Increasing heart size and age attenuate anesthetic preconditioning in guinea pig isolated hearts

Anesthetic preconditioning (APC) reduces myocardial ischemia/reperfusion injury. Recent investigations have reported that older hearts are not susceptible to APC. We investigated if increasing heart size with age determines the susceptibility to APC in young guinea pigs. Langendorff-prepared guinea pig hearts of different weights (1.1-2.2 g) and ages (2-7 wks) were exposed to 1.3 mM sevoflurane for 15 min followed by 30 min washout (APC; n = 20) before 30 min global ischemia and 120 min reperfusion. Control hearts (n = 20) were not subject to APC. Left ventricular pressure was measured isovolumetrically and infarct size was determined by triphenyltetrazolium staining. Functional data were not different between groups at the beginning of the experiments nor did they correlate with heart weight or age. At 120 min reperfusion, left ventricular pressure, coronary flow, and tissue viability showed significant negative correlations with increasing heart weight and age in APC but not in control hearts; i.e., APC improved function and attenuated infarct size better in smaller/younger hearts than in larger/older hearts. Thus, increasing age and heart size attenuate the susceptibility for APC even in younger guinea pigs. This may have important implications for further basic science research and the possible clinical applicability of APC in humans.     

Noradrenaline inhibits autonomous activity in the isolated guinea pig bladder

OBJECTIVE: To investigate the actions of noradrenaline and the specific alpha-adrenergic agonists cirazoline (alpha1) and UK14304 (alpha2), and beta-receptor agonists formoterol (beta2) and BRL37344 (beta3) on the phasic activity induced by muscarinic stimulation on the isolated guinea pig bladder, as the physiological significance of this activity is unknown but it may underlie non-micturition contractions (NMCs, which can be inhibited by sympathetic nerve stimulation) and the generation of bladder sensations. MATERIALS AND METHODS: All experiments were conducted using whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra and suspended in a heated chamber containing oxygenated Tyrode's solution at 33-35 degrees C and the intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface. RESULTS: Exposure to noradrenaline reduced the amplitude and frequency of the phasic activity. When noradrenaline was washed off there was a transient increase in frequency. There was marked desensitization with repeated applications of noradrenaline. Applying the specific beta3-agonist BRL37344 reduced the amplitude of the phasic activity while formoterol, a specific beta2-agonist, had no effect. Cirazoline, a specific alpha1-agonist, reduced the amplitude of the responses and significantly reduced the frequency of the phasic activity. UK14304, a specific alpha2-agonist, had no effect. Stimulation of the hypogastric nerve to the guinea pig bladder generates contractions. Prolonged nerve stimulation at low frequency (6.5 Hz) generated phasic rises in intravesical pressure which were inhibited by noradrenaline. Using short (5 s) periods of stimulation noradrenaline inhibited nerve-mediated contractions at all frequencies but was more effective at <10 Hz. CONCLUSION: These experiments show that sympathomimetic stimulation in the isolated whole bladder results primarily in an inhibition of phasic activity, but also a stimulation. Two receptor subtypes appear to be involved in the inhibition, alpha1 and beta3, suggesting that there may be many sites of action. These results are discussed in terms of the possible physiological significance of phasic activity and the potential importance of its inhibition, in the context of the causes of pathological changes in the bladder, particularly those associated with bladder overactivity, and the pharmacological approach to the alleviation of clinical symptoms.     

