Improved myocardial preservation with short hyperthermia prior to cold cardioplegic ischemia in immature rabbit hearts.

OBJECTIVE: Recent observations have been shown that the induction and accumulation of heat shock proteins (HSPs) by short exposure to nonlethal whole-body hyperthermia with normothermic recovery are closely associated with transient resistance to subsequent ischemia-reperfusion challanges. Here, this study was performed to investigate whether a shortly heat shock pretreatment affects the left ventricular (LV) function after cold cardioplegic ischemia in reperfused neonatal rabbit hearts. METHODS: Hearts from neonatal New Zealand White rabbits were isolated perfused (working heart preparation) and exposed to 2 h of cold cardioplegic ischemia followed by reperfusion for 60 min. To induce the heat shock response neonatal rabbits (n=5, HT-group) were subjected to whole-body hyperthermia at 42.0-42.5 degrees C for 15 min, followed by a normothermic recovery period of 60 min, before harvesting and the onset of global hypothermic cardioplegic arrest. Another set of hearts (n=5, control group) without a heat treatment underwent a similar perfusion and ischemia protocol served as control. The postischemic recovery was assessed by measuring several parameters of LV function. LV biopsies from all control and heat treated animals were taken before ischemia and at the end of reperfusion to examine myocardial HSP levels by Western blot analysis. RESULTS: At 60 min of reperfusion the HT-group showed significant better recovery of ventricular function such as LV developed pressure (DP) (74.6+/-10 vs. 52.1+/-8.5%, P<0.05), LV positive dP/dt (910+/-170 vs. 530+/-58 mmHg/s, P<0.01) and LV end-diastolic pressure (LVEDP) (8+/-2 vs. 18.4+/-5 mmHg, P<0.05) than control. Myocardial oxygen consumption (MVO(2)) was significantly higher in the HT-group compared with control (0.054+/-0.006 vs. 0.041+/-0.002 ml/g per min, P<0.05). Significant postreperfusion lower level in lactate production was observed in the HT-group (0.83+/-0.11 vs. 1.67+/-0.8 mmol/l, P<0.05). Also, the recovery of hemodynamic parameters such as aortic flow, coronary flow and cardiac output was significantly superior (P<0.05) in the HT-group. Furthermore, high expression of HSP72(+)/73(+) were detected in the myocardial tissue samples of heat-treated rabbits by immunoblotting, appearing even at 60 min of normothermic recovery after heat stress. CONCLUSIONS: These data in the immature rabbit heart indicate that previous shortly heat treatment with high level expression of heat shock proteins (HSP72(+)/73(+)) before hypothermic cardioplegic ischemia provides transient tolerance against myocardial injury and could be an improvement for the postischemic functional recovery of neonatal hearts.     

芬太尼联合七氟烷后处理对离体大鼠缺血/再灌注心功能的影响

目的 研究芬太尼联合七氟烷后处理对离体大鼠缺血/再灌注(ischemia/reperfusion,I/R)心脏心功能的影响.方法 建立离体大鼠心脏缺血40 min,再灌注120 min模型.根据再灌注开始10 min的不同处理,使用随机数字表法将实验动物随机分为4组(n=10):I/R对照组(Con),七氟烷后处理组(...     

The influence of infused calcium on the postischemic myocardium

Despite evidence for calcium-induced damage in the postischemic myocardium, calcium remains a frequently used inotropic agent following cardiopulmonary bypass surgery with cardioplegic arrest. The purpose of this study was (1) to challenge the postischemic myocardium with incremental doses of ionized calcium, and (2) to relate postischemic calcium reperfusion concentration to final recovery of left ventricular contractile function. Rabbit hearts (N = 38) were perfused and equipped with a ventricular balloon to monitor developed pressure (DP) ±dp/dt, and left ventricular end diastolic pressure (LVEDP). Hearts underwent 40 min of global ischemia. Hearts were then assigned to one of four groups to receive a variable calcium concentration (0.6, 1.2, 2.5, 5.0 mM) for the initial 5 min of reperfusion followed by 55 min of reperfusion (Ca⁺² = 1.25 mM). No differences were found between groups for final recovery of DP ±dp/dt, or final LVEDP. It was concluded that: (1) within the physiologic range, variable calcium infusions during the first 5 min of postischemic reperfusion do not impair final recovery of LV contractile function, (2) irreversible partial recovery of left ventricular function appears due to mechanisms other than mitochondrial or myofibrillar calcium loading during reperfusion, and (3) infused calcium is a safe inotropic agent even in the postischemic myocardium.     

