Efficacy of Precordial Percussion Pacing Assessed in a Cardiac Standstill Microminipig Model.

BACKGROUND: Potential cardiovascular benefits of precordial percussion pacing (PPP) during cardiac standstill are unknown.Methods and Results:A cardiac standstill model in amicrominipigwas created by inducing complete atrioventricular block with a catheter ablation technique (n=7). Next, the efficacy of cardiopulmonary resuscitation by standard chest compressions (S-CPR), PPP and ventricular electrical pacing in this model were analyzed in series (n=4). To assess the mechanism of PPP, a non-selective, stretch-activated channel blocker, amiloride, was administered during PPP (n=3). Peak systolic and diastolic arterial pressures during S-CPR, PPP and ventricular electrical pacing were statistically similar. However, the duration of developed arterial pressure with PPP was comparable to that with ventricular electrical pacing, and significantly greater than that with S-CPR. Amiloride decreased the induction rate of ventricular electrical activity by PPP in a dose-related manner. Each animal survived without any neurological deficit at 24, 48 h and 1 week, even with up to 2 h of continuous PPP. CONCLUSIONS: In amicrominipigmodel of cardiac standstill, PPP can become a novel means to significantly improve physiological outcomes after cardiac standstill or symptomatic bradyarrhythmias in the absence of cardiac pacing. Activation of the non-selective stretch-activated channels may mediate some of the mechanophysiological effects of PPP. Further study of PPP by itself and together with S-CPR is warranted using cardiac arrest models of atrioventricular block and asystole.

Impedance Threshold Device Combined With High-Quality Cardiopulmonary Resuscitation Improves Survival With Favorable Neurological Function After Witnessed Out-of-Hospital Cardiac Arrest.

BACKGROUND: The quality of cardiopulmonary resuscitation (CPR) has been recently shown to affect clinical outcome. The Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation Impedance Valve and Early Versus Delayed Analysis (PRIMED) trial showed no differences in outcomes with an active vs. sham impedance threshold device (ITD), a CPR adjunct that enhances circulation. It was hypothesized the active ITD would improve survival with favorable neurological outcomes in witnessed out-of-hospital cardiac arrest patients when used with high-quality CPR. METHODS AND RESULTS: Using the publicly accessible ROC PRIMED database, a post-hoc analysis was performed on all witnessed subjects with both compression rate and depth data (n=1,808) who received CPR within the study protocol definition of adequate CPR quality (compression rate 80-120/min and depth 4-6 cm; n=929). Demographics were similar between sham and active ITD groups. In witnessed subjects who received quality CPR, survival with favorable neurological function was 11.9% for the active ITD subjects (56/470) vs. 7.4% for the sham (34/459) (odds ratio 1.69 [95% confidence interval 1.08, 2.64]). There were no statistically significant differences for this primary outcome when CPR was performed outside the boundaries of the definition of adequate CPR quality. Multivariable models did not change these associations. CONCLUSIONS: An active ITD combined with adequate-quality conventional CPR has the potential to significantly improve survival after witnessed cardiac arrest. (Circ J 2016; 80: 2124-2132).

Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study.

Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients.

A Phase II study of polyclonal anti-TNF-α (AZD9773) in Japanese patients with severe sepsis and/or septic shock.

Because tumor necrosis factor-alpha (TNF-α) induces many of the pathophysiological signs and symptoms observed in sepsis, it is a potential therapeutic target for treatment. The primary objective of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple intravenous (i.v.) infusions of two doses of AZD9773 in Japanese patients with severe sepsis and/or septic shock. In this Phase II, double-blind, placebo-controlled, dose-escalation study (ClinicalTrials.gov Identifier: NCT01144624), Japanese patients were randomized to two successive treatment cohorts (cohort 1, loading/maintenance doses of 250/50 U/kg or placebo; cohort 2, loading/maintenance doses of 500/100 U/kg or placebo) for a 5-day treatment period, then a follow-up period to day 29. Twenty patients were enrolled (AZD9773 cohort 1, n = 7; AZD9773 cohort 2, n = 7; placebo, n = 6), and all completed the study. Most treatment-emergent adverse events (TEAEs) were mild or moderate and none led to discontinuation. The most common TEAEs in the AZD9773 cohorts were pleural effusion (64.3%) and peripheral edema (28.6%). Pharmacokinetic data demonstrated an approximately proportional increase in concentration with increasing dose. Treatment with AZD9773 led to a decrease in TNF-α concentrations, which was more discernible in the AZD9773 cohort 2; TNF-α concentrations generally decreased with time in patients receiving placebo. A similar pattern of response was observed with interleukin-6 (IL-6) and IL-8. AZD9773 was generally well tolerated with dose-proportional pharmacokinetics in Japanese patients with severe sepsis/septic shock.

