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。     

Calcium-accentuated ischemic damage during reperfusion: the time course of the reperfusion injury in the isolated working rat heart model

The purpose of this study was to determine the time course of calcium-induced postischemic reperfusion injury to the myocardium, using an initial short-term calcium-enriched reperfusion solution. The isolated rat heart model was subjected to 30 min of normothermic potassium cardioplegia-induced ischemic arrest. Control hearts received normal calcium Krebs-Henseliet buffer (KHB) reperfusion. Experimental hearts were challenged with 10 min of calcium-enriched (KHB) reperfusion starting at 0, 1, 2, 5, 15, and 30 min after the beginning of reperfusion. Aortic flow recovery 60 min after reperfusion was used to determine functional recovery. Control hearts recovered 82 +/- 3% of preischemic aortic flow. Hearts which received calcium challenge at 0 and 1 min after the start of reperfusion recovered 43 +/- 4 and 69 +/- 3% of preischemic aortic flow, respectively (P less than 0.01 and P less than 0.05, respectively). Hearts which received calcium challenge 2, 5, 15, and 30 min after reperfusion recovered 75 +/- 2, 80 +/- 2, 85 +/- 2, and 83 +/- 2% of preischemic aortic flow, respectively. Our results indicate that the postischemic myocardium is very susceptible to calcium-accentuated ischemic damage during the initial period of reperfusion. The postischemic heart, however, quickly recovers its ability to withstand a calcium challenge. Five minutes after the start of reperfusion the heart is not influenced by calcium challenge.     

Changes in left ventricular function after cardiac arrest and reperfusion in hypertropheral hearts.

Hypertrophied hearts may be more susceptible to ischemia/reperfusion during cardiac surgery than normal hearts, so we designed to compare the alterations in left ventricular function after ischemia/reperfusion, in hypertrophied hearts (Group H) with those in normal hearts (Group C), using a rabbit heart model of hypertrophy induced by banding of the ascending thoracic aorta. The pre and postischemic left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), positive and negative dP/dt, and coronary flow were measured. The percent recovery of coronary flow and negative dP/dt were significantly lower in Group H than in Group C (p < 0.05). The LVEDP was significantly greater in Group H, and the LVEDP increased significantly from the base line value in Group H (p < 0.05). There was no significant difference in other value between two groups. These findings demonstrated that LV diastolic dysfunction rather than LV systolic dysfunction occurred in the early ischemic stage, especially to hypertrophied hearts, indicating that better protection is required for these hearts.     

七氟醚后处理对大鼠离体心脏缺血再灌注时心肌细胞凋亡的影响

目的 探讨七氟醚后处理对大鼠离体心脏缺血再灌注(IR)时心肌细胞凋亡的影响.方法 雄性SD大鼠48只,随机分4组(n=12),制备离体心脏灌注模型,K-H液平衡灌注30 min后,C组灌注K-H液120 min;IR组缺血30 min,K-H液再灌注90 min;缺血后处理组(IP组)缺血30 min后行4个循环复灌20 s/缺血20 s,再灌注K-H液;七氟醚后处理组(SP组)缺血30 min后灌注含七氟醚的K-H液5 min,K-H液冲洗10 min,再灌注K-H液.IP组和SP组再灌注总时间90 min.灌注期间测定心功能,灌注结束时取心脏测定心梗面积、Bcl-2、细胞色素C和Caspase-3蛋白表达水平,计算心肌细胞凋亡指数(AI).结果 与C组比较,其余各组左心室最大上升或下降速率(±dp/dt)、左心室发展压(LVDP)、HR降低,左心室舒张末压(LVEDP)和AI升高,Bel-2、细胞色素C和Caspase-3蛋白表达上调(P<0.05);与IR组比较,IP组和SP组±dp/dt、LVDP升高,LVEDP和AI降低,心梗面积减小,Bcl-2表达上调,细胞色素C和Caspase-3蛋白表达下调(P<0.05).结论 七氟醚后处理可减少大鼠离体心脏IR时心肌细胞凋亡,其机制与其下调细胞色素C和Caspase-3蛋白表达,上调Bcl-2表达有关.     