心麻液预处理的心肌保护效果

目的 研究Ｓｔ．Ｔｈｏｍａｓ晶体心麻液预处理和缺血预处理对大鼠缺血／再灌注心肌收缩功能的影响。方法 应用离体Ｌａｎｇｅｎｄｏｒｆｆ逆行灌注模型,观察晶体心麻液预处理的缺血预处理时心肌缺血及再灌注前后ＬＶＥＤＰ,ＤＰ,＋ｄｐ／ｄｔ－,ＣＦ冠脉流出液中蛋白含量和ＬＤＨ活性以及再灌注后心肌ＳＯＤ活性,ＭＤＡ和ＡＴＰ含量的变化。结果 在缺血期间,晶体心麻液预处理显著延迟了心肌缺血性挛缩的发生时间。     

Effects of Unloaded Reperfusion on Mitochondrial Function in the Postischemic Myocardium

Abstract: The effect of mechanical unloading on recovery of postischemic myocardial performance, high energy phosphate content, and mitochondrial function was tested in an isolated working rabbit heart model. After 30 min of global ischemia, prolonged unloaded reperfusion could prevent complete loss of contractility, deterioration of mitochondrial function, and depletion of the ATP pool as was found when only short-term unloading was performed. Aortic flow recovered to 21% of preischemic control, and left ventricular dP/dt max to 46% (p < 0.05 vs. short-term unloading). OPR and ADP/O stabilized at 42 and 72%, respectively (p < 0.05 vs. short-term unloading), and ATP at 33% of control (p < 0.05 vs. short-term unloading). These results show the beneficial effect of prolonged unloading in postischemic hearts.     

利多氟嗪加强间断缺血心停搏心肌保护作用的实验研究

报道常温下用利多氟嗪（ｌｉｄｏｆｌａｚｉｎｅ）预处理加强间断主动脉阻断心停搏心肌保护作用的实验研究。１６只犬随机分为对照组和实验组。结果发现，实验组心脏血流动力学的恢复要明显优于对照组。二组间心肌组织ＡＴＰ、腺苷和肌苷以及冠脉回流液中ＣＰＫ、ＣＰＫＭＢ、ＬＤＨ、ＳＯＤ和ＭＤＡ值均有显著性差异（Ｐ＜０．０１）。结论：冠脉搭桥术中采用间断缺血心停搏时加用利多氟嗪有利于保存心肌能量，减轻心肌再灌注损伤和术后迅即恢复心脏功能     

Cold-blood potassium cardioplegia: evaluation of glutathione and postischemic cardioplegia

Potassium (34 mEq/L) cardioplegia was induced with cold blood (CBK) in three groups of six dogs undergoing 60 minutes of myocardial ischemia at a systemic temperature of 27 degrees +/- 2 degrees and a myocardial temperature of 7 degrees +/- 2 degrees C (crushed ice). Group 1 (CBK) animals were reperfused initially with 400 ml cold blood over 8 to 10 minutes at increasing pressures of up to 75 mm Hg. Group II (CBK-K) dogs were reperfused in the same manner as Group I with the addition of potassium chloride, 30 mEq/L. In Group III (CBKG-KG) glutathione, 30 mg/100 ml, was added to both the pre- and postischemic perfusions with CBK. After 30 minutes of reperfusion control studies were repeated. Heart rate, peak systolic pressure, rate of rise of left ventricular pressure, maximum velocity of contractile element, pressure-volume curves, coronary flow distribution, muscle stiffness, and heart water were not significantly different from control values. Total coronary flow and myocardial uptake of oxygen, lactate, and pyruvate did not serve to separate the three groups; the same was true for right ventricular creatine phosphate, adenosine triphosphate, and adenosine diphosphate during ischemia and recovery. Ultrastructural myofibrillar lesions were noted in all groups. thus, postischemic cardioplegia and use of a physiological reducing agent do not enhance CBK cardioplegia with topical and systemic hypothermia.     

