Nonischemic Areas Research Articles

Abstract 235: Ischemia-Reperfusion Injury Decreases Myocardial Hydration Potential Without Changing Flow Resistance in the Interstitial Matrix

Interstitial edema is an early response to myocardial ischemia, leading to fibrosis and remodeling in several heart failure conditions. We aimed to clarify whether osmotic, frictional, or mechanical forces drive fluid accumulation. Equilibrium and dynamic interstitial hydration parameters were determined, compared, and analyzed using osmotic stress approaches in explants from ischemic and nonischemic myocardial regions of pig heart. They were isolated after injury induced by ligating 3-4 branches of the left anterior descending coronary artery, for 85 min followed by 3 hours’ reperfusion. Their volume changed (Δ V max ) linearly with colloidosmotic pressure in both ischemic and nonischemic areas, yielding interstitial compliance values of 1.04 ± 0.09 and 1.08 ± 0.05 µl/g/ mmHg , which do not differ significantly, and hydration potentials from the abscissa intercepts at Δ V max = 0, of -121.4 ± 28 and -14.7 ± 7.6 mmHg, which do (mean ± SE, n = 5 , P-value = 0.001). These hydration potential differences manifest ex-vivo influx rates 8.5 ± 2.7- fold slower in ischemic than nonischemic myocardium. Surprisingly, interstitial flow resistance values derived from net-flow rates at an imposed pressure difference of 216 mmHg were 0.23 ± 0.08 and 0.19 ± 0.01 µl -1 . g. min and did not differ significantly between the areas. The similarity in interstitial compliance and fluid resistance indicates that the more negative hydration potential and faster efflux rates in at-risk regions after reperfusion are due to increased hydrostatic pressure rather than decreased osmotic or frictional forces. Tissue distends due to interstitial fluid accumulation against matrix mechanical forces, including elastic recoil of the collagen elastin mesh and fibroblast action, consistent with impaired drainage and persistent diastolic-like conditions during reperfusion of at-risk areas in vivo . These results indicate changes in pressure gradient magnitude and may have clinical and therapeutic implications; for example, reversal of paracrine interstitial flows during early remodeling

The Effect of Acute Versus Delayed Remote Ischemic Preconditioning on Reperfusion Induced Ventricular Arrhythmias

The effect of remote ischemic preconditioning (RIPC) on arrhythmias in in vivo models is unknown. Our purpose was to determine effects of both acute and delayed RIPC on arrhythmias. In the acute protocol anesthetized open chest rats were exposed to 5 minutes of proximal left coronary artery occlusion (CAO) and 10 minutes of reperfusion. Rats were either untreated (ischemia/reperfusion, IR group, n = 17) or received RIPC (n = 14) with 5 minutes bilateral femoral occlusions followed by 5 minutes of reperfusion times 3, started 30 minutes before CAO. At reperfusion, onset of ventricular tachycardia (VT) was delayed in RIPC group (25.7 seconds) versus IR (8.8 seconds; P = 0.04). Number of episodes of VT was 17.0 in IR versus 3.0 in the RIPC group (P = 0.01) and duration of VT was 54.1 seconds in IR versus 4.9 seconds in RIPC (P = 0.019). Number of ventricular premature complexes (VPC) was 26.0 in IR and 10.0 in RIPC rats (P = 0.04). Levels of reperfusion injury salvage kinases (RISK), that is, phospho-Akt and phospho-p70S6 in the risk area of IR and RIPC hearts were similarly higher compared to the nonischemic areas both at 1 and 10 minutes into reperfusion. Delayed RIPC was induced on day 1 and on day 2, myocardial IR was induced. Delayed RIPC did not affect VT or VPC. Acute RIPC of the lower limbs induced a powerful delay in/and reduction in IR induced ventricular arrhythmias, but without evoking the RISK pathway; a late protective phase of RIPC on arrhythmias did not occur.

