OBJECTIVE: The basal activity of p38 MAPK has recently been shown to impair myocardial contractility. This kinase is activated by ischemia and short-term hibernation. We hypothesized that p38 MAPK activation may contribute to the contractile deficit that characterizes low-flow ischemia. METHODS: In Langendorff-perfused isolated C57BL/6 mouse hearts, perfusion pressure was ...

INTRODUCTION: The objective of this study was to determine whether the simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple-parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A) receptor antagonist (ET(A)-RA) or isotonic saline. ...

BACKGROUND: In order to test the hypothesis that cardiac protein degradation contributes to the pathogenesis of myocardial stunning, the effect of protease inhibitor leupeptin on the postischemic hemodynamics and metabolic functioning was measured in isolated rat hearts. MATERIAL/METHODS: Isolated rat hearts were perfused in Langendorff mode in the presence or ...

The aims of the present study were to investigate the effects of exogenous peroxynitrite (ONOO(-)) on reperfusion arrhythmias in anaesthetized rats, and to detect endogenous and exogenous ONOO(-)-induced chemiluminescence (CL) signals in rat whole blood, which was collected during baseline and in the first minute of reperfusion. ONOO(-) infusion in ...

This study investigated the differential effect of losartan, an AT1 receptor blocker, when administered in pre- and postischemic phases, on the biochemical, hemodynamic and oxidative stress associated with regional ischemic-reperfusion injury in cat. Losartan (5 microg/kg/min) or normal saline was administered intravenously in open chest barbiturate anesthetized cats, 15 min ...

OBJECTIVE: We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeability transition (MPT) pore opening. METHODS: In protocol 1, New Zealand White rabbits underwent either no intervention (sham group) or 10 min of ischemia followed by 5 min of reperfusion, preceded (PC) or not (C; control) by one episode of ...

It is well-known that ischemia causes disruption of the blood-brain barrier (BBB), which leads to the formation of vasogenic brain edema. One major mechanism of BBB opening is enhanced pinocytotic vesicle formation that may be induced after transient focal ischemia by several mechanisms, including nitric oxide production, release of neurotransmitters, ...

BACKGROUND AND PURPOSE: The present study was performed to determine whether antisense inhibition of intercellular adhesion molecule-1 (ICAM-1) protein expression decreases focal ischemic brain damage. METHODS: Male spontaneously hypertensive rats underwent 1-hour middle cerebral artery occlusion (MCAO) and 24-hour reperfusion. Rats were infused with ICAM-1 antisense or control oligodeoxynucleotides (ODNs) ...

BACKGROUND: Reperfusion injury is a vital problem in non-heart-beating donor (NHBD) organs. The sodium-hydrogen inhibitor cariporide is thought to improve cellular integrity after ischemia and reperfusion. Recently, we demonstrated the possibility of preserving hearts with in situ perfusion after circulatory death. The purpose of this study was to determine whether ...

Cardioprotective effect of a free radical-scavenging compound (HO-3073) was examined during ischaemia-reperfusion (IR) in isolated heart perfusion system and its influence on the pro-survival Akt signalling pathway was addressed. Rat hearts were perfused according to the Langendorff method and subjected to a global 25-min ischaemia and 15, 45 and 90-min ...

BACKGROUND: The effects of inhibition of the Na+/H+ exchanger (NHE) on postischemic recovery of the injured neonatal rabbit heart were examined. The NHE may be an important mechanism for reperfusion injury in the neonate heart. The effects of two NHE inhibitors, HOE 642 (HOE) and 5-(N,N-dimethyl)-amiloride (DMA), given during hypothermic ...

AIM: To determine overall cardiac effects of flavonoid catechin on ischemia-reperfusion injury in isolated rat hearts in vitro and in vivo. METHODS: After perfusing hearts at the pressure of 70 mm Hg, coronary perfusion was interrupted for 30 minutes and then re-established. There were four experimental groups, with 10 rats ...

