Thrombus fragments are globular and likely to completely obstruct

Thrombus fragments are globular and likely to completely obstruct terminal vessels. In contrast, previous work with “”atheroemboli”" of needle-like cholesterol crystals rarely cause occlusions or infarctions instead creating small foci of inflammation. In this work, we asked if microthrombi would occlude terminal vessels land create lacunar type infarctions in the PSI-7977 order subcortical tissues of the rat brain where, as in human brain, collateral flow is limited relative to the cortex.

Methods:

Three treatment groups of adult male Sprague-Dawley rats were studied. All groups underwent general anesthesia with monitoring of temperature and blood pressure during cannulation of the right internal carotid artery. In the group embolized with thrombus fragments (n = 12), animals had injections of 300 fragments of thrombus size 60 to 100 microns, the cholesterol group (n = 6) had injections of 300 cholesterol crystals of similar size, and the control group (n = 4) had injections of saline. Brains were harvested at 4 days with perfusion fixation and were examined by immunohistochemical staining for breaks in the blood brain barrier (BBB) (albumin), microglial activation (CD11b), astrocyte activation (GFAP), and infarction (loss of NeuN staining). Size and location of the

areas Selleck AZD1080 of injury and infarction were recorded.

Results. Clot fragments caused discreet infarcts in 10/12 animals that were 0.1-1.7 mm in diameter and coincided with activation of microglia and astrocytes.

In some areas, necrosis was already underway at this selleck chemicals early time point. Consistent with our previous work, the infarcts caused by cholesterol crystals were smaller (P = .014). Foci of BBB disruption and microglial activation were distributed throughout the brain whereas areas of infarction were found almost exclusively in subcortical tissues (P = .029).

Conclusions. Injecting microthrombi reproducibly caused areas of necrosis resembling lacunar type infarctions. These were primarily located in the striatum and thalamus presumably because these areas lack the branching, collateral network seen in the cortex. In addition, these data give further evidence that the extent of brain injury from emboli depends upon composition and shape as well as size.”
“Two hypotheses concerning cerebellar function and predictive behavior are the sensory prediction hypothesis and the timing hypothesis. The former postulates that the cerebellum is critical in generating expectancies regarding forthcoming sensory information. The latter postulates that this structure is critical in generating expectancies that are precisely timed; for example, the expected duration of an event or the time between events. As such, the timing hypothesis constitutes a more specific form of prediction. The present experiment contrasted these two hypotheses by examining the mismatch negativity (MMN) response in patients with cerebellar cortical atrophy and matched controls.


“Background To investigate the association between nicoti


“Background. To investigate the association between nicotine dependence (ND), by cigarette smoking and use of smokeless tobacco (UST), and mental disorders.

Method. Face-to-face surveys (n = 43 093) were conducted in the 2001-2002 National CP-690550 price Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Nicotine use, ND, and mental

disorders were assessed using DSM-IV criteria.

Results. UST-ND was associated with a significantly increased likelihood of any anxiety disorder, specific phobia, alcohol abuse and dependence. Consistent with previous findings, cigarette smoking-ND was associated with an increased likelihood of all mental disorders examined. Among those without ND, cigarette smoking was specifically associated with panic attacks and panic disorder; non-dependent

UST was not associated with mental disorders.

Conclusions. Our findings suggest that the association between ND and mental disorders is relatively specific to the mode of nicotine administration. Among those who are nicotine dependent, cigarette use is associated with most major psychiatric disorders, whereas UST is associated with dysthymia and specific phobia. Among those who use tobacco but are not nicotine dependent, cigarette use is associated with Palbociclib clinical trial dysthymia and panic disorder; UST is not associated with any major mood or anxiety disorders. The link between mental disorders and nicotine is complex, and is associated primarily with dependence, and not with non-dependent use.”
“Objective: Experimental and clinical studies www.selleck.cn/products/tubastatin-a.html have suggested that intramyocardial bone marrow stem cell

transplantation combined with coronary artery bypass grafting might improve left ventricular function in the setting of chronic ischemic heart disease. We therefore conducted a systematic review and meta-analysis of available publications regarding the efficacy and safety of intramyocardial bone marrow stem cell transplantation during coronary artery bypass grafting.