Imaging of Perfusion, Angiogenesis, and Tissue Elasticity after Stroke

Blood flow interruption in a cerebral artery causes brain ischemia and induces dramatic changes of perfusion and metabolism in the corresponding territory. We performed in parallel positron emission tomography (PET) with [(15)O]H(2)O, single photon emission computed tomography (SPECT) with [(99m)Tc]hexamethylpropylene-amino-oxime ([(99m)Tc]HMPAO) and ultrasonic ultrafast shear wave imaging (SWI) during, immediately after, and 1, 2, 4, and 7 days after middle cerebral artery occlusion (MCAO) in rats. Positron emission tomography and SPECT showed initial hypoperfusion followed by recovery at immediate reperfusion, hypoperfusion at day 1, and hyperperfusion at days 4 to 7. Hyperperfusion interested the whole brain, including nonischemic areas. Immunohistochemical analysis indicated active angiogenesis at days 2 to 7, strongly suggestive that hyperperfusion was supported by an increase in microvessel density in both brain hemispheres after ischemia. The SWI detected elastic changes of cerebral tissue in the ischemic area as early as day 1 after MCAO appearing as a softening of cerebral tissue whose local internal elasticity decreased continuously from day 1 to 7. Taken together, these results suggest that hyperperfusion after cerebral ischemia is due to formation of neovessels, and indicate that brain softening is an early and continuous process. The SWI is a promising novel imaging method for monitoring the evolution of cerebral ischemia over time in animals.

Anti‐arrhythmic effect of remote ischemic preconditioning is accompanied by changes in the salvage kinases in the rat heart non‐ischemic area

Remote ischemic preconditioning (RIPC) by intermittent ligation and reperfusion of femoral arteries decreases the occurrence and the duration of reperfusion arrhythmias. We sought to study whether salvage kinases (RISK) are involved in this phenomenon. Rats in the RIPC group were subjected to 3 cycles of bilateral femoral artery occlusion + reperfusion (5 min each) followed by 5 min of coronary artery occlusion with subsequent 1 min of reperfusion. In the ischemia/reperfusion (IR) group femoral arteries were exposed but not ligated. After a 30 min waiting period coronary artery was occluded and reperfused as in the RIPC group. At the end of the reperfusion the risk area was delineated with blue dye and hearts were frozen in liquid nitrogen. Non‐ischemic (NI) and ischemic (Isc) areas were separated and Western blots were performed for phospho‐Akt (p‐Akt) and phospho‐p70S6 (p‐p70S6). In the NI area the levels of kinases were reduced in the RIPC vs. IR group by 55% and 58% for p‐Akt and p‐p70S6 respectively (p<0.05). In the Isc vs. NI area of both groups kinases were equally increased and reached levels of ~2.7 baseline‐normalized units. The Isc/NI ratio in the RIPC vs. IR group was increased by 131% and 154% for p‐Akt and p‐p70S6 respectively (p<0.05). Our data suggest that RIPC increased parameters of RISK in the ischemic area to equivalent of IR alone, but reduced these parameters in the NI zone to a greater extent than IR.

Evaluation of fully automated motion corrected first pass myocardial perfusion MRI with semi quantitative perfusion parameter maps in patients with ischemic heart disease

Summary The purpose of the study is to evaluate a fully automated motion corrected first pass myocardial perfusion (FPMP) MRI with semi quantitative perfusion parameter maps in patients with suspected ischemic heart disease. Background Coronary heart disease is the leading cause of death and disability in the US. FPMP MRI is increasingly used to assess ischemic heart disease; however respiratory motion is one of the major problems for myocardial blood flow quantification. An algorithm for motion correction, surface coil correction, temporal denoising and robust pixel-wise parameter map generation model was previously desribed [Xue H et al MICCAI 2009).This work evaluates automated workflow in a clinical setting to diagnose ischemic heart disease comparing free breathing and motion correcteted images and corresponding pixel-wise parameter map. Methods Stress and rest FPMP images were acquired using a 1.5T scanner (MAGNETOM Avanto, Siemens Healthcare) in 39 patients with suspected ischemic heart disease. Short axis slices were acquired during infusion of 0.075 mMol/kg of Gadolinium (Magnevist, Bayer HealthCare Pharmaceuticals, USA) and adenosine (Adenoscan, AstellasPharma, USA) infusion (0.14 mg/kg/min; duration: 4 min) was administrated to induce stress. Free breathing, motion-corrected images and corresponding perfusion maps were assessed by 2 radiologists independently using the AHA 16 model and evaluated using a four point Likert scale (poor to excellent) to evaluate image quality and confidence level in presence or absence of hypo-perfusion regions. Upslope index of both free breathing and motion corrected images during stress and rest were manually calculated in nonischemic and ischemic areas and compared to the corresponding pixel-wise parameter map generated based on motion corrected images. FPMP MRI results were subsequently compared to coronary angiogram, stress echocardiography, or SPECT.

