Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. METHODS: From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. RESULTS: The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). WHAT IS NEW AND CONCLUSION: Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care.

Sparing Native Upper Lobes in Living-Donor Lobar Lung Transplantation: Five Cases From a Single Center.

Living-donor lobar lung transplantation (LDLLT) is indicated for rapidly deteriorating patients, and the total volume of two lower lobe grafts must be sufficient for the recipient. To rescue patients with small lobar grafts, we performed five LDLLTs sparing native upper lobes. This strategy was used when upper lobes or segments were preoperatively less impaired. There were no hospital deaths. Extracorporeal circulation time and operative time were similar to those of conventional LDLLTs. The length of intensive care unit stay was also similar. Late complications attributed to the spared lungs were airway infection in one recipient and pneumothorax in two but they were successfully managed. All recipients were discharged without supplemental oxygen. The spared lung volumes measured by volumetry did not change after LDLLT. Lung perfusion scintigraphy performed at 1 year showed remaining perfusion in the spared lungs, although much less than in the grafts. These results suggested that the spared lobes kept adequate space in the thoracic cavity and kept functioning to a limited extent. The new lobar-sparing strategy appears feasible and effective in LDLLT using small grafts for selected patients when the upper lobes or segments are less impaired.

Right and left inverted lobar lung transplantation.

Adult recipients frequently withdraw from living-donor lobar lung transplantation because of the small size of donor grafts. The right lower lobe is 120% larger than the left lower lobe. We developed a novel surgical technique in which an inverted right lower lobe graft can be transplanted into the left thorax. The first patient was a 43-year-old woman with end-stage idiopathic interstitial pneumonia. Her husband was the only eligible donor for living-donor lobar lung transplantation. His right lower lobe was estimated to provide 45% of the recipient's predicted forced vital capacity, which would provide the borderline function required for living-donor lobar lung transplantation. Since lung perfusion scintigraphy of the recipient showed a right-to-left ratio of 64:36, transplanting the right lower lobe graft into the left thorax and sparing the native right lung was considered the only treatment option. We simulated this procedure using three-dimensional models produced by a three-dimensional printer. In living-donor lobar lung transplantation, all anastomoses were performed smoothly as planned preoperatively. Because of the initial success, this procedure was performed successfully in two additional patients. This procedure enables larger grafts to be transplanted, potentially solving critical size matching problems in living-donor lobar lung transplantation.

[Off-pump coronary artery bypass grafting supported by intra-aortic balloon pumping in a patient with moyamoya disease].

A 48-year-old woman was admitted to the hospital for coronary artery bypass grafting (CABG) of ischemic coronary disease, including left main trunk disease. She had a history of moyamoya disease with bilateral internal carotid artery occlusion. Her cerebral blood flow and cerebral vascular reactivity were evaluated by single photon emission computed tomography. Her collateral blood flow and cerebral vascular reserve were the lower limit of normal. We performed off-pump CABG supported by intra-aortic ballon pumping to maintain appropriate cerebral blood flow intraoperatively. Moreover, during operation, systolic blood pressure and blood Paco2 level were constantly maintained above 100 mmHg and 40 mmHg. Her postoperative course was uneventful without transient ischemic attacks or stroke.

Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells.

Malignant pleural mesothelioma (MPM) is resistant to chemotherapy and thus shows a dismal prognosis. Osteopontin (OPN), a secreted noncollagenous and phosphoprotein, is suggested to be involved in the pathogenesis of MPM. However, the precise role of OPN, especially in the multidrug resistance of MPM, remains to be elucidated. We therefore established stable transfectants (ACC-MESO-1/OPN), which constitutively express OPN, to determine its role in the chemoresistance observed in MPM. The introduction of the OPN gene provides MPM cells with upregulated multidrug resistance through the mechanism of enhanced hyaluronate (HA) binding. The expression of CD44 variant isoforms, which inhibit HA binding, significantly decreased in ACC-MESO-1/OPN cells in comparison to control transfectants. Interestingly, the inhibition of the HA-CD44 interaction abrogated multidrug resistance in the ACC-MESO-1/OPN, thus suggesting the involvement of the surviving signal emanating from the HA-CD44 interaction. An enhanced level of the p-Akt in ACC-MESO-1/OPN cells was observed, and was diminished by CD44 siRNA. Inhibition of the Akt phosphorylation increased in number of the cells underwent apoptosis induced by NVB, VP-16 and GEM. Collectively, these results indicate that OPN is strongly involved in multidrug resistance by enhancing the CD44 binding to HA.

Robotic assessment of locomotor recovery in spinal contused rats.

