Carotid Artery Cannulation Research Articles

Transverse Sternal Split: a Safe Mini-invasive Approach for Perventricular Device Closure of Ventricular Septal Defect.

ObjectivePerventricular device closure of ventricular septal defect through midline sternotomy avoids the cardiopulmonary bypass, however, lacks the cosmetic advantage. Perventricular device closure of ventricular septal defect with transverse split sternotomy was performed to add the cosmetic advantage of mini-invasive technique.MethodsThirty-six pediatric patients with mean age 7.14±3.24 months and weight 5.00±0.88 kg were operated for perventricular device closure of ventricular septal defect through transverse split sternotomy in 4th intercostal space under transesophageal echocardiography guidance. In case of failure or complication, surgical closure of ventricular septal defect was performed through the same incision with cervical cannulation of common carotid artery and internal jugular vein for commencement of cardiopulmonary bypass. All the patients were postoperatively followed, and then discharged from hospital due to their surgical outcome, morbidity and mortality.ResultsProcedure was successful in 35 patients. Two patients developed transient heart block. Surgical closure of ventricular septal defect was required in one patient. Mean duration of ventilation was 11.83±3.63 hours. Mean intensive care unit and hospital stay were 1.88±0.74 days and 6.58±1.38 days, respectively. There was no in-hospital mortality. A patient died one day after hospital discharge due to arrhythmia. No patients developed wound related, vascular or neurological complication. In a mean follow-up period of 23.3±18.45 months, all 35 patients were doing well without residual defect with regression of pulmonary artery hypertension as seen on transthoracic echocardiography.ConclusionTransverse split sternotomy incision is a safe and effective alternative to a median sternotomy for perventricular device closure of ventricular septal defect with combined advantage of better cosmetic outcomes and avoidance of cardiopulmonary bypass.

Inwardly rectifying K+ channels are major contributors to flow-induced vasodilatation in resistance arteries.

Endothelial inwardly rectifying K+ (Kir2.1) channels regulate flow-induced vasodilatation via nitric oxide (NO) in mouse mesenteric resistance arteries. Deficiency of Kir2.1 channels results in elevated blood pressure and increased vascular resistance. Flow-induced vasodilatation in human resistance arteries is also regulated by inwardly rectifying K+ channels. This study presents the first direct evidence that Kir channels play a critical role in physiological endothelial responses to flow. Inwardly rectifying K+ (Kir) channels are known to be sensitive to flow, but their role in flow-induced endothelial responses is not known. The goal of this study is to establish the role of Kir channels in flow-induced vasodilatation and to provide first insights into the mechanisms responsible for Kir signalling in this process. First, we establish that primary endothelial cells isolated from murine mesenteric arteries express functional Kir2.1 channels sensitive to shear stress. Then, using the Kir2.1+/- heterozygous mouse model, we establish that downregulation of Kir2.1 results in significant decrease in shear-activated Kir currents and inhibition of endothelium-dependent flow-induced vasodilatation (FIV) assayed in pressurized mesenteric arteries pre-constricted with endothelin-1. Deficiency in Kir2.1 also results in the loss of flow-induced phosphorylation of eNOS and Akt, as well as inhibition of NO generation. All the effects are fully rescued by endothelial cell (EC)-specific overexpression of Kir2.1. A component of FIV that is Kir independent is abrogated by blocking Ca2+ -sensitive K+ channels. Kir2.1 has no effect on endothelium-independent and K+ -induced vasodilatation in denuded arteries. Kir2.1+/- mice also show increased mean blood pressure measured by carotid artery cannulation and increased microvascular resistance measured using a tail-cuff. Importantly, blocking Kir channels also inhibits flow-induced vasodilatation in human subcutaneous adipose microvessels. Endothelial Kir channels contribute to FIV of mouse mesenteric arteries via an NO-dependent mechanism, whereas Ca2+ -sensitive K+ channels mediate FIV via an NO-independent pathway. Kir2 channels also regulate vascular resistance and blood pressure. Finally, Kir channels also contribute to FIV in human subcutaneous microvessels.

