Quantitative evaluation of intra-aortic flow disturbance by the fluid momentum index: Effect of the left ventricular systolic function on the hemodynamics in the aorta.

The combined hemodynamics in the left ventricle and aorta were analyzed numerically to investigate how the hemodynamics in the aorta varies with changes in left ventricular systolic function quantified as the ejection fraction (EF). EFs of 0.3, 0.5, and 0.7 were defined by controlling the total volume ejected during systole, while maintaining the ventricular volume at the end of diastole. The results showed that although the variation in left ventricular systolic function resulted in a change in the magnitude of the flow velocity, the intraventricular and aortic flows, including the secondary flows at the aortic valve orifice, were essentially the same regardless of the EF. To evaluate the strength of the secondary flow relative to the axial flow, the flow momentum index, FMI, was proposed. Spatiotemporal maps of the FMI obtained with different EFs had similar topological patterns, suggesting that the left ventricular systolic function contributed less to the efficiency of conveying blood in the axial direction in the aorta. Systolic function had a minimal effect on the spatiotemporal distribution of the maximum wall shear stress (WSS). A comparison of the spatiotemporal maps of the FMI and WSS revealed that the spatiotemporal maximum of WSS that occur in peak systole did not correspond to that of the FMI, demonstrating that the spatiotemporal maximum WSS was not induced by the helical flow. These results demonstrated that the left ventricular systolic function is not reflected in the global hemodynamics in the aorta and addressed potential of the FMI as an index to quantify the aortic flow disturbances.     

Effects of atypical antipsychotics and haloperidol on PC12 cells: only aripiprazole phosphorylates AMP-activated protein kinase

By converting changes in intracellular energy status to changes in cell membrane polarization, ATP-sensitive K⁺ (K_ATP) channels in hypothalamic appetite-regulating neurons play a critical role in linking neuronal electrochemical function, metabolic and energy status, and feeding behavior. Most atypical antipsychotics (AAPs) increase the appetite of patients with schizophrenia and thus cause obesity. This study aimed to explain the mechanism underlying AAP-induced appetite stimulation, based on the fact that the efficiency of fatty acid uptake into mitochondria generating ATP through β-oxidation is determined by the rate of fatty acid synthesis. Using PC12 cells exposed to clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, and haloperidol, we measured intracellular ATP and mRNA and protein expression of enzymes and related substances involved in fatty acid synthesis and K_ATP channel function. Forty-eight-hour treatment of cells with 50 μM aripiprazole in 5.6 mM glucose decreased intracellular ATP. Only 50 μM aripiprazole phosphorylated AMP-activated protein kinase (AMPK); none of the other antipsychotics did so to a detectable level. Expression of carnitine palmitoyltransferase 1a, uncoupling protein 2, and sulfonylurea receptor 1 was unaffected by the antipsychotics, although expression of their mRNA was affected by AAPs. Pyrilamine (H₁ receptor antagonist), ketanserin (5HT₂ receptor antagonist), and raclopride (D₂ receptor antagonist) alone or in combination had no effect on expression of the aforementioned proteins. Therefore, although this study did not differentiate orexigenic and non-orexigenic AAPs, it suggests that aripiprazole is unique in its ability to activate AMPK.     

Malignant transformation of cerebello-pontine angle epidermoid

A 55-year-old woman presented with fever and a stiff neck due to an intracranial poorly differentiated carcinoma at the right cerebellopontine angle. The patient suffered from typical trigeminal pain and had undergone a removal of the right cerebellopontine angle epidermoid 13 years before at another hospital. On admission, MRI imaging showed a lesion at the right cerebellopontine angle with marked contrast enhancement. Partial removal of the tumor was achieved. A histological examination of the tumor showed a poorly differentiated carcinoma accompanied by typical desquamated tissue of the epidermoid. The patient died 3 months after the operation because of aggressive meningeal carcinomatosis.     

Inhibition of the vanilloid receptor subtype-1 attenuates tnbs-colitis

Primary sensory neurons are important in regard to the initiation and propagation of intestinal in.ammation. The vanilloid receptor subtype-1 (VR-1) is a cation channel located on the sensory nerves that, when stimulated, release proinflammatory peptides. Previous reports have indicated that inhibition of VR-1 with capsazepine (CPZ), a VR-1 antagonist, attenuates dextran sodium sulfate (DSS) colitis in rats. DSS-induced colitis resembles ulcerative colitis with regard to its pathologic features. In this study, we examined the effect of CPZ on trinitrobenzene sulfonic acid (TNBS)-induced colitis, an experimental model of intestinal inflammation that most closely resembles the histologic and microscopic features of Crohn’s disease. Colitis was induced by administering a single enema of 100 mg/ kg TNBS in 50% ethanol via catheter to lightly anesthetized rats. Subsets of rats were treated with either 1 μmol/kg/ml of CPZ or CPZ-vehicle via enema for 6 days. Seven days after TNBS administration, rats were sacrificed and inflammation was assessed using a validated macroscopic damage score (MDS) and by measuring myeloperoxidase (MPO) activity. In addition, histologic examination was performed. TNBS administration resulted in reproducible chronic erosive lesions extending into the muscularis propria and extensive recruitment of neutrophils in the distal colon. MDS and MPO scores were considerably elevated in the TNBS colons when compared with the TNBS vehicle animals. TNBS rats treated with CPZ enemas exhibited a substantial reduction in MDS and MPO scores and demonstrated dramatically improved pathologic findings. Topical CPZ resulted in considerable attenuation of TNBSinduced colitis. These results support the role of VR-1 and sensory neurons with regard to intestinal inflammation. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (oral presentation). This work was supported by the American Surgical Association Fellowship Award and a Career Development Award from the American Society of Colon and Rectum Surgery (C.R.M.).     

