Acute Perfusion Research Articles

Use of levosimendan in cardiogenic shock

Cardiogenic shock (CS) is acute inadequate tissue perfusion caused by the heart's inability to pump an adequate amount of blood. Due to the failure of classic inotrope agents, a sensitizer agent, levosimendan, has been used as a rescue therapy in such situations. In order to assess the effectiveness of levosimendan to treat CS, we studied its hemodynamic effects on patients with CS. A retrospective study was conducted at the ICU of the Military Hospital of Tunis between January 2004 and December 2009, and between January 2011 and December 2013. Twenty-six patients with CS refractory to catecholamines were included in our study. When catecholamines failed to improve the hemodynamic condition, levosimendan was introduced. This treatment was administered in two steps: a loading dose of 12 µg/kg/min was infused for 30 min; and then continuous infusion was given for 24 h at a dose of 0.1 µg/kg/min. Levosimendan significantly increased mean arterial pressure to 76 ± 7 mmHg at 48 h and cardiac index to 3.19 ± 0.68 L/min/m2 and decreased pulmonary wedge pressure to 17 ± 3 mmHg at 48 h. Pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure, and mean pulmonary arterial pressure were significantly reduced at 24 h. A significant decrease in lactate from 3.77 ± 2.93 to 1.60 ± 1.32 mmol/L, by 72 h, was also noted. Levosimendan significantly reduced systemic vascular resistance and pulmonary vascular resistances. Administration of levosimendan also reduced the need for catecholamines. Our study confirms the efficacy of levosimendan to stabilize hemodynamic parameters in patients with CS.

CT perfusion imaging as an early biomarker of differential response to stereotactic radiosurgery in C6 rat gliomas.

BackgroundThe therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model.MethodsRats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival >15 days were designated as responders while those with survival ≤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline.ResultsEarly signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P<0.04). Responders to stereotactic radiosurgery showed lower relative blood volume (rBV), and permeability-surface area (PS) product on day 7 post-stereotactic radiosurgery when compared to controls and non-responders (P<0.05). rBV and PS on day 7 showed correlations with overall survival (P<0.05), and were predictive of survival with 92% accuracy.ConclusionsResponse to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation.

The effect of acute coronary perfusion change on cardiac function measured by Shear Wave Elasticity Imaging.

The possibility of measuring cardiac function noninvasively has generated wide interest in elastography imaging techniques. Shear Wave Elasticity Imaging (SWEI) is an ultrasound-based elastography technique used to measure stiffness of tissues. While this technique has been studied extensively in static homogenous tissues such as liver, breast or prostate, there is still a significant need to study its capabilities to measure cardiac stiffness and function. In this research, we have studied the potential of SWEI to evaluate the coronary perfusion pressure effect on systolic and diastolic stiffness referred to as elastance and compliance of the heart. Five isolated rabbit hearts were used in this study in a Langendorff preparation. SWEI measurements of stiffness were recorded in two steps. In the first step, coronary perfusion was set to normal and then was reduced to half-normal. After 40 minutes of half-normal perfusion, it was returned to normal perfusion for the second step. SWEI velocity decreased from 6.003 m/s to 4.713 m/s in systole and from 1.948 m/s to 1.507 m/s in diastole in the first step. During the second step raising the perfusion to normal, SWEI stiffness showed an increase from 3.760 m/s to 5.468 m/s in systole and from 1.678 m/s to 2.156 m/s during diastole. Our results show that SWEI measurements of stiffness can characterize the cross talk between coronary perfusion and cardiac stiffness and also has the potential to measure compliance and elastance of the heart in systole and diastole.

Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for high-resolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.

Imaging findings in diagnosis of mesenteric ischemia: how can we be sure?

Mesenteric ischemia (MI) remains a complex disease entity characterized by acute or chronic perfusion abnormality to the GI tract. Because it presents with nonspecific symptoms and laboratory findings, MI remains a clinical diagnostic challenge. Given that MI is associated with high morbidity and mortality rates, early diagnosis remains critical for appropriate management and best clinical outcome. Over the past decade, significant technical improvements have been seen in computed tomography and MRI, particularly in their use for noninvasive angiographic imaging. These techniques are now the preferred test for initial evaluation of suspected MI. This article focuses on computed tomography and MRI features of MI in both the acute and chronic clinical settings, with a review of anatomy, etiopathogenesis and clinical features.