Effects of testosterone on mean arterial pressure and aquaporin (AQP)-1, 2, 3, 4, 6 and 7 expressions in the kidney of orchidectomized, adult male Sprague-Dawley rats

We hypothesized that higher blood pressure in males than females could be due to testosterone effects on aquaporin (AQP) expression in kidneys. Methods: Orchidectomized adult male Sprague-Dawley (SD) rats received seven days subcutaneous testosterone treatment (125 μg/kg/day or 250 μg/kg/day), with or without flutamide or finasteride. Following completion of treatment, MAP was determined in rats under anaesthesia via carotid artery cannulation. In another cohort of rats, kidneys were removed following sacrifice and AQP-1, 2, 3, 4, 6 and 7 protein and mRNA levels were determined by Western blotting and Real-time PCR respectively. Distribution of AQP subunits' protein in the nephrons were visualized by immunofluorescence. ResultsTestosterone caused MAP, AQP-1, 2, 4, 6 and 7 protein and mRNA levels in kidneys to increase while AQP-3 protein and mRNA levels in kidneys to decrease (p < 0.05). AQP-1 and 7 were found to be distributed in the proximal convoluted tubule (PCT) while AQP-2, 3, 4 and 6 were found to be distributed in the collecting ducts (CD). Effects of testosterone were antagonized by flutamide and finasteride. ConclusionsElevated expression of AQP-1, 2, 4, 6 and 7 under testosterone influence in kidneys could lead to increase H2O reabsorption which eventually lead to increase in blood pressure.

Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function.

Our purpose was to determine if endoplasmic reticulum stress inhibition lowers blood pressure (BP) in hypertension by correcting vascular dysfunction. The spontaneously hypertensive rat (SHR) was used as a model of human essential hypertension with its normotensive control, the Wistar Kyoto rat. Animals were subjected to endoplasmic reticulum stress inhibition with 4-phenylbutyric acid (4-PBA; 1 g/kg per day, orally) for 5 weeks from 12 weeks of age. BP was measured weekly noninvasively and at endpoint with carotid arterial cannulation. Small mesenteric arteries were removed for vascular studies. Function was assessed with a Mulvany-Halpern style myograph, and structure was assessed by measurement of medial-to-lumen ratio in perfusion fixed vessels as well as three-dimensional confocal reconstruction of vessel wall components. Endoplasmic reticulum stress was assessed by quantitative real time-PCR and western blotting; oxidative stress was assessed by 3-nitrotyrosine and dihydroethidium staining. 4-PBA significantly lowered BP in SHR (vehicle 206.1 ± 4.3 vs. 4-PBA 178.9 ± 3.1, systolic) but not Wistar Kyoto. 4-PBA diminished contractility and augmented endothelial-dependent vasodilation in SHR small mesenteric arteries, as well as reducing media-to-lumen ratio. 4-PBA significantly reduced endoplasmic reticulum stress in SHR resistance vessels. Normotensive resistance vessels, treated with the endoplasmic reticulum stress-inducing agent, tunicamycin, show decreased endothelial-dependent vasodilation; this was improved with 4-PBA treatment. 3-Nitrotyrosine and dihydroethidium staining indicated that endoplasmic reticulum stress leads to reactive oxygen species generation resolvable by 4-PBA treatment. Endoplasmic reticulum stress caused endothelial-mediated vascular dysfunction contributing to elevated BP in the SHR model of human essential hypertension.

Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry.

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. Indeed, research focusing on the discovery of new potential therapeutic targets using genetically altered mice requires a reliable, long-term assessment of the systemic arterial pressure variation. Currently, the gold standard for obtaining long-term measurements of blood pressure in ambulatory mice uses implantable radio-transmitters, which requireartery cannulation. This technique eliminates the need for tethering, restraining, or anesthetizing the animals which introduce stress and artifacts during data sampling. However, arterial blood pressure monitoring in mice via catheterization can be rather challenging due to the small size of the arteries. Here we present a step-by-step guide to illustrate the crucial key passages for a successful subcutaneous implantation of radio-transmitters and carotid artery cannulation in mice. We also include examples of long-term blood pressure activity taken from freely moving mice after a period of post-surgery recovery. Following this procedure will allow reliable direct blood pressure recordings from multiple animals simultaneously.

Population Pharmacokinetic Modeling of Etoposide Free Concentrations in Solid Tumor.