Temporal changes of strain parameters in the progress of chronic ischemia: with comparison to transmural infarction

The aim of this study was to reveal the temporal and spatial changes of strain parameters during the progression of chronic coronary ischemia. Fourteen pigs received occluder implantation to create gradual ischemia (CI), while six pigs underwent a sham surgery (Control). Six pigs after myocardial infarction were also studied (MI). Strain analysis was performed using a speckle-tracking algorithm. Eleven of the 14 animals with occluder implantation had total occlusion of the left anterior descending artery with collaterals at 1 month (early occlusion group), whereas three pigs had occlusion at 3 months (late occlusion group). Both radial strain (RS) and circumferential strain (CS) of ischemic area deteriorated at 1 month in the early occlusion group and remained at the same level throughout the remaining 2 months of the experiment. In the late occlusion group, RS gradually declined, while CS took the same course as Control until the 2 month time point. Thereafter, both metrics reached the same level as the early occlusion group at the time of occlusion. Interestingly, RS in the remote area decreased moderately, whereas CS remained normal in CI pigs. The comparison between CI and MI revealed preserved CS at the ischemic area in CI pigs. Both RS and CS deteriorate by the time total coronary occlusion was established and remain at the same level thereafter. Altered RS in the remote area may be an indicator of remodeling in the non-ischemic area, whereas CS may be useful for distinguishing between transmural and non-transmural scar.

Abstract P310: Connective Tissue Growth Factor Antibody Protects from Adverse Left Ventricular Remodeling Following Myocardial Infarction

Ischemic heart disease (IHD) is the most common cause of death in most Western countries, but the therapies for IHD are lacking. We aimed to determine the potential of connective tissue growth factor (CTGF) antibody in protecting myocardium from long-term deleterious effects of myocardial infarction. Healthy 8-week old mice were subjected to myocardial infarction (MI) and at 1 week post-MI the animals were randomized for treatment with vehicle, metoprolol or CTGF monoclonal antibody. After six weeks of treatment, CTGF antibody treated animals showed significantly better left ventricular (LV) systolic function than the vehicle-treated animals. LV diastolic function or LV dimensions were not affected by treatments. Analysis of cardiac sections revealed no difference in infarct scar size between the experimental groups. However, RT-PCR analysis revealed a decrease in the expression levels of fibrosis-related genes in non-ischemic area in the hearts of CTGF antibody treated animals. In addition, cardiomyocyte size was significantly reduced in LV sections of CTGF antibody treated animals compared to vehicle-treated animals. This was accompanied with a significant decrease in B-type natriuretic peptide mRNA levels in the LV, whereas expression levels of atrial natriuretic peptide or beta-myosin heavy chain were similar in MI groups. There was also a slight decrease in mRNA levels of interleukin-6 and CTGF in the hearts of CTGF antibody treated animals. Treatments had no effect on mRNA levels of transforming growth factor-β1, tumor necrosis factor-α and vascular endothelial growth factor A following MI. In conclusion, CTGF antibody treatment attenuates LV hypertrophy and improves LV systolic function following MI. Blocking CTGF function by a specific antibody may be useful for prevention of adverse myocardial remodeling and heart failure.

Abstract P272: Physiological and Pathological Functions of Nox2 and Nox4 in Ischemia/Reperfusion Injury