Metabolic and functional cardiac impairment after reperfusion with persantine

The effect of dipyridamole (DYP) on postischemic myocardial function and metabolism was studied using the isolated rabbit heart model. Twenty-one isolated rabbit heart preparations were divided into two groups: KH (control N = 10) were reperfused after 24 min normothermic hyperkalemic arrest with modified Krebs-Henseleit buffer (KH) while DYP (N = 11) were reperfused with KH and 5 X 10(-6) M DYP. Hearts were analyzed for myocardial function (DP, developed pressure, +dp/dt, -dp/dt) and metabolic function (ATP, CrP, ADP, AMP, purines, and lactate levels). Data analysis revealed significant reperfusion depression in DYP myocardial function compared with KH (P less than 0.05): DP (42 +/- 6 vs 89 +/- 7 mm Hg), +dp/dt (390 +/- 21.6 vs 1227 +/- 48.4), and -dp/dt (280 +/- 20.1 vs 677 +/- 19.8). Comparison of DYP to KH metabolic parameters was also significantly different (P less than 0.05): ATP (5.8 +/- 0.7 vs 9.5 +/- 1.4), ADP (2.1 +/- 0.2 vs 3.2 +/- 0.6), CrP (9.6 +/- 0.3 vs 17.2 +/- 1.3). Tissue purines (adenosine and inosine) were significantly elevated (P less than 0.01) in the DYP group, while coronary sinus purines and lactate loss were similar. Thus, the data suggest that DYP, present during postischemic reperfusion, depresses myocardial function by inhibiting adenosine phosphorylation, thereby decreasing the generation of high-energy phosphates without increased substrate loss or ischemia.     

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.     

Recovery of contractile function of stunned myocardium in chronically instrumented dogs is enhanced by halothane or isoflurane

Following brief periods (5-15 min) of total coronary artery occlusion and subsequent reperfusion, despite an absence of tissue necrosis, a decrement in contractile function of the postischemic myocardium may nevertheless be present for prolonged periods. This has been termed "stunned" myocardium to differentiate the condition from ischemia or infarction. Because the influence of volatile anesthetics on the recovery of postischemic, reperfused myocardium has yet to be studied, the purpose of this investigation was to compare the effects of halothane and isoflurane on systemic and regional hemodynamics following a brief coronary artery occlusion and reperfusion. Nine groups comprising 79 experiments were completed in 42 chronically instrumented dogs. In awake, unsedated dogs a 15-min coronary artery occlusion resulted in paradoxical systolic lengthening in the ischemic zone. Following reperfusion active systolic shortening slowly returned toward control levels but remained approximately 50% depressed from control at 5 h. In contrast, dogs anesthetized with halothane or isoflurane (2% inspired concentration) demonstrated complete recovery of function 3-5 h following reperfusion. Because the anesthetics directly depressed contractile function, additional experiments were conducted in which a 15-minute coronary artery occlusion was produced during volatile anesthesia; however, each animal was allowed to emerge from the anesthetized state at the onset of reperfusion. Similar results were obtained in these experiments, demonstrating total recovery of contractile function within 3-5 h following reperfusion. Thus, despite comparable degrees of contractile dysfunction during coronary artery occlusion in awake and anesthetized dogs, the present results demonstrate that halothane and isoflurane produce marked improvement in the recovery of segment function following a transient ischemic episode. Therefore, volatile anesthetics may attenuate postischemic left ventricular dysfunction occurring intraoperatively and enhance recovery of regional wall motion abnormalities during reperfusion.     

Cold Blood–Diltiazem Cardioplegia

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood–potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7° ± 2°C) after coronary perfusion with 200 ml of cold blood (5° ± 1°C) containing diltiazem, 400 μg per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 μg/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 μg/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used.Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak ? dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p < 0.025) and compliance decreased (p < 0.02). In both groups, coronary vascular resistance declined (p < 0.001) and recovery of adenosine triphosphate (p < 0.001), adenosine diphosphate (p < 0.025), and the adenosine pool (p < 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2.Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.     

