparation. After a baseline record of increase in coronary flow induced by 10(-7) M 5-HT and 10 micrograms/mL nitroglycerin, the hearts were perfused for 30 or 60 minutes with either St. Thomas' solution or Bretschneider solution containing 20 mmol/L of potassium or for 30 minutes with either solution containing 30 mmol/L of potassium (n = 8 in each). Initially, 5-HT and nitroglycerin caused a 39.0% +/- 3.3% and 39.7% +/- 2.8% increase in coronary flow, respectively. After 30 or 60 minutes' perfusion with St. Thomas' solution containing 20 mmol/L of potassium, there was little change in the response to 5-HT or nitroglycerin (5-HT, 43.1% +/- 4.1%; nitroglycerin, 38% +/- 3.2%). Similarly, perfusion with Bretschneider solution (20 mmol/L K+) for 30 or 60 minutes did not alter the degree of vasodilation (5-HT, 39.2% +/- 2.9%; nitroglycerin, 38.0% +/- 3.3%). However, perfusion with St. Thomas' solution containing 30 mmol/L of potassium for 30 minutes abolished the endothelial-dependent 5-HT-induced vasodilation (5-HT, -1.6% +/- 1.4%; nitroglycerin, 36.9% +/- 2.2%). Perfusion with Bretschneider solution (30 mmol/L K+) gave similar results (5-HT, -2.1% +/- 1.2%; nitroglycerin, 36.4% +/- 1.7%). We conclude that the concentration of potassium in cardioplegic solutions plays a critical role in causing functional endothelial damage.     

Assessment of hemodynamic function and tolerance to ischemia in the absence or presence of calcium antagonists in hearts of Isoproterenol-treated, exercise-trained, and sedentary rats

The effects of cardiac hypertrophy on the structure, function and tolerance to ischemia of rat hearts have been investigated. Multiple injections of low doses of isoproterenol (ISO) resulted in an increase of heart weight/body weight ratio by 60%, and a decrease of myocardial creatine kinase activity by 25%, as compared to normal rats. Compared to age-matched control rats, rats submitted to a swimming program had a higher heart weight by 20%, but similar values of heart weight to body weight ratio. In isolated perfusion, the functional capacities of hearts from ISO-trated rats were severely depressed compared to normal rat hearts whereas exercise-trained rat hearts performed as well or even better than control hearts. The functional recovery of ISO-treated hearts following cardioplegia-induced arrest for 20 min at 37°C was significantly worse than the recovery of normal hearts, but hearts of exercise-trained rats showed a significantly better recovery than control hearts. Exercise training results in improvement of myocardial blood supply resulting in better preservation of the heart during ischemia, compared to normal hearts. Addition of a combination of verapamil and diltiazem to the cardioplegic solution followed by ischemic arrest for 20 min at 37°C resulted for ISO-treated rat hearts in an improved recovery of cardiac output (99%) compared to cardioplegia in the absence of these drugs (72%). In exercise-trained and control rat hearts, calcium antagonists improved the recovery from cardioplegic arrest of cardiac output from 90% to 92% and from 71% to 87%, respectively. Myocardium of ISO-treated rats showed foci of subendocardial infarction and fibrosis, whereas the myocardium of physically stressed animals and of normal rats had no abnormalities. Considering the histological similarities between ISO-treated rat hearts and lesions observed in human hearts with coronary artery disease and cardiac hypertrophy, the present study suggests that the presence of verapamil and diltiazem during cardioplegic arrest favors the functional recovery from cardiac surgery.     

Risk of low calcium and high magnesium in continuous warm hyperkalemic cardioplegia.

BACKGROUND: The recent introduction of operations on a warm heart has prompted clinical reports on the usefulness of continuous blood cardioplegia, but no in-depth basic evaluation of continuous cardioplegia has been done. The cardioprotective effects of magnesium (Mg) and calcium (Ca) in continuous warm hyperkalemic crystalloid cardioplegic solutions were investigated in an isolated rat heart model. METHODS: Isolated rat hearts were arrested for 180 minutes at 37 degrees C with a continuous warm hyperkalemic (20 mmol/L) modified Krebs-Henseleit bicarbonate buffer solution containing 1.2, 8.0, or 16.0 mmol/L of Mg and 0.1 to 2.5 mmol/L of Ca in different concentrations. Recovery of cardiac function and tissue damage were estimated. RESULTS: For each Mg concentration, the percentage recovery of aortic flow generated dose-response curves depending on Ca concentration. However, as Mg concentration increased, the recovery of aortic flow decreased in the groups with 0.5 mmol/L of Ca or less. CONCLUSIONS: In continuous warm cardioplegia the combination of low Ca and high Mg concentration caused severe cardiac injury, and normal Ca concentration avoids cardiac injury regardless of Mg concentrations.     

L-aspartate improves the functional recovery of explanted hearts stored in St. Thomas' Hospital cardioplegic solution at 4 degrees C

Explanted rat hearts were subjected to cardioplegic arrest by 3 minutes' perfusion with oxygenated St. Thomas' Hospital solution no. 2 and then were stored by immersion in the same solution at 4 degrees C. Prearrest and postischemic left ventricular functions were compared by means of an isolated working heart apparatus. Hearts (n = 8 per group) arrested and stored for up to 8 hours all resumed the spontaneous rhythm of contraction during reperfusion for 30 minutes at 37 degrees C. There was good recovery of aortic flow rate (105% +/- 3%) against a pressure of 100 cm H2O, of heart rate (102% +/- 2%), and of aortic pressure (86% +/- 5% of prearrest values). Hearts stored for 10 and 20 hours showed poor or no postischemic recovery of cardiac pump function (aortic flow, 16% +/- 11% and 0%, respectively). Enrichment of St. Thomas' Hospital solution with L-glutamate (20 mmol/L) also failed to improve functional recovery of hearts subjected to 10 hours of storage, but hearts treated with St. Thomas' Hospital solution containing L-aspartate (20 mmol/L) or L-aspartate plus L-glutamate (20 mmol/L each) reestablished aortic flow rates of 99% +/- 5% and 93% +/- 4%, respectively. These results indicate that the addition of L-aspartate to St. Thomas' Hospital solution improves the functional recovery and extends the safe preservation of explanted hearts stored at 4 degrees C.     

The effect of supplementing hypothermic crystalloid cardioplegia with catalase plus allopurinol in the isolated rabbit heart

The effect of adding allopurinol and catalse to hypothermic cardioplegia for ischemic-reperfusion injury was investigated in the isolated rabbit heart. Hearts were divided into two groups, namely: Group C (n=7), which received a hypothermic crystalloid cardioplegic solution alone (4°C), and group T (n=7), which received the hypothermic cardioplegic solution with allopurinol (148 mol/L)¹³ and catalase (37 nmol/L).¹² The cardioplegic solution was infused continuously into the isolated hearts, which had been placed in ice-cold saline, during a 12 h preservation. Subsequently, the hearts were mounted on a noncirculating, nonpulsatile perfusion circuit using Krebs-Henseleit buffer solution at 37°C for 1 h at a constant perfusion pressure of 75 mm Hg. The left ventricular developed pressure (LVDP), maximum rate of pressure change (max dp/dt), and percent recovery of coronary flow were higher, while the creatine phosphokinase concentration and left ventricular end diastolic pressure (LVEDP) were lower in group T. The tissue malondialdehyde concentration and water content were similar in both groups. Thus, cardiac function after a 12 h preservation was enhanced by the added combination of allopurinol and catalase to the cardioplegic solution, supporting its role in the prevention of free radical reperfusion injury in cardiac preservation.