Omentin Prevents Myocardial Ischemic Injury Through AMP-Activated Protein Kinase- and Akt-Dependent Mechanisms

This study examined the impact of omentin on myocardial injury in a mouse model of ischemia/reperfusion (I/R) and explored its underlying mechanisms. Obesity is a major risk factor for ischemic heart disease. Omentin is a circulating adipokine that is down-regulated by obesity. In patients who underwent successful reperfusion treatment after acute myocardial infarction, cardiac function and perfusion defect were assessed by using scintigraphic images. Mice were subjected to myocardial ischemia followed by reperfusion. This study found that high levels of plasma omentin were associated with improvement of heart damage and function after reperfusion therapy in patients with acute myocardial infarction. Systemic administration of human omentin to mice led to a reduction in myocardial infarct size and apoptosis after I/R, which was accompanied by enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Akt in the ischemic heart. Fat-specific overexpression of human omentin also resulted in reduction of infarct size after I/R. Blockade of AMPK or Akt activity reversed omentin-induced inhibition of myocardial ischemic damage and apoptosis in mice. In cultured cardiomyocytes, omentin suppressed hypoxia/reoxygenation-induced apoptosis, which was blocked by inactivation of AMPK or Akt. Our data indicate that omentin functions as an adipokine that ameliorates acute ischemic injury in the heart by suppressing myocyte apoptosis through both AMPK- and Akt-dependent mechanisms.

The Severity of Ischemia Varies in Sprague-Dawley Rats from Different Vendors

The purpose of this study was to compare acute cerebral perfusion measured by computed tomography, stroke lesion volume measured by magnetic resonance imaging, and motor function in Sprague-Dawley rats supplied by Charles River (Charles River, Quebec, Canada) and Harlan (Harlan, Michigan, USA). During the acute stages of ischemia (&lt;3 hours), Sprague-Dawley rats supplied by Harlan had a greater reduction in blood flow (67%) than rats supplied by Charles River (37%). MRI at days 1 and 6 after ischemia showed larger lesions in the Charles River animals compared to Harlan animals (P&lt;0.05) at both time points. Lesion volume decreased in both Charles River and Harlan rats at day 6 compared to day 1 (P&lt;0.05) and corresponded to lesion size on histology. The Harlan animals had significant functional deficits (P&lt;0.05) one day after surgery in postural hang reflex, forelimb placement, and tactile fraction first tests, whereas rats supplied by Charles River had no significant functional impairment as a result of surgery. The current study provides evidence that differences in response to ischemia between rats of the same strain supplied by different vendors should be an important consideration when animals are selected for the study of cerebral ischemia.

Acute Injection and Chronic Perfusion of Kisspeptin Elicit Gonadotropins Release but Fail to Trigger Ovulation in the Mare1

Kisspeptin has emerged as the most potent gonadotropin-releasing hormone (GnRH) secretagogue and appears to represent the penultimate step in the central control of reproduction. In the sheep, we showed that kisspeptin could be used to manipulate gonadotropin secretion and control ovulation. Prompted by these results, we decided to investigate whether kisspeptin could be used as an ovulation-inducing agent in another photoperiodic domestic mammal, the horse. Equine kisspeptin-10 (eKp10) was administered intravenously as bolus injections or short- to long-term perfusions to Welsh pony mares, either during the anestrus season or at various stages of the cycle during the breeding season. In all the experimental conditions, eKp10 reliably increased peripheral concentrations of both luteinizing hormone and follicle-stimulating hormone. The nature of the response to eKp10 was consistent across experimental conditions and physiological states: the increase in gonadotropins was always rapid and essentially transient even when eKp10 was perfused for prolonged periods. Furthermore, eKp10 consistently failed to induce ovulation in the mare. To gain insights into the underlying mechanisms, we used acute injections or perfusions of GnRH. We also cloned the equine orthologues of the kisspeptin precursor and Kiss1r; this was justified by the facts that the current equine genome assembly predicted an amino acid difference between eKp10 and Kp10 in other species while an equine orthologue for Kiss1r was missing altogether. In light of these findings, potential reasons for the divergence in the response to kisspeptin between ewe and mare are discussed. Our data highlight that kisspeptin is not a universal ovulation-inducing agent.