NADPH oxidases (Noxes) represent an enzyme system whose primary function is to produce reactive oxygen species (ROS). Both Nox2 and Nox4 play an important role in regulating oxidative stress and growth/death of cardiomyocytes (CMs). However, the role of Nox2 and Nox4 during ischemia/reperfusion (I/R) is poorly understood. In order to elucidate the function of the Nox isoforms, wild type (WT), Nox2 KO (Nox2-/-), and cardiac specific Nox4 KO (cNox4-/-) mice were subjected to 30 minutes ischemia followed by 24 hours reperfusion. Myocardial infarction size/area at risk (MI/AAR) as evaluated by TTC staining was significantly smaller in Nox2-/- and cNox4 -/- than in WT mice (32 ± 3.1% and 28.0 ± 6.1% vs. 40.3 ± 8.3%, p < 0.05). O 2 - production in Nox2 -/- and cNox4 -/- hearts was significantly lower than in WT hearts, as evaluated with the lucigenin-chemiluminescence assay (433 ± 52, 580 ± 106 vs. 1250 ± 236 RLU, p < 0.05). The I/R experiment was also conducted with mice in which both Nox2 and Nox4 are deleted (double KO mice). O 2 - production in the double KO heart was significantly lower than in the single KO ones (257 ± 42 RLU, p < 0.05). The MI/AAR in double KO mice was, however, significantly greater than that in WT mice (58.0 ± 6.3% vs. 40.3 ± 8.3%, p < 0.05). These results raised the possibility that marked suppression of ROS by combined downregulation of Nox2 and Nox4 exacerbates I/R injury. To elucidate the underlying mechanism, we examined expression of hypoxia inducible factor-1alpha (HIF-1 α ), using DN-Nox transgenic (Tg) mice, which we have shown also exhibited marked suppression of O 2 - and significantly greater MI/AAR after I/R. HIF-1 α is lower in DN-Nox Tg mice than in WT mice in both the ischemic and non-ischemic areas. A genetic cross between DN-Nox Tg and mice lacking prolyl hydroxylase 2, an enzyme mediating hydroxylation and downregulation of HIF-1 α , partially rescued I/R injury in DN-Nox mice (35.8 ± 5.9% vs 65.2 ± 10.3%, p<0.05). Taken together, these data show that both Nox2 and Nox4 mediate increases in oxidative stress and myocardial injury in response to I/R. However, combined downregulation of Nox2 and Nox4 induces marked downregulation of ROS, which in turn exacerbates I/R injury possibly through downregulation of HIF-1α and consequent impairment of hypoxic adaptation.

Abstract 9583: Remote Preconditioning Has a Powerful Antiarrhythmic Effect Independent of the Reperfusion Injury Salvage Kinase Pathways

Background: There is continuing need for non pro-arrhythmic antiarrhythmic therapies for life threatening ventricular arrhythmias associated with myocardial ischemia/reperfusion. A new form of endogenous cardio-protection, remote ischemic preconditioning (RPC) showed promise for reducing myocardial infarct size, but its effect on ventricular arrhythmias is largely unknown. The purpose of this study was to determine the effects of RPC on arrhythmias in a non-infarct producing model. Methods: Anesthetized open chest rats were exposed to 5 minutes of proximal left coronary artery occlusion and 10 minutes of reperfusion. Rats were either untreated controls (Ctrl, n=17) or received RPC (n=14) with 5 minutes bilateral femoral occlusions followed by 5 minutes of reperfusion times 3, started 30 minutes before coronary occlusion. Reperfusion arrhythmias were quantitated and in some rats Western Blot Analysis for pAKT and p-p70S6 kinase were studied. Results: Ischemic risk zone (blue dye technique) was similar in Ctrl (35% of LV) and RPC (32%) as were heart rate and blood pressure throughout the study. At reperfusion, onset of ventricular tachycardia (VT) was delayed in RPC group (45.8 ± 17.1 sec; mean + SEM) versus Ctrl (11.5 ± 3.3 sec; p=0.04). The number of episodes of VT was 18.1 ± 5.1 in Ctrl versus 5.2 ± 1.7 in the RPC group (p=0.01) and duration of VT was 67.2 ± 13.2 sec in Ctrl versus 24.9 ± 11.1 sec in RPC (p=0.019). Sustained VT (≥ 10 sec) occurred in 12 controls and 4 RPC rats (p=0.03); and duration of sustained VT was 40.2 ± 9.9 sec in Ctrl versus 14.6 ± 7.2 sec in RPC (p=0.03). Ventricular fibrillation occurred in 3 controls and 1 RPC rat. Mean number of ventricular premature beats was 38.2 ± 11.4 in Ctrl and 14.1 ± 3.1 in RPC rats (p=0.04). At the end of reperfusion p-Akt level in the risk area in control hearts was 2 times higher compared to the non-ischemic area, and was not different from its level in the risk area in the RPC hearts. In addition, the risk area in both Ctrl and RPC hearts demonstrated no difference in the p-p70S6 kinase level. Conclusion: Remote ischemic preconditioning of the lower limbs induced a powerful delay in/and reduction in ischemia/reperfusion induced ventricular arrhythmias, but without evoking the reperfusion injury salvage kinase pathway.