Early cerebral circulation disturbance in patients suffering from different types of severe traumatic brain injury: a xenon CT and perfusion CT study.

INTRODUCTION: Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). In particular, secondary brain insults have been reported to decrease CBF. The purpose of this study was to clarify the cerebral circulation in different types of TBI. METHODS: Sixty-nine patients with TBI were divided into four groups, the subdural hematoma group, the contusion/intracerebral hematoma group, the diffuse axonal injury group, and the diffuse brain swelling group. In these patients, we simultaneously performed Xe-CT and perfusion CT to evaluate the cerebral circulation on post-injury days 1-3. We measured CBF using Xe-CT and mean transit time using perfusion CT and calculated the cerebral blood volume using the AZ-7000 W98 computer system. RESULTS: There were no significant differences in the Glasgow Coma Scale score on arrival or the Glasgow Outcome Scale score between the groups. The patients who had suffered focal TBI displayed more significant cerebral circulation disturbances than those that had suffered diffuse TBI. We were able to evaluate the cerebral circulation of TBI patients using these parameters. CONCLUSION: Moderate hypothermia therapy, which decreases CBF, the cerebral metabolic rate oxygen consumption (CMRO2), and intracranial pressure might be effective against the types of TBI accompanied by cerebral circulation disturbance. We have to use all possible measures including hypothermia therapy to treat severe TBI patients according to the type of TBI that they have suffered.

Replacement of dynamic cultured biograft improves damaged heart function-comparative study of static cultured biografts-.

PURPOSE: To determine whether a dynamic cultured biograft can positively affect the function of the damaged heart. METHODS: We ligated the coronary artery (LAD) of rats to generate a model of myocardial infarction (MI) and then implanted them with the following grafts comprising vascular smooth muscle cells (VSMCs) derived from the rat aorta and seeded onto biodegradable patches (patch replacement therapy; (PRTx)): control without PRTx, PRTx without seeded cells, PRTx with static cultured VSMCs, PRTx with dynamic cultured VSMCs and sham-operated. Cultured VSMCs were labeled with PKH26 for identification after implantation, and the centre of the MI site was excised and replaced with an implanted biograft. Cardiac performance was monitored for 12 weeks thereafter and followed by a histological study. RESULTS: Although the ejection fraction of the damaged heart improved in all groups that were transplanted with grafts, remodeling was prevented only in groups with a dynamic or static cultured patch. More cells were α-SMA-positive in the group with the dynamic, rather than the static cultured patch. Cells were positive for PKH26 in the biograft and in the infarcted myocardium. CONCLUSIONS: Dynamic cultured biografts improved the function of the infarcted myocardium more than statically cultured biografts or those without cells.

The study of systemic general circulation disturbance during the initiation of therapeutic hypothermia: Pit fall of hypothermia.

AIMS: Neurointensive care has reduced the mortality and improved the outcome of patients for severe brain damage, over recent decades, and made it possible to perform this therapy in safety. However, we have to understand the complications of this therapy well. The purpose of our study was to determine the systemic circulation disturbance during the initiation of therapeutic hypothermia by using this continuous neurointensive monitoring system. MATERIALS AND METHODS: Ten severe brain damage patients treated with hypothermia were enrolled. All patients had Glasgow Coma Scale (GCS) less than or equal to 8, on admission. RESULTS: We verified that heart rate, cardiac output, and oxygen delivery index (DO2I) decreased with decreasing core temperature. We recognized that depressed cardiac index (CI) was attributed to bradycardia, dehydration, and increased systemic vascular resistance index (SVRI) upon initiation of hypothermia. CONCLUSION: Although the hypothermia has a therapeutic role in severe brain damage patients, we have to carry out this therapy while maintaining their cardiac output using multimodality monitoring devices during hypothermia period.

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study.

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.