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Introduction: Oxidative stress plays a major role in the pathology of hemorrhagic shock (HS). Acute kidney injury, cerebral edema (induced by increased AQP4 and NKCC1 expression) and cerebral perfusion pressure (CPP) drop are associated with high morbidity and mortality in HS. There is evidence that vasopressin is preferable to lactated Ringer's (LR) in HS. We hypothesized that terlipressin (TLP) protects the kidneys (K) and brain (B) in HS. Methods: We studied 35 female pigs (20-30 kg) in groups: sham; shock (60% reduction in blood volume-mean arterial pressure [MAP] of 40 mmHg for 30 min); LR (post-shock LR given at 3× the volume of blood removed); and TLP (2 mg of TLP given post-shock). At 60 min post-treatment, we evaluated CPP (mmHg), MAP (mmHg) and serum creatinine (Creat, mg/dl) and at 120 min post-treatment, we evaluated 2-thiobarbituric acid reactive substances (TBARS, nmol/g) (in B and K), as well as immunoblotting for AQP2, NKCC2 and Bax (in K); and AQP4, NKCC1 and Bax (in B). Results: Data are mean±SEM. MAP was markedly lower in Shock and LR than in Sham and TLP (49 ± 4.8 and 55 ± 2.9 vs. 71 ± 2.1 and 63 ± 3.0, P < 0.05). TLP treatment completely inhibited the decrease of CPP observed in Shock and LR (59 ± 2.6 vs. 45 ± 4.4 and 47 ± 2.9, P < 0.05) and was similar to Sham (65 ± 1.6). The TBARSB level was higher in Shock and LR groups than in Sham group (264 ± 46 and 308 ± 96 vs. 34.7 ± 5.7, P < 0.05). Although significantly different from Shock and LR groups, the TBARSB level observed for the TLP group (137 ± 9.5) differed significantly from the Sham group. Serum levels of creat were higher in Shock, LR and TLP groups than in Sham group (1.5 ± 0.08, 1.0 ± 0.09 and 1.3 ± 0.07 vs. 0.9 ± 0.07, P < 0.05). The TBARSk level was higher in Shock, LR and TLP groups than in Sham group (106 ± 23, 163 ± 62 and 108 ± 31 vs. 28.5 ± 1.1, P < 0.05). Expression of BaxB was markedly higher in shock and LR groups than in Sham (190 ± 30% and 154 ± 16% vs. 97 ± 2.5%, P < 0.05). TLP treatment completely inhibited the upregulation of BaxB (102 ± 2.6%). Similar, expression of Baxk was markedly higher in shock and LR groups than in Sham group (139 ± 5.1% and 130 ± 10% vs. 99 ± 0.6%, P < 0.05). TLP treatment completely inhibited the upregulation of BaxB (97.5 ± 8.5%). AQP2 expression was comparable in Sham and TLP pigs (97 ± 3.0% and 107 ± 5.0%) and was significantly lower in Shock (22 ± 2.5%) and LR (43 ± 12%) compared to Sham and TLP groups ( P < 0.05). NKCC2 expression was lower in Shock and LR pigs than in Sham and TLP pigs (27.5 ± 4.8% and 50 ± 21% vs. 102 ± 1.7% and 92.5 ± 12.5%, P < 0.05). Shock-induced increases in AQP4 (217%) and NKCC1 (237%) were reversed by TLP but not by LR. Conclusions: TLP-related protection appears to depend on sodium/water transporter regulation and be attributable, in part, to inhibition of oxidant injury.

Abstract 161: TRPC6 Activator Hyperforin Facilitates Arrhythmias Via Activating Store-operated Calcium Entry