热休克预适应诱导HSP72提高兔心长期保存效果的实验研究

目的：通过热休克预适应模型,观察其是否可以改善心脏后心功能的恢复,提高心脏的保存质量,探讨此模型中心肌保护作用的分子基础。方法：健康成年新西兰白兔20只,随机分为两组,每组10只,I组为对照组;Ⅱ组为热休克组,将兔体温升高到42℃,保持15min,自然环境下恢复24h后处理;两组实验方法相同,心肌保存前用K－H液灌注35min,然后用4℃STS液使心脏停搏并4℃保存6h,保存后用K－H复灌30min。保存前、复灌后工作心期末测定心率（HR）,冠脉流量（CF）、左室收缩末期压（LVESP）和左室舒张末期压（LVEDP）,心功能恢复率以保存前的百分率表示,再灌注期末取心肌组织进行热休克蛋白72（HSP72）的定量和定位检测,测定心肌内NO、肌酸激酶同功酶（CK－MB）、乳酸脱氢酶（LDH）的含量,测定超氧化物歧化酶（SOD）和脂质过氧化物（LPO)的含量,测定心肌含水量。结果：热休克组功能恢复明显好于对照组,且与心肌内HSP72含量相关（r＝0．95）,其心肌内NO含量亦明显高于对照组。结论：热休克预适应可明显改善心脏保存6h后心功能的恢复,减轻心肌酶的漏出,减轻缺血－再灌注损伤。且其分子基础是HSP72,其保护机制可能与内皮细胞保护有关。     

Sevoflurane and isoflurane do not enhance the pre- and postischemic eicosanoid production in guinea pig hearts

Eicosanoids and volatile anesthetics can influence cardiac reperfusion injury. Accordingly, we analyzed the effects of sevoflurane and isoflurane applied in clinically relevant concentrations on the myocardial production of prostacyclin and thromboxane A2 (TxA2) and on heart function. Isolated guinea pig hearts, perfused with crystalloid buffer, performed pressure-volume work. Between two working phases, hearts were subjected to 15 min of global ischemia followed by reperfusion. The hearts received no anesthetic, 1 minimum alveolar anesthetic concentration (MAC) isoflurane (1.2 vol%), or 0.5 and 1 MAC sevoflurane (1 vol% and 2 vol%), either only preischemically or pre- and postischemically. In additional groups, cyclooxygenase function was examined by an infusion of 1 microM arachidonic acid (AA) in the absence and presence of sevoflurane. The variables measured included the myocardial production of prostacyclin, TxA2 and lactate, consumption of pyruvate, coronary perfusion pressure, and the tissue level of isoprostane 8-iso-PGF2alpha. External heart work, determined pre- and postischemically, served to assess recovery of heart function. Volatile anesthetics had no impact on postischemic recovery of myocardial function (50%-60% recovery), perfusion pressure, lactate production, or isoprostane content. Release of prostacyclin and TxA2 was increased in the early reperfusion phase 5-8- and 2-4-fold, respectively, indicating enhanced AA liberation. Isoflurane and sevoflurane did not augment the eicosanoid release. Only 2 vol% sevoflurane applied during reperfusion prevented the increased eicosanoid formation in this phase. Infusion of AA increased prostacyclin production approximately 200-fold under all conditions, decreased pyruvate consumption irreversibly, and markedly attenuated postischemic heart work (25% recovery). None of these effects were mitigated by 2 vol% sevoflurane. In conclusion, only sevoflurane at 2 vol% attenuated the increased liberation of AA during reperfusion. Decreased eicosanoid formation had no effect on myocardial recovery in our experimental setting while excess AA was deleterious. Because eicosanoids influence intravascular platelet and leukocyte adhesion and activation, sevoflurane may have effects in reperfused tissues beyond those of isoflurane. IMPLICATIONS: In an isolated guinea pig heart model, myocardial eicosanoid release was not increased by isoflurane or sevoflurane, either before or after ischemia. Sevoflurane (2 vol%) but not isoflurane attenuated the increased release of eicosanoids during reperfusion.     

Modulation of autonomous contractile activity in the isolated whole bladder of the guinea pig