Bidirectional Glenn procedure for an infected modified Blalock-Taussig shunt.

A 1-month-old girl underwent right modified Blalock-Taussig shunt (mBTS) for pulmonary atresia with hypoplastic right ventricle. Five months after palliation, she suffered from sepsis and progressive desaturation following otitis media. Computed tomography and angiography revealed a pseudoaneurysm surrounding the mBTS graft. After stabilization of the infection, we performed pseudoaneurysm resection, shunt-graft removal, and the bidirectional Glenn (BDG) procedure under cardiopulmonary bypass. Her condition improved, and she was discharged on the 17th day after surgery. When parameters for the partial right heart bypass should permit, the BDG procedure can be a beneficial recovery procedure for the cases of infected pseudoaneurysm after mBTS in Fontan candidates.

Fontan conversion with novel direct ablation after childbirth: report of a case.

A 38-year-old woman underwent atriopulmonary Fontan surgery at age 18 years and subsequently successfully delivered a girl by cesarean section at age 34. Her condition later deteriorated due to atrial tachyarrhythmia and progressed to New York Heart Association (NYHA) class IV heart failure. Her treatment, at age 36, comprised total cavopulmonary connection conversion, direct right atrial ablation with bipolar radiofrequency devices, the creation of an atrial septal defect, and placement of a dual-chamber permanent pacemaker. Three years after the conversion, her condition has improved to NYHA class I.

Optimal culture conditions for constructing durable biografts for repairing the impaired heart--dynamic cell culture with pre-seeding.

BACKGROUND: Tissue engineering with cell seeded biodegradable material has attracted attention as a novel means of treating the severely impaired heart. Here, we consider optimal preparation of a durable biograft using dynamic and static cultures. METHODS: Vascular smooth muscle cells (VSMCs) derived from the rat aorta were seeded onto biodegradable material P (LA/CL) (poly-L-lactide-ε-caprolactone copolymer) and cultured as follows: a) Static culture (n = 11), b) dynamic culture (n = 12), c) 0 h pre-seeding (n = 12), d) 24 h pre-seeding (n = 5) and e) 1 week pre-seeding (n = 12). Dynamic culture: Cells were cultured in spinner flasks. Pre-seeding: Static cell seeding and culture before dynamic culture. EVALUATION: The conditions of the P (LA/CL) in the five groups were evaluated as cell proliferation and by histological studies. RESULTS: VSMCs proliferated both in and on the biodegradable materials. The quality of the dynamic culture cell with pre-seeding increased. Although the duration of pre-seeding exerted no significantly different effects, cell attachment and proliferation were widely scattered in the 0 h pre-seeding group, whereas cells proliferating on the front of the scaffold obstructed proliferation inside the biodegradable material in the 1 week pre-seeding group . CONCLUSIONS: Dynamic cell culture with 24 h pre-seeding is effective for constructing ideal biografts.

Successful surgical repair of an infectious thoracic aortic pseudoaneurysm accompanied by aortobronchopulmonary fistula and advanced hepatic dysfunction without assisted circulation.

The patient was a 59-year-old female. Because of massive hemoptysis, she was brought to our emergency center by ambulance. Thoracic computed tomography led to a diagnosis of an infectious thoracic aortic pseudoaneurysm accompanied by an aortobronchopulmonary fistula. Emergency surgery followed. Also noted was an advanced hepatic dysfunction, assessed as Child-Pugh score B, caused by an alcoholic liver disease. A localized affected area made it possible for us to perform an aneurysmectomy using a temporary bypass rather than assisted circulation. A patch plasty using expanded polytetrafluoroethylene completed the procedure. Streptococcus agalactiae (GBS) was detected in a sample obtained during the surgery from an abscess located in the aneurysm. The patient made satisfactory postoperative progress and left the hospital walking unaided on the 36th postoperative day.

[Case of serious renal failure induced by ingesting large volume of MAKIRON].