The effects of the novel calpain inhibitor A-705239 were studied in isolated perfused rabbit hearts subjected to 45 min of global ischemia, followed by 60 min of reperfusion. During 15 min of perfusion the inhibitor accumulated in myocardial tissue up to 16 times the concentration in the perfusate. Almost complete ...

Using a Langendorff-perfused rat heart preparation and selective electrodes, we determined nitric oxide (NO) and oxygen levels in cardiac tissue. An NO-selective electrode that was calibrated by electron spin resonance (ESR) spectroscopy was inserted into the middle of the myocardium in the left ventricle. Simultaneously, we used an O2-selective electrode ...

1. The aims of the present study were to examine the response of the murine heart to ischaemia and reperfusion and to determine whether these responses are influenced by the strain of mouse. 2. Isolated, paced (600 b.p.m.) murine (T/O mice) hearts were perfused aerobically (2.6 mL/min) with buffer for ...

OBJECTIVES: Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood cardioplegic solution containing the natural erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or 7.2 (nonbuffered), and this was tested alone and after pretreatment with Na(+)-H(+) exchange blockade (cariporide) to define ...

PURPOSE: Volatile anesthetics can protect the heart against reperfusion injury. When sevoflurane is given for the first 15 min of reperfusion, a concentration corresponding to one minimum alveolar concentration (MAC) provides a maximum protective effect. The present study addresses the question of how long sevoflurane has to be administered to ...

Left ventricle (LV) hypertrophy is associated with an increased risk of sudden death, which may be due in part to a greater vulnerability to severe ventricular arrhythmias. Our objectives were to determine (i) whether pressure overload-induced LV hypertrophy increases susceptibility to ischemia- and/or reperfusion-induced ventricular fibrillation (VF), and (ii) whether ...

BACKGROUND: Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals. METHODS: Hearts ...

Human high-density lipoproteins (HDLs) protect the heart against ischemia/reperfusion injury. In the present study, the cardioprotective effects of synthetic high-density lipoproteins (sHDLs) made of phosphatidylcholine and apolipoprotein A-I were investigated in isolated rat hearts, which underwent a 20-min low-flow ischemia followed by a 30-min reperfusion. The administration of sHDL during ...

The mechanisms of recovery of the isolated rat heart were studied after 30 min of global ischemia. Functional recovery was assessed by the percentage recovery of developed pressure after 30 min reperfusion and by the magnitude of the contracture on reperfusion. After a control ischemia, developed pressure recovered to only ...

BACKGROUND: This study determines whether controlled reperfusion or diazoxide improves intramyocyte Na(+) homeostasis using a porcine model of severe ischemia-reperfusion injury. METHODS: Three groups (n = 10 pigs per group) had 75 minutes of left anterior descending artery occlusion during bypass. Group 1 had no treatment (control group), group 2 ...

OBJECTIVES: To assess the physiologic and biochemical changes resulting from ischemia and reperfusion. Effective therapy for ischemic priapism reestablishes corporal venous outflow and arterial inflow and results in increased corporal partial pressure of oxygen. Data are limited concerning reperfusion injury of ischemic erectile tissue associated with reactive oxygen species (ROS) ...

Pharmacological studies indicate that Na+-H+ exchanger isoform 1 (NHE1) plays a central role in myocardial ischemia-reperfusion injury; however, confirmation by alternative methods is lacking. To address this issue, we examined the role of NHE1 in ischemia-reperfusion injury using gene-targeted NHE1-null mutant (Nhe1-/-) mice. Nhe1-/- and wild-type hearts were perfused in ...

Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS), which ischaemia/reperfusion (I/R) injury plays an important role. The main goal of the management of ACS is to lower the intra-abdominal pressure despite reperfusion injury. Octreotide (OCT), a synthetic somatostatin analogue, lowers the splanchnic perfusion. The aim of ...

The present study investigated the response of the hypothyroid heart to ischaemia-reperfusion. Hypothyroidism was induced in Wistar rats by oral administration of propylthiouracil (0.05%) for 3 weeks (HYPO rats), while normal animals (NORM) served as controls. Isolated hearts from NORM and HYPO animals were perfused in Langendorff mode and subjected ...