Hyperforin, a major antidepressant constituent of St. John’s wort ( Hypericum perforatum ), exhibits high selectivity in activating the canonical transient potential channel 6 (TRPC6). Our previous studies have shown that TRPC6 may modulate Ca 2+ handling via store-operated Ca 2+ entry (SOCE) in adult ventricular myocytes. In the present study, we aim to test whether hyperforin is arrhythmogenic by facilitating Ca 2+ waves. Intracellular Ca 2+ fluorescence (F/F 0 ) was imaged in Fluo-4-AM loaded ventricular myocytes isolated from adult mice (2-4 month old). SOCE was evaluated by increasing the external Ca 2+ concentration ([Ca 2+ ] o ) from 0 to 1 mM after caffeine (10 mM) and thapsigargin (10 µM) were used to completely deplete SR Ca 2+ . Hyperforin (0.1-10 µM) perfusion increased SOCE up to 3.7 folds (F/F 0 = 3.73 ± 0.42, n = 7, compared to the control F/F 0 = 1.69 ± 0.37, n = 9, p &lt; 0.05), in a concentration dependent fashion. Whole-cell currents were recorded using ramp pulses from -110 mV to +50 mV, while K + , Na + , L-type Ca 2+ , and Na + -Ca 2+ exchange currents were pre-blocked. Hyperforin at a lower concentration (0.1 µM) induced a significant increase of inward current (from -1.44 ± 0.23 pA/pF to -2.56 ± 0.36 pA/pF, n = 8, p &lt; 0.05), which was then inhibited by the SOCE blocker Gd 3+ (1 mM) (-0.43 ± 0.22 pA/pF, n = 8, p &lt; 0.05). Hyperforin promotes spontaneous CaWs ([Ca 2+ ] o 4 mM) by increasing the frequency to 180± 14 % (n = 11. p &lt; 0.05), which can be attenuated by Gd 3+ (1 mM), or SKF-96265 (10 μM). In addition, both the amplitudes of Ca 2+ transients (F/F 0 =1.92 ± 0.09 to 2.09 ± 0.10, n = 12, p &lt; 0.05) and calcium content (control: F/F 0 = 2.03 ± 0.11, n=16 to 2.12 ± 0.13, n = 11, p &lt; 0.05) were enhanced by acute hyperforin perfusion (0.1 µM), when the cells were paced at a pacing cycle length of 2 seconds. The proarrhythmic effect of hyperforin was also confirmed in Langendorff-perfused hearts, from which optical membrane voltage mapping and EKG were simultaneously recorded. In conclusion, the TRPC6 activator hyperforin exhibits an arrhythmogenic effect in the heart. Its action is likely to be mediated by generating an inward current and increasing the calcium load in cardiac myocytes through the SOCE pathway. Caution should be taken when prescribing this drug to patients with heart disease.

NMDA-Receptor Activation but Not Ion Flux Is Required for Amyloid-Beta Induced Synaptic Depression

Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (Aβ) in the etiology of Alzheimer’s disease. Historically, AD research has mainly focused on the long-term changes caused by Aβ rather than analyzing its immediate effects. Here we show that acute perfusion of hippocampal slice cultures with oligomeric Aβ depresses synaptic transmission within 20 minutes. This depression is dependent on synaptic stimulation and the activation of NMDA-receptors, but not on NMDA-receptor mediated ion flux. It, therefore, appears that Aβ dependent synaptic depression is mediated through a use-dependent metabotropic-like mechanism of the NMDA-receptor, but does not involve NMDA-receptor mediated synaptic transmission, i.e. it is independent of calcium flux through the NMDA-receptor.

Pathophysiological Concepts in Mild Traumatic Brain Injury: Diffusion Tensor Imaging Related to Acute Perfusion CT Imaging

BackgroundA subgroup of patients with mild traumatic brain injury (TBI) experiences residual symptoms interfering with their return to work. The pathophysiological substrate of the suboptimal outcome in these patients is a source of debate.ObjectiveTo provide greater insight into the pathophysiological mechanisms of mild TBI.MethodsDiffusion tensor imaging (DTI) was performed during follow-up of 18 patients with mild TBI and compared with healthy control subjects. DTI data of the patient group were also compared with perfusion CT imaging in the acute phase of injury.ResultsIn patients with mild TBI, a trend was observed for a decreased fractional anisotropy (FA) in widespread bilateral frontal white matter areas with increased mean diffusivity (MD) in the parieto-temporal regions, compared to healthy control subjects. Cerebral blood volume (CBV) correlated significantly with FA in several white matter tracts including the corpus callosum, the internal capsule, the inferior fronto-occipital fascicle, the corticospinal tract, the superior and the inferior longitudinal fascicle.ConclusionIn mild TBI with normal conventional imaging significant associations between cerebral perfusion in the acute phase of injury and DTI analyses in the chronic phase of injury were discerned. The pathophysiological concept of these findings is being outlined.

