Termination Of Infusion Research Articles

P1510Values of left ventricular area strain during 4D-strain-stress echocardiography with adenosine triphosphate in healthy subjects

Abstract Background Use of adenosine triphosphate (ATP) instead of adenosine in stress echocardiography is more cost-effective. Earlier we have proposed new ATP stress echocardiography algorithm (Figure). This modified algorithm includes 1) stepwise increase in dose of ATP in the absence of signs of adequate vasodilation (decrease in systolic blood pressure and increase in heart rate), 2) triple registration of echocardiographic data sets (before ATP infusion, during phase of adequate vasodilation and 5 minutes after the termination of ATP infusion). Purpose In this study we aimed to a) assess the safety of ATP high doses infusion algorithm, b) determine the values of left ventricular (LV) systolic global and segmental area strain (AS) during 4D-strain-stress echocardiography with ATP in healthy volunteers. Material and methods 13 healthy subjects (male 9, mean age 35.3±11.0 years) underwent ATP LV 4D strain-stress-echocardiography (Vivid E95, AFI technology). Mean values of global and regional (16 segments model) AS were determined. Results 4 subjects appeared to be “non responders” to initial dose of ATP 140 μg/kg/min. In three subjects it was necessary to increase the dose of ATP to 175 and in one to 210 μg/kg/min in order to achieve adequate vasodilation. No major side effects of ATP infusion (complete heart block, bronchospasm, myocardial infarction) were registered and no aminophylline injections were required. In all cases interpretable 4D LV Echo data sets for automatic strain analysis were obtained. Mean values of global systolic AS in healthy individuals before, at time and after ATP infusion were −25.8±4.8, −27.2±4.4 and −25.7±4.8%, respectively. Mean values of systolic AS in each of 16 segments were also calculated (Table). LV segment AS before ATP (%) AS ATP infusion (%) AS after ATP (%) LV segment AS before ATP (%) AS ATP infusion (%) AS after ATP (%) 1 −29.6±11.3 −31.2±11.1 −28.6±8.3 9 −27.8±6.5 −29.3±6.8 −30.8±6.0 2 −26.6±8.5 −28.2±4.9 −26.2±7.3 10 −26.1±5.2 −274±5.5 −25.8±6.0 3 −25.6±6.8 −29.6±5.2 −27.2±7.2 11 −25.3±6.1 −26.1±7.5 −24.9±5.3 4 −26.2±7.2 −24.9±9.1 −25.2±6.7 12 −28.1±7.3 −28.5±6.1 −25.3±5.6 5 −26.5±6.8 −29.3±10.9 −24.3±7.7 13 −22.9±6.5 −23.4±6.5 −23.2±6.4 6 −25.2±6.7 −26.0±7.9 −25.5±7.0 14 −25.7±7.6 −28.5±6.0 −26.2±6.8 7 −24.8±7.3 −25.6±6.1 −22.8±6.0 15 −26.5±6.5 −29.8±6.0 −28.5±5.5 8 −25.8±6.6 −26.5±5.6 −25.8±5.5 16 −24.2±7.1 −25.4±6.2 −25.1±6.6 Conclusions 4D strain-stress-echocardiography ATP infusion algorithm is safe and well tolerated by patients. Values of LV systolic global and segmental AS in healthy subjects were determined.

Retrospective study on the timing of termination of erythrocyte infusion in patients with severe postpartum hemorrhage