OBJECTIVE: To investigate the actions of the nonhydrolysable analogue of ATP, alpha,beta-methylene ATP (alpha,beta-MATP) and the sensory peptide, substance P, on the phasic activity generated by muscarinic stimulation in the isolated whole bladder. Isolated bladder can generate complex contractions resulting in phasic rises in intravesical pressure (the autonomous bladder): activity thought to underlie nonmicturition activity in vivo and which may be important in generating bladder sensations. MATERIALS AND METHODS: Experiments were conducted on whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra, suspended in a heated chamber containing oxygenated solution at 33-36 degrees C and intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface of the bladder. RESULTS: When alpha,beta-MATP (30-3000 nmol/L) or substance P (30-300 nmol/L) was added to resting bladders there were small rises in intravesical pressure (<2 cmH2O). However, in the presence of phasic activity generated by exposing the bladder to the muscarinic agonist arecaidine (100-300 nmol/L) or the nicotinic ligand lobeline (10-30 micromol/L) similar or lower concentrations of alpha,beta-MATP or substance P produced more dramatic effects: alpha,beta-MATP and substance P (both at 100 nmol/L) activated a rise in basal pressure of > 15 cmH2O and increased the frequency of the phasic activity. On removing alpha,beta-MATP or substance P, there was a slowing of phasic activity indicative of an inhibitory mechanism. CONCLUSION: In addition to direct effects on smooth muscle the agonists alpha,beta-MATP and substance P appear to be potent regulators of the mechanisms generating phasic activity. A developing concept is that the mechanisms responsible for generating phasic activity underlie nonmicturition activity are the target for excitatory and inhibitory inputs. Regulating such activity may be a factor in generating or modifying bladder sensation. Inappropriate or exaggerated phasic activity could underpin the pathological changes which cause the overactive bladder, thus adding another hypothesis to the neurogenic and myogenic hypotheses of bladder overactivity, i.e. that of the autonomous bladder.     

Direct comparative effects of isoflurane and desflurane in isolated guinea pig hearts.

The aim of this study was to test if myocardial and coronary vascular effects of desflurane and isoflurane were similar in the isolated heart. The cardiac effects of these anesthetics were examined in 12 guinea pig hearts perfused in a retrograde manner. Spontaneous heart rate, atrioventricular (AV) conduction time, systolic left ventricular pressure and coronary flow were measured. To differentiate direct vasodilatory effects of these anesthetics from an indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction were also monitored. Isoflurane and desflurane were injected directly into sealed bottles containing oxygenated perfusate solution. Each heart was perfused randomly with these anesthetics. Anesthetic concentrations in the perfusate were 0.28 +/- 0.02 and 0.52 +/- 0.02 mM for isoflurane and 0.59 +/- 0.01 and 1.02 +/- 0.09 mM for desflurane (mean +/- standard error of the mean). Calculated vapor concentrations were 1.3 and 2.5 vol % for isoflurane and 6.8 and 11.8 vol % for desflurane which correspond to approximately 1 and 2 MAC in vivo. Each anesthetic similarly decreased heart rate and prolonged AV conduction time in a concentration-dependent manner. Left ventricular pressure (control 93 +/- 4 mmHg) decreased by 11 +/- 1% and 24 +/- 2% with isoflurane and by 15 +/- 1% and 30 +/- 2% with desflurane. The decreases in heart rate and pressure were accompanied by decreases in MVO2 of 12 +/- 2% and 30 +/- 3% with isoflurane and of 19 +/- 3% and 40 +/- 4% with desflurane from a control of 57 +/- 2 microliters.g-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardioprotective effects of propofol in isolated ischemia-reperfused guinea pig hearts: role of KATP channels and GSK-3β

PURPOSE: Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on K(ATP) channel opening and the inhibition of GSK-3beta activity in ischemia-reperfused hearts. METHODS: Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion. The hearts were incubated for ten minutes, with or without propofol (25 or 50 microM), or for five minutes with 500 microM 5-hydroxydecanoate (a mitochondrial K(ATP) channel blocker) or 30 microM HMR1098 (sarcolemmal K(ATP) channel blocker), followed by five minutes with 50 microM propofol before ischemia. Action potentials on the anterior epicardial surface of the ventricle were monitored using a high-resolution charge-coupled device camera system, and at five minutes after reperfusion, GSK-3beta phosphorylation at the serine residue, Ser9, was examined. RESULTS: After 35 min of reperfusion, propofol (25 and 50 microM) blunted the adverse effects of I/R and reduced infarct size (P < 0.05). In addition, prior incubation with 5-hydroxydecanoate or HMR1098 had no effect on functional recovery improved by 50 microM propofol. At five minutes after reperfusion, propofol (25 and 50 microM) shortened the duration of the action potential and increased the levels of phospho-GSK-3beta (P < 0.05). CONCLUSIONS: Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3beta play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial K(ATP) channels do not.     

