A case of pulmonary edema due to guanfacine intoxication with measurement of serum guanfacine concentrations.

Guanfacine hydrochloride extended-release (GXR) is used to treat attention deficit hyperactivity disorder. It is a selective α2A-adrenorecepor agonist that was reported to cause QT prolongation and hypotension in the event of overdosing. We report the case of a 17-year-old man who took 226 tablets of GXR 3 mg for attempted suicide. He was found complaining of dyspnea, and emergency medical services were called. When the patient was transferred to our hospital, his Glasgow coma scale was 12 (E4V3M5). He was agitated and hypoxemic. He was intubated for invasive mechanical ventilation under sedation. His chest X-ray and computed tomography scan showed pulmonary edema. Transthoracic echocardiography showed markedly reduced cardiac function. His serum guanfacine concentration peaked on day 3 after admission. His pulmonary edema improved quickly after a decrease in serum guanfacine concentration, but cardiac decompensation persisted for about 1 month. This case reveals that the decline in cardiac function after guanfacine intoxication is prolonged even after its serum concentration has decreased.

Time Course of Coagulopathy Evaluated with Rotational Thromboelastometry in Patients with Severe Coronavirus Disease 2019.

Objectives Coronavirus disease 2019 (COVID-19) reportedly causes thromboembolic complications due to coagulopathy with hypercoagulability and a hypofibrinolytic state. We evaluated the time-course of coagulopathy in patients with severe COVID-19 from admission to discharge from our intensive-care unit (ICU). Methods We conducted a retrospective study of adults with severe COVID-19 admitted to our ICU between January 20, 2021, and March 31, 2022. We obtained clinical information, laboratory data, and rotational thromboelastometry (ROTEM) parameters at admission and discharge. Results Fifteen patients were included. Fibrinogen and D-dimer values did not change significantly but were above the normal ranges at admission and discharge. Regarding ROTEM parameters, the maximum clot firmness in fibrinogen function (FIBTEM), a marker of hypercoagulability, did not change significantly but was above the normal range at admission and discharge [median (interquartile range), admission vs. discharge: 31 (25-34) mm vs. 31 (27-32) mm, p=0.589]. The maximum lysis at 60 minutes in the extrinsic coagulation pathway (EXTEM) and intrinsic coagulation pathway (INTEM), as markers of the fibrinolytic function, were both significantly lower at discharge than at admission [median (interquartile range), admission vs. discharge: EXTEM, 3 (2-4) vs. 1 (0-2), p=0.011; INTEM, 3 (1-6) vs. 1 (0-2), p=0.008]. Conclusion This study revealed a persistent hypercoagulable state at ICU discharge and a worse hypofibrinolytic state at discharge than at admission. These results may contribute to a better understanding of coagulopathies in the acute to subacute phases of severe COVID-19.

Resuscitative hysterotomy in a patient with peripartum cardiomyopathy.

Resuscitative hysterotomy (RH) is a resuscitation technique, allowing the restoration of a pregnant patient's heartbeat. Here, we reported a case of RH performed in a patient with cardiac arrest as a complication of a peripartum cardiomyopathy. A 29-year-old woman with suspected hemolysis, elevated liver enzymes, low platelet syndrome was admitted to the hospital. Cardiopulmonary resuscitation and RH were initiated at 30 weeks of gestation. The infant was successfully delivered 2 min after the mother's cardiac arrest, weighting 1388 g. At the first minute, the Apgar score was 3 and the 5th minute was 6. After delivery, defibrillation was performed on the mother and restoration of spontaneous circulation was observed. However, she was hemodynamically unstable and approximately 2 months later she died. After cardiac arrest, it is possible that RH could improve the hemodynamic status. The opportunity of performing a RH is rare; however, it is necessary to be familiarized with the technique as a resuscitation method.

A Case of a Pregnant Woman with Thrombosis in an Artificial Aortic Valve Resulting in Severe Cerebral Hemorrhage in the Newborn.