Objective To evaluate the appropriate time and reasonable indicator of ending the erythrocyte transfusion in patients with severe postpartum hemorrhage. Methods A retrospective study was performed, where the hemoglobin (Hb) and hematocrit (Hct) values were taken as test variables and the infusion of erythrocytes was stopped, and the Hb>70 g/L of 24 h after the infusion of erythrocytes was taken as the state variable, and the receiver operating characteristic (ROC) curve was drawn to calculate area under receiver operating characteristic curve(AUC) and cut-off value. Based on the AUC area in the ROC curve, the study was conducted. Patients with severe postpartum hemorrhage whose test variables were less than or equal to cut-off value were divided into group A(n=34), and the rest were divided into group B(n=53). Bleeding volume, blood transfusion volume, hemoglobin content after red blood cell infusion were stopped, and heart rate (HR), mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were compared 24 h after red blood cell infusion was stopped. The damage of new organs, length of stay and total cost of hospitalization were compared in the two groups. Results The AUC area of Hb was calculated as 0.825 [95%confidence interval (CI) 0.725-0.925] when the infusion was stopped, and the cut-off value of Hb when the infusion was stopped was 86.5 g/L (sensitivity 72.5%, specificity 87.5%). The AUC area of Hct was 0.780 (95%CI 0.665-0.895) when the infusion was stopped, and the cut-off value of Hct when the infusion was stopped was 27.65% (sensitivity 65.2% and specificity 71.2%). There was no significant difference in bleeding volume between the two groups (P>0.05). The mean Hb values of the patients in the two groups were (79±6) g/L in group A and (100±10) g/L in group B, respectively, after the transfusion of erythrocytes was stopped. The difference between the two groups was statistically significant (P 0.05). The incidence of oxygenation index 0.05). Conclusions Hb is better than Hct in evaluating the indicators of stopping transfusion of red blood cells in patients with severe postpartum hemorrhage. When the body Hb reached 86.5 g/L, it was possible the appropriate time for ending erythrocyte transfusion, with beneficial effects on the body. It was also found that the occurrence of organ injury rises with the increase of erythrocyte transfusion. Key words: Postpartum hemorrhage; Erythrocyte infusion; Terminating time; Receiver operating characteristic curve

Schisandrin Attenuates Lipopolysaccharide-Induced Lung Injury by Regulating TLR-4 and Akt/FoxO1 Signaling Pathways.

Objective: Acute lung injury is a severe clinic condition with limited therapeutic approaches. This study evaluated whether schisandrin (Sch), an ingredient of Schisandra chinensis, has preventive effects on endothelium and epithelium injury induced by lipopolysaccharide (LPS) and the underlying mechanisms.Methods: Male Wistar rats were continuously infused with LPS (5 mg/kg/h) via the left jugular vein for 90 min. In some rats, Sch (2.5 mg/kg/h) was administrated through the left jugular vein 30 min before LPS infusion. Leukocyte recruitment, levels of inflammatory cytokines, lung histology and edema, vascular and alveolar barrier disruption and related proteins were evaluated at indicated time point after LPS challenge.Results: LPS infusion for 90 min resulted in an increased leukocyte adhesion to pulmonary venules and overproduction of cytokine and chemokine in both serum and lung homogenate. At 8 h after termination of LPS infusion, obvious Evans blue extravasation and lung edema were observed, along with an increased apoptosis, a decreased expression of tight junction and adherent junction proteins, and a reduction in von Willebrand factor (vWF) and keratin, all of which were attenuated by Sch treatment. Meanwhile, the LPS-elicited activation of TLR-4/NF-κB/MAPK and FoxO1 signaling was inhibited by Sch.Conclusion: The present study revealed that pretreatment with Sch alleviated lung endothelium and epithelium injury after LPS stimulation, which is attributable to inhibition of cell injury and activation of cell regeneration via regulation of TLR-4/NF-κB/MAPK and Akt/FoxO1 signaling pathway.

Impact of pharmacological stress agent on patient motion during rubidium-82 myocardial perfusion PET/CT

BackgroundPatient motion has been demonstrated to have a significant impact on the quality and accuracy of rubidium-82 myocardial perfusion PET/CT. This study aimed to investigate the effect on patient motion of two pharmacological stressing agents, adenosine and regadenoson. Methods and ResultsDynamic data were retrospectively analyzed in 90 patients undergoing adenosine (n = 30), incremental adenosine (n = 30), or regadenoson (n = 30) rubidium-82 myocardial perfusion PET/CT. Severity of motion was scored qualitatively using a four-point (0-3) scale and quantitatively using frame-to-frame pixel shifts. The type of motion, returning or non-returning, and the frame in which it occurred were also recorded. There were significant differences in both the qualitative and quantitative scores comparing regadenoson to adenosine (P = .025 and P < .001) and incremental adenosine (P = .014, P = .015), respectively. The difference in scores between adenosine and incremental adenosine was not significant. Where motion was present, significantly more adenosine patients were classed as non-returning (P = .018). The median frames for motion occurring were 12 for regadenoson and 14 for both adenosine cohorts. ConclusionsThe choice of stressing protocol impacts significantly on patient motion. Patients stressed with regadenoson have significantly lower motion scores than those stressed with adenosine, using local protocols. This motion is more likely to be associated with a drift of the heart away from a baseline position, coinciding with the termination of infusion.