This study aimed to determine free etoposide (ETO) concentrations in two regions of Walker-256 (W256) solid tumor using microdialysis and to establish a population pharmacokinetic (popPK) model to describe simultaneously free tumor and total plasma concentrations. W256 tumor-bearing Wistar rats received ETO 10 or 20mg/kg i.v. bolus. Free ETO concentrations were sampled from central and peripheral regions of the tumor via CMA/20 probes for up to 7h, whereas blood samples were collected via carotid artery cannulation. Total plasma and free tumor concentration-time profiles were analyzed by non-compartmental approach using WinNonlin® v. 5.3. PopPK modeling was conducted using MONOLIX v.4.3.3. ETO penetration was higher in the periphery (61 ± 15% and 61 ± 29%) than in tumor center (34 ± 6% and 28 ± 11%) following 10 and 20mg/kg doses, respectively (ANOVA, α = 0.05). A 4-compartment model fitted ETO concentration-time profiles in all sampling compartments. The popPK model allowed the simultaneous fitting of plasma and tumor concentrations and a better understanding of ETO distribution in solid tumors. ETO plasma concentrations are not a good surrogate for tumoral exposure, emphasizing the importance of knowing intratumoral concentrations to predict drug response.

Abstract 19743: Electrophysiological and Cerebrovascular Effects of Selective Antegrade Cerebral Perfusion in Moderate Hypothermia vs. Deep Hypothermic Circulatory Arrest in a Rat Model

Introduction: Selective antegrade cerebral perfusion (SACP) is adopted by many surgical groups as an alternative to deep hypothermic circulatory arrest. However there are still no preclinical evidences to support this strategy. Hypothesis: We hypothesize that SACP in moderate hypothermia vs DHCA could have different modulation of electrophysiological and cerebrovascular processes in vivo. Methods: Extra-corporeal circulation with central cannulation was instituted in male Wistrar rats. Animals were randomized to DHCA (16-18°C) or SACP (left carotid artery cannulation; 10 ml/kg/min) in moderate hypothermia (26-28°C). After 20 min of circulatory arrest, rats underwent 60 min of reperfusion / rewarming. EEG activity was recorded during all experiments. Neurological deficit score and survival were determined after 24 hours. Thereafter animals were scarified and brain snap-frozen and analyzed. Results: EEG activity 2-40 Hz (Power Spectrum Analysis) decreased in all rats during circulatory arrest. However, SACP determined fast recovery of brain activity and less decreased EEG power spectral density compared to DHCA (p &lt;0.05). After 24 h survival and neurologic deficit scores were not different in the two groups. However histological damage scores, brain TNF-α, caspase-3, TUNEL and GSH/GSSG ratio were attenuated in SACP compared to DHCA (all p&lt;0.05). Conclusions: Selective antegrade cerebral perfusion in moderate hypothermia is superior to DHCA in restoring brain electrical activity and in reducing apoptosis, oxidative stress and neuroinflammation.

Usefulness of a Transbrachial Guide Sheath Specifically Designed for Direct Common Carotid Artery Cannulation in Common Carotid Artery Stenting

The transfemoral approach is a common technique for carotid artery stenting(CAS)and involves the risk of distal embolism when a high-grade stenosis occurs at the common carotid artery(CCA). In this study, to minimize the risk of thromboembolic complications, we used a guide sheath that was specifically designed for direct cannulation to the CCA without the use of a guidewire or coaxial catheter. This study included 5 patients who underwent CAS of the CCA by using a guide sheath. Of these patients, 2 had right CCA stenosis and the other 3 had left CCA lesions. In all cases, direct cannulation to the target CCA by using the guide sheath was achieved, and CAS was performed safely. The median time from puncture to the end of the procedure was 61 min(interquartile range: 53-63). No periprocedural complications or cardiovascular events occurred within 30 days after CAS. CAS was safely and successfully performed for CCA stenosis by using the transbrachial guide sheath that was specifically designed for direct cannulation to the CCA.

