Comparative evaluation of standard maintenance-dose clopidogrel versus low-dose prasugrel in patients with stable coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Treatment with low-dose prasugrel might be more beneficial even in chronic stable coronary artery disease (CAD) patients treated with clopidogrel. We compared platelet reactivity between standard maintenance-dose and low-dose prasugrel in stable CAD patients. METHODS: This multicenter study enrolled 164 stable CAD patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Patients were randomly assigned to continue treatment with 75-mg clopidogrel daily (n = 80) or switch to 3.75-mg prasugrel daily (n = 84). Platelet reactivity was evaluated by measuring P2Y12 reaction unit (PRU) before randomization and at 5 and 30 days thereafter using the VerifyNow® assay. Patients were classified into three groups according to CYP2C19-clopidogrel metabolic phenotype: extensive (without a *2 or *3 allele), intermediate (one *2 or *3 alleles), or poor (two *2 or *3 alleles) metabolizers. RESULTS: The PRU level was comparable between the two groups at baseline but was significantly lower in the prasugrel group than in the clopidogrel group on days 5 (133.0 vs. 156.8 PRU, P = 0.005) and 30 (124.3 vs. 158.0 PRU, P < 0.001). On day 30, the PRU level was lower in the prasugrel group among patients categorized as poor and intermediate metabolizers but not among extensive metabolizers. CONCLUSIONS: Low-dose prasugrel achieves more consistent antiplatelet effects than clopidogrel irrespective of the metabolic phenotype in Japanese patients with stable CAD. Low-dose prasugrel might be also beneficial in the chronic phase without increasing the bleeding risk among stable CAD patients in other countries.

Early in vivo evaluation of ventricular assistance with a miniature centrifugal blood pump (TinyPump) in rabbits.

We have developed an ultraminiature centrifugal pump, TinyPump, with a priming volume of 5 ml. The in vivo performance of TinyPump was compared with that of HPM-05 for left ventricular support. Each pump group included seven rabbits weighing 3.4-3.8 kg. One rabbit in the TinyPump group and two rabbits in the HPM-05 group died of unsuccessful cannulation. The remaining rabbits (six in the TinyPump group and five in the HPM-05 group) were instrumented and observed for 240 minutes. The pump flow was maintained at around 200 ml/min. The priming volumes of the entire circuits were 25 and 45 ml for TinyPump and HPM-05, respectively. TinyPump required a higher rotation speed (2214 +/- 47 vs. 1261 +/- 87 rpm, p < 0.05) because of its small priming volume but showed a similar plasma free hemoglobin level to HPM-05. The hematocrit values were kept higher in the TinyPump group during ventricular support (24.3 +/- 1.4% vs. 20.1 +/- 1.4% at 240 minutes, p < 0.05). The mean arterial pressure did not differ between the two groups. The biochemical parameters were also equivalent in the two groups. Overall, TinyPump exhibited a feasible in vivo performance. This ultraminiature device would offer promising outcomes for neonates and infants with intractable heart failure.

Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits.

OBJECTIVE: Paraplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits. METHODS: Eighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4 degrees C) and fasudil (group 2, n = 6, 4 degrees C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared. RESULTS: Two days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2. CONCLUSION: These results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.

Atypical presentation of an apical pseudoaneurysm in a patient on prolonged left ventricular mechanical support.

Prolonged support with left ventricular assist system (LVAS) increases the risk of device-related infection. We experienced a rare complication of LVAS: an infectious aneurysm at the apical cannula, which appeared with atypical presentation. A 27-year-old male, who developed acute aggravation of dilated cardiomyopathy, was placed on extra-corporeal type LVAS. Six months later, the patient suffered from methicillin-resistant Staphylococcus aureus (MRSA) sepsis that lasted for as long as three months despite intensive antibiotic therapy. At 17 months after the implantation, he presented with obstructive ileus. Monthly assessment with transthoracic echocardiography (TTE) did not document any abnormalities around the ventricle. A contrast computed tomographic (CT) scan revealed a huge apical aneurysm protruding into the preperitoneal space. The aneurysm oppressed the transverse colon, resulting in obstructive ileus. Aneurysmectomy was carried out and MRSA was identified from the resected tissue. We reached the precise diagnosis with a CT-scan, although routine assessment with TTE failed to reveal abnormalities. Knowledge of this complication is essential in LVAS management. This is certainly rare, but possibly occurs in all the patients on prolonged LVAS support. Early and accurate diagnosis together with aggressive intervention would bring favorable outcome in such serious cases.