The purpose of this study was to investigate the ability of a robotic device, "the rat stepper", to assess intrinsic locomotor recovery following spinal cord contusion injury in adult rats. The device consists of a motorized body weight support mechanism that precisely controls the load to the hindlimbs during stepping, and two small robotic arms that measure and manipulate hindlimb movement. Sixteen rats received a contusion injury to the mid thoracic spinal cord with different severity levels (mild, moderate, severe, and sham). The animals were then evaluated weekly using the rat stepper, beginning one week after injury and continuing for a period of twelve weeks, across a range of body weight support levels. The contused animals demonstrated recovery in a standard locomotor assessment score (the BBB score), with most of the recovery occurring by four weeks post injury. We analyzed fourteen robotic measures of stepping and found that the measures that were most sensitive to intrinsic recovery were step velocity and inter limb coordination. These measures were also significantly correlated with the BBB score. The number of steps taken during testing was not sensitive to intrinsic recovery, nor correlated to the BBB score. These results suggest that step quality, rather than quantity, best reflects recovery after contusion injury in adult, untrained rats. Thus, robotic motion capture of only a few steps can provide a sensitive, valid measure of locomotor recovery after contusion.

Primary leiomyosarcoma of the pulmonary artery mimicking massive pulmonary thromboembolism.

A 57-year-old man with dyspnea and dry cough exhibited pulmonary embolism. Pulmonary arteriography demonstrated absent perfusion of the left main and the right upper and middle lobe pulmonary arteries. A diagnosis of chronic pulmonary thromboembolism was assumed and surgical thromboendarterectomy was attempted under standard cardiopulmonary bypass. At operation, a tumor had invaded far into both the right and left pulmonary arteries and radical resection was impossible. The final pathological diagnosis was primary leiomyosarcoma of the pulmonary artery. The patient refused any adjuvant therapy and died 63 days after the surgery. The clinical presentation of this case was similar to that of pulmonary thromboembolism and its diagnosis and treatment were very difficult.

[Evaluation of right ventricular function by intraoperative transesophageal echocardiography for patients with left ventricular dysfunction].

We evaluated right and left ventricular function by intraoperative transesophageal echocardiography for the patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) < or = 40) who underwent isolated coronary artery bypass grafting (CABG). We divided these patients into two groups; group 1 who had difficulty of weaning from cardiopulmonary bypass due to hypotension (n = 8) and group 2 who did not have any difficulty of it (n = 17). Basement characteristics (age, gender, history of myocardial infarction, congestive heart failure, LVEF, severity of the right coronary artery disease) of both groups were not different significantly. Intraoperative characteristics (the number of distal anastomoses, duration of aortic cross-clamp and cardiopulmonary bypass, and bypass to the right coronary artery) were also not different between two groups. However, mean duration of ICU stay and in-hospital mortality were significantly longer and higher in group 1 than group 2. On the other hand, right ventricular systolic function was severely impaired, particularly postoperatively, in group 1 compared with group 2. Right and left ventricular systolic function of group 2 was fairly improved postoperatively. These results may indicate that right ventricular dysfunction is a potent predictor of postoperative morbidity and mortality for the patients with left ventricular dysfunction who undergo isolated CABG.

Increase in production of ascorbate radical in tissues of rat treated with paraquat.

The production of ascorbate radical (A*-) was investigated in tissues of rats intoxicated with paraquat (PQ) to know the protective role of antioxidant ascorbate (AH-) in tissues. The electron spin resonance (ESR) method is applied to observe A*-. To eliminate increased biosynthesis of ascorbic acid (AH2) by PQ intoxication, ODS rats were chosen and fed with or without 250 ppm PQ in the diet. The radical A*- was detected only in the lung and spleen homogenates of both intoxicated and control rats at the beginning of ESR measurement. The radical levels of intoxicated rat lung and spleen were increased rapidly to twice the initial level after 3 h and decreased to 0.2-0.6 times the initial level after 24 h, whereas those of control rats were increased slowly to 1.1 times the initial level after 4 h and decreased slowly to 0.7 times the initial level after 24 h at 4 degrees C. In other organs such as liver, kidney, heart and testis, A*- was not detected initially but detected afterwards. Higher A*- level was observed in the intoxicated rat liver than the control but no appreciable differences of A*- levels were observed between the intoxicated kidney, heart and testis and the respective controls. In the intoxicated rat lung the concentration of AH2 is only half but that of A*- is twice as high as that of the control. Larger amounts of A*- produced in the intoxicated rats decayed more quickly than those in the control rats. The simple addition of PQ to the control organ enhanced neither A*- production nor A*- quenching. These facts suggest that the tissues damaged by PQ require larger amounts of AH- to detoxicate harmful oxidants, resulting in concomitant production of A*-.

