AIMSAntihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H-1 receptor occupancy (H1RO) in the brain using positron emission tomography (PET). The aim was to measure H1RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine.METHODSEight healthy male volunteers (mean age +/- SD 24.4 +/- 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with C-11-doxepin in a crossover study design. Binding potential ratio and H1ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H1RO was examined.RESULTSH1RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H1ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H1ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001).CONCLUSIONOral bepotastine (10 mg), with its relatively low H1RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.
Changes in the autonomic nervous activity can be induced by various sensory and emotional stimuli. The authors examined whether the power spectral analysis of heart rate variability (HRV) could detect changes in autonomic tone following a lavender aroma treatment or not. Healthy young women (n=10, 23+/-3 years old) underwent continuous electrocardiographic (ECG) monitoring before and after (10, 20, 30 minutes) the lavender fragrance stimuli. HRV was expressed by three indices: low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components (nLF and nHF, respectively) as well as LF/HF ratio. Increases in the parasympathetic tone were observed after the lavender fragrance stimulus as seen as increases in the HF component and decreases in the LF/HF. Additional measurement with positron emission tomography (PET) demonstrated the regional metabolic activation in the orbitofrontal, posterior cingulate gyrus, brainstem, thalamus and cerebellum, as well as the reductions in the pre/post-central gyrus and frontal eye field. These results suggested that lavender aromatic treatment induced not only relaxation but also increased arousal level in these subjects.
Artificial heart (AH) and ventricular assist devices (VAD) are widely used in the clinical setting to assist severe heart failure patients. The concept of direct cardiac compression (DCC) has been in use for several decades and has advantages over intravascular VAD. The process involves compressing the dysfunctional heart from its epicardial surface to avoid the thromboembolic events and decrease the complications and mortality. An Electro-hydraulic Artificial Myocardium (EHAM) system was designed and fabricated by Tohoku University. This system may assist cardiac contraction and create pulsatile blood flow. The aim of this study was to clearly define the hemodynamic efficiency of the EHAM system in myocardial tissue perfusion during its application in acute animal experiment. Eight healthy adult goats were used; left lateral thoracotomy was performed and the chest was opened by the resection of the 4th and 5th ribs. Hemodynamic parameters including ECG, blood pressure and cardiac output were continuously monitored. Myocardial tissue perfusion was measured by using Omega flow laser fiber attached to the surface of the heart. During the EHAM compression, and increase in blood pressure and myocardial tissue perfusion was observed in all animals when compared with pre-assisted mode. To conclude, EHAM effectively improves myocardial tissue perfusion and increases the pressure on the initiation of direct cardiac compression immediately. Thus it can be a potentially valuable adjunct in the management of severe heart failure.
UNLABELLED:Artificial hearts and ventricular assist devices have been widely used clinically to assist patients with severe heart failure. Unfortunately, direct contact between the device and the patient's blood leads to thromboembolic events, and then the need for anticoagulation and infections contribute significantly to complication and mortality. Compressing the dysfunctional heart from its epicardial surface, a nonblood-contacting method of direct mechanical ventricular actuation could provide ventricular support, pulsatile blood flow, and avoid interactions between blood and the surface of the artificial assistance system. An ElectroHydraulic Artificial Myocardial (EHAM) assist system that might assist heart muscle contraction has been developed. The purpose of this study is to determine the efficiency of the EHAM system in perfusing myocardial tissue in an acute animal experiment.METHOD:Healthy adult goats (n = 8) were used in acute animal experiments. A left lateral thoracotomy was done and the chest was opened through the 4th and 5th rib resection. Hemodynamic parameters were continuously monitored including ECG, aortic blood pressure, left ventricular pressure, and pulmonary artery pressure. Myocardial tissue perfusion was measured by using an Omega flow laser fiber attached on the surface of the heart.RESULTS:All the animals achieved significantly increased blood pressure, pulmonary artery flow, and myocardial tissue perfusion during the EHAM compression compared with the nondriving (pre-assisted) mode.CONCLUSIONS:The EHAM system can effectively improve myocardial tissue perfusion and increase blood pressure thus demonstrating a potential for treating failing cardiac performance.
It is well known that a rotary blood pump (RP) is effective as a small ventricular assist device (VAD). It might be still more effective if pulsation was available. The undulation pump (UP), which is a type of small RP, can also produce pulsation. In Japan, a development project for an implantable type UP ventricular assist device (UPVAD) is now advanced. Six universities and some companies together have been in charge of the development project for 5 years. In this study, the influence which the UP under development has on circulation in internal organs was investigated. Goats with the same weight as an average Asian person were used for the experiment. The left chest cavity was opened after resection of the fourth rib and the heart was approached. A cannula was inserted in the left ventricle from the apex. An outflow cannula was inserted into the left descending aorta. Heart muscle was excised using a newly developed puncher. The UPVAD was implanted using a left-heart bypass system. The myocardial blood flow, carotid arterial blood flow, and the kidney blood flow were recorded together with an electrocardiogram, blood pressure, and the flow rate. In these animal experiments, the blood circulation dynamic state was stabilized and sufficient support of the left heart was observed. Myocardial blood flow, carotid arterial flow, and a kidney blood flow increase resulting from UPVAD support was observed. Often the problem of multiple organ failure is important at the time of clinical application of a ventricular assist device. Assisting circulation to internal organs is important for prevention of multiple organ failure. It was concluded that the UPVAD might be useful for prevention of multiple organ failure.
The development of a rotary blood pump (RP) is desirable as it can be used as a small ventricular assistance device (VAD). However, a RP does not generate any pulse. It may be physiologically better for the patient if the RP could generate a pulse. We have attempted to develop a device that produces a pulse in the RP. Intra-aortic balloon pumping (IABP) is effective in producing a pulse. However, the IABP cannot be implanted inside the body. Therefore, an attempt was made to develop pulse-generating equipment that was not driven by air pressure. The ball screw motor was considered as a possible candidate. In the future, we plan to apply small shape memory alloys. An electrohydraulic system was adopted, and actuator power output was connected to the diaphragm. The diaphragm was placed outside the ventricle. Most RPs developed throughout the world drain blood from the ventricle. The pulse wave should be generated if a pulse is added by the part from which blood is being drawn. In this study, animal experiments were conducted and the output assistance was tested from outside the ventricle. The device operated effectively in the animal experiment. The RP can easily be equipped with this device at the time of performing the implant operation. For a patient with problems of peripheral circulation and the internal organ fiunction, it may prove to be an effective device.