Postischemic [Ca2+] repletion improves cardiac performance without altering oxygen demands

The positive inotropism expected with correction of postischemic hypocalcemia might be counterbalanced by potential aggravation of reperfusion injury, in particular by calcium overload. We evaluated the effect of normalizing blood calcium concentration ([Ca2+]) on postischemic left ventricular systolic and diastolic mechanics using oxygen consumption and indices derived from pressure-diameter relations. In 10 open-chest dogs on cardiopulmonary bypass, the hearts underwent 30 minutes of normothermic global ischemia followed by one hour of multidose hypothermic (4 degrees C), hypocalcemic (0.3 mmol/L) blood cardioplegia. After reperfusion, systemic [Ca2+] had decreased to 70% of control (p = 0.017). The left ventricular inotropic state was significantly depressed from baseline (control) values, but was restored to baseline levels by resumption of normocalcemia after one hour of reperfusion. Chamber stiffness increased by 308% (p = 0.006) after hypocalcemic reperfusion but decreased significantly after [Ca2+] correction. Recovery of left ventricular performance with [Ca2+] correction did not augment myocardial oxygen consumption from the postischemic uncorrected state (5.0 +/- 0.3 mL O2/min/100 g versus 5.3 +/- 0.3 mL O2/min/100 g). We conclude that normalizing [Ca2+] after blood cardioplegia improves postischemic left ventricular performance without adversely affecting compliance or oxygen consumption.     

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.     

Cardiac oxidase systems mediate oxygen metabolite reperfusion injury

To investigate the mechanism of cardiac ischemia reperfusion injury, we fed rats tungsten (3 weeks) to inhibit molybdenum-dependent oxidase enzymes. Tungsten-treated isolated perfusion hearts (Langendorff, ventricular balloon, 37 degrees C) had negligible xanthine oxidase activity (less than 0.3 vs greater than 8.0 U/gm myocardium) and improved recovery of developed pressure (DP), contractility (+dP/dt), and compliance (-dP/dt) after 20 minutes of global ischemia (37 degrees C) and 40 minutes of reperfusion. Furthermore, the addition of dimethylthiourea, a freely diffusible O2 metabolite scavenger, but not equimolar urea, a non-O2 metabolite scavenger, improved recovery. High-dose urea improved recovery more than control but less than dimethylthiourea. Combining tungsten and equimolar urea improved recovery the same as dimethylthiourea. We conclude that: (1) inhibition of myocardial oxidase enzymes (including xanthine oxidase) improves recovery of ventricular function after ischemia and reperfusion in the isolated rat heart, (2) infusion (during reperfusion) of a permeable O2 metabolite scavenger (dimethylthiourea) but not equimolar urea improves recovery of ventricular function, (3) infusion of higher concentrations of urea improves postischemic function, and (4) myocardial reperfusion injury is distinguishable from ischemic injury.     

Early and late post-ischaemic recovery of contractile function is affected to different degrees by isoflurane and halothane in the anaesthetized rabbit model

The protective efficacy of halogenated anaesthetics on myocardial injury has never been compared during early reperfusion and late reperfusion in an in vivo animal model. We compared recovery of left ventricular function under isoflurane (0.5 MAC) and halothane (0.5 MAC) anaesthesia after a brief period of regional ischaemia (15 min) in acutely instrumented rabbits. Rabbits were instrumented for the measurement of regional segment length and left ventricular pressure. Rabbits receiving isoflurane showed greater recovery of systolic shortening fraction (%SS) both during early and late reperfusion compared with halothane anaesthesia. Isoflurane protected the post- ischaemic myocardium to a greater extent than halothane anaesthesia. Early recovery of contractile function may be a predictor of contractile recovery during the later stages of reperfusion.      

Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C?