热休克预处理对严重烧伤大鼠胃黏膜的保护作用及机制

目的观察热休克预处理（HS）对严重烧伤大鼠胃黏膜热休克蛋白（HSP）60、HSP70表达及线粒体超氧化物歧化酶（SOD）、细胞色素氧化酶（CCO）活性的影响，探讨HS对严重烧伤大鼠胃黏膜的保护作用及机制。方法将Wistar大鼠随机分为烧伤组（40只）：烧伤后即制作急性胃黏膜损伤模型；另取8只大鼠不致伤作为空白对照。HS组（40只）：于烧伤前20h行HS，另取8只大鼠仅行HS不烧伤，作为实验对照。放线菌素D组（40只）：在HS前30min静脉注射放线菌素D0．1mg／kg，随后的处理同HS组；另取8只大鼠只注射放线菌素D不烧伤，作为实验对照。于伤后3、6、12、24、48h处死各组大鼠（每组每时相点8只）。取胃黏膜组织检测胃黏膜损伤指数（UI）、HSP70 mRNA、HSP60、HSP70的表达及SOD、CCO的活性。结果大鼠烧伤后uI呈时间依赖性增加，烧伤组伤后24h胃黏膜损伤程度最严重，UI为12．8±1．9。除伤后3h外，HS组大鼠各时相点uI均低于烧伤组（P＜0．05或0．01）。放线菌素D组大鼠胃黏膜损伤程度明显重于烧伤组及HS组（P＜0．05）。烧伤组、HS组除伤后24、48h外其余各时相点HSP70 mRNA均增加，而放线菌素D组伤后24、48h有所增加。与烧伤组比较，HS组大鼠胃黏膜HSP60及HSP70表达显著增加，除伤后48h外其余各时相点比较，差异均有统计学意义（P＜0．05或0．01）。放线菌素D组大鼠HSP60和HSP70表达明显受抑（P＜0．05）。大鼠烧伤后胃黏膜CCO、SOD活性不断降低，经HS后CCO及SOD下降不明显，在伤后6、12、24h均高于同时相点烧伤组（P＜0．05或0．01）。结论HS对大鼠严重烫伤后急性胃黏膜损害具有保护作用，其机制可能与HSP60、HSPT0诱导表达增强，线粒体SOD及CCO活性增加等有关。     

Effects of halothane on electrophysiologic properties and cyclic adenosine 3',5'-monophosphate content in isolated guinea pig hearts.

We studied the effects of halothane on the electrophysiologic and biochemical properties of both Langendorff perfused hearts and single ventricular myocytes isolated from guinea pigs. Isometric contractions of left ventricles in perfused hearts, elicited by atrial pacing, decreased to 14% of control after exposure to 2% halothane-equilibrated perfusate. Subsequently the slow inward Ca2+ current (ICa) was recorded in isolated myocytes with a whole cell voltage clamp technique. ICa, recorded in response to 100-ms depolarizations from -40 mV to 0 mV, was decreased by 2% halothane to 28.4% of control. Halothane-induced ICa depression did not exhibit use dependency. To define a possible site at which halothane acts, we measured the cyclic adenosine 3',5'-monophosphate (cAMP) content of single ventricular myocytes using a radioimmunoassay. Two percent halothane decreased myocardial cAMP content to 68.9% of control. Further addition of dibutyryl cAMP (10(-3) mol/L) partially reversed the depressed contractility during 2% halothane administration in perfused hearts. In conclusion, the present study demonstrated that the decrease of myocardial cAMP by halothane was due to a direct action, at least partly, and not to other factors such as catecholamines, and suggested that the decreases in contractility and ICa were induced possibly through the decrease in cellular cAMP.     

Landiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts

PURPOSE: Beta blockers are thought to exert beneficial effects on the ischemic heart. The authors examined the effects of landiolol (ONO 1101), a highly selective beta1 antagonist, propranolol, a nonspecific beta blocker, and esmolol, a selective beta1 antagonist, on postischemic contractile recovery. Drugs were given prophylactically. METHODS: Ischemia-reperfusion in isolated guinea pig hearts was induced by stopping the perfusion for 45 min and reperfusing for 60 min. Hearts (n = 7 in each group) were treated with or without propranolol (1 or 10 microM), esmolol (5 or 50 microM), or landiolol (20, 100 or 500 microM) ten minutes before inducing ischemia. RESULTS: At the end of reperfusion, left ventricular pressure (LVP) recovered to 64 +/- 3% of the baseline value in the control group. With 1 and 10 microM propranolol, LVP recovered to 90 +/- 5% and 100 +/- 6% of the baseline value at 60 min after reperfusion, respectively. Fifty microM but not 5 microM of esmolol resulted in restoration of LVP to 97 +/- 17% of the pre-ischemic value at 60 min after reperfusion. In hearts pretreated with 100 and 500 microM landiolol, LVP was restored to 109 +/- 5% and 104 +/- 5% of the baseline value, respectively. Landiolol 100 microM did not depress LVP in the pre-ischemic period. CONCLUSIONS: The present study shows that landiolol, an ultra-short-acting cardioselective beta1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three beta blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period.     

Differential protective effects of halothane and isoflurane against hypoxic and reoxygenation injury in the isolated guinea pig heart

The authors investigated the effects of halothane (HAL) and isoflurane (ISO) on cardiac depression produced by global hypoxia and the recovery of function following reoxygenation is isolated guinea pig hearts perfused with Krebs' solution at constant pressure. Isovolumetric left ventricular systolic (LVSP) and end-diastolic pressures (LVEDP) were measured by placing a saline filled, latex balloon into the left ventricle. Bipolar electrodes were placed in the right atrium and right ventricle for measurements of heart rate (HR), atrioventricular conduction time (AVCT), and determination of the incidence and severity of dysrhythmias occurring during hypoxia and reoxygenation. Hearts were divided into three groups: control (n = 20), halothane (n = 12), and isoflurane (n = 13). All hearts were exposed in sequence to oxygenated perfusate (PO2, 530 mmHg), moderately hypoxic perfusate (PO2, 91 mmHg) for 30 min, and then to oxygenated perfusate for 40 min. Halothane (1%, 0.4 mM) or isoflurane (1.5%, 0.5 mM) were administered 10 min before hypoxia, during hypoxia, and during the first 10 min of reoxygenation. Exposure to halothane and isoflurane before hypoxia produced a 14 and 11% decrease in heart rate, a 32 and 23% increase in AVCT, and a 47 and 28% decrease in LVSP (all P less than or equal to 0.001) for halothane and isoflurane, respectively, and no significant change in LVEDP. During hypoxia, HR decreased and AVCT increased similarly in both groups. Left ventricular systolic pressure (LVSP) decreased sharply with a narrowing of the prehypoxic differences among the groups. In the control and isoflurane groups, LVEDP increased during hypoxia but remained unchanged in the halothane group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of histamine, ethanol, and a detergent on exudation and absorption across guinea pig airway mucosa in vivo.

This study examined effects of three substances that cause mucosal provocation (histamine, ethanol, and the detergent dioctylsodium sulphosuccinate (DOSS] on the flux of solutes across airway vascular mucosal barriers in anaesthetised guinea pigs. The inward flux was assessed as absorption of iodine-131 labelled albumin (MW 69,000) from the tracheobronchial surface into the circulation and the outward flux as the exudation of two intravenously administered plasma tracers--125I albumin (MW 69,000) and fluorescein isothiocyanate conjugated (FITC) dextran (MW 70,000)--into the airway. The absorption of technetium-99m labelled DTPA (MW 492) from the tracheobronchial airways was determined in separate experiments. Histamine (5.0 nmol) dissolved in 40 microliters saline and superfused on the tracheobronchial mucosal surface caused significant and similar entry of 125I albumin and FITC dextran into the airway lumen. This dose of histamine did not, however, alter the absorption of small (99mTc DTPA) or large (131I albumin) solutes across the airway mucosa. Ethanol (0.17 mumol), superfused in the same way, also caused significant exudation of the plasma tracers into the airway lumen. In addition, ethanol increased the absorption of 131I albumin without causing change in the disappearance rate of 99mTc DTPA. The detergent, DOSS (0.28 nmol), dissolved in ethanol (0.17 mumol), caused a pronounced increase in exudation and much increased absorption of small and large tracer solutes. Thus three patterns of change in airway mucosal barriers were found. The agents that are toxic to membranes, ethanol and DOSS, caused a bidirectional increase in permeability across the mucosa, whereas histamine caused only an outward exudative flux. The results obtained with histamine are similar to those seen previously with bradykinin, capsaicin, and allergen, suggesting that endogenous inflammatory mediators have a role in mucosal defence, producing entry of plasma exudates into the airway lumen without increasing the mucosal absorption of luminal material.     