The results in this study confirm and expand previous reports that ischemia-modified albumin (IMA) is an early marker of ischemia in the setting of percutaneous coronary intervention (PCI). We observed that IMA levels are related to the number of inflations, inflation pressure, and duration of inflations. It is therefore likely ...

OBJECTIVE: The circulatory shock following intestinal ischemia-reperfusion injury has been attributed to hypovolemia. The purpose of the current study is to clarify the pathophysiology of this type of shock and to test the hypothesis that hypoxemic compared with normoxemic reperfusion improves hemodynamics. DESIGN: Randomized animal study. SETTING: Medical school laboratory. ...

Cariporide (HOE 642) inhibits the Na+/H+ exchanger and would be expected to reduce lactate accumulation during ischaemia and stimulate lactate/H+ co-transporter upon reperfusion. The aim of this study was to determine the effect of cariporide on lactate production during global ischaemia and release during reperfusion. Guinea-pig hearts perfused in the ...

This study investigated the impact of testosterone on myocardial ischemia-reperfusion injury and corresponding intracellular calcium ([Ca2+]i) metabolism. Nonorchiectomized mature male Wistar rats were randomly assigned to placebo, a single dose of testosterone undecanoate, or 5alpha-dihydrotestosterone. In a further series, orchiectomized rats were treated with placebo. After 2 wk of treatment, ...

AIMS: The present study investigated if the inotropic effect of angiotensin II (AngII) is altered during post-ischaemic reperfusion in hearts subjected to mild and severe ischaemia. The possible involvement of protein kinase C (PKC) in the change in the inotropic effect was also investigated. METHODS: Isolated Langendorff-perfused rat hearts were ...

OBJECTIVE: To examine the mitochondrial function in the myocardium after hemorrhagic shock and reperfusion and to evaluate the protective effect of urinary trypsin inhibitor (UTI) on mitochondria. DESIGN: Animal experiment. SETTING: University research laboratory. SUBJECTS: Wistar rats receiving 50,000 units/kg/hr of UTI (n = 27; UTI group) and control rats ...

OBJECTIVE: Experimental study has shown that myocardial ischemic tolerance is reduced during middle-age. We investigated the effect of propofol on ischemic tolerance of middle-aged rat hearts. METHODS: Hearts of young adult (10 weeks old, Y) and middle-aged rats (20 weeks old, M) were assigned to propofol (P-Y, P-M) and control ...

Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular integrity and development. The purpose of the study was to test the hypothesis that Ang1 will promote angiogenic response to VEGF in the spontaneous Watanabe heritable hypercholesterolemic (WHHL) rabbit model of acute hindlimb ischemia. Immediately after the ligation ...

Ischemia-reperfusion generates peroxynitrite (ONOO-), which interacts with many of the systems altered by ischemia-reperfusion. This study examines the influence of endogenously produced ONOO- on cardiac metabolism and function. Nitro-L-arginine (an inhibitor of ONOO- biosynthesis) and urate (a scavenger of ONOO-) were utilized to investigate potential pathophysiological roles for ONOO- in ...

OBJECTIVE: Our study was undertaken to clarify the impact of the shear stress-induced reactive hyperemia (associated with reperfusion) in preconditioning-mediated protection. METHODS: In control rat hearts, a 40-minute preischemic perfusion (constant pressure: 70 mm Hg) period was followed by 25-minute global low-flow ischemia (constant flow: 0.3 mL/min) and 30-minute reperfusion ...

Male and female Hartley strain guinea pigs weighing 280 +/- 10 g were given acetaminophen-treated water ad libitum for 10 days. Sham-treated control animals were given similar quantities of untreated tap water (vehicle-treated control group). On Day 10, hearts were extracted, instrumented, and exposed to an ischemia (low-flow, 20 min)/reperfusion ...

To determine the functional role of growth hormone (GH) secretagogue in myocardium with ischemia, left ventricular (LV) pressure gauge, wall thickness crystals, coronary occluder, pacers, and catheters were implanted in 26 dogs. Beginning 1 week after ventricular pacing (240 beats/min) was initiated, dogs were treated (s.c.) with GH releasing peptide-6 ...