Effects of nucleoside transport inhibition on long-term ex vivo preservation of canine hearts.

The effect of nucleoside transport inhibition on 24-hour preservation of canine hearts was studied in 36 hearts arrested either with a cold hyperkalemic cardioplegic solution without (group I) or with supplementation of a specific nucleoside transport inhibitor (R75231, 1 mg/L) (groups II and III). The hearts were excised and stored for 24 hours at 0.5 degrees C. Then they were reperfused for 3 hours with use of a closed perfusion system primed with normal blood (groups I and II) or with blood supplemented with the same nucleoside transport inhibitor (0.32 mg/L) (group III). Serial biopsy specimens for determination of myocardial purines were taken. Creatine kinase and heat-stable lactate dehydrogenase release from the myocardium were examined during reperfusion. Recovery of function was studied during reperfusion by measurement of isometric contraction in a fluid-filled intraventricular balloon. After 24 hours of preservation, without the use of the drug, myocardial inosine and hypoxanthine accumulated to, respectively, 4.05 +/- 1.18 and 0.28 +/- 0.08 mumol/gm dry weight. In the drug-treated groups (II and III pooled), significantly less inosine and hypoxanthine accumulated (1.68 +/- 0.33 and 0.05 +/- 0.02 mumol/gm dry weight, respectively) (p < 0.05 versus group I). Upon reperfusion, intramyocardial adenosine was lost in the control hearts and maintained in the drug-treated hearts. Hypoxanthine accumulated significantly (p < 0.05) during reperfusion in group I (1.08 +/- 0.43 versus 0.16 +/- 0.13 in group II and 0.03 +/- 0.03 mumol/gm dry weight in group III). The rate of creatine kinase and heat-stable lactate dehydrogenase release was significantly lower (p < 0.05) in group III (that is, pretreatment and posttreatment with the drug) than in the control group. Functional recovery of hearts in group III was superior to that in group II (p < 0.05), while hearts in group I showed no recovery at all. We conclude that nucleoside transport inhibition improves long-term preservation of the heart and that the mechanism of this protection may be related to an increase in endogenous adenosine and reduction of myocardial hypoxanthine content.     

Optimal hypothermic preservation of arrested myocardium in isolated perfused rabbit hearts: a 31P NMR study

The purpose of this study was to (1) relate myocardial high-energy phosphate stores to functional recovery after ischemia and reperfusion, (2) assess the bioenergetics and functional influence of clinically relevant myocardial hypothermia, and (3) examine tissue pH as an independent indicator of postischemic recovery of function. Rabbit hearts were perfused via a modified Langendorff technique, monitored for developed pressure (DP) and left ventricular end-diastolic pressure (LVEDP) via an isovolumic left ventricular balloon catheter, and placed in a Brucker NMR magnet (4.7 tesla) to measure phosphocreatine (PCr), adenosine triphosphate (ATP), and pH. Hearts underwent 1 hour of global ischemia at 7 degrees, 17 degrees, 27 degrees and 37 degrees C initiated by one dose of K+ cardioplegia followed by 30 minutes of reperfusion. After reperfusion, DP (expressed as a percentage of preischemic control) and LVEDP (mm Hg) in 7 degrees and 17 degrees C hearts were no different (96 + 5% vs 97 +/- 3%; 5 +/- 2 mm Hg vs 6 +/- 2 mm Hg; p = NS), but were better (p less than 0.01) than 27 degree hearts (72 +/- 6%, 17 +/- 6 mm Hg) and 37 degree hearts (31 +/- 7%, 60 +/- 6 mm Hg). PCr was severely depleted in all groups. ATP was 90 +/- 7% and 87 +/- 5% of preischemic control in the 7 degree and 17 degree hearts, which was significantly better than the 68 +/- 3% and 21 +/- 3% in the 27 degree and 37 degree groups (p less than 0.01). The pH at end ischemia was 6.83, 6.89, 6.54, and 5.86 for the 7 degree, 17 degree, 27 degree, and 37 degree hearts, respectively (7 degrees vs 27 degrees or 37 degrees, p less than 0.01; 17 degrees vs 27 degrees or 37 degrees, p less than 0.01). Linear regression of DP on end-ischemic ATP (EIATP) and end-ischemic pH revealed: DP = 0.96 (EIATP) + 20 (r = 0.92) and DP = 60 (pH) -317 (r = 0.86). We conclude that (1) end-ischemic ATP predicts recovery of ventricular function, and, furthermore, there appears a threshold ATP concentration (80% of control) below which full recovery of function will not occur; (2) end-ischemic pH predicts recovery of ventricular function; (3) 7 degrees C hypothermic ischemia does not cause a clinically significant cold injury; and (4) in a single-dose crystalloid cardioplegia model, end-ischemic pH is linearly related to recovery of function (r = 0.86).     