F24. Evaluation of cardiovascular parameters during intravenous loading dose of lacosamide

Several recent reports have described the efficacy of intravenous (IV) lacosamide (LCS) in the management of acute seizures and status epilepticus (SE). Based on data from 3 randomized control trials LCS appeared to be well tolerated. However, previous studies of patients on maintenance LCS therapy have reported Electrocardiographic (ECG) changes including conduction disturbances and sinus node dysfunction. A study of IV LCS boluses of 200, 300, and 400 mg administered over 15 min to outpatient subjects with epilepsy showed no changes in ECG during the infusions. We performed a retrospective review of adult patients who received IV LCS of 400–1400 mg and evaluated for changes in cardiovascular parameters during and immediately after the loading dose. With IRB approval, patients were identified that received IV LCS in the ICU for acute treatment of seizures during the years 2013–2016. Data elements collected were age, gender, weight, duration of infusion, change or termination of infusion because of immediate side effects, heart rate changes, blood pressure changes, oxygen saturation changes, and use of vasopressor agents one hour before, during and up to one hour after the infusion completed. All loading doses were administered over 30–60 min. No concurrent other anti-epileptic medication was given during loading dose of LCS. Three hundred and fifty-four adult patients were identified that were treated with LCS for seizures and SE in the ICU. 318/354 patients had IV loading dose of 400–1400 mg. Demographics were male/female (130/188), average weight 83.7 kg (range 40.8–219.5), and average age was 60 yrs (18–97). Ranges of the bolus doses included 400–600 mg (210 pts), 601–800 mg (78 pts) and 801–1400 mg (30 pts). No patients required a change or discontinuation of the infusion due to acute side effects. No patients required vasopressors from blood pressure changes during the bolus. The systolic blood pressure (mm Hg) 1 h prior, during, and 1 h post bolus were 137.56 ± 25.3, 133.4 ± 24.87, and 131.6 ± 25.89 (measured with 1 standard deviation). Similarly, the diastolic measurements were 72.3.9 ± 12.87, 72.7 ± 13.78, and 69.94 ± 13.46. Similarly, the heart rate measurements were 86.98 ± 19.73, 85.92 ± 18.85, and 85.22 ± 18.25. Patients with refractory SE who require anesthetic agents or repeated doses of benzodiazepines are most vulnerable to severe hypotension which complicates the management and increases risk for organ hypo-perfusion and mortality. The choice of IV antiepileptic medications is limited since IV fosphenytoin has been associated with substantial hypotension. In our study IV bolus doses of LCS appears to have no deleterious cardiovascular effects thus favoring its use in the management of acute seizures and SE. Furthermore, we did not identify any malignant changes in heart rate related to the bolus dose ranging from 400 to 1400 mg.

Epidural Analgesia During the Second Stage of Labor: A Randomized Controlled Trial

(Obstet Gynecol. 2017;130(5):1097–1103) Although epidural analgesia provides effective labor pain relief, studies have found an association with a prolonged duration of second stage labor, and thus, increased risk of adverse outcomes. Subsequently, many obstetric care providers request termination of epidural infusions for the second stage of labor. In the present study, the authors evaluated the use of low-concentration epidural local anesthetics and hypothesized that this management technique would have minimal effect on second stage labor.

Monitoring whole-lung lavage using lung ultrasound: The changing phases of the lung.

Lung ultrasound (LUS) has been proven to yield valuable information for lung and pleural pathology. It is well validated for assessing extravascular lung water. It can also be used to monitor stages of controlled lung de-aeration in whole lung lavage (WLL) which is the treatment for Pulmonary Alveolar Protienosis (PAP),characterized by abnormal surfactant in the alveoli affecting gas exchange .LUS can help decide the point of termination of lung flooding. A 55 year old lady with biopsy proven pulmonary alveolar proteinosis presented with respiratory failure. WLL was planned. LUS was used to study the stages of lung flooding as previously described for ARDS model.6 areas screened based on six areas that are normally examined like upper zone, mid zone and lower zone showed alveolar interstitial pattern. One lung ventilation (OLV) was done and isolation of lavage lung was confirmed which was seen as lung collapse (lung pulse) on LUS. Saline infusion resulted in increase in B lines followed by tissue like pattern with fluid bronchogram on LUS(alveolar flooding) in all the areas. During the lavage of the second lung, appearance of alveolar flooding pattern resulted in termination of saline infusion. The use of LUS in monitoring WLL reduced amount of saline used for lavage, pick up complications like pleural effusion and spillage.

Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia.

The present study assessed the effects of γ-aminobutyric acid (GABA) from β-cells on glucose levels and glucagon secretion, and identified channels via which glucagon secretion is initiated. An in vivo experiment was performed containing three groups: Intrapancreatic artery infusion of GABA alone, GABA plus insulin or insulin alone in rats with diabetes. Rats infused with GABA and insulin were also subdivided in groups receiving additional infusion of K+-channel activator diazoxide (DIA), K+-channel blocker tolbutamide (TLB) and calcium channel blocker nifedipine (NIF). In the hypoglycemic state, termination of infusion of insulin and insulin plus GABA resulted in signaling to the α-cells to secrete glycogen, while that of GABA alone did not. However, intrapancreatic artery infusion of K+-channel activator DIA, K+-channel blocker TLB or calcium channel blocker NIF in addition to GABA and insulin had no effect on glucagon secretion. In conclusion, if the delivery of insulin or GABA plus insulin in rats with hypoglycemia is terminated, β-cells are stimulated and signal the α-cells to secrete glucagon. Thus, the detection of a sudden decrease in zinc levels by β-cells as well as a decrease in GABA in the periportal circulation induces signaling to α-cells to stimulate them to secrete glucagon.

Correlation between time lag of arterial–plethysmographic waveforms and systemic vascular resistance: a prospective study

Blood pressure (BP), a surrogate of cardiac output (CO), is also dependent on systemic vascular resistance (SVR). But SVR is not routinely monitored in daily clinical practice. We hypothesise that the time difference between the peripheral arterial waveform and the finger plethysmographic waveform (time lag index - TLi) could indicate the systemic vascular resistance. In this study, we correlated TLi with the systemic vascular resistance measured by minimally invasive CO monitor (pulse contour analysis). SVR changes in response to administration of mannitol were studied. American Society of Anesthesiologists (ASA) class I and II patients undergoing major intracranial surgeries were recruited. Arterial cannulation and pulse-oximetry recordings were done in the same limb. Arterial and plethysmographic waveforms were recorded before mannitol infusion (baseline) and at every 10 minutes for 60 minutes after the termination of mannitol infusion. Simultaneously, SVR was recorded from the Vigileo FLotrac CO monitor. Using custom-made programme, the time difference between both waveforms was calculated and corrected for heart rate (TLi). The correlation between time lag and the systemic vascular resistance was assessed using a mixed effect model, adjusting for the subject. Data of one hundred subjects were analysed. Following mannitol administration, there was a significant decrease in the SVR and the TLi (p < .001). The patient characteristics influenced both the baseline values of SVR (intercept) and the changes in SVR over time (slope). As both the baseline value and the change over time for SVR were different in each patient, we used mixed effect model analysis to assess the relationship between SVR and TLi for different time periods. The effect of TLi on SVR was significant (β = 877.16, p = .008). The high beta coefficient suggests that when SVR increases, the TLi also increase and vice versa. A strong correlation between SVR and TLi was demonstrated for a given patient. Further studies are needed to explore the possibility of utilising this parameter to follow up changes in SVR in an individual patient at a particular point in time in different clinical scenarios.

Population Pharmacokinetics of Levofloxacin in Plasma and Bone of Patients Undergoing Hip or Knee Surgery.

Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before they enter the operation theater. This treatment intends to reduce the incidence of peri- or postsurgical infections. Here, we calculated the uptake kinetics of levofloxacin into bone to see whether levofloxacin could be obtained from the trabecular and cortical bone and at what time concentrations are sufficiently high to inhibit the usual hospital infections. Patients (n= 42) undergoing routine surgery were treated with 500mg levofloxacin intravenously immediately prior to the operation. Plasma samples were taken before and at 3 points after termination of drug infusion. After replacement of the bones, extracts were obtained from them. Levofloxacin was quantified using high-performance liquid chromatography. The kinetics of levofloxacin and its distribution into bone were analyzed using a population approach (ADAPT5). Clearance was 14.0 L/h, and distribution volume was 77 L. Bone uptake t½ was calculated as 4.2 and 5.4hours for cortical bone and trabecular bone, respectively. In knee samples (but not in hip samples), we noted that the cortical bone contained higher levels of levofloxacin than the trabecular bone. From our data, we can conclude that levofloxacin might be useful for prophylactic use in bone surgery.