A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig

A new model for measuring gastric secretory parameters in awake guinea pigs is described. A chronic cannula was surgically implanted in the stomach of each guinea pig. The rates of gastric secretion and changes in intragastric volume were measured using a dye dilution technique. In contrast to previous techniques in small laboratory animals, there was no collection of gastric juice via drainage, no oral intubation for aspiration was involved, no special or sophisticated equipment was used, no anesthesia was employed, and there was no stress associated with acute surgery. This method offers a valuable advantage by combining the chronic gastric cannula with a dye dilution technique in that the same animal can be used several times and finally, several gastric secretory parameters can be measured simultaneously. The animals were used from 3 weeks to 10 months after surgery and as many as 15 studies were performed on the same guinea pig. Samples were collected at 10-min intervals and analyzed for acid and dye concentration from which the onset and kinetics of gastric secretion were followed. Basal gastric secretion (11.8 +/- 1.6 mueq/kg/min; all mean +/- 1 SEM) was increased within 20 min after subcutaneous infusion of histamine (30 micrograms/kg/hr) and peaked by 40-60 min at a mean acid output rate of 41 +/- 3 mueq/kg/min. Histamine also increased the intragastric volume from 6.3 to 13.4 ml as it increased fluid output from 1.6 +/- 0.1 ml/10 min to 3.4 +/- 0.2 ml/10 min. The increase in acid output caused by histamine was inhibited by the H2-antagonists cimetidine (3 mumole/kg) and ranitidine at 0.5 mumole/kg. Omeprazole (1.2 mumole/kg), an H-K-ATPase inhibitor, almost abolished acid output under both basal and histamine-stimulated conditions. Thus, the present method is simple and suitable to study the physiology and pharmacology of gastric secretion in the guinea pig with a particular emphasis on the action of histamine. Furthermore, because of the species involved, there is also a significant economical advantage and the guinea pig can also be used as a potential model for studying experimental ulcer.     

Experimental study of pegylated liposomal hemoglobin on norepinephrine release and reperfusion arrhythmias in isolated guinea pig hearts.

PURPOSE: Under myocardial reperfusion conditions, hemoglobin (Hb)-based artificial blood showed effectiveness for post-ischemic dysfunction. However, there are no studies about the effects of this product on reperfusion arrhythmias (ventricular fibrillation, VF) associated with norepinephrine (NE) release. This study was to evaluate the effects of the timing of the administration of pegylated liposomal Hb (LHb, P(50)=40-45 mmHg, 1 mg/mL) on NE release and VF. MATERIALS AND METHODS: Isolated guinea pig hearts (n=6 in each group) were randomly divided into four groups in Krebs-Henseleit solution being supplemented or not with LHb as follows: pre-ischemia (PRE), reperfusion (REP), or PRE+REP groups. The hearts were perfused for 30 min (preischemic period) and then subjected to 30 min of global ischemia, followed by 30 min of reperfusion with a normothermic Langendorff apparatus at 30 mm Hg aortic pressure in a constant pressure model. RESULTS: No differences were documented among the four groups in heart rate, left ventricular-developed pressure, or coronary flow rate. However, the REP group significantly decreased the duration of VF and NE release, but it did not inhibit the incidence of VF. CONCLUSION: These results suggest that the administration of LHb, especially with the timing of reperfusion, might prevent reperfusion arrhythmias linked to the inhibition of NE release.