The coincidence of myocardial reperfusion injury and hydrogen peroxide production in the isolated rat heart

To investigate the specific nature and timing of oxygen (O2) metabolite reperfusion injury, we used a rat-heart model (Langendorff's solution, 37 degrees C) and hydrogen peroxide (H2O2)-dependent aminotriazole inactivation of catalase as a measure of myocardial H2O2 before, during, and after ischemia. We found that after ischemia (20 minutes, global, 37 degrees C), ventricular functional loss--as assessed by measurement of developed pressure (DP), +dp/dt, and -dp/dt with a ventricular balloon--occurred at 10 minutes of reperfusion and that myocardial H2O2 production was maximal by this time. Furthermore, H2O2 production did not occur during ischemia, and inhibition of xanthine oxidase by tungsten feeding or infusing a permeable O2 metabolite scavenger during reperfusion (dimethylthiourea) prevented ventricular functional loss. We conclude that (1) reperfusion injury is in part mediated by toxic oxygen metabolites, (2) H2O2 is the central O2 metabolite responsible for reperfusion injury, and (3) the timing of H2O2 production coincides with the timing of ventricular functional loss.     

Transportation or noise is associated with tolerance to myocardial ischemia and reperfusion injury

Myocardial stress can result in myocellular phenotypic changes including enhanced activity of antioxidant enzyme systems. Accordingly, endogenous tissue antioxidant enzyme activity has been associated with resistance to cardiac ischemia and reperfusion injury. The present study was designed to determine if environmental perturbations could alter myocardial antioxidant enzyme (catalase) activity and function after ischemia. Isolated perfused rat hearts (Langendorff apparatus, 37 degrees C) were subjected to 20 min global ischemia (37 degrees C) and 40 min reperfusion. Rats studied immediately following shipment had increased myocardial catalase activity (1330 +/- 3.5 U/g, P < 0.05 vs quarantined control) and increased resistance to ischemia and reperfusion injury (end reperfusion developed pressure, DP 55 +/- 4.0 mm Hg, P < 0.05 vs quarantined control). However, control rats that were quarantined for 4 weeks exhibited a progressive decrease in catalase activity (760 +/- 10 U/g) for 3 weeks of quarantine. There was a concurrent decrease in resistance to myocardial ischemia and reperfusion injury (DP 40 +/- 3.6 mm Hg). Similarly, quarantined rats subjected to construction-related noise levels in excess of 90 dB (A scale) had increased myocardial catalase activity (1140 +/- 3.3 U/g, P < 0.05) and functional tolerance to ischemia and reperfusion (DP 66 +/- 3.3 mm Hg, P < 0.05). Finally, rats experiencing 90-dB noise levels for 2 days exhibited increased myocardial catalase activity (1125 +/- 30 U/g, P < 0.05) and myocardial ischemia and reperfusion injury tolerance (DP 62 +/- 1.7 mm Hg, P < 0.05). We conclude that variations in environmental conditions can relate to changes in antioxidant defense mechanisms and tolerance to myocardial ischemia and reperfusion injury in the rat.     