Lack of an Effect of Gastric Capsaicin on the Rectal Component of the Gastrocolonic Response.

Eighteen healthy volunteers participated twice, at least 1week apart, in this double-blind, placebo-controlled crossover study. Participants swallowed a gastric tube for capsaicin or saline infusion. A barostat tube was placed in the rectum to measure rectal tone before and during gastric capsaicin (40µg/ml, 2.5ml/min) or placebo infusion and to conduct distension experiments before and after gastric infusions. Gastric infusions were terminated after 60min or when epigastric discomfort occurred. Differences in rectal tone, compliance, and sensitivity between gastric placebo and gastric capsaicin were determined. On both study days, basal rectal volumes, compliance, and sensitivity parameters were comparable (NS) before gastric infusions. Gastric capsaicin infusion induced epigastric discomfort that necessitated termination of infusion after 29.6±12.3min (saline: 54.7±8.9min; p<0.01). Rectal tone, aggregate perception scores, and rectal compliance did not differ between placebo and capsaicin trials (p>0.05). Rectal tone increased significantly only when capsaicin induced epigastric discomfort (p<0.05). The reproducibility of the barostat trial was acceptable with significant correlations of volumes, pressures (<0.05; r 2 from 0.41 to 0.55), rectal compliance (p<0.01; r 2=0.44), and aggregate perception scores (p values all<0.05; r 2 from 0.44 to 0.0.65) between the two barostat trials. Gastric perfusion with capsaicin does not directly influence rectal physiology through a reflex arc.

5-HT causes splanchnic venodilation.

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg-1·min-1) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure.NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT7 receptor, an in vitro observation (venorelaxation) with in vivo events (venodilation and fall in blood pressure). This supports the idea that splanchnic venodilation plays a role in blood pressure regulation.

Effectiveness of heart rate control on hemodynamics in critically ill patients with atrial tachyarrhythmias managed by amiodarone

Atrial tachyarrhythmias (AT) are common in intensive care unit (ICU) patients and might contribute to hemodynamic instability if heart rate (HR) is persistently too rapid. We aimed to assess if HR control below 115 or 130bpm with amiodarone improves hemodynamics in ICU patients with AT.This observational study included 73 ICU patients with disabling AT receiving amiodarone for HR control. A total of 525 changes (mainly within 4–8h) in mean arterial pressure (MAP) and 167 changes in plasma lactate in response to HR variations above 115 or 130bpm were analyzed. Epinephrine, sedative drugs, fluid loading, use of diuretics, continuous renal replacement therapy and amiodarone dosing were among covariables assessed.Univariable analysis showed that HR variations above 115bpm were poorly correlated to change in MAP (r=0.11, p<0.01). Multivariable analysis showed that changes in MAP were still positively associated to HR variation (p<0.05) and to initiation or termination of epinephrine (p<0.05) or sedatives infusions (p<0.05). Changes in plasma lactate did not correlate to HR variations above 115bpm. When considering 130 bpm as a threshold, HR variations were not associated to changes in MAP or to changes in plasma lactate. Amiodarone dose was associated to HR decrease but not to MAP or plasma lactate increase.In ICU patients with AT, strict HR control below 115bpm or 130bpm with amiodarone does not improve hemodynamics. A prospective randomized trial assessing strict versus lenient HR control in this setting is needed.

Treatment Acute Myeloid Leukemia Using Cytoreductive Chemotherapy Cytarabine (Ara-C) Followed Azacitidine (AZA) Maintenance: A Real Life Single Center Experience