BACKGROUND: Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs. METHODS: Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 microg/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals. RESULTS: There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P<0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dt(max)) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12+/-8% of baseline), in contrast to those that received isoflurane (75+/-7% recovery). Bisindolylmaleimide at a dose of 2 microg/min alone enhanced recovery of segment shortening (50+/-7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 microg/min bisindolylmaleimide further enhanced recovery of contractile function (79+/-8% of baseline). In contrast, 8 microg/min bisindolylmaleimide alone (32+/-12%) or combined with isoflurane (37+/-17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs. CONCLUSIONS: The results indicate that protein kinase C inhibition using low doses of bisindolylmaleimide alone produces cardioprotection, and isoflurane further enhances this protection. In contrast, high doses of bisindolylmaleimide are not cardioprotective in the presence or absence of isoflurane. A role for protein kinase C during isoflurane-induced recovery of the stunned myocardium cannot be excluded.     

Effect of pyruvate on regional ventricular function in normal and stunned myocardium.

The prolonged ventricular dysfunction following brief periods of coronary artery occlusion that does not produce irreversible damage has been termed the "stunned" myocardium. Although ventricular function returns to preischemic values by 1 to 7 days after reperfusion is established, inotropic therapy may be necessary to enhance contractility in the stunned heart. The purpose of this study was to determine the effect of pyruvate on ventricular function in normal and stunned myocardium. Eight chloralose/urethane anesthetized dogs were instrumented with ultrasonic crystals to measure systolic wall thickening in the left anterior descending artery (LAD) and left circumflex artery perfused regions of the left ventricle. Pyruvate (1 ml/min of 150 mM sodium pyruvate, pH 7.4) was infused directly into the LAD prior to and 30 minutes after a 10 minute LAD occlusion. Prior to LAD occlusion, LAD pyruvate infusion increased systolic wall thickening in the LAD-perfused region from 16.2% +/- 4.3% to 23.4% +/- 5.1% (p less than 0.05). Thirty minutes after LAD occlusion, regional wall thickening was depressed (3.3% +/- 2.6%; p less than 0.05), which is indicative of stunned myocardium. Subsequent LAD pyruvate infusion increased wall thickening in the stunned myocardium to 12.7% +/- 2.5%. The improvement of regional ventricular function was maintained only during the pyruvate infusion, as function returned to prepyruvate levels within 20 minutes after cessation of pyruvate infusion. These data indicate that pyruvate exerts a positive inotropic effect in normal and stunned myocardium. If pyruvate, a key intermediate in energy-producing pathways, exerts its inotropic effect through an enhancement of the energy state of the heart, it may have advantages over traditional inotropic agents in the treatment of postischemic contractile dysfunction.     

Evaluation of myocardial preservation using 31P NMR

The purpose of this study was (1) to monitor myocardial high-energy phosphate content and recovery of left ventricular (LV) contractile function following normothermic graded cardiac ischemia and single-dose hypothermic potassium cardioplegia, and (2) to assess the temporal limits of LV functional recovery during single-dose cardioplegia maintained at 17 degrees C. Rabbit hearts (30) were perfused, equipped with an LV balloon, paced at 240 beats/min, and placed in a nuclear magnetic resonance (NMR) magnet. Hearts underwent either graded, global normothermic ischemia or potassium cardioplegia arrest maintained at 17 degrees C for 1 hr. Myocardial high-energy phosphate level, LV contractility, and temperature were monitored continuously. Phosphocreatine (PCr) fell to 10 +/- 2, 2 +/- 1, and 0% of control and ATP to 70 +/- 3, 19 +/- 7, and 0% of control at 10, 40, and 60 min of 37 degrees C ischemia. After 1 hr of reperfusion, regression analysis of final developed pressure (DP) on end ischemic ATP (EIATP) content revealed: DP = 1.02 EIATP + 18 (r = 0.95). Following single-dose cardioplegia, maintained at 17 degrees C, PCr fell to 16 +/- 3% of control at 60 min while ATP fell only to 92 +/- 5% control. With reperfusion, recovery of DP was 100%. It was concluded that (1) PCr serves as an energy buffer for ATP, (2) EIATP predicts recovery of LV function, (3) single-dose cardioplegia maintained at 17 degrees C provides complete myocardial preservation for up to 60 min.     

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).     