Role of Imaging for Acute Chest Pain Syndromes

Acute chest pain suggestive of ischemic cardiac origin, with a normal or nondiagnostic electrocardiogram and negative initial cardiac markers for myocardial necrosis represent a significant diagnostic dilemma for clinicians. Multiple imaging modalities play a pivotal role in early diagnosis and safe discharge of these patients. In this review, we compare the current imaging modalities available for these patients including their diagnostic accuracy, feasibility, and cost effectiveness. Acute rest myocardial perfusion imaging significantly improves the clinical outcome in these patients and reduces the overall cost when incorporated into the decision making pathway. The choice of imaging modality recommended should be based on local institutional expertise and the overall clinical presentation. The imaging modality with high diagnostic accuracy and negative predictive value will provide for precise risk stratification which is important to clinical decision making, including patients who require admission to the hospital and those who can be safely discharged.

Abstract WP33: Reduced Cerebral Blood Flow on Acute Whole Brain CT Perfusion Best Predicts Hemorrhagic Transformation

Objective: Hemorrhagic transformation in ischemic stroke is a potentially life threatening complication of thrombolysis. Using perfusion MRI, very low cerebral blood volume (VLCBV) strongly predicts hemorrhagic transformation after reperfusion. CT perfusion (CTP) is currently more widely accessible than MRI and recent data have shown that CT relative cerebral blood flow (relCBF) provides a better estimate of infarct core than CBV. We aimed to determine the optimal parameter to predict hemorrhagic transformation using whole brain CTP. Methods: Patients with ischemic stroke were imaged with whole brain CTP within 6hrs of symptom onset. Hemorrhagic transformation was assessed on CT/MRI within 7 days of stroke using ECASS grade. CBF and CBV were analyzed within a relative time to peak &gt;4sec region of interest. Results were expressed as volumes below a given percentile relative to the contralateral hemisphere (relCBF and relCBV). Receiver operating characteristic (ROC) and logistic regression analysis were performed to determine the optimal parameter and percentile threshold correlating with parenchymal hemorrhage (PH). Results: 128 patients with acute CTP were analyzed, median age 76yr (IQR 66-83), median NIHSS 13 (IQR 9-16), 59% received IV thrombolysis. 11 patients had PH on follow-up. On ROC analysis, the optimal threshold for very low CBF (VLCBF) was at the &lt;0 th centile. VLCBF was significantly associated with PH in ROC analysis (AUC=0.760, p&lt;0.01) whereas VLCBV (AUC 0.638 at &lt;5 th centile, 0.618 at &lt;2.5 th centile, 0.440 at &lt;0 th centile) was not significant. Using VLCBF, the optimal lesion volume to predict PH was &gt;3mL with OR 12.0 (95%CI 2.4-58), sensitivity 0.82 (95%CI 0.48-0.98), specificity 0.73 (95%CI 0.64-0.80), negative predictive value 0.98 (95%CI 0.92-1.0) and positive predictive value 0.22 (95%CI 0.11-0.38). In logistic regression, PH was associated with increased VLCBF (p&lt;0.01) but not with VLCBV (p=0.08). The Bayesian information criterion for VLCBF compared to VLCBV was +5 indicating improved model fit. Conclusions: VLCBF appears to be more reliably associated with hemorrhagic transformation than VLCBV when CT perfusion is used. This may be due to reduced ability of VLCBV to distinguish regions of ischemia from normal white matter.

Abstract WP219: Whole Brain Perfusion In Tia

Transient ischemic attack (TIA) is the major predictor of future ischemic stroke risk. However clinical diagnosis of TIA is extremely inaccurate. We aimed to investigate whole brain perfusion CT as a screening tool for TIA. Methods: Patients presenting to the John Hunter Hospital with a clinical diagnosis of TIA were scanned within 6 hours of symptom onset with 320 slice CT, which allows whole brain perfusion (CTP). Patients then underwent diffusion weighted MRI within 24 hours of symptom onset. A pixel based analysis was undertaken to determine perfusion based anomalies, and correlate findings to the 24 hour DWI lesion. Results: 156 patients with a clinical diagnosis of TIA were enrolled in the study. Whole brain perfusion imaging in 79 patients was normal, 35 patients had a delay time hypoperfusion lesion (&gt;2 seconds compared to normal tissue) &gt; 10mL, and 44 showed hyperperfusion at a threshold of Cerebral blood flow &gt;120% . The volume of the delay 2 seconds lesion was strongly correlated to the acute NIHSS r=0.769 p=0.05. 44 patients had a DWI lesion of &gt;5mL. Most patients with an acute delay 2 seconds lesion would develop a DWI infarct at 24 hours (41 patients, p=0.01). Discussion: Clinical assessments of resolving or mild neurological symptoms are poorly sensitive, and as a result imaging is required. We have shown that acute perfusion imaging findings are a sensitive and specific marker for recent (&lt;24 hours) TIA.