Effects of ulinastatin on hemorrhagic shock and resuscitation-induced acute lung injury in rats

Objective To evaluate the effects of ulinastatin on hemorrhagic shock and resuscitation (HS/R) -induced acute lung injury in rats. Methods Fifteen SPF adult Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were divided into 3 groups (n=5 each) using a random number table: sham operation group (group S) , HS/R group and ulinastatin group (group U) . Carotid arteries were cannulated for blood pressure monitoring and blood-letting.HS/R was induced by blood-letting and maintained for 1 h, followed by resuscitation with autologous blood transfusion and infusion of normal saline.After cannulation of carotid arteries (T0) , at 5 min after hemorrhagic shock (T1) , before resuscitation (T2) , at 5 min after the expected blood pressure was achieved following resuscitation (T3) , and at 30 min, 1.5 h and 2.5 h after resuscitation (T4-6) , arterial blood samples were collected for determination of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations (by enzyme-linked immunosorbent assay) . Arterial blood samples were collected at T0, T2 and T6 for blood gas analysis.The pH value, partial pressure of arterial carbon dioxide (PaCO2) , and base excess (BE) value were recorded, and oxygenation index (PaO2/FiO2) was calculated.Lungs were removed at T6, and pulmonary specimens were obtained for examination of pathological changes which were scored, and nucleus was extracted for determination of nuclear factor-kappa B (NF-κB) p65 expression by enzyme-linked immunosorbent assay. Results Compared with group S, the pH values, , BE values and OI were significantly decreased, and PaCO2, plasma IL-6 and TNF-α concentrations, expression of NF-κB p65 in lung tissues, and pathological scores were increased in U and HS/R groups.Compared with group HS/R, the plasma concentrations of IL-6 and TNF-α, expression of NF-κB p65 in lung tissues, and pathological scores were significantly decreased, and no significant changes were found in parameters of blood gas analysis in group U. Conclusion Although ulinastatin can alleviate HS/R-induced acute lung injury, it is insufficient to improve lung oxygenation in rats. Key words: Trypsin inhibitors; Shock, hemorrhagic; Cardiopulmonary resuscitation; Respiratory distress syndrome, adult

Effect of Pre‐ and Peri‐natal Feeding of High Salt Diet on Cardio‐Renal Functions of Female Offsprings of Sprague‐Dawley Rats

To evaluate the effect of pre- and perinatal high salt diet on the female offsprings of Sprague Dawley rats. Weanling female rats, 6 weeks old, body weight 140 – 190g were fed with normal (0.3%) or high salt diet (HSD) (8% Nacl) for 12 weeks. During the 4th week, males were introduced to cycling proestrous females. Fluid balance was determined from the differences between 24 hours water intake and urine output that was measured during the last week of the experiment. At the end of the experimental period, blood pressure was measured via carotid artery cannulation, Plasma and urinary concentration of electrolytes- (mmol/l) were measured. Plasma nitrite concentration (PNC) – umol/100g protein was determined using Griess assay. Oxidative status of the kidney was determined by measurement of lipid peroxidation (LP), superoxide dismutase (SOD) – mg/ml, catalase – mg/ml and reduced glutathione (GSH) – umol/ml, levels in the kidney homogenates. HSD increased mean arterial blood pressure (MABP) - mmHg, kidney weight index, fluid retention (FR) - ml/24hr, urinary sodium concentration - mmol/l and LP -nmol/ml, in the dams as well as in the offsprings. However, HSD decreased PNC, urinary potassium concentration (UPC), SOD, catalase and GSH in the dams and also in the offsprings. It thus appears that pre and perinatal high salt diet impact on cardiovascular and renal functions of the female offsprings possibly by mechanisms involving oxidative stress and nitric oxide pathway. Acknowledgement: Medical Education Partnership Initiative in Nigeria (MEPIN) 03 Mentored Research Award

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma.

Carotid artery cannulation in aortic surgery: why not?