Left ventricular performance in aortic valve replacement.

We analyzed the mid-term left ventricular (LV) performance after aortic valve replacement (AVR). We measured LV contractility (end-systolic elastance: Ees), afterload (effective arterial elastance: Ea) and efficiency (ventriculoarterial coupling: Ea/Ees; ratio of stroke work and pressure-volume area: SW/PVA) based on transthoracic echocardiography data obtained before, after and approximately 1 year after isolated AVR in 263 patients with aortic stenosis (AS group; n=116), aortic regurgitation (AR group; n=93) or aortic stenosis and regurgitation (ASR group; n=54). The LV volume was calculated by the Teichholz M-mode method. Ees and Ea were approximated as follows: Ees=mean blood pressure/minimal LV volume; Ea=systolic blood pressure/(maximal LV volume-minimal LV volume). Thereafter, Ea/Ees and SW/PVA were calculated. Arterial blood pressure was measured using manchette methods. Ees and Ea decreased after AVR in the AS group, but increased in the AR group. Ea/Ees and SW/PVA worsened after AVR in the AR group, but improved during a 1-year period after AVR in all groups. Contrasting effects of AVR on LV contractility and afterload between AS and AR were clearly demonstrated. The mid-term LV contractility and efficiency after AVR were excellent and satisfactory. However, LV efficiency worsened early after AVR in AR patients.

Left ventricular performance of pulmonary atresia with intact ventricular septum after right heart bypass surgery.

OBJECTIVE: The left ventricular performance in patients with pulmonary atresia with intact ventricular septum who were Fontan candidates before and after the bidirectional Glenn procedure and a staged total cavopulmonary connection was compared with that in patients with tricuspid atresia. METHODS: Contractility (end-systolic elastance), afterload (effective arterial elastance), and ventricular efficiency (ventriculoarterial coupling, arterial elastance/end-systolic elastance ratio), and the ratio of stroke work and pressure-volume area were approximated on the basis of cardiac catheterization data before the bidirectional Glenn procedure, before and after staged total cavopulmonary connection, and approximately 1 year after the completion of total cavopulmonary connection in 20 patients with pulmonary atresia with intact ventricular septum and 21 patients with tricuspid atresia. RESULTS: The end-systolic elastance of the pulmonary atresia with intact ventricular septum group was significantly inferior to that of the tricuspid atresia group after bidirectional Glenn procedure and total cavopulmonary connection (1 year after total cavopulmonary connection 1.85 +/- 0.51 mm Hg . m 2 . mL -1 vs 2.84 +/- 0.96 mm Hg . m 2 . mL -1 , P < .01). The arterial elastance was not different between groups throughout the assessment period and tended to increase in a stepwise fashion after bidirectional Glenn procedure and total cavopulmonary connection. The arterial elastance/end-systolic elastance ratio and ratio of stroke work and pressure-volume area of the pulmonary atresia with intact ventricular septum group tended to worsen, whereas those of the tricuspid atresia group tended to improve. The difference reached statistical significance 1 year after total cavopulmonary connection (1.15 +/- 0.35 vs 0.82 +/- 0.23 and 64.2% +/- 6.7% vs 71.3% +/- 5.7%, respectively, P < .05 and P < .05, respectively). CONCLUSION: The contractility and ventricular efficiency of patients with pulmonary atresia with intact ventricular septum are inferior to those of patients with tricuspid atresia after bidirectional Glenn procedure and total cavopulmonary connection. A high-pressure residual right ventricle may impair the left ventricular performance of patients with pulmonary atresia with intact ventricular septum after bidirectional Glenn procedure and total cavopulmonary connection.