In vitro and in vivo proliferation, differentiation and migration of cardiac endothelial progenitor cells (SCA1+/CD31+ side‐population cells)

Side-population (SP) cells are a select population identified by a capacity to efflux Hoechst dye and are enriched for stem/progenitor cell activity. Previous studies suggested that cardiac SP (CSP) cells could be divided into SCA1(+)/CD31(-) and SCA1(+)/CD31(+) CSP cells. SCA1(+)/CD31(-) CSP cells have been shown to be cardiac stem/progenitor cells. However, SCA1(+)/CD31(+) CSP cells have not been fully characterized. The aim of the present study was to characterize SCA1(+)/CD31(+) CSP cells in the adult mouse heart, and investigate their abilities to proliferate, differentiate, vascularize and migrate in vitro and in vivo. Using fluorescence-activated cell sorting (FACS), RT-PCR, and assays of cell proliferation, differentiation and migration, and a murine model of myocardial infarction (MI), we showed that SCA1(+)/CD31(+) CSP cells express stem cell and endothelial-specific genes, and reside in the blood vessels. These cells were able to proliferate, differentiate, migrate and vascularize in vitro and in vivo. After MI, SDF-1α and CXCR4 were up-regulated in the damaged myocardium and on SCA1(+)/CD31(+) CSP cells, respectively. Our results further showed that SDF-1α induced migration of these cells in vitro. Importantly, we found that SCA1(+)/CD31(+) CSP cells could migrate into the ischemic region from the non-ischemic area within the myocardium and form a vascular tube-like structure after MI. Based on the gene expression profile, localization of SCA1(+)/CD31(+) CSP cells, and their ability to proliferate, differentiate, migrate and vascularize in vitro and in vivo, we postulate that SCA1(+)/CD31(+) CSP cells may represent endothelial progenitor cells in the mouse heart.

Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after acute myocardial ischemia/reperfusion.

Chymase is activated after acute myocardial ischemia/reperfusion (AMI-R) and is associated with an early activation of matrix metalloproteinase-9 (MMP-9), which increases infarct size after experimental AMI, and late fibrosis. We assessed the effect of chymase inhibition on myocardial protection and early signs of fibrosis after AMI-R. Fourteen pigs underwent AMI-R and received intravenously either vehicle (V; n = 7) or chymase inhibitor (CM; n = 7). Separately, rat myocardial fibroblast was incubated with vehicle (n = 4), low-dose chymase (n = 4), high-dose chymase (n = 4), or high-dose chymase plus chymase inhibitor (n = 4). Infarct size (V, 41 ± 5; CM, 24 ± 5; P < 0.01) and serum troponin T (P = 0.03) at the end of reperfusion were significantly reduced in CM. Chymase activity in both the area at risk (AAR) (P = 0.01) and nonischemic area (P = 0.02) was significantly lower in CM. Myocardial levels of pro, cleaved, and cleaved/pro-MMP-9 in the AAR were significantly lower in CM than V (P < 0.01, < 0.01, and = 0.02, respectively), whereas phospho-endothelial nitric-oxide synthase (eNOS) (P < 0.01) and total eNOS (P = 0.03) were significantly higher in CM. Apoptotic cells (P = 0.05), neutrophils (P < 0.05), and MMP-9-colocalizing mast cells (P < 0.05) in the AAR were significantly reduced in CM. Interleukin-18 (P < 0.05) and intercellular adhesion molecule-1 (P < 0.05) mRNA levels were significantly lower in CM. In cultured cardiac fibrosis, Ki-67-positive cells were significantly higher in the high-dose chymase groups (P < 0.03). This study demonstrates that chymase inhibition plays crucial roles in myocardial protection related to MMP-9, inflammatory markers, and the eNOS pathway. It may also attenuate fibrosis induced by activated chymase after AMI-R.

The Anesthesiologist's Expanding Role in Perioperative Liver Protection

The Anesthesiologist's Expanding Role in Perioperative Liver Protection

In vivo identification of alteration of inner neurosensory layers in branch retinal artery occlusion

Background/aimsTo characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain optical coherence tomography.MethodsIn this observational case...

HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat

High mobility group box 1 (HMGB1) acts as an early mediator in inflammation and organ injury. Ischemia reperfusion (I/R) injury induces HMGB1 translocation and expression in ischemic areas. However, it is unknown whether selective warm liver I/R injury also induces the expression of HMGB1 in non-ischemic lobes. The present study aimed to test the hypothesis that selective liver I/R injury also causes HMGB1 translocation and up-regulates its expression in non-ischemic liver areas. In the present study, selective I/R injury was induced by clamping the median and left lateral liver lobes for 90min followed by 0.5, 6 and 24h reperfusion. We used male inbred Lewis rats; six animals for each point in time and six animals for the normal control group. Selective hepatic I/R injury induced morphological changes not only in ischemic lobes but also in non-ischemic lobes. HMGB1 translocation and expression was increased in a time-dependent manner in the ischemic lobes, and increased in with delayed onset in the non-ischemic lobes. Serum HMGB1 levels were increased after reperfusion. Furthermore, liver I/R injury up-regulated the expression of HMGB1 receptors (Toll-like receptor 4 and receptor for advanced glycation end products and pro-inflammatory cytokines (Tumor necrosis factor-alpha and interleukin-6) in both ischemic lobes, however, the up-regulation of these cytokines was more prominent in the ischemic lobes. In conclusion, selective warm I/R induces a substantial "sympathetic/bystander" effect on the non-ischemic lobes in terms of HMGB1 translocation and local cytokine production.

In vivo characterization of ischemic retina in diabetic retinopathy

ObjectiveThe aim of this article is to characterize pathomorphologic changes within particular layers of fluorescein angiographically ‘ischemic’ compared to ‘nonischemic’ retina in patients with diabetic retinopathy.MethodsCross-sectional images of ischemic retinal areas were obtained using Heidelberg Spectralis optical coherence tomography (OCT). Presumed retinal ischemia was defined as focal hypofluorescence in early or early and late phase fluorescein angiography. Pathomorphologic changes on OCT were evaluated and the thickness of retinal layers measured and compared with nonischemic retina at corresponding topographic locations in a matched-pairs design based on 22 eyes (mean age 64 ± 14).ResultsIn all eyes, based on spectral domain-OCT cross-section images, the retina layers in ischemic retinal areas could be segmented. Total retinal thickness was significantly increased in ischemic compared to nonischemic areas (381 ± 94 μm versus 323 ± 89 μm, P = 0.005). Middle retinal layers (inner nuclear layer, outer plexiform layer, and outer nuclear layer) were significantly thickened in retinal ischemic areas (215 ± 82 μm versus 168 ± 62 μm, P = 0.002). The inner retinal layers (retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer) showed a nonsignificant change (117 ± 53 μm versus 98 ± 30 μm), while the outer layers were slightly thinned (photoreceptors plus retinal pigment epithelium layer; 51 ± 9 μm versus 57 ± 8 μm, P = 0.02) in ischemic versus nonischemic retina.ConclusionsIschemic diabetic retina seems to be thickened due to thickening of, in particular, middle retinal layers, which can be measured with high-resolution OCT.

Clinical diagnosis of segmental arterial mediolysis: Differentiation from vasculitis and other mimics

