Long-term effects of statins on arterial pressure and stiffness of hypertensives.

Although lowering blood pressure (BP) reduces aortic stiffness, achieving the recommended BP goal can be difficult. Recent studies have shown that short-term use of statins can reduce BP significantly. To determine the long-term effects of statins on BP and aortic stiffness, a single-blind randomized prospective study was performed on 85 hyperlipidaemic hypertensive patients whose BP was insufficiently controlled by antihypertensive therapy. Every 3 months, aortic stiffness was assessed by measuring pulse wave velocity (PWV). Patients were randomly allocated to groups treated with pravastatin, simvastatin, fluvastatin, or a nonstatin antihyperlipidaemic drug. No significant differences in patient characteristics, kinds of antihypertensive drugs, BP, ankle brachial index, PWV, or serum lipid, creatinine, or C-reactive protein levels were found between the four groups at the start of the study. During the 12-month treatment period, PWV did not change in the pravastatin group or nonstatin group, but it was transiently reduced in the simvastatin group and significantly decreased in the fluvastatin group, even though the doses of the statins used in this study were lower than the usually prescribed dose. All four antihyperlipidaemic drugs significantly decreased serum cholesterol levels without affecting BP, ankle brachial index, or serum triglyceride levels. The C-reactive protein serum levels decreased significantly in the three statin groups but not in the nonstatin group. These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP.

[Intra-arterial infusion chemotherapy in non-resectable pancreatic cancer using angiotensin-II and implantable drug delivery system].

Over the past 6 years, we have treated 25 cases of pancreatic cancer, 6 cases of cholangioma in pancreas-head and 3 cases of cancer in duodenal papilla (2 cases Stage I, 5 cases stage II, 2 cases stage III, 25 cases stage IV). Twelve cases (10 unresectable cases, 1 hepatic metastasis case, 1 recurrent case) were treated with intra-arterial infusion chemotherapy using implantable Drug Delivery System, combined with angiotensin-II to increase the concentration of anti-cancer agents in cancer tissue. Twenty-four cases (70%) died in less than one year, so operation is not effective except for curative resection of cholangioma and duodenal papilla cancer. But exploratory laparotomy or inoperable cases given intermittent transcatheter arterial infusion chemotherapy (5-FU + ADM + MMC + angiotensin-II), showed favorable results (decrease of tumor size and pain in 2 cases; recanalization of obstruction in choledochus of 1 case). Especially trans-femoral or left subclavian arterial catheterization proved to be effective therapy for possibly giant or recurrent inoperable pancreatic cancer and hepatic metastasis. Using the drug delivery system, the technical approach to arterial infusion therapy and angiography has been readily undertaken. Quality of life has been improved, and course observation of the patient has been possible by imaging diagnosis and multidisciplinary treatment for advanced pancreatic cancer.

Inflammatory reaction following cataract surgery and implantation of acrylic intraocular lens in rabbits with endotoxin-induced uveitis.

PURPOSE: To investigate whether inflammatory responses are more severe in uveitic eyes than nonuveitic eyes when acrylic intraocular lens (IOL) is implanted after cataract surgery. METHODS: Clear lens removal (phacoemulsification and aspiration) was conducted and the hydrophobic acrylic IOL (AR40e, AMO) was implanted in adult albino rabbits. Just after the operation, rabbits were divided into two groups. One group (nine rabbits) received intravitreal injection of lipopolysaccharide (LPS, 200 ng/10 microl) into both eyes to induce endotoxin-induced uveitis (EIU) and the other group (nine rabbits) received intravitreal injection of phosphate-buffered saline (PBS, 10 microl) into both eyes as the control. Aqueous humour (AH) and IOLs were harvested 1, 3 , and 7 days after the intravitreal injection. The infiltrating cell number in AH was counted and the protein concentration of AH was measured. IOLs were evaluated morphologically. RESULTS: At 1 day after intravitreal injection, both the infiltrating cell number in AH and protein concentration of AH were significantly higher in the LPS-injected group than in the PBS-injected group. Similarly, more inflammatory cells attached to the surfaces of the IOLs in the LPS-injected group. However, 7 days later, inflammatory reactions subsided and no clear differences in any of the parameters examined were observed between the two groups. CONCLUSIONS: At 7 days after the operation, inflammatory reactions in eyes implanted with the hydrophobic acrylic IOLs were similar in uveitic eyes and nonuveitic eyes. The data suggest that the hydrophobic acrylic IOLs may be suitable for patients with uveitis.