Abstract 14: Predicting Hemorrhagic Transformation in Ischemic Stroke - Very Low Cerebral Blood Volume versus Permeability Analysis

Background and purpose: Hemorrhagic transformation is the major complication of reperfusion therapies and carries a high risk of disability and death. Very low cerebral blood volume (VLCBV) and increased blood brain barrier permeability, both markers of severe ischemia, have been proposed as imaging predictors of hemorrhage risk. We aimed to compare the prognostic power of these two approaches using data from the DEFUSE 2 study. Methods: Acute ischemic stroke patients had perfusion-diffusion MRI before and within 12 hr after endovascular therapy. Baseline cerebral blood volume (CBV) maps were generated and the volume of VLCBV (CBV&lt;2.5 th percentile of the normal hemisphere) was calculated. Permeability was assessed using two recirculation parameters: "relative recirculation" (rR): the difference in area encompassed by the observed tissue-concentration curve and a theoretical fit of the first pass bolus; and "percent recovery" (%Recovery): the difference in signal intensity between peak bolus and average post-bolus. Parenchymal hematoma (PH) was defined using ECASS criteria. Reperfusion was defined as &gt;50% reduction in Tmax&gt;6sec lesion volume between baseline and post-procedure MRI. Logistic regression models were compared using Bayesian Information Criterion (BIC). Results: In DEFUSE 2, MRI prior to catheter angiography was performed in 110 patients, 59 had tPA pre-treatment and 25 developed PH. In 103 patients with technically adequate acute perfusion MR, preliminary receiver operating characteristic analysis identified &gt;40%rR and &lt;50%Rec as the optimal thresholds to assess the volume of tissue with increased permeability. In logistic regression, PH was associated with increased VLCBV (p=0.02) and rR permeability (p=0.05) but not %Recovery (p=0.17). The VLCBV model had better fit than rR permeability (BIC difference +2.1) and there was no significant interaction between parameters (p=0.33). Reperfusion was strongly associated with PH (p=0.01) and improved fit of the VLCBV model (BIC +7.2). Conclusions: VLCBV was a stronger predictor of early PH after reperfusion than permeability parameters in patients treated with endovascular therapy.

Comparison of Diagnostic Usefulness of Multi-Channel CT Perfusion and Conventional Brain CT in the Acute Pontine Infarct

Copyrights © 2013 The Korean Society of Radiology Purpose: CT perfusion (CTP) is an important modality in the diagnosis of acute stroke, and the range of its use is gradually expanding from supratentorial to whole brain stroke. We assessed the diagnostic value of multichannel CTP in comparison with conventional CT (CT) in acute pontine infarct. Materials and Methods: CTP and follow-up diffusion weighted magnetic resonance imaging were performed in 74 patients diagnosed with acute pontine infarct among 178 suspicious ones. Diagnostic accuracy of CTP and CT was evaluated and quantitative analysis was performed to define the factors that may influence the detection rate. Results: In the diagnosis of acute pontine infarct, the sensitivity, specificity, and accuracy of CTP was 56.8%, 91.4%, and 77.0% and of conventional CT scan was 47.3%, 93.3%, and 74.2%, respectively. There was no statistically significant difference. Receiver operation characteristic curve revealed both types of imaging to have diagnostic usefulness (p < 0.01) in acute pontine infarct. Among the factors that may affect the detection rate, infarct volume was found to be statistically significant (CTP: p < 0.01, CT: p = 0.01). Conclusion: This is the first study that analyzed the difference between CTP and CT in the diagnostic accuracy of acute pontine infarction. Both CTP and CT are useful diagnostic tools although CTP seems to have a slightly higher detection rate than CT. Index terms Acute Pontine Infarction Multidetector CT Perfusion Conventional CT Diffusion Weighted Magnetic Resonance Imaging Comparison of Diagnostic Usefulness of Multi-Channel CT Perfusion and Conventional Brain CT in the Acute Pontine Infarct 급성 허혈성 교뇌경색에서 다중채널 관류전산화단층촬영과 고식적 전산화단층촬영의 진단적 유용성의 비교