ATP precursor depletion and postischemic myocardial recovery

Although cardioplegia reduces myocardial metabolism during ischemia, adenosine triphosphate (ATP) depletion occurs, which may contribute to poor functional recovery after reperfusion. Augmenting myocardial adenosine during ischemia is successful in improving ATP repletion and myocardial recovery following ischemia. If adenosine is an important determinant of ischemic tolerance, then depletion or elimination of myocardial adenosine should lead to poor functional and metabolic recovery after ischemia. To test this hypothesis, isolated, perfused rabbit hearts were subjected to 120 min of 34 degrees C ischemia. Hearts received St. Thomas cardioplegia alone or cardioplegia containing 200 microM adenosine, or cardioplegia containing 15, 5, 2.5, or 0.025 micrograms/ml adenosine deaminase (ADA), which catalyzes the breakdown of adenosine to inosine, making adenosine unavailable as an ATP precursor. Functional recovery was determined and myocardial nucleotide levels were measured before, during, and after ischemia. Following ischemia and reperfusion, control hearts recovered to 51 +/- 3% of preischemic developed pressure (DP). There was significantly better recovery in adenosine-augmented hearts (68 +/- 7%), while ADA hearts had significantly worse recovery. Hearts treated with 0.025 microgram/ml ADA recovered to only 29 +/- 5% of DP and higher dose ADA hearts failed to demonstrate any recovery of systolic function. Furthermore, adenosine enhanced metabolic recovery, whereas ADA resulted in greatly depleted ATP and precursor reserves. Postischemic developed pressure closely paralleled the availability of myocardial adenosine, consistent with the hypothesis that myocardial adenosine levels at end ischemia and early reperfusion are important determinants of functional recovery after global ischemia.     

温血停搏液术终灌注对缺血再灌注心肌的保护作用

利用猫体外循环模型观察含甘露醇的温血停搏液术终灌注对缺血再灌注心肌的保护作用。心肌缺血恢复正常血液灌注前，从主动脉根部以５～６ｋＰａ的压力注入３７℃含甘露醇的低钾温血停搏液５０ｍｌ。结果显示用含甘露醇的温血停搏液术终灌注可保护缺血后再灌注心肌的功能，提高心肌能量储备，降低线粒体丙二醛含量。结论：含甘露醇的温血停搏液术终灌注，可提高心肌对氧自由基的清除能力，减轻线粒体膜脂质过氧化，提高心肌能量储备，有利于再灌注后心肌功能的恢复     

The differential effects of isoproterenol on +dp/dt max and -dp/dt max under volatile anesthetics in rat

BACKGROUND: The purpose of this study is to examine the effects of isoproterenol on +dp/dt max and -dp/dt max under volatile anesthetics in rat. METHODS: Firstly, under different halothane or isoflurane (0, 0.5 MAC, 1.0 MAC, 2.0 MAC) concentrations, hemodynamic parameters were recorded simultaneously. Secondly, under different halothane or isoflurane concentrations (0, 0.5 MAC, 1.0 MAC, 2.0 MAC), the inotropic response to isoproterenol was also studied with cumulative (0, 5, 50, 100, 500, 1000 pg) concentrations and hemodynamic parameters were simultaneously recorded. RESULTS: There were significant decreases in +dp/dt max and -dp/dt max in halothane and isoflurane treated rats. The decreases in +dp/dt max and -dp/dt max were greater in halothane treated rats than those in isoflurane treated rats (P < 0.05) under 2 MAC halothane. The responses of +dp/dt max and -dp/dt max to 500 and 1000 pg isoproterenol were significantly reduced by 2 MAC halothane compared with the control (P < 0.05). There were no significant changes in +dp/dt max and -dp/dt max by administration of isoproterenol under isoflurane anesthesia. CONCLUSIONS: Isoflurane has less effects on +dp/dt max and -dp/dt max, compared with halothane. It is possible that halothane, but not isoflurane, has some effects on the responsiveness to isoproterenol.     