A new diquat derivative appropriate for colourimetric measurements of biological materials in the presence of paraquat.

A new colourimetric method is described for the quantification of diquat using a yellow-coloured derivative produced by heating diquat in alkaline solution at 80 degrees C. The absorption maximum of the yellow derivative is 420 nm and the molar absorption coefficient is 2.76 x 10(4) (0.15 in 1 microgram diquat/ml with 1 cm light path). The absorption at 420 nm shows a linear concentration dependence in the range 0.1-10 micrograms/ml and fading of the colour is about 5% after 1 h. Under the same conditions, paraquat does not produce any coloured products. The concentration of diquat in the solution containing both diquat and paraquat can be determined by the absorption of diquat derivative at 420 nm without interference from paraquat. By adding sodium dithionite to the solution the concentration of paraquat can be determined by the absorption of paraquat radicals at 600 nm without interference from diquat, because the yellow derivative does not react with dithionite. This yellow diquat derivative can be extracted completely with cyclohexanol by saturating the solution with Na2SO4. The absorption maximum in cyclohexanol shifts to 440 nm with the same molar absorbance and the same half-band width as in water. Fading of the colour is less than 5% after 24 h in cyclohexanol. Perchloric acid (3%) and trichloroacetic acid (4.5%) which are often used for deproteinization of tissue homogenates, do not inhibit production of the coloured derivative at pH 13.5 or extraction of the derivative with cyclohexanol. This method is suitable for a quick determination of small amounts of diquat in tissues, since the extraction with cyclohexanol not only concentrates the derivative rapidly but also quite efficiently eliminates the coloured substances in tissue homogenates. The detection limit of diquat is 0.02 microgram/ml for blood and 0.05 microgram/g for liver when 1 ml or 1 g is used for analysis. In three human cases of fatal intoxication, both paraquat and diquat were quantified using 50 microliters of serum. In non-toxic dosing of diquat to rats for 14 days, the diquat level was highest in the spleen followed by the kidneys.

Influence of peripheral vascular occlusive disease on the morbidity and mortality of coronary artery bypass grafting.

The impact of peripheral vascular occlusive disease (PVD) on outcome for patients who have undergone coronary artery bypass grafting (CABG) was assessed by comparing preoperative and intraoperative patient characteristics and outcome in 2 groups of patients who underwent CABG (patients with PVD, n=96; patients without PVD, n=593). Patients with PVD were significantly older (69+/-8.4 vs 63+/-8.7; p<0.0001), and had a higher incidence of diabetes mellitus (48% vs 32%; p<0.01), hypertension (62% vs 46%; p<0.01), preoperative cerebral infarction (26% vs 12%; p<0.001) and chronic renal dysfunction (11% vs 4.4%; p<0.01) than those without PVD. Postoperative morbidity and mortality were assessed, after those risk factors were adjusted, using multivariate logistic regression analysis. The perioperative myocardial infarction (PMI) rate and in-hospital mortality rate were significantly higher in patients with PVD than in patients without PVD (9.4% vs 3.0%; p=0.0108, 17% vs 2.7%; p=0.0003, respectively). The odds ratio of PMI and in-hospital mortality were 3.4 (95% confidence intervals (CI): 1.3-8.6) and 4.3 (95% CI: 2.0-9.5), respectively. Although the excess mortality rate was mainly the result of cardiac problems, such as low output syndrome or arrhythmia, in most of the cases, PVD, which may frequently prevent the use of the intraaortic balloon pump, also seemed to have a strong relation to postoperative morbidity and mortality.

[Clinical experience with gelatin-resorcine-formol glue for repair of postinfarction ventricular septal rupture].

We report a surgical technique for treatment of postinfarction ventricular septal rupture (VSR). An 82-year-old woman underwent successful surgical repair of a VSR two days after suffering anterior myocardial infarction. After repair of the VSR with a Dacron patch, the left ventriculotomy was closed with mattress sutures over felt strips using the gelatin-resorcine-formol glue to reinforce the left ventricular wall. The patient was doing well four months after surgery.

[Coronary bypass surgery within thirty days of acute inferior myocardial infarction].