Perfusion CT in Acute Stroke: A Comprehensive Analysis of Infarct and Penumbra

To perform a large-scale systematic comparison of the accuracy of all commonly used perfusion computed tomography (CT) data postprocessing methods in the definition of infarct core and penumbra in acute stroke. The collection of data for this study was approved by the institutional ethics committee, and all patients gave informed consent. Three hundred fourteen patients with hemispheric ischemia underwent perfusion CT within 6 hours of stroke symptom onset and magnetic resonance (MR) imaging at 24 hours. CT perfusion maps were generated by using six different postprocessing methods. Pixel-based analysis was used to calculate sensitivity and specificity of different perfusion CT thresholds for the penumbra and infarct core with each postprocessing method, and receiver operator characteristic (ROC) curves were plotted. Area under the ROC curve (AUC) analysis was used to define the optimum threshold. Delay-corrected singular value deconvolution (SVD) with a delay time of more than 2 seconds most accurately defined the penumbra (AUC = 0.86, P = .046, mean volume difference between acute perfusion CT and 24-hour diffusion-weighted MR imaging = 1.7 mL). A double core threshold with a delay time of more than 2 seconds and cerebral blood flow less than 40% provided the most accurate definition of the infarct core (AUC = 0.86, P = .038). The other SVD measures (block circulant, nondelay corrected) were more accurate than non-SVD methods. This study has shown that there is marked variability in penumbra and infarct prediction among various deconvolution techniques and highlights the need for standardization of perfusion CT in stroke. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120971/-/DC1.

What does the liver tell us about the failing heart?

This editorial refers to ‘Liver function abnormalities, clinical profile, and outcome in acute decompensated heart failure’, by M. Nikolaou et al. , doi:10.1093/eurheartj/ehs332 The high metabolic activity of the liver results in a high perfusion rate of ∼1 mL/g/min. Under resting conditions, this is about a quarter of the bodýs total blood supply. The oxygen-rich blood of the hepatic artery contributes to about a quarter of the total liver perfusion that may rise substantially under conditions of excessive oxygen demand. The complex blood supply makes the liver extraordinarily vulnerable to acute circulatory disturbances. Both the severity and the pattern of hepatic injury depend on the relative contribution of passive congestion and diminished perfusion.1 Increased central venous pressure results in passive hepatic congestion and causes elevations of alkaline phosphatase (AP), γ-glutamyltransferase (GGT), and direct and indirect serum bilirubin. This ‘congestive hepatic injury’ is known as nutmeg liver on pathology. Decreased cardiac output with impaired organ perfusion is associated with acute centrilobular (zone 3 of the acinus) hepatocellular damage and necrosis. ‘Hepatic ischaemic injury’ results in elevations in serum aminotransferases ( Figure 1 ).2,3 Figure 1 Haemodynamic disturbances in heart failure and mechanisms resulting in different patterns of elevated liver enzymes. Congestive hepatic injury (left panel) and ischaemic hepatic injury (right panel). In contrast to acute perfusion abnormalities, prolonged and chronic haemodynamic disturbances may result in bridging fibrosis, ‘cardiac’ cirrhosis, and impaired hepatic function with decreased synthesis of coagulation factors and albumin. Hepatic congestion occurs without particular symptoms in most cases. Some patients may suffer from jaundice, stretching of the liver capsule with right upper quadrant discomfort, and ascites. Rare cases of congestive heart failure (HF) associated with fulminant hepatic failure have been reported. However, most such cases occur in the setting of superimposed cardiogenic shock and consecutive hepatic ischaemic injury.4 …

Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory

Aging is characterized by a progressive cognitive decline that leads to memory impairment. Because the cyclic nucleotide cascade is essential for the integrity of synaptic function and memory, and it is down-regulated during aging and in neurodegenerative disorders, we investigated whether an increase in cGMP levels might rescue age-related synaptic and memory deficits in mice. We demonstrated that acute perfusion with the phosphodiesterase-5 inhibitor sildenafil (50nM) ameliorated long-term potentiation in hippocampal slices from 26–30-month-old mice. Moreover, chronic intraperitoneal injection of sildenafil (3mg/kg for 3 weeks) improved age-related spatial learning and reference memory as tested by the Morris Water Maze, and recognition memory as tested by the Object Recognition Test. Finally, sildenafil restored central cAMP responsive element-binding protein (CREB) phosphorylation, which is crucial for synaptic plasticity and memory. Our data suggest that inhibition of phosphodiesterase-5 may be beneficial to treat age-related cognitive dysfunction in a physiological mouse model of aging.