Exogenous adenosine accelerates recovery of cardiac function and improves coronary flow after long-term hypothermic storage and transplantation.

Impaired coronary flow during postischemic reperfusion may limit functional recovery. In the present studies we used the heterotopically transplanted rat heart and the isolated working rat heart to assess whether adenosine, given during reperfusion, could improve either the rate or the extent of postischemic recovery. Hearts were arrested (2 minutes at 4 degrees C) with the St. Thomas' Hospital cardioplegic solution and stored by immersion in the same solution for 8 hours at 4 degrees C. Hearts were then transplanted into the abdomen of homozygous recipients. Immediately before reperfusion, adenosine (0.5 ml of a 1 mumol/L solution, equivalent to 0.13 micrograms) was injected into the left ventricle (control rats received an equivalent amount of saline). Hearts were reperfused in vivo for 30 minutes or 24 hours, after which they were excised and perfused (Langendorff) for 20 minutes for the assessment of function. They were then freeze clamped and taken for metabolic analysis. After 50 minutes of reperfusion, left ventricular developed pressure was 75 +/- 5 mm Hg (4 mm Hg end-diastolic pressure) in the adenosine group versus 61 +/- 4 mm Hg in the control group (p less than 0.05); however, after 24 hours function was identical in the two groups (52 +/- 4 versus 52 +/- 3 mm Hg). After 50 minutes of reperfusion coronary flow was greater in the adenosine group (11.0 +/- 0.4 versus 9.7 +/- 0.4 ml/min in control rats; p less than 0.05), a difference that was sustained for 24 hours (12.8 +/- 0.3 versus 11.4 +/- 0.4 ml/min in control rats; p less than 0.05). Adenosine triphosphate and creatine phosphate contents recovered to similar extents in control and adenosine groups after both 50 minutes and 24 hours of reperfusion. In further studies with an identical storage protocol (8 hours at 4 degrees C), hearts were not transplanted but were reperfused with crystalloid medium in the Langendorff mode for 15 minutes (creatine kinase leakage measured) and in the working mode for 180 minutes. In an attempt to mimic the heterotopic transplant protocol, adenosine (1 mumol/L) was included in the perfusion fluid for the first 2 minutes of reperfusion. Similar results to those of the transplant studies were obtained, with coronary flow being consistently improved in the adenosine group; however, this benefit was lost after only 2 hours of reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Low dose cyclophosphamide rescues myocardial function from ischemia-reperfusion in rats.

Objectives: The effect of low dose of cyclophosphamide (CP) protecting cardiac function from ischemia-reperfusion injury was studied on rats. The premise is that CP inhibits immune and inflammatory process, thereby limits I/R injury and improves myocardial function. Methods: Open chest rats were submitted to 30min of ischemia followed by 3h, 12h or 24h of reperfusion. Rats were divided into sham group, I/R group and CP group, and each group included 3 time-point subgroups (3h, 12h and 24h; n=8 for each subgroup). A total of 750mg/m(2) cyclophosphamide was intraperitoneally administrated in CP group and saline was given to I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure (LVSP) and +/-dp/dt(max). At the end of the experiment, hearts were harvested for histopathological assessment and infarct size determination. Results: Compared with I/R group, rats treated with low dose CP showed a significant recovery in myocardial function with improved LVSP (88+/-11 vs 69+/-11mmHg of 3h; 92+/-11 vs 64+/-14 mmHg of 12h; 90+/-11 vs 64+/-14mmHg of 24h; p<0.01 respectively). The +/-dp/dt(max) also had the similar trends. The myocardial infarct size was reduced in CP group compared to that in I/R group; the infiltration of polymorph nuclear leukocytes (PMNs) in myocardium was decreased in CP group. The histopathological damage score was also attenuated. Conclusions: These findings suggest that low dose CP rescues cardiac function from ischemia-reperfusion injury by alleviating histopathological damage in rat myocardium.     