Between April 1988 and November 1998, 82 patients underwent isolated coronary artery bypass grafting within 30 days of acute myocardial infarction. The infarct-related artery was the proximal right coronary artery (27 patients; group 1) and the left coronary artery (55 patients; group 2). In group 2 the infarct-related artery was the left main coronary artery (8 patients), the left anterior descending coronary artery (33 patients), and the left circumflex coronary artery (14 patients). There was no difference between groups 1 and 2 with regard to sex, age (65 +/- 9 vs 66 +/- 10, respectively), presence of diabetes, renal insufficiency, previous myocardial infarction, and preoperative use of an intraaortic balloon pump (67% vs 71%, respectively). Compared with group 2, group 1 patients more often had three-vessel or left main disease (93% vs 65%, respectively; p = 0.018), a higher number of bypass grafts (3.0 +/- 0.8 vs 2.5 +/- 0.7, respectively; p = 0.014), and a greater incidence of postoperative complete atrioventricular (AV) block (30% vs 6%, respectively; p = 0.005). The hospital mortality rate for patients who underwent surgery within 48 hours after acute myocardial infarction did not differ between groups 1 and 2 (22% vs 18%, respectively). However, patients in both groups who underwent surgery between 48 hours and 30 days after infarction had significantly different mortality rates (22% vs 0%, respectively; p = 0.037). Patients with postoperative complete AV block had high mortality rates of 38% in group 1 and 67% in group 2. We conclude that patients who undergo coronary bypass surgery within 30 days of acute inferior myocardial infarction have a high incidence of postoperative complete AV block, which result in increased mortality.

[Effects of coronary artery bypass surgery on the stunned and hibernating myocardium in the cases with depressed left ventricular function].

Chronic left ventricular (LV) dysfunction may result from irreversible damage (cell death), stunned myocardium (ST), or hibernating myocardium (HB). However, both of ST and HB are expected to be reversible. In this report, the effects of coronary artery bypass grafting on the regions of ST and HB were evaluated in 37 patients with less than 40% of LV ejection fraction. The patients were divided into two groups. Group I consisted of the patients whose postoperative LV ejection fraction rose by more than 10% compared to the preoperative value. Group II included the remaining patients with no significant improvement. After successful revascularization, 61% of HB changed to ST and 52% of ST to normal in group I. These changes were significant in comparison with group II because 48% of HB and 83% of ST in group II remained unchanged. Immediate or rapid recovery of HB hardly occurred in both of the groups. To recover normal function, HB may pass through a stage of ST on reperfusion. On the other hand, it is difficult to determine whether HB and ST with no significant changes after reperfusion are irreversibly damaged or reversible and take time to return to normal.

[ASO as a risk factor of emergency CABG].

The presence of lower extremity arterial occlusive disease (arteriosus sclerosis obliterance of lower extremity) is an important risk factor for patients undergoing emergency coronary artery bypass operations. Those patients had higher mortality and morbidity rates related to the complications of intraaortic balloon pumps (IABP). If lower extremity ischemia is observed, rapid procedures such as removal of the IABP with or without thrombectomy and femorofemoral crossover interposition of a graft should be performed.

Two-stage repair for aortic regurgitation complicated by severe coarctation of the thoracoabdominal aorta due to Takayasu's arteritis.

Takayasu's arteritis is a rare inflammatory aortoarteritis of unknown etiology and causes stenoocclusive disease of the aorta and its branches as well as aortic regurgitation. A surgical case of Takayasu's arteritis is presented. A 56-year-old female exhibited aortic regurgitation complicated by severe coarctation of the thoracoabdominal aorta due to Takayasu's arteritis. In this case, a 2-staged repair, consisting of an axillofemoral bypass and an aortic valve replacement, was successfully performed.

Primary leiomyosarcoma of the left atrium.

A 69-year-old woman with symptoms of congestive heart failure had a left atrial leiomyosarcoma, an extremely rare cardiac tumor, which obstructed the mitral valve and pulmonary veins. Surgical resection was performed, but no other adjuvant therapy was administered because the patient refused it. Recurrence of the tumor occurred soon after surgery and the patient died 81 days postoperatively.

Surgical treatment for Scheie's syndrome (mucopolysaccharidosis type I-S): report of two cases.

Scheie's syndrome (mucopolysaccharidosis type I-S) is a rare genetic lysosomal storage disease affecting mucopolysaccharide metabolism, and is known to include cardiovascular disease. Surgical treatment was carried out in 2 patients with Scheie's syndrome. Patient 1 was a 56-year-old man with triple-vessel coronary artery disease, who successfully underwent coronary artery bypass grafting. Patient 2 was a 52-year-old man with aortic and mitral valve stenosis, who successfully underwent combined aortic and mitral valve replacement. The literature on Scheie's syndrome associated with valvular and coronary artery disease is also reviewed.