Methods: The databases PUBMED, MEDLINE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (all from their inception to May 2009) were searched for randomized controlled trials and cohort studies of intramyocardial bone marrow stem cell transplantation during coronary artery bypass grafting to treat ischemic heart disease. Six studies were included.

Results: Compared with control groups, the bone marrow stem cell transplantation group showed a significant improvement of left ventricular ejection fraction from baseline to follow-up (5.40%; 95% confidence interval, 1.36-9.44; P = .009). Moreover, the overall change of left ventricular end-diastolic volume from baseline to follow-up favored the bone marrow stem cell therapy group (9.55 mL; 95% confidence interval, -2.82 to 21.92; P = .13).

Fourteen healthy comparison subjects did not take any psychotropi

Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance Vorasidenib mouse images revealed lithium-induced increases in gray matter volume, which peaked at week 10-12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with BD or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained

increases in cerebral gray matter volume in patients with BD and that these changes are related to the therapeutic efficacy of lithium. Neuropsychopharmacology (2010) 35, 1743-1750; doi:10.1038/npp.2010.41; published online 31 March

2010″
“Objective: Our objective was to evaluate long-term stability of mitral repair and reverse remodeling in patients with severe ischemic left ventricular dysfunction and functional find more mitral regurgitation.

Methods: Since June 2000, a total of 37 patients with ischemic functional mitral regurgitation have benefited from a double-level mitral repair that comprises an intraventricular peripapillary muscle sling completed by a classic intra-atrial mitral annuloplasty ring (mean age, 56 years; left ventricular end-diastolic diameter, 70 +/- 0 mm; left ventricular end-systolic diameter, 55 +/- 5.6 mm; ejection selleck inhibitor fraction, 15% to 45%; pulmonary hypertension > 60 in all patients; all were in New York Heart Association class III-IV). All patients had

both papillary muscles encircled with a 4-mm polytetrafluoroethylene tube, correcting their lateral and downward displacement. Annuloplasty rings were moderately undersized or normal. Efficiency was evaluated on mitral stability, ventricular parameters, and functional status. According to the Leyden algorithm based on preoperative end-diastolic and end-systolic left ventricular diameters, only a minority of our patients were expected to experience reverse remodeling.

Results: Regurgitation is none to trivial in 31 and mild to moderate in 4. Follow-up (3-84 months; mean, 55 +/- 22 months) shows stability of all initially successful double-level mitral repairs. Follow-up beyond 1 year shows improvements in ventricular diameters (56 +/- 5 mm), ejection fraction (49 +/- 6), volume (130 +/- 10 mL), and sphericity index (0.55). Two patients died during follow-up and 1 underwent transplantation.

Conclusion: Reapproximating the papillary muscles has an immediate effect on mitral leaflet mobility by suppressing the tethering resulting from displacement of the papillary muscles. It has an effect in preventing recurrent mitral regurgitation by avoiding further papillary muscle displacement. In this cohort of severely disabled patients, reverse remodeling can be expected with the double-level repair.

The results were compared by analyzing markers related to various

The results were compared by analyzing markers related to various end points such as oxidative stress, AG-120 molecular weight dopamine (DA) metabolism, proteasome function,

survival and apoptosis. The experimental system and anti-oligomerization strategies were recapitulated in vitro in M17 dopaminergic cells overexpressing mutant alpha S-A53T triggered with Cu(II)-mediated oxidative stress, and the experimental data prospectively corroborated with the predictive results. Through this analysis, we found that intervention in the early part of the aggregation pathway by prevention of oligomer formation and increased clearance is indeed a good neuroprotective strategy, whereas anti-aggregation efforts to break up the aggregate at later stages has negative effects on the system. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“In patients with active cancer, the management of chronic pain is an essential element in a comprehensive strategy for palliative care. This

strategy emphasises multidimensional assessment and the coordinated use of treatments that together mitigate suffering and provide support to the patient and family. Mdm2 antagonist This review describes this framework, an approach to pain assessment, and widely accepted techniques to optimise the safety and effectiveness of opioid drugs and other treatments. The advances of recent decades suggest a future that includes increased evidence-based targeting of specific analgesic interventions within an individualised plan of care learn more that is appropriate