Long-Term In Vivo Left Ventricular Assist Device Study for 284 Days with Gyro PI Pump

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, the Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart (TAH), 2 week screening tests for anti-thrombogenecity, and a 1 month system feasibility study. Based upon these results, a metallic prototype, the Gyro PI 700 series, was subjected to long-term in vivo left ventricular assist device (LVAD) studies of over 1 month. The Gyro PI 700 series has the same inner dimension and same characteristics of the Gyro PI 601 such as an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI metallic pump is also driven with the Vienna DC brushless motor actuator like the PI 601. The pump-actuator package was implanted in 3 calves in the preperitoneal space, bypassing from the left ventricular (LV) apex to the descending aorta. Case 1 achieved a 284 day survival. Case 2 was euthanized early at 72 postoperative days as a result of the functional obstruction of the inlet port due to the excessive growth of the calf. There was no blood clot inside the pumps of either case. Case 3 is on-going (22 days on July 24, 1998). During these periods, all cases showed no physiological abnormalities. In conclusion, the PI 700 series pump has excellent results as a long-term implantable LVAD.     

Attenuated anterior cingulate activation during a verbal fluency task in elderly patients with a history of multiple-episode depression.

OBJECTIVE: Previous studies have suggested that, in elderly patients, prior depression plays a role in the recurrence of depression. The aim of this study was to investigate cerebral brain function in recovered depressed elderly and investigate the relationship between this brain function and the number of depressive episodes. METHODS: Twenty elderly depressive patients in recovery and 10 healthy volunteers were included in this study. The depressive patients were divided into those who had experienced a single depressive episode and those who had experienced multiple episodes. Functional magnetic resonance imaging was performed in each participant during a verbal fluency task. The data were analyzed using statistical parametric mapping. RESULTS: Activation in the anterior cingulate cortex was significantly attenuated in patients who had experienced multiple depressive episodes, compared with the other two groups. There were no significant differences in areas of activation between patients with a single depressive episode and healthy volunteers. CONCLUSIONS: These findings suggest that attenuated activation in the anterior cingulate cortex may be associated with multiple episodes of depression in the elderly and with the vulnerability to cycling or recurrence.     

Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients.

When observed in elderly hypertensive patients, increased pulse pressure (PP) and arterial stiffness are known to be independent risk factors for cardiovascular diseases. Increased systolic blood pressure (SBP) leads to left ventricular hypertrophy, while decreased diastolic blood pressure (DBP) results in decreased coronary circulation. It is known that increased arterial stiffness is the major cause of increased PP. Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness, and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives. In this study, we compared the effects of an angiotensin-receptor blocker (ARB: valsartan), an angiotensin-converting enzyme inhibitor (ACE-I: temocapril), and long-acting Ca antagonists (L- and N-type Ca channel blocker: cilnidipine; and L-type Ca channel blocker: nifedipine CR) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months. The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity (baPWV), followed by the ACE-I and L- and N-type Ca channel blocker, while the L-type Ca channel blocker yielded no improvement. The effects on arterial stiffness and PP thus varied among the drug characteristics. Although ARB achieved the largest reduction in baPWV, this decrease was not associated with any reductions in PP, SBP, DBP, or mean blood pressure, as were the baPWV-decreases achieved by the other drugs, suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect.     

Identification of the right ventricular pacing site for cardiac resynchronization therapy (CRT) guided by electroanatomical mapping (CARTO).

BACKGROUND: The optimal left ventricle (LV) pacing site for cardiac resynchronization therapy (CRT) has been investigated, but less is known about the optimal site in the right ventricle (RV). The present study examined whether electrical resynchronization guided by electroanatomical mapping (CARTO) results in mechanical resynchronization. METHODS AND RESULTS: The study group included 13 patients indicated for CRT: 10 with nonischemic cardiomyopathy, 2 with ischemic cardiomyopathy and 1 with cardiac sarcoidosis, (mean LV ejection fraction: 32+/-10%). CARTO of the RV septum was performed to identify the site with the most delayed conduction time during LV pacing. Hemodynamic measurements were performed during conventional biventricular pacing with the RV apex and LV (C-BVP) and during biventricular pacing with the most delayed site of the RV (d-RV) and LV (D-BVP). Lead placement at 15 coronary sinus veins was examined in the 13 patients. During pacing from anterolateral veins (n=2), the d-RV was the RV apex (RVA) in 1 patient and the mid-septum in the other. During pacing from lateral veins (n=9), the d-RV comprised the RVA (n=3), the mid-septum (n=5), and the right ventricular outflow tract (RVOT) (n=1). During pacing from the posterolateral veins (n=3), the d-RV was the RVOT in all cases. In 11 of 15 sites, d-RV differed from conventional RVA. Compared with C-BVP, D-BVP produced a significant improvement in LV dp/dt. Furthermore, RV mid-septum and LV pacing markedly increased LV dp/dt and pulse pressure (PP), but RVOT and LV pacing did not. D-BVP vs C-BVP: %LV dp/dt 30+/-20 and 15+/-15%, p<0.05; RV mid-septum and LV pacing vs C-BVP: %LV dp/dt 35+/-20 and 10+/-15%, p<0.02, and vs PP 33+/-20 and 10+/-29 mmHg, p<0.02. CONCLUSIONS: For pacing from the LV lateral vein, potential improvement of cardiac performance compared with that by conventional RVA placement may be realized with concomitant pacing from the d-RV (mid-septum).