Segmental arterial mediolysis (SAM) is a rare vasculopathy of unknown etiology characterized by disruption of the arterial medial layer, with resultant susceptibility to vessel dissection, hemorrhage, and ischemia. Since the first case of SAM described by Slavin and Gonzalez-Vitale in 1976 (1), approximately 50 cases have been reported in the literature (2). Although the abdominal visceral arteries are most frequently affected in SAM (3), any vessel may be involved, including the retroperitoneal (4), intracranial (2, 5, 6) and coronary arteries (7–9). The histopathologic changes begin with vacuolar degeneration of smooth muscle cells in the arterial media, followed by fibrin deposition at the medial-adventitial junction (7). This in turn predisposes to dissecting aneurysms (3, 10). The angiographic appearance of SAM is variable, ranging from arterial dilation to aneurysm formation (single or multiple) to stenoses or occlusion, frequently with dissection (3, 11). Correspondingly, symptoms arise both from stenoses and occlusions (e.g., postprandial pain from intestinal ischemia) and from dissections and aneurysms (e.g., sudden and catastrophic intraperitoneal bleeding). In contrast to true vasculitis, inflammatory cells in SAM are present inconsistently and, when present, are thought to be secondary rather than primary to the pathogenesis of the disease (1). The differential diagnosis of SAM includes atherosclerosis, fibromuscular dysplasia, infection (e.g., mycotic aneurysm and endocarditis), connective tissue diseases (e.g., Bechet’s disease and polyarteritis nodosa), neurofibromatosis, and inherited defects in vessel wall structural proteins (e.g., type IV Ehlers Danlos and Marfan’s syndrome) (Table 1). Herein, we describe two cases of SAM seen at our instituation over the past 20 years and review the salient clinical presentation and treatment of SAM. We report characteristics that may be helpful in distinguishing cases of SAM from other entities in the differential diagnosis. Table 1 Clinical and laboratory features distinguishing Segmental Arterial Mediolysis (SAM) from its mimics*. Case 1 The patient was a 25-year-old female who was admitted to the hospital with an eleven-month history of intermittent episodes of anorexia, abdominal pain, and diarrhea. Symptoms had persisted despite discontinuation of oral contraception and initiation of low-dose aspirin therapy. Her past medical history was unremarkable. Family history was unremarkable except for benign hypermobility syndrome in the patient’s mother. On physical examination, the patient was normotensive and had normal height and arm span. She had no carotid, subclavian, abdominal, or femoral bruits. Skin, chest, abdominal, and neurologic examinations were normal. Joint exam was remarkable only for hyperextensibility of the knees, reducible flexion contractures of the fingers, and hammertoe deformities of the feet. Complete blood count revealed anemia with hemoglobin of 11 g/dl. Serum creatinine, liver enzymes, amylase, and lipase were normal, and urine pregnancy test was negative. Antinuclear antibody assay (ANA) was positive to a low titer of (1:80). The erythrocyte sedimentation rate was 20 mm/hr. The remainder of the serologic, metabolic, immunologic, and hematologic evaluations were within normal limits, including negative hepatitis serologies, negative double-stranded DNA, anti-Smith, and anti-ribonucleoprotein (RNP) antibodies, and normal complement C3 and C4 levels. Computed tomography (CT) of the abdomen showed thickening of the colonic wall with mucosal enhancement and fat stranding surrounding the splenic flexure. Colonoscopy revealed ischemic colitis of the splenic flexure. Biopsies of the ischemic areas were not obtained due to risk of possible perforation. Biopsies of the non-ischemic areas were normal, as was magnetic resonance angiography (MRA) of the abdomen. Conventional mesenteric angiography revealed focal stenoses of the right and left hepatic arteries, occlusion of the left colic artery near the splenic flexure with collateral vessel formation, and hyperemia of multiple branches of the splenic artery (Figure 1). Figure 1 Angiographic and histologic features of segmental arterial mediolysis in Case 1. (a) Focal stenoses of the right and left hepatic arteries (arrows). (b) Hyperemic blush in the left colonic flexure, suggesting formation of small collateral vessels from ... Because of persistent ischemic colitis, the patient underwent a partial colectomy of the splenic flexure. Vascular pathology of the colonic arteries showed patchy, isolated destruction of the arterial media involving both the internal and external elastic laminae (Figure 1). In a few sections the media was absent, with direct juxtaposition of the intima and the adventitia. In areas of medial destruction, there was intimal proliferation with marked luminal narrowing. All of the lesions were of a similar age. There was no evidence of inflammation, and giant cells, neutrophils, and cholesterol deposits were absent. After two years of followup, the patient remains asymptomatic.

E0116 The cardioprotective effect of ischaemic preconditioning and the expression of adiponectin in rat myocardial ischaemic preconditioning model

BackgroundA number of recent studies have reported the protective effect on ischaemic myocardial by ischaemic preconditioning (IPC) and adiponectin. Method and Result IPC model and MI model was set up....

Regional myocardial blood flow measured by stress multidetector computed tomography as a predictor of recovery of left ventricular function after coronary artery bypass grafting