throughout the course of illness.”
“Butyrate is a critical cancer-preventive element in the colon milieu whose mechanism of action is unclear, but appears to be mediated through inhibition of histone deacetylases (HDACs) and consequent alterations in global protein acetylation. Cytokeratins (CKs) have roles in cytoskeletal function as components of the intermediate filaments (IFs) and this involves CKs in the regulation of tissue homeostasis of high-turnover epithelia such as the colon. We used a 2-D gel/MS analysis to characterise the proteome of IFs, and a novel monitoring-initiated detection and sequencing (MIDAS) approach to identify acetylation sites on principal proteins. We report that CKs are highly acetylated in a colon cancer cell line, with five acetylation sites characterised on CK8 and a further one on CK18. Acetylation of CK8 is responsive to butyrate. HDAC5 is the deacetylase associated with IFs. These data indicate a novel action of butyrate as a cancer preventive agent. Acetylation of CK8 may be associated with IFs stabilisation and thereby provide a candidate mechanism for the appropriate retention or loss of epithelial cells from the flat mucosa.

The current findings suggest that ER stress pathway plays a role

The current findings suggest that ER stress pathway plays a role in the homeostatic control

of NREM sleep in response to sleep deprivation and provides a mechanistic explanation LY294002 in vivo for the sleep modulation by molecules signaling the need for brain protein synthesis. Published by Elsevier Ltd on behalf of IBRO.”
“Viruses encode RNA silencing suppressors to counteract host antiviral silencing. In this study, we analyzed the suppressors encoded by potato virus M (PVM), a member of the genus Carlavirus. In the conventional green fluorescent protein transient coexpression assay, the cysteine-rich protein (CRP) of PVM inhibited both local and systemic silencing, whereas the triple gene block protein 1 (TGBp1) showed suppressor activity only on systemic silencing. Furthermore, to elucidate the roles of these two suppressors during an active viral infection, we performed PVX vector-based assays and viral movement complementation assays. CRP increased the accumulation of viral RNA at the AZ 628 chemical structure single-cell level and also enhanced viral cell-to-cell movement by inhibiting RNA silencing. However, TGBp1 facilitated viral movement but did not affect viral accumulation in proto-plasts. These data suggest that CRP inhibits RNA silencing primarily

at the viral replication step, whereas TGBp1 is a suppressor that acts at the viral movement step. Thus, our findings demonstrate a sophisticated viral infection strategy that suppresses host antiviral silencing at two different steps via two mechanistically distinct suppressors. AZD2014 This study is also the first report of the RNA silencing suppressor

in the genus Carlavirus.”
“In mammals, new neurons are recruited into restricted brain areas throughout life. Adult-born neurons produced in the subventricular zone of the lateral ventricle migrate rostrally towards the olfactory bulb. Although thousands of neurons reach this central structure every day, the functional impact of their integration into mature circuits remains a matter of debate. Recent investigations have revealed no striking sensory deficits per se when adult bulbar neurogenesis is challenged. However, some cognitive functions, such as perceptual learning and olfactory memory, are clearly impaired. In this review we highlight the role of network activity in shaping ongoing neurogenesis and, in turn, how the integration of adult-born neurons refines pre-existing network function, and consequently olfactory behavior.”
“Several studies have indicated that cytokines may be involved in the pathophysiology of schizophrenia. Previous studies, however, have yielded contradictory results; in this study we assess the plasma levels of both T-helper-1 (Th 1) and T-helper-2 (Th2) cytokines in patients with acute exacerbations of schizophrenia.


“The synthesis and release of dynorphin are increased in t


“The synthesis and release of dynorphin are increased in the caudate/putamen (CPU) and nucleus accumbens (NAc) of nicotine-withdrawn P5091 research buy mice, suggesting a role in the nicotine abstinence syndrome.

This study aims to investigate the consequences of enhanced dynorphinergic activity on kappa-opioid receptor (KOPr) expression, coupling, and function in CPU and NAc following

chronic nicotine administration and withdrawal.

Mice were injected with nicotine-free base 2 mg/kg, or saline, sc, four times daily for 14 days and experiments performed at 24, 48, and 72 h after drug discontinuation. KOPr binding and mRNA were evaluated by [(3)H]-U69,593 autoradiography and in situ hybridization. KOPr coupling and function were investigated by agonist (U69-593)-stimulated [(35)S]GTP gamma S binding autoradiography and inhibition of adenylyl cyclase activity.