Many patients, after artificial valve replacement surgery, receive warfarin anticoagulant therapy. However, it has been reported that warfarin administration during pregnancy can cause fetal teratogenicity. With reference to this case, we will discuss how warfarin administration in mid-pregnancy caused severe cerebral hemorrhage in the newborn child. The 36-year-old patient in this case underwent aortic valve replacement surgery when she was 11 years old; this requires the continued use of warfarin after surgery. Although she was advised otherwise, the patient became pregnant. The warfarin treatment was discontinued at 5 weeks of gestation and she began self-injection of heparin; however, her health quickly deteriorated requiring an emergency, warfarin treatment. On gestation week 21, she was admitted to our hospital with a high likelihood of a spontaneous abortion. A week later, transesophageal ultrasonography revealed a thrombus in the patient's aortic valve. Because of this finding, we re-started warfarin administration. At 32 weeks of gestation, cardiotocography showed decreased fetal heart rate; thus, an emergency Cesarean section was performed. A baby was delivered, weighing 1,702 g with an Apgar Score of 1 at 1 minute and 4 at 5 minutes. Cranial computed tomography of the infant showed bilateral intraventricular hemorrhage and ventricular dilation. In order to protect the mother and prevent hemorrhage in the newborn, it is recommended that a continuous heparin infusion should be administered to the pregnant woman after the 36th week of gestation. Regarding the impact on the infant, it is considered that continuous intravenous administration of heparin is safer during the third trimester of pregnancy. However, administration of heparin alone makes the preventive effect of thrombosis uncertain. When warfarin is administered in pregnancy, pregnancy management should be performed bearing the risk of fetal cerebral hemorrhage in mind.

Efficacy of pimobendan on survival and reoccurrence of pulmonary edema in canine congestive heart failure.

The aim of this study was to evaluate the efficacy of pimobendan with conventional therapies on survival and reocurrence of pulmonary edema in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). Records of 197 client-owned dogs from 14 veterinary hospitals were included in this study. Dogs were administered conventional treatments with or without pimobendan. Sixty-four dogs received a standard dose of pimobendan (0.20-0.48 mg/kg every 12 hr (q12hr)), 49 dogs received a low dose of pimobendan (0.05-0.19 mg/kg q12hr), and 84 dogs received conventional therapy alone. Dogs in the standard-dose and low-dose pimobendan groups had significantly longer median survival times than dogs in the conventional group (334, 277 and 136 days, respectively; P<0.001). The reoccurrence rate of pulmonary edema in the standard-dose group was significantly lower than in the low-dose and conventional groups (43%, 59% and 62%, respectively; P<0.05). Combination of pimobendan with a conventional treatment regimen significantly prolonged survival time after an initial episode of pulmonary edema in dogs with CHF caused by MMVD. There was no difference in survival between dogs administered standard and low doses of pimobendan, but pimobendan did prevent the reoccurrence of pulmonary edema in a dose-dependent manner.

Plasma cytokine levels in dogs undergoing cardiopulmonary bypass.

UNLABELLED: Currently, there are no reports of inflammatory responses to CPB in dogs. We investigated the time course of pro- and anti-inflammatory cytokine levels during and after CPB. ANIMALS: The study group included 11 dogs that underwent mitral valve repair with CPB, and the control group included 7 healthy dogs that underwent ovariohysterectomy. METHODS: Blood samples from the study group dogs were collected before, during and after surgery and analyzed for plasma levels of interleukin-6 (IL-6), tissue necrosis factor-α (TNF-α), interleukin-10 (IL-10), white blood cells (WBC), and C-reactive protein (CRP). Each inflammatory parameter was also compared with that of the control group dogs. RESULTS: After CPB, plasma levels of IL-6, WBC counts, and CRP levels were significantly higher than preoperative levels, and IL-6 levels in the study group were significantly higher than those in the control group. CONCLUSIONS: CPB induces a systemic inflammatory response in dogs.

Comparison of the diuretic effect of furosemide by different methods of administration in healthy dogs.

OBJECTIVE: To compare the diuretic effects of subcutaneous (s.c.) administration of furosemide to conventional methods of administration including intravenous (i.v.), per os (p.o.), and constant rate infusion (CRI) in healthy dogs. DESIGN: Prospective, randomized, cross-over study. SETTING: Veterinary university research facility. ANIMALS: Seven healthy, adult mongrel dogs (3 males, 4 females). INTERVENTION: Each dog in the study was randomly assigned to receive a 2 mg/kg dose of furosemide via a single s.c., i.v., or p.o. dose at the beginning (time 0) of an 8-hour study, or via CRI during an 8-hour study period. Urine was collected by emptying the bladder using an indwelling catheter and blood samples were obtained via venipuncture at time 0 for baseline measurements and at 1, 2, 4, 6, and 8 hours into the study. Hourly urine output was calculated in all dogs for each study. Complete blood count, plasma total protein, blood urea nitrogen, creatinine, and renin concentration were measured for each sample. MEASUREMENTS AND MAIN RESULTS: The s.c. administration of furosemide resulted in a urine output per hour (UOP/h) that peaked at 1 hour with UOP/h returning to baseline at 4 hours after injection. Following i.v. administration, UOP/h also peaked at 1 hour but returned more rapidly to baseline levels at 2 hours after injection. With p.o. administration, UOP/h reached a maximum UOP/h at 2 hours but time to return to baseline levels was prolonged to 6 hours after administration. With CRI administration, the time to the maximum UOP/h was delayed to 4 hours after injection but UOP/h was then maintained throughout the study period. CONCLUSIONS: Total urine output following s.c. administration of furosemide in healthy dogs was similar when compared to the i.v. and p.o. route. Subcutaneous route may be an effective means for administration of furosemide in dogs, particularly when i.v. access is difficult.