A 23-year-old male patient ingested 150 mL of MAKIRON in a suicide attempt and was transferred to the hospital emergency room approximately 30 hours after ingestion. Upon admission, components of MAKIRON, including naphazoline (1.4 microg/mL), chlorpheniramine (0.81 microg/mL), dibucaine (3.2 microg/mL) and benzethonium (5.5 microg/mL) were detected in the patient's plasma. Direct hemoperfusion and hemodiafiltration enforcement were carried out and the chemical components of MAKIRON were not detected the following day. At the time of hospitalization, the patient presented with serious hepatopathy, pneumonia and acute renal failure. The hepatopathy and pneumonia resolved several days later; however, the patient required continuation of dialysis three times per week for seventeen days due to persistence of anuria. Few case reports on renal failure induced by MAKIRON have been published, whereas there are occasional reports of MAKIRON poisoning. Serious renal dysfunction in this case is thought to be due to both the large volume of MAKIRON ingested and the time delay between ingestion and treatment.

[Effects on proliferation ability of vascular smooth muscle cells by static and/or dynamic cell culture: utility of pre-seeding technique for dynamic cell culture].

OBJECTIVES: Conventional biomaterials are not viable, do not grow, and do not provide contractile effects in cardiac tissue. Foreign synthetic material may become thrombogenic or infected. The most recent cardiac constructs consist of biodegradable material which has the potential to solve these problems. However, dynamic three-dimensional cell culture is necessary because conventional culture is limited to construct tough biografts. METHODS: Vascular smooth muscle cells derived from rat aorta were seeded to poly-L-lactide-epsilon-capro-lactone copolymer in three groups; static culture group (static cell seeding + static cell culture), dynamic culture group (dynamic cell seeding + dynamic cell culture), and pre-seeding group [static cell seeding and culture for 1 week (pre-seeding) + dynamic cell culture]. The dynamic cell culture system used an original spinner flask. The pre-seeding technique used static cell seeding and culture before dynamic culture. The three groups were evaluated by cell proliferation and histologic studies. RESULTS: Vascular smooth muscle cells could be proliferated in/on the biodegradable materials. The pre-seeding group cells grew much more efficiently than the other groups. Very few cells were found in the biodegradable materials with the dynamic groups. However, there were many cells in the materials with the static culture group and pre-seeding group, especially the pre-seeding group. CONCLUSIONS: Dynamic culture is useful for constructing tough biografts by the pre-seeding technique.

The variations in the immunologic features and interleukin-6 levels for the surgical treatment of cardiac myxomas.

PURPOSE: In this study, we propose the existence of a relationship between cardiac myxomas and the immunologic features or interleukin-6 (IL-6), while also considering the optimal treatment of cardiac myxoma, especially "familial myxoma." METHODS: In a 19-year period at our hospital, 20 patients underwent 21 operations for cardiac myxomas. The immunologic features and the IL-6 levels were measured pre-operatively in 13 cases and post-operatively in 10 cases. A case of "familial myxoma" was diagnosed based on molecular genetic analyses. RESULTS: No patients died in the hospital. The tumor size correlated with the preoperative IL-6 and/or alpha1-globulin values (P < 0.05). In addition, all of the immunologic features and IL-6 levels normalized by 4 weeks after surgery. "Familial myxoma" demonstrated recurrence without showing increases in either the immunologic features, inflammatory signs, or serum IL-6 levels. CONCLUSIONS: Patients with cardiac myxoma should therefore be operated on immediately because the possibility that the tumor size might be large when IL-6 and/or alpha1-globulin values are high. In addition, cases of "familial myxoma" require careful observation and periodic echocardiography after surgery to identify any possible recurrence. Recently, molecular genetic analyses are therefore considered to be an important diagnostic tool for cardiac myxoma, especially "familial myxoma." Our "familial myxoma" case demonstrated a C769T PRKAR1a mutation, which has also been observed in other cases of "familial myxoma."

Intravascular ultrasound imaging for detection of pseudoaneurysm with aortobronchopulmonary fistula after graft replacement of descending aorta.

A 63-year-old man had undergone graft replacement of the descending aorta due to dissection of aortic aneurysm nine years before and closure of an aortobronchopulmonary fistula two years before. He was admitted to our hospital because of massive hemoptysis. Angiography and chest computed tomography (CT) revealed a pseudoaneurysm on the proximal end caused by graft detachment. Intravascular ultrasound clearly revealed half round detachment on both ends of the graft. Replacement of the ascending, arch and distal aorta including the graft was performed, and the patient's postoperative course has been satisfactory. We have concluded that intravascular ultrasound is a useful method for detecting pseudoaneurysm after graft replacement which is not evident on cineangiography, CT or distal subtraction angiography.