Since the first use of cardiopulmonary bypass during replacement of the aortic arch in the early 1960s, the techniques of arterial cannulation have been highly variable. Yet, during several decades, the problem was considered as solved. The femoral artery was almost systematically used and it took almost 30 years to get aware that this technique could be harmful in some patients and the cause of severe complications, such as embolism and malperfusion, even rupture of the aorta, in particular in cases of acute dissection. It became obvious then that a satisfactory arterial cannulation should provide an antegrade flow to the whole aorta, and that it should allow possibly performing a proper cerebral protection during the time of arch exclusion and repair. Many solutions were proposed and described but not systematically adopted as they were either too complicated, or were associated with too many drawbacks. In 1995, Sabik et al. [1] proposed to use the right axillary artery. This approach had indeed many advantages and was obviously fulfilling most of the requirements of the surgical community. The technique was rapidly popularized and adopted by most groups dealing with aortic surgery, especially aortic arch replacement. But, as nothing is perfect in this small world, the use of this arterial site proved through many large experiences, to also have drawbacks and complications that could represent some disincentive for its systematic use. So, in 2006, Urbanski [2] proposed to use systematically the common carotid artery through a side graft and for both the whole cardiopulmonary bypass and the cerebral protection. In this paper of the MMCTS, Urbanski [3] perfectly describes the technical features of this mode of cannulation and perfusion. The text is clear, and well written; the video perfectly shows the surgical procedure and, quite interestingly, the necessary time to achieve it in ~15 min that, obviously, is less than for the axillary artery and no more than for the femoral artery in most patients. Moreover, the rationale for using this technique is appropriately developed and convincing enough. In particular, the drawbacks of the other modes of cannulation are well presented and discussed. One exception, though: I do not totally agree with the author’s criticism of the innominate artery cannulation. It is stated, indeed ‘it (the innominate artery) is frequently involved in aortic pathology, regardless if it is dissection or arteriosclerosis, and these pathological changes could be identified as predictors for increased neurological morbidity. Therefore, the IA cannulation is, in our opinion, suitable for cases with limited aortic repairs, e.g. hemi-arch replacements, in which the arch and proximal portions of the supra-aortic arteries are not pathologically changed’. The right common carotid artery being a branch of the innominate artery, the same comments should apply to this structure. In addition, even though the use of the innominate artery has been presented in recent years as a new and original technique, this is not the case. It is used by some groups for decades and I have used it as a routine mode of cannulation during the last 30 years in all types of cardiac and aortic surgery and not only for hemi-arch replacements. Another point of slight disagreement could be the fact that the author states having encountered no complications at all in more than 1000 cases. With all due respect to Paul Urbanski and to the excellent results reported here, it is somewhat difficult for me to agree that a vascular surgical approach, whatever its nature, would never provide any bleeding requiring reopening and drainage, small local (skin, muscles?) infection, small thrombus embolism or any complication of the kind. Why this technique that has been first described one decade ago is not more popular and used by most surgical groups? One reason could be unconscious and irrational. The carotid arteries provide the blood flow directly to the brain and the fear that any local complication occurring during the cannulation or the perfusion would lead to an immediate catastrophe might prevent many colleagues from using it. On the other hand, it is also possible that many groups remain faithful to their usual mode of cannulation, whatever its sophistication and drawbacks and are somewhat reluctant to try a new system. One may regret it as the technique as it is described in this paper seems rather promising and free from most of the disadvantages of the other available techniques. Indeed, this paper, associated with the various articles by Paul Urbanski and his group published in the cardiovascular literature in the last decade, demonstrates that the technique of using the common carotid arteries as a site of arterial cannulation during thoracic aortic surgery is sound, easy and safe, and provides excellent results in terms of whole body and selective cerebral perfusion. Undoubtedly, this technique should be more often used and have a much larger popularity worldwide.

Missed Carotid Artery Cannulation: A Line Crossed and Lessons Learnt

We report a case of an infusion of intra-aortic propofol after the missed inadvertent placement of a central venous catheter into the right common carotid artery. Radiological imaging revealed bilateral ischaemic infarcts in the posterior fossa and right cerebral artery territories consistent with an embolic source. The potential causes of the neurological injuries sustained in this case are explored. Discussion focuses on the sequelae, management and prevention of an iatrogenic carotid artery injury from a central venous catheter insertion. Finally, we propose an algorithm for management of iatrogenic carotid artery cannulation.

Involvement of inducible nitric oxide synthase and dimethyl arginine dimethylaminohydrolase in Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension.