Successful implantation of autologous valved conduits with self-expanding stent (stent-biovalve) within the pulmonary artery in beagle dogs.

OBJECTIVES: To evaluate the functionality of an autologous heart valve with stent (Stent-biovalve or SBV) after implantation in the pulmonic valve position in beagle dogs. ANIMALS: Five beagle dogs. METHODS: A mold with an aperture of a tri-leaflet structure was constructed from a pair of concave and convex rods to which a nitinol (NiTi) stent was mounted. This mold was embedded in a dorsal subcutaneous pouch in beagle dogs for 4 weeks. At the time of the removal, the surfaces of the molds were completely covered with connective tissues, tri-leaflet valves were formed and the NiTi stent was tightly connected to the structure. RESULTS: The mean burst strength of the SBV leaflet was 2710 mmHg (range 2280-3116 mmHg), which was approximately equal to that of the native pulmonic valve leaflet. After implantation in the pulmonary position, the SBV showed good functionality as a pulmonic valve. At 84 days after implantation, the SBV was replaced with autologous fibroblasts and collagenous tissues, and showed organization similar to that of native heart valves. CONCLUSION: Stent-Biovalves achieved good valvular function with laminar flow in the pulmonic valve position of beagle dogs.

Phenotypic and functional properties of feline dedifferentiated fat cells and adipose-derived stem cells.

It has been reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells show multilineage differentiation potential similar to that observed in mesenchymal stem cells. Since DFAT cells can be prepared from a small quantity of adipose tissue, they could facilitate cell-based therapies in small companion animals such as cats. The present study examined whether multipotent DFAT cells can be generated from feline adipose tissue, and the properties of DFAT cells were compared with those of adipose-derived stem cells (ASCs). DFAT cells and ASCs were prepared from the floating mature adipocyte fraction and the stromal vascular fraction, respectively, of collagenase-digested feline omental adipose tissue. Both cell types were evaluated for growth kinetics, colony-forming unit fibroblast (CFU-F) frequency, immunophenotypic properties, and multilineage differentiation potential. DFAT cells and ASCs could be generated from approximately 1g of adipose tissue and were grown and subcultured on laminin-coated dishes. The frequency of CFU-Fs in DFAT cells (35.8%) was significantly higher than that in ASCs (20.8%) at passage 1 (P1). DFAT cells and ASCs displayed similar immunophenotypes (CD44(+), CD90(+), CD105(+), CD14(-), CD34(-) and CD45(-)). Alpha-smooth muscle actin-positive cells were readily detected in ASCs (15.2±7.2%) but were rare in DFAT cells (2.2±3.2%) at P1. Both cell types exhibited adipogenic, osteogenic, chondrogenic, and smooth muscle cell differentiation potential in vitro. In conclusion, feline DFAT cells exhibited similar properties to ASCs but displayed higher CFU-F frequency and greater homogeneity. DFAT cells, like ASCs, may be an attractive source for cell-based therapies in cats.

Mitral valve repair under cardiopulmonary bypass in small-breed dogs: 48 cases (2006-2009).