KOPr binding density and mRNA in CPU and NAc were unaltered during nicotine withdrawal; however, KPOr mRNA was increased in midbrain. U69,593-stimulated [(35)S]GTP gamma S binding was attenuated in both striatal regions, especially in NAc. In NAc shell and core, stimulated [(35)S]GTP gamma S binding was significantly decreased by 24 h and further declined over the 72 h observation period. In CPU, significant changes were observed only at 72 h. Basal adenylyl cyclase activity

decreased early during nicotine withdrawal and recovered by 48 h. Stimulation with U69,593 failed to inhibit adenylyl cyclase activity at Selleck SB431542 all times studied.

These observations suggest that KOPr coupling and function are impaired in NAc and CPU during nicotine withdrawal, and imply receptor desensitization. KOPr desensitization might be a mechanism to ameliorate aversive behavioral symptoms, as nicotine withdrawal evolves.”
“We examined the effect of perinatal hypothyroidism on auditory function in rats using a prepulse inhibition paradigm. Pregnant rats were treated with the antithyroid drug methimazole (1-methyl-2-mercaptoimidazole) from gestational day 15 to postnatal day 21 via drinking water at concentrations (w/v) of 0 (control),

0.002 (low dose), or 0.02% (high dose). Rats from methimazole-treated mothers were tested at ages 1, 6, and 12 months using techniques to examine prepulse inhibition and startle response. The startle stimulus consisted of 40 ms of white noise at 115 dB, whereas the prepulse, Bcl-w which preceded the startle stimulus by 30 ms, consisted of 20 ms of white noise at 75, 85, or 95 dB. When the prepulse intensity was 75 or 85 dB, the high-dose group showed decreased prepulse inhibition percentages compared with the control and low-dose groups. The reduced percentages of prepulse inhibition did not return to control levels over the 12-month study period. In contrast, no differences in prepulse inhibition were observed among the three dose groups when prepulse intensity was 95 dB. Moreover, the high-dose group displayed excessive reaction to auditory startle stimuli compared with the other groups.


“Background/Aim: To test the short-term clinical usefulnes


“Background/Aim: To test the short-term clinical usefulness of venesection associated with lifestyle counselling as against counselling alone on insulin resistance and liver GSK461364 enzymes in subjects with non-alcoholic fatty liver disease (NAFLD), using a propensity score approach.

Methods: We carried out a 6- to 8-month observational analysis of 198 NAFLD patients in

three Italian referral centres (79 venesection and 119 counselling alone). Insulin resistance was measured by the homeostasis model assessment (HOMA) method. Logistic regression was used to identify factors associated with normal HOMA and normal alanine aminotransferase (ALT) at the end of observation. The results were adjusted for the propensity score to be enrolled in the venesection programme, based on clinical and laboratory data, including common HFE polymorphisms and liver biopsy (available in 161 cases).

Results: After adjustment for propensity and changes in BMI,

venesection was significantly associated with normal HOMA PLX-4720 mw [all cases: odds ratio (OR) 3.00; 95% confidence interval (CI) 1.51-5.97; cases with histology: OR 2.29; 95% CI 1.08-4.87] and ALT within normal limits (all cases: OR 2.56; 95% CI 1.29-5.10; cases with histology: OR 2.81; 95% CI 1.20-5.24). The results were confirmed in an analysis of 57 pairs matched for propensity, where venesection similarly increased the probability of normal HOMA IWR-1 nmr (OR 3.27; 95% CI 1.16-7.84) and normal ALT (OR 5.60; 95% CI 2.09-15.00). Similar data were obtained in the subset of cases with normal basal ferritin (<350 ng/ml).

Conclusion: Iron depletion by venesection favours the normalization of insulin resistance and raised liver enzymes in non-haemochromatosis patients with NAFLD.”
“Neuroendocrine secretion often requires prolonged voltage-gated Ca2+ entry; however, the ability of Ca2+ from intracellular stores, such as endoplasmic

reticulum or mitochondria, to elicit secretion is less clear. We examined this using the bag cell neurons, which trigger ovulation in Aplysia by releasing egg-laying hormone (ELH) peptide. Secretion from cultured bag cell neurons was observed as an increase in plasma membrane capacitance following Ca2+ influx evoked by a 5-Hz, 1-min train of depolarizing steps under voltage-clamp. The response was similar for step durations of >= 50 ms, but fell off sharply with shorter stimuli. The capacitance change was attenuated by replacing external Ca2+ with Ba2+, blocking Ca2+ channels, buffering intracellular Ca2+ with EGTA, disrupting synaptic protein recycling, or genetic knock-down of ELH. Regarding intracellular stores, liberating mitochondrial Ca2+ with the protonophore, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), brought about an EGTA-sensitive elevation of capacitance.