Chronic administration of Nω-nitro-L-arginine methyl ester (L-NAME) in rats is a chemical method to study the induction and progression of nitric oxide (NO) deficiency-induced endothelial dysfunction. Male Wistar rats received L-NAME (50 mg/kg/day in drinking water) or no drug for 6 weeks. Mean arterial pressure (MAP) was measured on Day 43 by carotid artery cannulation. Plasma interleukin 1β (IL-1β) level was measured by enzyme-linked immunosorbent assay. Aorta and carotid artery were isolated for determination of basal nitrite, cGMP production, soluble guanylylcyclase (sGC) activity, phosphodiesterase-5 (PDE5) activity, and dimethylarginine dimethylaminohydrolase (DDAH) activity. mRNA expression studies were done by real time-polymerase chain reaction. L-NAME induced an increase in MAP and plasma IL-1β. The treatment had varied effect on endothelial nitric oxide synthase (eNOS), sGC, and PDE5 but showed an increase in inducible NOS (iNOS) mRNA expression and plasma asymmetric dimethyl arginine levels. Basal nitrite, cGMP levels, sGC activity, and DDAH activity were significantly decreased in the tissues. Brief incubation of tissues in vitro with 1400 W, a specific iNOS blocker, partially reversed sGC activity, and cGMP levels. The results of this study showed that L-NAME-mediated inhibition of eNOS is only partially responsible for the vascular pathology observed in this model. Secondary effects that include an increase in iNOS and a decrease in DDAH activity are likely to be the causative factors for the progression of vascular dysfunction.

Operative techniques in patients with type A dissection complicated by cerebral malperfusion.

Early mortality and morbidity after surgical treatment for acute type A aortic dissection (AAAD) has remained high over the last decades despite technical improvements and is still in the range of 10–30% [1–6]. The most important risk factor for this still high early mortality is the preoperative status of the patients [4, 7]. Especially end-organ malperfusion contributes significantly to perioperative death and is present in approximately one-third of all patients with acute aortic dissection [3, 7–9]. Coronary, cerebral, visceral and lower extremity malperfusion syndromes are most often associated with type A dissection. A significant surgical dilemma is the treatment of AAAD patients with preoperative cerebral malperfusion [7]. Intimal tears in the proximal aorta often up to 37% [10] result in the involvement of the supra-aortic branches. Consequently, the impaired flow in the brainsupplying arteries is, besides coronary arteries, the most frequent form of malperfusion [7]. The reported incidence of neurological deficit before surgery in AAAD varies between 14% [7] and 20% [11]. The general surgical strategy in AAAD patients is directed towards (i) cannulation and perfusion of the true lumen, (ii) perfusion of all body regions intraoperatively, (iii) a certain degree of hypothermia, (iv) avoiding aortic cross-clamp during distal repair (open distal anastomosis), (v) avoiding changing arterial cannulation site and uncertain de-airing manoeuvres when resuming total body perfusion after distal aortic repair and (vi) unrestricted global perfusion postoperatively. To develop an individual surgical plan for those patients with supra-aortic malperfusion, preoperative assessment of the extent of dissection and type of malperfusion is of utmost importance. This assessment is usually done with computed tomography angiography (CTA) preoperatively, which translates to only a few minutes of delay on the way to the operating theatre and is just as important for the surgical outcome as surgical experience [6, 12]. Malperfusion can be further validated intraoperatively by using transoesophageal echocardiography (TEE), orbital Doppler and near-infrared spectroscopy (NIRS) [9]. One has to keep in mind, however, that NIRS does not provide information in the basilar artery region [9]. There is an ongoing debate about the best surgical strategy for AAAD in general and even more for the high-risk subgroup of patients with cerebral malperfusion [9]. Despite a consensus that the true lumen of the arterial system should be cannulated [13], the approaches vary considerably. This lack of evidence to enable any recommendations for the choice of surgical methods is related to the fact that randomized studies in AAAD (with wide variations of pathologies) are very unlikely to be performed. Even though a meta-analysis of 14 papers between axillary artery and femoral artery perfusion has shown that axillary arterial perfusion had a significantly lower complication rate [14], routes that are currently advocated for AAAD include subclavian (right and left) cannulation, common carotid artery (right and left) cannulation [15, 16], cannulation of the innominate artery, peripheral cannulation of a non-dissected artery (femoral), ascending aortic cannulation (Fig. 1) [17] or apex of the left ventricle (transapical). There is also no agreement about optimal protection (e.g. temperature) during circulatory arrest; however, even the best method of protection would be useless if the cerebral perfusion and other end-organ perfusion have not been restored during cardiopulmonary bypass (CPB) and aortic repair. In this ‘Great Debate’, different approaches are being described and the rationale for doing so is explained by world-known experts in this field. Special emphasis will be placed on common carotid, subclavian and innominate artery cannulation for antegrade cerebral perfusion (ACP). The rationale of retrograde cerebral perfusion (RCP) during selective cerebral perfusion is also described.