Multidetector-row computed tomography (MDCT) applications have expanded to evaluation of myocardial blood flow (MBF) and viability. We quantified regional MBF pre- and post-coronary artery bypass grafting (CABG) using adenosine stress and cardiac 64-MDCT, and investigated whether the results predict MBF and left ventricular (LV) function recovery after CABG. We studied 321 regions in 19 CABG patients who underwent adenosine stress 64-row MDCT perfusion imaging and cine magnetic resonance imaging pre- and post-CABG. Myocardial blood flow was estimated from linear regression equation slopes using Patlak plot analyses and compared with LV function by measuring wall thickening (%WT) using cine magnetic resonance imaging. Overall mean MBFs were 1.39 +/- 0.49 and 1.95 +/- 0.49 mL/(g min) pre- and post-CABG (P < .0001). Myocardial blood flow in revascularized areas increased significantly (pre-CABG 1.18 +/- 0.45, post-CABG 1.99 +/- 0.66 mL/[g min], P < .001), whereas nonischemic areas showed no difference (1.79 +/- 0.70 and 1.97 +/- 0.46 mL/[g min], P = .14). Revascularized areas with preoperative MBF > or = 0.9 mL/(g min) showed significantly greater MBF improvement than those with preoperative MBF <0.9 mL/(g min) (P = .04). In patients with preoperative LV dysfunction (ejection fraction <40%), %WT in revascularized areas with pre-CABG MBF > or = 0.9 mL/(g min) improved significantly after CABG (pre-%WT 40.9 +/- 22.9, post-%WT 52.8 +/- 20.6, P = .03) versus those with pre-CABG MBF <0.9 mL/(g min) (pre-%WT 53.2 +/- 35.5, post-%WT 42.5 +/- 17.0, P = .40). Our results demonstrated more significantly increased MBF post-CABG than pre-CABG, particularly in revascularized areas. Regional MBF before CABG may predict MBF and LV function recovery, in the short term, after CABG.

Effects of omentopexy combined with granulocyte colony-stimulating factor in a rabbit heart model

We investigated whether omentopexy combined with subcutaneously administered granulocyte colony-stimulating factor (G-CSF) reduces infarction areas and improves left ventricular dysfunction in a rabbit model of coronary occlusion and reperfusion. A coronary artery of a male Japanese white rabbit was ligated for 30 min and then reperfused. An omental pedicle graft was fixed onto the myocardial ischemic area after abrading the epicardium. G-CSF (10 μg kg(-1)day(-1)) was subcutaneously administered for 5 days postoperatively. Animals were assigned to groups (n = 7 per group) as follows: group N, saline; group O, omentopexy and saline; group G, G-CSF; and group OG, omentopexy and G-CSF. At 4 weeks postoperatively, left ventricular ejection fraction and left ventricular end-diastolic diameter were evaluated by echocardiography. Harvested left ventricles were stained with Evans blue and triphenyltetrazolium chloride to measure necrotic and fibrotic areas. The arteriolar density in ischemic and nonischemic areas was evaluated. At 7 days postoperatively, the intrathoracic omentum was evaluated (n = 6 per group). Echocardiography at 4 weeks postoperatively revealed significant improvement in the left ventricular dysfunction of group OG. Necrosis and fibrosis in ischemic areas were significantly reduced in groups G and OG. Arteriolar density in the ischemic area and intrathoracic omentum weight were increased largely in group OG than in the other groups. Omentopexy with G-CSF offers more potential benefits for the ischemic heart than G-CSF alone.

Myocardial imaging with 99mTc-Tetrofosmin: Influence of post-stress acquisition time, regional radiotracer uptake, and wall motion abnormalities on the clinical result

BackgroundWe previously demonstrated that early (15′, T1) post-stress myocardial imaging with Tetrofosmin could be more accurate than standard acquisitions (45′, T2) in identifying coronary artery disease. Methods and ResultsTo clarify this phenomenon, 120 subjects (age 61 ± 10 years) with both T1 and T2 scans were divided into Group 1 (53/120 pts) with more ischemia at T1 vs T2 imaging (T1-T2SDS ≥ 3); Group 2 (67/120 pts) with similar results (T1-T2SDS ≤ 2). Myocardial areas were categorized as control nonischemic, ischemic, and scarred on the basis of perfusion/contraction properties and coronary anatomy. In each area, regional myocardial count statistic and semiquantitative wall motion/thickening values were obtained. Analysis of T1 and T2 post-stress myocardial counts demonstrated a significant Tetrofosmin wash-out rate that was higher in Group 1 control nonischemic regions (15 ± 8% vs 13.6 ± 9.6%, P < .02), significantly lower in Group 1 ischemic regions (7 ± 10% vs 12.2 ± 9.5%, P < .0001), and comparable between scarred areas of the two groups (P = NS). Δ post-stress wall thickening (T1-T2) was lower in Group 1 ischemic regions (−4.5 ± 9.15% vs −1.90 ± 7.0%, P < .001) and comparable in both control nonischemic and scarred areas of the two groups (P = NS). ConclusionThe clinical result of Tetrofosmin gated-SPECT can be influenced by the post-stress acquisition time because of ischemic-induced regional wall thickening abnormalities and the existence of a differential radiotracer myocardial wash-out.