Effect of free radical scavengers on myocardial function and Na+, K+-ATPase activity in stunned rabbit myocardium

OBJECTIVES: The role of reactive oxygen species (ROS) in the mechanism of myocardial stunning was investigated. MATERIAL AND METHODS: Isolated Langendorff-perfused rabbit hearts were subjected to 15 min normothermic ischemia followed by 10 min reperfusion with Krebs-Henseleit solution+/-mannitol or histidine. RESULTS: In hearts reperfused without free radical scavenger the left ventricular developed pressure as well as its maximal positive and negative first derivatives (+dP/dt, -dP/dt) was significantly depressed, whereas end diastolic pressure (LVEDP) increased when compared to preischemic values. Treatment with mannitol had little protective effects, whereas singlet oxygen scavenger histidine significantly improved the recovery of LVEDP and -dP/dt. Sarcolemmal Na+, K+-ATPase activity (control, 400+/-41 nmol Pi.min-1.mg-1) was depressed in untreated stunned hearts (260+/-27 nmol Pi.min-1.mg-1), but was almost completely recovered in hearts pretreated with histidine (364+/-27 nmol Pi.min-1.mg-1). The inhibition of Na+, K+-ATPase was only slightly prevented by mannitol (302+/-29 nmol Pi.min-1.mg-1l). CONCLUSIONS: The results suggest that ROS-induced inhibition of Na+, K+-ATPase activity is involved in the mechanism of postischemic contractile dysfunction and support the view that singlet oxygen may be one of the major causes of oxidative injury during ischemia and reperfusion.     

Effects of Hot shot on recovery after hypothermic ischemia in neonatal lamb heart

BACKGROUND: Terminal warm blood cardioplegia, "Hot shot", is the method for providing an energy replenishment and/or early recovery of aerobic metabolism without electromechanical activity at initial reperfusion. The mechanism of beneficial effects of this Hot Shot is multifactorial. This study was designed to assess the effects of terminal warm blood cardioplegia by comparing with oxygenated terminal warm crystalloid cardioplegia. METHODS: In Group HS-B, n=8 (oxygenated blood; 37 degrees C, Ht: 20%, K+ 20 mEq/l, pH 7.237, PO2 219 mmHg) and in Group HS-C, n=8 (bloodless oxygenated (5% CO2+95%O2) crystalloid, 37 degrees C, K+ 20 mEq/l, pH 7.435, PO2 624 mmHg), terminal warm cardioplegia (20 ml/kg for 5 minutes) was studied in the isolated blood perfused neonatal lamb heart following 2 hr of cardioplegic ischemia. Another eight hearts served as control without any kind of terminal cardioplegia. After 60 min of reperfusion, LV function was measured. Coronary blood flow (CBF), oxygen content, and oxygen consumption (MVO2) were measured and the oxygen extraction ratio was calculated in Group HS-B and HS-C during terminal cardioplegia and/or reperfusion. Results are given as % recovery of preischemic values. RESULTS: HS-B as well as HS-C groups showed better functional recovery in maximum developed pressure (DP: 78.0+/-8.3 in HS-B vs 65.2+/-9.2%; p=0.018), maximum dp/dt (67.3+/-6.2 in HS-B, 65.3+/-7.4 in HS-C vs 55.8+/-5.0%; p=0.003, p=0.02), DP V10 (87.1+/-8.5 in HS-B vs 67.2+/-9.9%; p=0.0001), and peak dp/dt V10 (76.4+/-7.6 in HS-B, 69.8+/-8.1 in HS-C vs 58.6+/-6.9 %; p=0.0001) than the control group. Between the HS-B and HS-C groups, HS-B showed better functional recovery in terms of DP V10 (p=0.01). Oxygen delivery of terminal cardioplegia was almost four times higher in HS-B group (90.4+/-17.7 vs 18.7+/-1.1 mcl/ml), contrarily, HS-C group showed four times higher oxygen extraction ratio compared to HS-B group (0.78+/-0.06 vs 0.18+/-0.11), thus oxygen consumption during hot shot was maintained at the same level in both groups. CBF in the control group was lower than that in the other groups at 60 min of reperfusion. CONCLUSIONS: Reperfusion with both terminal warm cardioplegia including blood and oxygenated crystalloid cardioplegia resulted in better recovery of function and higher levels of CBF with slightly better function in terminal warm blood cardioplegia.     