The Association of Carotid Artery Cannulation and Neurologic Injury in Pediatric Patients Supported With Venoarterial Extracorporeal Membrane Oxygenation*

To describe the prevalence of neurologic injury in a recent cohort of patients 18 years old or younger cannulated for venoarterial extracorporeal membrane oxygenation. To evaluate the association of carotid artery cannulation with neurologic injury when compared with other cannulation sites. To determine if age impacts the association of carotid artery cannulation with neurologic injury. Retrospective analysis of data from the Extracorporeal Life Support Organization registry. Neonatal and pediatric medical/surgical and cardiac ICUs of 118 international tertiary care centers worldwide. Pediatric patients 18 years old or younger cannulated for venoarterial extracorporeal membrane oxygenation and reported to the Extracorporeal Life Support Organization registry during 2007 and 2008. None. Two thousand nine hundred seventy-seven patients underwent venoarterial extracorporeal membrane oxygenation during the study period. Indications for extracorporeal membrane oxygenation included pulmonary (n = 1,390, 47%), cardiac (n = 1,168, 39%), extracorporeal membrane oxygenation during cardiopulmonary resuscitation (n = 418, 14%), and unknown (n = 1). Arterial cannulation sites were aorta (n = 938, 32%), femoral artery (n = 118, 4%), and carotid artery (n = 1,921, 64%). Overall, 611 patients (21%) had evidence of neurologic injury defined as seizures, infarction, and/or hemorrhage. The occurrence of neurologic injury varied significantly by cannulation site: femoral artery (n = 18, 15%), aorta (n = 160, 17%), and carotid artery (n = 433, 23%); p equals 0.001. Neonates represented the largest group of patients cannulated for venoarterial extracorporeal membrane oxygenation (n = 1,807, 61%), the majority of patients cannulated via the carotid artery (n = 1,276, 66%), and had the highest burden of neurologic injury (n = 398, 22%). Age, preextracorporeal membrane oxygenation high-frequency oscillatory ventilation use, preextracorporeal membrane oxygenation arterial pH and serum bicarbonate level, and preextracorporeal membrane oxygenation cardiac arrest were independently associated with neurologic injury in a covariate model. Carotid artery cannulation site was added to this adjusted model and found to independently increase odds of neurologic injury (odds ratio, 1.4 [95% CI, 1.01-1.69]). An interaction term containing age and cannulation site was not associated with neurologic injury (odds ratio, 1.06 [95% CI, 0.84-1.34]). Carotid artery cannulation for venoarterial extracorporeal membrane oxygenation in patients 18 years old or younger is associated with statistically significant increased odds of neurologic injury. These increased odds are present across all age groups.

ABSTRACT 544

Background and aims: Children with severe cardio-respiratory failure run a higher mortality. Aims: To analyze the effects of ECMO (extracorporeal membrane oxygenation) treatment to children with severe cardio-respiratory failure in PICU. Methods: 15 children cases (non-cardiac surgical diseases) with ECMO (BIO-CONSOLE®560; BIO-PUMP®BP50) treatment during 2011.12~2013.11 were analyzed retrospectively. All cases fail to response to conventional therapy including mechanical ventilation before ECMO, and with no irreversible fatal underling disorders. Results: Etiology of 15 cases included: 8 cases with severe pneumonia, 5 cases with cardiac compromise, 2 cases with septic shock. Patients’ ages varied from 1 month to 11 years (average 2 years old). All patients were given VA ECMO through right carotid artery and internal jugular vein cannulation. ECMO blood flow were kept in 70~100 ml/kg/min, gas flow in 1~4 l/min to maintain good oxygen delivery, and heparin infusion to keep ACT in 180~220 sec. The ECMO running time varied from 15 hours ~ 11days (average 125 hours). 7 cases were added CRRT treatment due to oliguria. After ECMO treatment, 10 cases (66%) were successfully weaned from ECMO and finally be discharged from hospital. The main ECMO complications we have met in ECMO include mechanical failure, oxygenator leakage, bleeding or thrombosis.Table 1: Outcome of children with ECMOConclusions: ECMO is a useful life support method in PICU for severe cardio-respiratory failure who fails to response to all treatment. Above half of the patients could be rescued by ECMO.