Comparative myocardial protection with calcium-free versus calcium-containing potassium cardioplegic solutions

The present study was designed to determine if the addition of calcium to a potassium cardioplegic solution results in improved myocardial protection during ischemic arrest. An isolated perfused cat heart preparation was used. Hearts were made ischemic for 60 min and then reperfused for 45 min. Four groups were studied with the myocardial temperature during ischemia being maintained at 37°C in one and at 27°C in the remaining three groups. Two of these latter three groups received cardioplegic solutions while one remaining hypothermic group served as a hypothermic control. The cardioplegic solutions differed in that one was a calcium-free moderately hyperkalemic solution while the other contained 2 mM calcium, 16 mM magnesium, and 1 mM procaine in addition to being moderately hyperkalemic. Myocardial gas tensions were monitored by mass spectrometry and isovolumic ventricular function assessed by developed pressure and maximum dP/dt. Hypothermia alone resulted in significantly better recovery of ventricular function than normothermic ischemia. Recovery was further enhanced by the addition of cardioplegia. The best return of left ventricular function was seen in the group which had received the calcium-free cardioplegic solution and this group also developed the least myocardial edema following reperfusion. This study demonstrates that the omission of calcium as well as magnesium and procaine, from a cardioplegic solution, rather than being hazardous, may in fact be beneficial.     

Improved myocardial ischemic tolerance by contractile inhibition with 2,3-butanedione monoxime.

Contracture of the arrested myocardium during prolonged storage of the heart results in both systolic and diastolic dysfunction, and is a major limitation to extended preservation. We studied the effects of a reversible contractile inhibitor, 2,3-butanedione monoxime (BDM), on myocardial ischemic tolerance. Isolated rabbit hearts were flushed with University of Wisconsin (UW) solution with and without 30 mmol/L BDM and 1 mmol/L CaCl, stored at 4 degrees C for 24 hours, and subsequently reperfused for 60 minutes. Left ventricular pressure-volume relationships and adenine nucleotide content were determined before reperfusion. Left ventricular systolic pressure, diastolic volume, and adenine nucleotide content were measured after reperfusion. Hearts stored in UW solution underwent contracture and adenosine triphosphate (ATP) depletion during storage, and exhibited systolic dysfunction, impaired diastolic relaxation, and poor ATP regeneration upon reperfusion. The addition of calcium worsened contracture and ATP depletion (p < 0.005) and slightly improved function and ATP regeneration (p = not significant). Hearts stored in the presence of BDM experience no contracture during storage; ATP was preserved (10.7 versus 15.7 nmol/mg; p < 0.05), and left ventricular systolic pressure and ATP content recovered to 74% and 93% of control on reperfusion, respectively (p < 0.005). Left ventricular diastolic volume remained depressed, however, although less than with UW solution (0.87 versus 0.45 mL; p < 0.001). When both BDM and calcium were included in the UW solution, calcium-stimulated ATP hydrolysis and contracture were prevented, left ventricular systolic pressure returned to 87% of control, and left ventricular diastolic volume and ATP content returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrionatriuretic peptide improves left ventricular function after myocardial global ischemia-reperfusion in hypoxic hearts

Atrionatriuretic peptide (ANP) is reported to be useful for attenuating myocardial ischemia–reperfusion injury and improving left ventricular function after reperfusion. However, ANP may be either ineffectual or harmful in cases where the myocardium has been chronically hypoxic since birth. This can be a result of the concomitant high levels of cyclic guanosine monophosphate (cGMP) produced within the myocardium. This study aimed to verify the validity of using ANP to improve left ventricular function after myocardial ischemia–reperfusion injury. For this purpose, a cyanotic congenital disease model that was developed using isolated rat hearts was used. Hearts were obtained from Sprague‐Dawley rats that were housed from birth until 6 weeks of age either in a hypoxic environment with 13–14% FiO₂ (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1 µM) into the reperfusion solution was compared with those hearts that were not administered ANP in both hypoxic (without ANP: n = 6, with ANP: n = 6, with ANP and HS‐142‐1[an antagonist of ANP]: n = 6) and normoxic hearts (without ANP: n = 6, with ANP: n = 6). In the hypoxic hearts, ANP administration improved the percent recovery of the left ventricular developed pressure (76.3 ± 9.2% without ANP vs. 86.9 ± 6.7% with ANP), maximum first derivative of the left ventricular pressure (82.4 ± 1.1% without ANP vs. 95.8 ± 6.5% with ANP), and heart rate (85.6 ± 4.7% without ANP vs. 96.1 ± 5.2% with ANP) after reperfusion. The improvement and recovery of these cardiac functions were closely related to significantly increased levels of postischemic cGMP release after ANP administration. The effect of ANP was blocked by HS‐142‐1. The improvements observed in the hypoxic group were similar to those found in the normoxic group. ANP administration during reperfusion improved left ventricular function after myocardial acute global ischemia–reperfusion equally in both the chronically hypoxic and age‐matched normoxic groups.     