Enhancement of low coronary reflow improves postischemic myocardial function.

The effect of reperfusion coronary vasodilatation on postischemic myocardial mechanical function has been investigated in the isolated working rat heart. After a working period to assess control function, all the hearts were subjected to a single infusion (10 ml) of St. Thomas' Hospital cardioplegic solution No. 1 at 4 degrees C and were kept immersed in the same solution for 4 hours at 4 degrees C. Then hearts (six in each group) were initially reperfused at 37 degrees C for 10 minutes, either with ordinary reperfusate (Krebs-Henseleit bicarbonate buffer) or with reperfusate containing additional coronary dilator. After this period, all hearts were subjected to a further 5 minutes of ordinary reperfusate before being put back into the working mode to assess functional recovery. Mean reperfusion coronary flows and the steady coronary flow measured after 10 minutes of reperfusion in ml/min +/- SEM were--Krebs (control): 17.4 +/- 0.39 and 13.4 +/- 0.40; adenosine (3.75 mumol/L): 19.9 +/- 0.6 and 16.7 +/- 0.8; papaverine (0.05 mmol/L): 21.8 +/- 2.3 and 17.3 +/- 1.8; dipyridamole (2 mmol/L): 20.7 +/- 1.7 and 17.9 +/- 1.0; nitroglycerin (15 mg/L): 20.5 +/- 0.45 and 19.9 +/- 1.4; diltiazem (0.05 mmol/L): 19.6 +/- 2.98 and 17.7 +/- 1.8; calcitonin gene-related peptide (0.03 mmol/L): 20.8 +/- 0.69 and 18.0 +/- 1.3; 5-hydroxytryptamine (0.01 mmol/L): 19.2 +/- 0.53 and 16.9 +/- 0.80. Mean postischemic recovery of cardiac output, peak aortic pressure, and differentiation of pressure were expressed as percent of preischemic control +/- SEM were--Krebs: 54.1 +/- 2.8, 69.1 +/- 2.8, and 53.9 +/- 3.0; adenosine: 78.0 +/- 5.6, 89.5 +/- 2.9, and 69.1 +/- 1.9; papaverine: 81.8 +/- 3.9, 91.8 +/- 3.1, and 71.0 +/- 4.1; dipyrdamole: 67.3 +/- 3.3, 84.3 +/- 2.3, and 75.0 +/- 2.7; nitroglycerin: 83.1 +/- 4.8, 79.7 +/- 2.7, and 69.0 +/- 0.5; diltiazem: 76.5 +/- 3.7, 85.9 +/- 2.9, and 73.3 +/- 1.7; calcitonin gene-related peptide: 79.5 +/- 3.6, 90.0 +/- 4.9, and 75.4 +/- 3.9; 5-hydroxytryptamine: 71.6 +/- 3.2, 85.5 +/- 3.5, and 67.9 +/- 4.8. There was a positive correlation between mean reperfusion coronary flow, steady coronary flow, and postischemic recovery of cardiac output, peak aortic pressure, and differentiation of pressure. Mean reperfusion coronary flow, steady coronary flow, and postischemic recovery of cardiac output, peak aortic pressure, and differentiation of pressure were significantly greater in groups reperfused with vasodilators (p < 0.05) compared with control values.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prevention of myocardial reperfusion injury by poly(ADP-ribose) synthetase inhibitor, 3-aminobenzamide, in cardioplegic solution: in vitro study of isolated rat heart model.

OBJECTIVE: Cardioplegic arrest remains the method of choice for myocardial protection in cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction by preventing energy depletion associated with oxidative stress. We investigated the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest. METHODS: Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n = 8) were perfused with a standard cardioplegic solution and terminal warm cardoplegia, whereas the 3-AB(+) group (n = 8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis. RESULTS: During reperfusion, the 3-AB(+) group showed significantly higher (P = 0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK; P = 0.003 GOT; P < 0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P < 0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P = 0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group. CONCLUSION: Cardioplegic solution supplemented with 3-AB provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress and overactivation of PARS.