OBJECTIVE: To determine whether mitral valve repair (MVR) under cardiopulmonary bypass would be an effective treatment for mitral regurgitation in small-breed dogs. DESIGN: Retrospective case series. ANIMALS: 48 small-breed dogs (body weight, 1.88 to 4.65 kg [4.11 to 10.25 lb]; age, 5 to 15 years) with mitral regurgitation that underwent surgery between August 2006 and August 2009. PROCEDURES: Cardiopulmonary bypass was performed with a cardiopulmonary bypass circuit. After induction of cardiac arrest, a mitral annuloplasty was performed, and the chordae tendineae were replaced with expanded polytetrafluoroethylene chordal prostheses. After closure of the left atrium and declamping to restart the heart, the thorax was closed. RESULTS: Preoperatively, cardiac murmur was grade 3 of 6 to 6 of 6, thoracic radiography showed cardiac enlargement (median vertebral heart size, 12.0 vertebrae; range, 9.5 to 14.5 vertebrae), and echocardiography showed severe mitral regurgitation and left atrial enlargement (median left atrium-to-aortic root ratio, 2.6; range, 1.7 to 4.0). 45 of 48 dogs survived to discharge. Three months after surgery, cardiac murmur grade was reduced to 0/6 to 3/6, and the heart shadow was reduced (median vertebral heart size, 11.1 vertebrae, range, 9.2 to 13.0 vertebrae) on thoracic radiographs. Echocardiography confirmed a marked reduction in mitral regurgitation and left atrium-to-aortic root ratio (median, 1.7; range, 1.0 to 3.0). CONCLUSIONS AND CLINICAL RELEVANCE: We successfully performed MVR under cardiopulmonary bypass in small-breed dogs, suggesting this may be an effective surgical treatment for dogs with mitral regurgitation. Mitral valve repair with cardiopulmonary bypass can be beneficial for the treatment of mitral regurgitation in small-breed dogs.

Post-mortem evaluation of expanded polytetrafluoroethylene (ePTFE) used in mitral valve repair in dogs.

Mitral valve repair is one of the treatment options for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) is a polymer that has been widely used in cardiovascular surgery. In this case series, we report the autopsy and histological findings in 6 dogs that underwent cardiopulmonary bypass for mitral annuloplasty using ePTFE sheets and chordoplasty using ePTFE sutures. From May 2005 to October 2009, 3 female and 3 male dogs with severe mitral regurgitation underwent mitral valve repair. This case series included 3 Cavalier King Charles spaniels, 2 Maltese, and 1 Shih Tzu. The survival period after surgery was 19-72 (35 ± 19) months. In all the cases, autopsy revealed that the ePTFE sheets and sutures were not damaged and well integrated into the surrounding highly differentiated, connective tissues. Low-power microscopy revealed that in all cases, the tissues surrounding the ePTFE sheet in the mitral valve annulus had almost completely been covered by granulation tissue. No inflammatory infiltrate or thrombogenesis was observed around the ePTFE in any of the cases. There was no evidence of reactive changes in the region surrounding the ePTFE. These results suggest that ePTFE has excellent tissue compatibility and durability and can be effectively used for canine mitral valve repair.

Estimating glomerular filtration rate in healthy dogs using inulin without urine collection.

The goals of this study were to determine if the glomerular filtration rate (GFR) in dogs could be estimated by plasma inulin clearance and/or infusion inulin clearance analyses without urine collection, and to compare these results with GFR values obtained by urinary inulin clearance analysis. The dogs included in this study were healthy 20 beagles. Inulin clearance values were obtained by urinary inulin clearance, infusion inulin clearance, and plasma inulin clearance techniques. Urinary inulin clearance was 4.09±0.52 ml min(-1) kg(-1) (body weight); infusion inulin clearance, 4.01±0.49 ml min(-1) kg(-1); and plasma inulin clearance, 4.14±0.66 ml min(-1) kg(-1). The urinary inulin clearance was strongly correlated with infusion inulin clearance and weakly correlated with plasma inulin clearance. The GFR for dogs can be estimated by infusion and plasma inulin clearance analyses by blood sampling alone, without urine collection.

Surgical closure of an atrial septal defect using cardiopulmonary bypass in a cat.

OBJECTIVE: To describe surgical repair of a large atrial septal defect (ASD) in a cat. STUDY DESIGN: Clinical report. ANIMAL: A 3-year-old, 3.3 kg, intact male Japanese domestic short-haired cat. METHODS: A 10.2-mm-diameter ASD detected by echocardiography was surgically corrected because pulmonary vascular resistance-to-systemic vascular resistance ratio (Qp /Qs ) was 3.2. Using cardiopulmonary bypass (CPB), open surgical repair was achieved with an expanded polytetrafluoroethylene (e-PTFE) graft. The priming volume of the CPB circuit was minimized by cutting the CPB tubing, and partially replacing the priming fluid with whole cat blood. To prevent hemodilution associated with use of cardioprotective agents, surgery was performed on the beating heart. RESULTS: At 1-year echocardiographic evaluation, the repair was intact, and at 3 years, the cat was alive without need of medication. CONCLUSIONS: Large ASD in a cat can be repaired using e-PTFE under CPB.