OBJECTIVE: The ATP-sensitive potassium channel (K(ATP)) activator nicorandil used as cardioplegic agent may protect the left ventricle during cardiac arrest. Nicorandil in cold blood was compared with standard hyperkalemic blood and crystalloid cardioplegia. METHODS: Twenty-one pigs were randomly assigned to three groups: (1) cold hyperkalemic crystalloid (n=7); (2) cold hyperkalemic ...

Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of the properties of inducible HO (HO-1) and its products, we hypothesized that HO-1 ...

BACKGROUND: The laparoscopic use of fluorescein and ultraviolet light may be a useful diagnostic tool that potentially could reduce the time until diagnosis and the subsequent mortality of mesenteric ischemia. METHODS: Eight pigs were subjected to a pneumoperitoneum pressure of 7 mmHg, and another eight pigs were exposed to a ...

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to upregulate endothelial nitric oxide synthase in isolated endothelial cells in a manner that is independent of their lipid-lowering effects. Nitric oxide inhibits polymorphonuclear leukocyte (PMN) adherence and attenuates cardiac dysfunction caused by PMNs after ischemia/reperfusion. Therefore, the authors hypothesized ...

AIM: Ischaemic preconditioning (IPC) has been demonstrated to protect heart function and viability, but has been predominantly studied in male animals. METHODS: We studied a possible influence of sex and oestrogen for protection in IPC. Infarct size and heart function after 40 min global ischaemia and 60 min reperfusion with ...

BACKGROUND: Inhibition of the Na+/H+ exchanger before ischemia protects against ischemia-reperfusion injury, but use as pretreatment before blood cardioplegic protection or as a supplement to controlled blood cardioplegic reperfusion was not previously tested in jeopardized hearts. METHODS: Control studies tested the safety of glutamate-aspartate-enriched blood cardioplegic solution in 4 Yorkshire-Duroc ...

Using both 31P and 1H cardiac magnetic resonance techniques, it is possible to monitor the functional (ejection fraction [EF]) and biochemical (pH) status of the heart following a reperfused ischemic insult. This study assessed the effects of Na+/H+ exchange inhibition with cariporide in a closed-chest canine ischemia/reperfusion model. Dogs received ...

BACKGROUND: Preconditioning and inhibition of sodium-proton exchange attenuate myocardial ischemia-reperfusion injury by means of independent mechanisms that might act additively when used together. The hypothesis of this study is that treatment with a sodium-proton exchange inhibitor and a mitochondrial adenosine triphosphate-sensitive potassium channel opener produces superior functional recovery and a ...

The purpose of this study was to use a microdialysis technique to demonstrate the metabolic changes that occur in the intestinal wall during ischemia in vivo. Continuous monitoring of glucose, lactate, and glycerol using a microdialysis technique was performed in the jejunal wall of 10 pigs during steady-state and occlusive ...

OBJECTIVE: We sought to investigate whether the addition of ethanol to a preservation solution (as an antifreeze agent) might allow a reduction of the storage temperature to 0 degrees C without causing freezing damage and improve lung function after prolonged (72 hours) ischemia. METHODS: Lungs from Sprague-Dawley rats were ventilated ...

BACKGROUND: Microelectrode technology is a promising tool for monitoring kidney ischemia and the changes induced by its therapeutic management. Ischemic preconditioning, that is, brief ischemic periods before sustained ischemia, has been shown to protect several organs, including the kidney, from ischemia-reperfusion injury. We tested whether the effect of preconditioning could ...

BACKGROUND: Pulmonary edema caused by increased microvascular permeability is an important feature of lung ischemia-reperfusion (I/R) injury. METHODS: We investigated the impact of co-aerosolized prostaglandin (PG)I(2) and the 3',5-cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase inhibitor rolipram on microvascular leakage following I/R injury. Buffer-perfused rabbit lungs were exposed to 270 minutes of ...