Background: Older patients (pts) with acute myeloid leukemia (AML) have a particularly dismal outcome, because of adverse features of AML in the elderly and frailty. The median duration of complete remission (CR) last less than 1 year. The optimal management of older AML pts in daily clinical practice has not been determined. Regular treatment options include best support care, low dose cytarabine (Ara-c) and intensive chemotherapy (anthracycline combined with ara-c). Recently, the DNA methyltransferase inhibitor Azacitidine (AZA) has demonstrated significant activity and favorable tolerability in AML pts also showing a survival advantage.Materials and Methods: Between May 2013 and July 2016, at our institution, 19 pts with a diagnosis of AML (13 males and 7 females) were judged to be ineligible for intensive chemotherapy due to age or comorbidities. They received a 5-day regimen of cytoreductive chemotherapy with ara-c at a dosage of 100 mg\\mq\\day i.v. continuous infusion. On the sixth day, on termination of Ara-c infusion, all pts had ≤30% bone marrow blasts. Therefore, AZA was administered at a dosage of 75 mg\\mq\\day subcutaneously for 7 days, continuing the therapy every 28 days. The median age of pts was 75 years (range, 49 to 79 years), with 17 pts (89%) aged over 65 years. Six pts (32%) had poor molecular and cytogenetic risks markers, and six other pts (32%) had either antecedent myelodisplastic/myeloproliferative diseases or therapy related AML. The response to therapy according to the AML IWG criteria was assessed by bone marrow aspiration immediately after Ara-c infusion, after one AZA cycle and every 6 months thereafter. Baseline pts characteristics are summarized in Table 1.Results: The median number of administered AZA cycles was 6 (range, 1-25 cycles). Fifty eight percent (11/19) of pts received ≥6 AZA clycles. The median overall survival was 6 months (range, 1-26 months). According to AML IWG criteria, 8 pts (42%) achieved CR after Ara-c and a single AZA cycle. Of these, 5 pts (62%) are currently alive in CR, with median duration of response of 7 months (range: 5-12 months), while 3 pts (38%) died after 4, 12, and 22 months after diagnosis. One pt (5%) achieved a partial response (PR) after one AZA cycle, maintaining at present the same response after 3 months of therapy. Other 8 pts (42%) obtained stable disease (SD). Of these, 3 pts (37%) are currently in SD after 2, 8 and 10 months of therapy, while 5 pts (64%) died within a median of 5 months (range: 2 - 18 months) after AML diagnosis. Finally 1 pt (5%) was refractory dying after 2 months of diagnosis, and another pt (5%) died after first AZA cycle for sepsis. Fever and infections were the most common non-hematologic toxic events after Ara-c chemotherapy and first AZA cycle (17/19 pts, 90%). While subsequent AZA cycles were well tolerated.Conclusion: We suggest that the use of Ara-c-AZA combination is feasible in elderly AML pts. However, the relatively small number of pts studied and short follow up preclude definitive conclusion. The study is still accruing patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of radiation safety in 177Lu-PSMA therapy and development of outpatient treatment protocol

The aim of this study is to investigate the outpatient treatment protocol and radiation safety of a new-emerging lutetium-177 (177Lu) prostate specific membrane antigen (PSMA) therapy.This work analyzed the dose rate of 23 patients treated with 7400 MBq 177Lu-PSMA at different distances (0, 0.25, 0.50, 1.0 and 2.0 m) and variable time marks (0, 1, 2, 4, 18, 24, 48 and 120 h) after the termination of infusion. Blood samples were withdrawn from 17 patients within the same group at 3, 10, 20, 40, 60 and 90 min and 2, 3, 24 h after termination of infusion. Seven different patients were asked to collect urine for 24 h and a gamma well counter was used for counting samples. Family members were invited to wear an optically stimulated luminescence dosimeter whenever they were in the proximity of the patients up to 4–5 d. The total dose of the medical team including the radiopharmacist, physicist, physician, nurse, and nuclear medicine technologist was estimated by an electronic personnel dosimeter. The finger dose was determined using a ring thermoluminescent dosimeter for the radiopharmacist and nurse.The mean dose rate at 1 m after 4 h and 6 h was 23 ± 6 μSv h−1 and 15 ± 4 μSv h−1 respectively. The mean total dose to 23 caregivers was 202.3 ± 42.7 μSv (range: 120–265 μSv). The radiation dose of the nurse and radiopharmacist was 6 and 4 μSv per patient, respectively, whereas the dose of the physicist and physician was 2 μSv. The effective half life of blood distribution and early elimination was 0.4 ± 0.1 h and 5 ± 1 h, respectively. Seven patients excreted a mean of 45% (range: 32%–65%) from the initial activity in 6 h.Our findings demonstrate that 177Lu-PSMA is a safe treatment modality to be applied as an outpatient protocol, since the dose rate decreases below the determined threshold of <30 μSv h−1 after approximately 5 h and degrades to 20 μSv h−1 after 6 h.

Use of Intra-arterial Thrombolytic Therapy for Acute Treatment of Frostbite in 62 Patients with Review of Thrombolytic Therapy in Frostbite.