Rat model of veno-arterial extracorporeal membrane oxygenation

BackgroundWe aim to develop a rat model of veno-arterial extracorporeal membrane oxygenation (VA-ECMO).MethodsVA-ECMO was established in twelve Male Sprague-Dawley rats (250-350 g) through cannulation of the right jugular vein for venous drainage and the right femoral artery for arterial reinfusion. Arterial blood pressure was measured using a conductance catheter through cannulation of the left carotid artery. Heart rate was monitored by electrocardiography and arterial blood gas parameters with a blood gas analyzer. The VA-ECMO circuit was tested by subjecting the rats to hypoxic cardiac arrest with resuscitation using VA-ECMO. Both load-dependent and load-independent measures of myocardial contractility were measured using pressure-volume loop analysis to confirm restoration of myocardial function post-resuscitation.ResultsFollowing hypoxic cardiac arrest VA-ECMO provided sufficient oxygenation to support the circulation. The haemodynamic and blood gas parameters were maintained at transition and during ECMO. All animals were resuscitated, regained cardiac function and were able to be weaned off ECMO post-resuscitation.ConclusionWe have established a safe, high-throughput, economical, functioning rat model of VA-ECMO.

Cannulation of the internal carotid artery in mice: A novel technique for intra-arterial delivery of therapeutics

We have developed a novel minimally invasive technique for the intra-arterial delivery of therapeutics to the mouse brain. CD-1 mice were anesthetized and placed in a lateral decubitus position. A 10mm midline longitudinal incision was made over the thyroid bone. The omohyoid and sternomastoid muscles were retracted to expose the common carotid artery and external carotid artery (ECA). To maximize delivery of administered agents, the superior thyroid artery was ligated or coagulated, and the occipital artery and the pterygopalatine artery (PPA) were temporarily occluded with 6-0 prolene suture. The ECA was carefully dissected and a permanent ligature was placed on its distal segment while a temporary 6-0 prolene ligature was placed on the proximal segment in order to obtain a flow-free segment of vessel. A sterilized 169μm outer diameter polyimide microcatheter was introduced into the ECA and advanced in retrograde fashion toward the carotid bifurcation. The catheter was then secured and manually rotated so that the microcatheter tip was oriented cephalad in the internal carotid artery (ICA). We were able to achieve reproducible results for selective ipsilateral hemispheric carotid injections of mannitol mediated therapeutics and/or gadolinium-based MRI contrast agent. Survival rates were dependent on the administered agent and ranged from 78 to 90%. This technique allows for reproducible delivery of agents to the ipsilateral cerebral hemisphere by utilizing anterograde catheter placement and temporary ligation of the PPA. This method is cost-effective and associated with a low rate of morbimortality.

Expanding the Availability of Extracorporeal Cardiopulmonary Resuscitation

A healthy 14-year-old presented to an emergency department in Alaska, complaining of shortness of breath, chest pain, and 72 hours of malaise and headache. On admission, her blood pressure was 80/50 mm Hg, and she had cool extremities. Electrocardiography revealed wide-complex ventricular tachycardia. She underwent synchronized electrical cardioversion. Although she initially converted to sinus rhythm, she subsequently became pulseless, with electrocardiographic evidence of ventricular tachycardia. Despite cardiopulmonary resuscitation, she failed to achieve a perfusing rhythm. Cardiovascular surgery consultation was obtained, and she was placed on partial cardiopulmonary bypass during 2 hours of ongoing chest compressions. Cardiopulmonary bypass flow was limited by the small size of her femoral arteries. She remained in refractory ventricular tachycardia. The cardiopulmonary bypass circuit was modified for transportation of the patient via air ambulance 1500 miles to a tertiary medical center that specializes in pediatric heart failure and mechanical cardiopulmonary support. Upon arrival at the tertiary medical center, she underwent carotid artery cannulation to improve total cardiopulmonary support and percutaneous balloon atrial septostomy to facilitate left ventricular decompression. Intravenous immunoglobulin and steroids were administered to treat presumed acute fulminant viral myocarditis. Extracorporeal life support was support was successfully discontinued after 14 days, but she experienced a thromboembolic stroke. The patient was discharged on hospital day 65 with moderate generalized left-sided weakness, but she was able to ambulate with minimal assistance. She subsequently returned to school and is progressing appropriately with her peers. Cardiac function has normalized, and she remains in normal sinus rhythm.