At >= 2 years after intervention, aneurysm diameter was reduce

At >= 2 years after intervention, aneurysm diameter was reduced in 62% of patients, 33% had no change, and 5% had a diameter enlargement. The stent graft complication rate during follow-up was 8.4%, the device fracture rate was 1.4%, and the device migration rate was 7%. The 5-year survival rate was 62.4%, with follow-up in 96.8% of the patients.

Conclusion: Endovascular repair has promising results in the descending

thoracic aortic region, although some stent grafts and their delivery systems can PF-02341066 price still be improved. Additional commercial developments and available stent grafts designed for use in the distal arch are urgently needed. (J Vasc Surg 2008;48:24S-29S.)”
“OBJECTIVE: Trigeminal schwannomas (TS) are benign tumors that are managed by surgical resection and/or stereotactic radiosurgery. Most radiosurgical series report results using the gamma knife. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is a frameless, robotic

stereotactic radiosurgical system. In this series, we report our experience using the CyberKnife in the treatment of TS.

METHODS: We retrospectively reviewed the medical records and diagnostic imaging in 13 consecutive patients with TS who were treated with the CyberKnife from 2003 to 2007. Seven patients had a previous surgical resection. The mean tumor volume was 6.3 mL (range, 0.39-19.98 mQ, and the mean marginal dose was 18.5 Gy. Six of the tumors were treated in a single session. The mean clinical follow-up period was 21.8 months (range, 7-53 months).

RESULTS: In this series, the tumor control rate was

100%. The average reduction in tumor volume was 45% (range, Selleck JQ-EZ-05 14-98%). A modest improvement in facial pain was noted in 4 of the 6 patients who presented with this symptom. One patient had improvement in facial numbness, and another had improvement in pretreatment headaches. CRM1 inhibitor One patient developed jaw weakness and facial dysesthesia, and another patient developed asymptomatic radiation necrosis.

CONCLUSION: Although the length of follow-up is limited, we report our initial experience with CyberKnife treatment of TS. Our results demonstrate tumor control rates and clinical outcomes that parallel those of previous reports using gamma knife radiosurgery; however, long-term follow-up studies are needed.”
“Objective: This study reports the initial clinical results and experience with the planning of branched stent grafts in high-risk patients with thoracoabdominal aortic aneurysms (TAAAs).

Methods: High-risk patients with TAAAs were considered for this study. Based oil evaluation with computed tomography angiography (CTA), 21 custom-made branched stent grafts were designed for the selected patients. Two patients had associated bilateral aneurysms of the common iliac arteries, so an iliac branched device was also used.

Results. Between August 2006 and April 2008, 23 patients (10 women, 13 men) were selected to undergo endovascular TAAA repair. Mean age was 72 years old.

7%) Preoperative chest tube drainage was performed in 36 patient

7%). Preoperative chest tube drainage was performed in 36 patients (35.6%), and thoracoscopy was used as the primary treatment in the remaining 65 patients. Complications occurred in 10 patients (9.9%); there were no mortalities. The median postoperative hospital stay was 13 days. Multivariate analyses showed that necrotizing pneumonia was significantly associated with the presence of complications, and that necrotizing TPCA-1 pneumonia, preoperative intensive care unit admission, and preoperative chest tube drainage were independent risk factors for a longer postoperative hospital stay.

Conclusion: The clinical presentations of empyema in children requiring thoracoscopy are diverse. Patients with necrotizing pneumonia and those requiring

preoperative intensive care unit admission and undergoing preoperative chest tube drainage are at high risk for developing complications and requiring longer hospital stay after thoracoscopy.”
“In an attempt to elucidate the involvement of cyclooxygenase