Amputations are common after severe frostbite injuries, often mediated by postinjury arterial thrombosis. Since 1994, the authors have performed angiography to identify perfusion deficits in severely frostbitten digits and treated these lesions with intraarterial infusion of thrombolytic agents, usually combined with papaverine to reduce vasospasm. A retrospective review was performed of patients admitted to the regional burn center with frostbite injury from 1994 to 2007. Patients with severe frostbite, without contraindications to thrombolytic therapy, underwent diagnostic angiography of the affected extremities. Limbs with perfusion defects received intraarterial thrombolytic therapy according to protocol and the response was documented. Delayed amputation was performed for mummified digits. Angiogram results and amputation rates were tabulated. In this 14-year review, 114 patients were admitted for frostbite injuries. There was a male predominance (84%) and the mean age was 40.4 years. Of this group, 69 patients with severe frostbite underwent angiography; 66 were treated with intraarterial thrombolytic therapy. Four treated were excluded due to incomplete data. In the remaining 62 patients, angiography identified 472 digits with frostbite injury and impaired arterial perfusion. At the termination of thrombolytic infusion, a completion angiogram was performed. Partial or complete amputations were performed on only four of 198 digits (2.0%) with distal vascular blush, and in 71 of 75 digits (94.7%) with no improvement. Amputations occurred in 73 of 199 digits (36.7%) with partially restored flow. Overall complete digit salvage rate was 68.6%. Angiography after severe frostbite is a sensitive method to detect impaired arterial blood flow and permits catheter-directed treatment with thrombolytic agents. Improved perfusion after such treatment decreases late amputations following frostbite injury.

Acute Beta Blockade at Peak Stress: Will It Alter the Sensitivity of Dobutamine Stress Echocardiography in Patients with Normal Resting Wall Motion?

We compared the accuracy of recovery phase images following administration of intravenous propranolol with peak stress images, for detection of coronary artery disease in patients with no resting wall motion abnormalities undergoing dobutamine stress echocardiography. We enrolled 100 consecutive patients with no resting wall motion abnormalities who underwent dobutamine stress echocardiography. Propranolol was injected after termination of dobutamine infusion. Positive peak stress images were defined as the induction of wall motion abnormalities at any stage before propranolol injection. Positive recovery phase images were defined as maintenance or worsening of wall motion abnormalities induced at peak stress, or the appearance of new wall motion abnormalities during recovery phase. Significant coronary stenosis was defined as ≥ 50% obstruction of ≥ 1 sizable artery by coronary angiography. Seventy-two patients (72%) had significant coronary artery disease. Analysis of peak stress images revealed sensitivity, specificity, positive and negative predictive values of 80.6%, 85.7%, 93.5%, and 63.2%; the overall accuracy was 82%. Analysis of the recovery phase images revealed sensitivity, specificity, positive and negative predictive values of 91.7%, 75%, 90.4%, and 77.8%; here, the overall accuracy was 87%. In patients with no resting wall motion abnormalities, acute beta blockade during dobutamine stress echocardiography improved the sensitivity of recovery phase images for detection of significant coronary artery disease versus peak stress images, but with reduced specificity. Accuracy; Beta blocker; Coronary artery disease; Dobutamine stress echocardiography; Recovery phase images.

Abstract 17429: A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Sustained Severe Hypertension

Background: Currently, the lack of well-established large animal models of heart failure with preserved ejection fraction (HFpEF) is one of the major hurdles for developing effective therapies for HFpEF. Here, we describe a large animal model of HFpEF induced by sustained hypertension (HT) that mimics human diseases. Methods: We induced sustained severe hypertension in 9 adult pigs using a combination of intravenous Angiotensin-II (Ang-II, 0.015mg/hr) delivery with an osmotic infusion pump and subcutaneous implantation of deoxycorticosterone acetate (DOCA) pellets (100mg/kg) for 10 weeks. All animals underwent invasive blood pressure (BP) telemetry monitoring and serial invasive pressure-volume (PV) loop assessment as well as echocardiographic examination at baseline, 10 weeks and 18 weeks. Results: Mean systolic and diastolic BP at baseline was 88/61 mmHg which increased immediately after Ang-II infusion plus DOCA (Week 0,158/105 mmHg) and progressively elevated up to Week 10 (171/126mmHg) that persisted out to Week 18 (183/137mmHg) despite termination of Ang-II infusion. Serial echocardiograms showed the development of left ventricular hypertrophy with significant increase in left ventricular mass with preserved left ventricular ejection fraction (Figure, upper panel). PV loop showed progressive elevation of pulmonary artery capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and end-diastolic pressure volume relationship (EDPVR) without change in end-systolic pressure volume relationship, suggestive of left ventricular diastolic dysfunction (Figure, lower panel). Conclusions: We successfully established a clinically relevant large animal model of HFpEF induced by sustained HT, which can be used for future investigation of new treatments for HFpEF.