Surgical repair of a complete endocardial cushion defect in a dog.

OBJECTIVE: To describe surgical repair of a complete endocardial cushion defect (ECD) in a dog. STUDY DESIGN: Clinical report. ANIMAL: A 5-month-old, 9.2 kg male Shetland sheepdog. METHODS: Echocardiographic examination revealed an ostium primum atrial septal defect (ASD), an inlet ventricular septal defect (VSD), mitral regurgitation (MR) and tricuspid regurgitation (TR), and a complete ECD was diagnosed. Surgical correction was performed using cardiopulmonary bypass (CPB) via right atriotomy. A polytetrafluoroethylene (PTFE) patch was secured along the margin of the inlet VSD using simple continuous suture, then the cleft in the septal mitral leaflet was sutured. Similarly, the cleft in the septal tricuspid leaflets was sutured. To complete inlet VSD closure, the VSD patch was secured to these sutured leaflets by simple continuous suture. Another PTFE patch was used to close the ostium primum ASD. RESULT: After surgery, MR, TR, and interventricular shunting were decreased. The dog was alive 6 years and 5 months after the surgery with no evidence of an interventricular shunt, TR, or other clinical signs. CONCLUSIONS: Complete ECD in a dog was corrected using a 2-patch technique under CPB.

Prenatal diagnosis of Kniest dysplasia with three-dimensional helical computed tomography.

OBJECTIVE: Fetal three-dimensional helical computed tomography (3D-CT) has attracted attention in the diagnosis of fetal skeletal dysplasias because of limited diagnostic capabilities of standard ultrasonography to delineate the skeleton. Here we report the first instance of diagnosing Kniest dysplasia with 3D-CT. METHODS: Fetal 3D-CT was performed for a fetus at 28 weeks' gestation after ultrasonography at 24 weeks had shown moderate shortening of the limbs, mild narrow thorax, and polyhydramnios. The imaging parameters were set so as to reduce estimated fetal irradiation dose to 12.39 mGy of the CT dose index volume and 442 of the dose length product. RESULTS: Fetal 3D-CT revealed dumbbell-shaped femora and platyspondyly with coronal cleft of the lumbar vertebral body. This warranted a diagnosis of Kniest dysplasia and corresponded well with postnatal radiographic findings. In retrospect, however, spinal deformation was somewhat underestimated due to image smoothing associated with image processing in 3D-CT. Genetic testing for COL2A1 confirmed Kniest dysplasia; i.e., a de novo mutation of A-C transversion at the splice acceptor site of the 3' end of intron 16. CONCLUSIONS: The combined use of 3D-CT with ultrasonography is a power tool for the prenatal diagnosis of congenital skeletal dysplasias.

Vaginal infection with Ureaplasma urealyticum accounts for preterm delivery via induction of inflammatory responses.

U. urealyticum, a member of the family Mycoplasmataceae, is often detected in the vagina of pregnant women. In this study, the possible association of ureaplasmal infection with preterm delivery was examined, as was the capacity of ureaplasmal LP to stimulate monocytes in vitro to produce pro-inflammatory cytokines relevant to preterm delivery. A hundred cases of normal delivery and 45 cases of preterm delivery were randomly selected. A mAb against U. urealyticum urease, that selectively and positively stained it in vaginal secretions of infected women but not in those of uninfected women, was generated. The preterm delivery group showed a significantly higher incidence of vaginal infection with this bacteria than the normal delivery group. Since the LP of Mycoplasma has potent biological activity, ureaplasmal LP was extracted. THP-1 cells, and human monocytic cells, produced IL-8, a potent pro-inflammatory cytokine associated with preterm delivery, and showed apoptotic cell death in response to the LP in vitro. These results suggest that U. urealyticum infection might play a causative role in preterm delivery via LP-induced IL-8 production and apoptosis.

A case of feline pancreatitis.

A 14-year-old, spayed female, domestic shorthair cat was referred to us with anorexia, pyrexia, and jaundice. Total bilirubin (TBIL) and feline trypsin-like immunoreactivity (fTLI) levels were remarkably high. Based on laparoscopic biopsy of the pancreas, the cat was diagnosed as having pancreatitis. As a result of treatment with a synthetic protease inhibitor and corticosteroid, the TBIL and fTLI values returned to normal and the clinical course was good.