(COX) enzymes, particularly COX-1, in epileptogenesis, the localization of COX-1 and COX-2 expression in the mouse kindling model was analyzed by immunohistochemistry. COX-2 was predominantly observed in brain neurons and its concentration in the hippocampus increased with progressing seizures, as Torin 1 concentration reported previously. COX-1 was predominant in microglia and its concentration was also enhanced in the hippocampus and areas around the third ventricle during the progression of seizures. These regions are thought to play an important role in the propagation of limbic seizures. Moreover,the administration of SC-560 (a selective COX-1 inhibitor) or indomethacin (a non-selective COX inhibitor) retarded the progress of seizures. Although the precise function of COX-positive cells in microglia and elsewhere tuclazepam is not clear, our results suggest that COX-1 as well as COX-2 may be involved in epileptogenesis, and that certain COX inhibitors can potentially prevent the occurrence of seizures. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Objective: The impact of segmentectomy for preservation of pulmonary function was quantified by using a co-registered perfusion single-photon-emission

computed tomography and multidetector computed tomography (SPECT/CT).

Methods: Pulmonary function tests and perfusion SPECT/CT were conducted before and after segmentectomy in 56 patients. Actual values of forced expiratory volume in 1 second (FEV(1)) after segmentectomy were compared with the FEV(1) after virtual lobectomy, which was calculated by SPECT/CT. The preoperative and postoperative FEV(1) of each lobe that had undergone segmentectomy was measured by SPECT/CT.

Results: The mean percent of FEV(1) preserved after segmentectomy was significantly higher than the value after virtual lobectomy (88% +/- 9% vs 77% +/- 7%; P < .001). Whereas the mean value of the preoperative FEV(1) of each lobe that was undergoing segmentectomy was 0.51 +/- 0.

Dissociation

Dissociation Idasanutlin purchase has also been related to other types of psychopathology. Few studies have been published on these connections among adolescents. We examined the association between Adolescent Dissociative Experiences Scale (A-DES) scores and those for the Toronto Alexithymia Scale (TAS), the 21-item Beck Depression Inventory (BDI-21) and the Youth Self-Report (YSR), as well as subscales of the TAS and the YSR, in a sample of Finnish adolescents aged 13 to 18 years (n = 4019). Factor analysis suggested that dissociation can be considered distinctive from other psychopathology. A-DES scores, however, associated strongly with

several other scales and subscales measuring psychiatric symptoms. In logistic regression models the strongest associations were observable between the A-DES and TAS subscale ‘difficulty identifying feelings’ (DIF) and the YSR subscale ‘thought problems’. Thus, dissociation and alexithymia can be considered distinctive but overlapping phenomena. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Objective:

The inhibition of adenosine deaminase with erythro-9 (2-hydroxy-3-nonyl)-adenine (EHNA) and the es-ENT1 transporter with p-nitro-benzylthioinosine (NBMPR), entraps myocardial intracellular adenosine during on-pump warm aortic crossclamping, leading to a complete Selleck ZD1839 recovery of cardiac function and adenosine triphosphate (ATP) during reperfusion. The differential role of entrapped intracellular and circulating adenosine in EHNA/NBMPR-mediated protection is unknown. Selective (8-cyclopentyl-1,3-dipropyl-xanthine) Linsitinib mouse or nonselective left perpendicular8-(p-sulfophenyl)theophylineright perpendicular A1 receptor antagonists were used to block adenosine A1-receptor contribution in EHNA/NBMPR-mediated cardiac recovery.

Methods: Anesthetized dogs (n = 45), instrumented to measure heart performance using sonomicrometry, were subjected to 30 minutes of warm aortic crossclamping and 60 minutes of reperfusion. Three boluses of the vehicle (series A) or 100 mu M EHNA and 25 mu M NBMPR (series B) were infused into the pump at baseline, before ischemia and before reperfusion. 8-Cyclopentyl-1,3-dipropyl-xanthine

(10 mu M) or 8-(p-sulfophenyl) theophyline (100 mu M) was intra-aortically infused immediately after aortic crossclamping distal to the clamp in series A and series B. The ATP pool and nicotinamide adenine dinucleotide was determined using high-performance liquid chromatography.

Results: Ischemia depleted ATP in all groups by 50%. The adenosine/inosine ratios were more than 10-fold greater in series B than in series A (P < .001). ATP and function recovered in the EHNA/NBMPR-treated group (P < .05 vs control group). 8-Cyclopentyl-1,3-dipropyl-xanthine and 8-(p-sulfophenyl) theophyline partially reduced cardiac function in series A and B to the same degree but did not abolish the EHNA/NBMPR-mediated protection in series B.