Electrocardiographic profile of adenosine pharmacological stress testing.

Adenosine stress testing in conjunction with radionuclide myocardial perfusion imaging has become a common approach for the detection of coronary artery diseases in patients who are unable to perform adequate levels of exercise. However, specific electrocardiographic alterations during the test have been rarely described. Using a Chinese population, the aim of the present study was to provide a detailed electrocardiographic profile of adenosine stress testing. The study population included 1,168 consecutive outpatients who had undergone adenosine-induced stress myocardial perfusion imaging. Electrocardiographic data during and immediately following the adenosine infusion were collected, and the corresponding myocardial perfusion images were assessed. During adenosine infusion, 174 transient and 47 persistent arrhythmic events occurred in 110 patients (9.42%). Furthermore, frequent premature atrial contractions occurred in 65 individuals and frequent premature ventricular contractions were observed in 73 individuals. Atrioventricular block (AVB) occurred in 75 patients [first degree (I°) AVB, 16; second degree (II°) AVB, 58; third degree AVB, 1), while sinoatrial block occurred in eight patients. ST depression emerged in 69 patients. Patients with a baseline I° AVB had an increased risk of a II° AVB, and patients exhibiting baseline ST depression were more likely to have a further depressed ST segment during the stress test (odds ratio, 28.68 and 5.01, respectively; both P<0.001). Following adenosine infusion, 10 patients (0.86%) exhibited newly occurred arrhythmic events. However, no patient presented with acute myocardial infarction or sudden mortality. In conclusion, the results demonstrated that adenosine infusion was a safe method, despite the relatively high incidence of arrhythmic events. The majority of arrhythmias that occurred during infusion were transient, were reversible with the termination of infusion and did not indicate abnormal perfusion results.

Abstract W P241: Identification of Neural Stem Cells in Neurogenic Niche After Stroke

Background: Adult neural stem cells (NSCs) are present in the rodent ventricular-subventricular zone (V/SVZ) of the lateral ventricles. However, their in vivo role in stroke-induced neurogenesis remains uncertain. Using an anti-mitotic agent (Ara-C) in combination with phenotype markers, we examined NSCs in whole-mount preparation of the lateral ventricle of ischemic brain. Methods and Results: Adult mice (n=28) were used. Focal cerebral ischemia was induced by occluding the right middle cerebral artery. Ara-C was infused on brain surface of mice for 7 days. BrdU was administered to label proliferating cells. Another 6 mice with non-ischemia, non-infusion were also given BrdU labeling as normal control. The architecture of NSCs identified by inhibitor of DNA binding/Differentiation 1 (Id1, a transcription factor)+/GFAP+ in the V/SVZ were examined in whole mount by means of a 3D confocal microscope. In a normal V/SVZ, 3% (at least 4,000 cells counted per each sample) cells were Id1+. Of these Id1+ cells, 16% cells were GFAP+, which were anchored by specialized apical end-feet in the center of the pinwheel of ependymal cells and they often extended basal processes at least 50 -80 um long; none of these cells were BrdU+ after 1h pulse labeling, indicating that these cells are relatively quiescent. However, 69 % of Id1+ cells were Mash+ and Olig2+ and the majority of these cells were BrdU+, indicating that these are active progenitor cells. 1h after termination of infusion, Id1+/Mash+ and Olig2+ cells were eliminated, whereas Id1+/GFAP+ cells in the center of pinwheels were not affected in non-ischemic and ischemic V/SVZ niches. At this time point, there were no actively proliferating cells measured by 1h BrdU pulse labeling. However, by 48h after termination of infusion, there were many proliferating cells with 59% and 75% of BrdU+ cells were Id1+ in non-ischemic and ischemic V/SVZ niches (p&lt;0.05), respectively. In the ischemic V/SVZ niche, in the center of pinwheels the majority of Id1+/BrdU+ cells were GFAP+ . Conclusion: Our in vivo data suggest that adult V/SVZ niche GFAP+/Id1+ astrocytes are “functional quiescent” NSCs. Stroke recruits quiescent NSCs in the V/SVZ niche to an active pool for enhancing the neurogenic process in response to ischemic insult.