心肌缺血/再灌注后多巴酚丁胺最佳应用时间探讨

目的 制作大鼠离体心脏缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)模型,比较再灌注后不同时间点给予多巴酚丁胺对心功能和心肌损伤的影响,以探索心肌缺血/再灌注(ischemia/reperfusion,I/R)后给予多巴酚丁胺的最佳时间.方法 雄性SD大鼠36只,按完全随机法分为4组(每组9只),各组在Langendorff灌注装置上建立离体心脏I/RI模型.平衡灌注15 min,缺血30 min,再灌注60 min,于再灌注期采取不同处理措施.单纯I/R组(I/R组)再灌注期全程以克-亨氏(Kreb'sHenseleit,K-H)液灌注;多巴酚丁胺一组(D1组)再灌注5 min时给予多巴酚丁胺灌注30 min,其余时间以K-H液灌注;多巴酚丁胺二组(D2组)再灌注15 min时给予多巴酚丁胺灌注30 min,其余时间以K-H液灌注;多巴酚丁胺三组(D3组)再灌注25 min时给予多巴酚丁胺灌注30 min,其余时间以K-H液灌注.其中,多巴酚丁胺输注剂量均为10 μg· kg-1·min-1.记录各组平衡灌注末(T0),再灌注10 min(T1)、20min(T2)、30min(T3)、60 min(T4)时的血流动力学指标:HR、左室舒张末压(left ventricular end diastolic pressure,LVEDP)、左室发展压(left ventricular developed pressure,LVDP)、左室内压上升/下降最大速率(the maximum rate of left ventricular pressure change,±dp/dtmax)及冠状动脉流量(coronary flow,CF).留取T0～T4各时点冠状动脉流出液,使用乳酸脱氢酶(lactate dehydrogenase,LDH)和肌酸磷酸激酶(creatine kinase,CK)试剂盒测定冠状动脉流出液中LDH和CK的活性.2,3,5-氯化三苯基四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)染色法测定心肌梗死面积(myocardial infarct size,MIS).Western blot法检测肌浆网钙泵(sarcoendoplasmic reticulum Ca2+-ATPase,SERCA2a)和兰尼碱受体(ryanodine receptors,RyR2)蛋白表达量. 结果 D1组在给予多巴酚丁胺后,HR、LVEDP、LDH、CK、MIS均比I/R组高,差异有统计学意义(P＜0.05);D2组、D3组在给予多巴酚丁胺后,HR、CF、LVDP、±dp/dtmax均高于I/R组,差异有统计学意义(P＜0.05),而LVEDP、LDH、CK、MIS比较,差异无统计学意义(JP＞0.05).多巴酚丁胺各组SERCA2a蛋白表达量和I/R组比较,差异无统计学意义(P＞0.05),而RyR2蛋白表达量则高于I/R组(P＜0.05).D2组与D3组相比在给予多巴酚丁胺后上述指标比较,差异均无统计学意义(P＞0.05). 结论 大鼠心肌FR 15 min时应用多巴酚丁胺要优于其他时间点.在这一时间点用药可以及时而有效地提高大鼠HR,增加CF,改善心肌收缩功能,且不会加重心肌损伤.