Hemodynamic changes in two patients with retinal circulatory disturbances shown by fluorescein angiography using a scanning laser ophthalmoscope.

PURPOSE: To assess hemodynamic changes in two patients with severely affected retinal circulation. METHODS: A 62-year-old man with central retinal artery occlusion and a 46-year-old woman with branch retinal vein occlusion were studied by fluorescein angiography with a scanning laser ophthalmoscope (SLO). Fluorescein angiography with SLO revealed hypofluorescent clumps of different sizes and hyperfluorescent dots in large retinal vessels. The velocities of the hypofluorescent clumps were calculated between two points on the same vessel, and movements of the hypofluorescent clumps and the hyperfluorescent dots were investigated. RESULTS: The velocities of the hypofluorescent clumps were slow and varied in the same vessel. The velocities of the hypofluorescent clumps increased at the sites with narrow calibers. The hypofluorescent clumps occasionally changed size in the bloodstream. The hypofluorescent clumps flowed along the walls of retinal vessels. Distance between consecutive hypofluorescent clumps was wide. Some vessels filled with hypofluorescent clumps were also detected. Rolling hyperfluorescent dots were seen in fluorescent plasma. CONCLUSIONS: The hypofluorescent clumps were concluded to be packed erythrocytes and the hyperfluorescent dots corresponded to leukocytes and platelets moving in the vessels. Fluorescein angiography with SLO is a useful method for evaluating hemodynamic changes using the hypofluorescent clumps in severely affected retinal circulation.

Development of a direct mechanical left ventricular assist device for left ventricular failure.

We have developed a direct mechanical left ventricular assist device (DMLVAD) for severe left ventricular failure. The DMLVAD was attached to the left ventricle and compressed the heart by a pneumatic driving unit. In a mock circulation model with an extracted nonbeating heart, a cardiac output (CO) of 1.93 L/min was obtained at a driving pressure of 200 mm Hg. In a canine left ventricular failure model induced by injection of sodium hydroxide into the myocardium, the systolic arterial pressure, systolic left ventricular pressure, maximum LV dP/dt, peak flow, and CO increased by 21, 24, 58, 144, and 37%, respectively. The mean left atrial pressure also decreased by 15% when the DMLVAD was driven. These effects were most prominent when the mean left atrial pressure was over 15 mm Hg, and the driving pressure was over 100 mm Hg. Compression at late systole was more effective in obtaining greater CO. We suggest that the DMLVAD could be an optional circulatory assist device for patients with left ventricular failure awaiting heart transplantation.

Numerical simulation of nonpulsatile left ventricular bypass.

A computer simulation was carried out to investigate the influence of nonpulsatile left ventricular assistance on hemodynamics. A simulation circuit was constructed to represent the circulatory system. A source of current was added to denote the nonpulsatile blood pump. The left and right ventricles were replaced by variable compliances. Left heart failure was simulated by decreasing the amount of compliance change of the left ventricle. We introduced a pulsatility indicator (PI) to clarify the pulsatility characteristics in the hemodynamics; this PI was defined as the ratio of the pulse pressure (PP) to the mean aortic pressure (AoP). When nonpulsatile bypass flow increased, the mean AoP, tension time index (TTI), and diastolic pressure time index (DPTI) increased, and cardiac output, PP, and PI decreased. When assisted flow increased with the constant total flow rate, the mean AoP and DPTI changed little; the PP, TTI, and PI decreased, and the endocardial viability rate increased. The PI would be helpful in evaluating the effect of pulsatility.

Trial manufacture of eccentric roller type total artificial heart.

Working toward a completely implantable total artificial heart, we have designed an eccentric roller type total artificial heart. The actuator of this artificial heart is a drum type eccentric roller that squeezes the blood chambers. The blood chambers are made of silicone rubber and are torus in shape. The shape of the artificial heart is an almost circular cylinder, and its length and diameter are 10 cm and 8 cm, respectively. The 2 main characteristics of this artificial heart are that it discharges blood in a pulsatile mode and that it requires no reversing of the motor. Because we have not completed the artificial heart yet, we have tested the eccentric roller mechanism on the prototype with an overflow type mock circulation with a 100 mm Hg afterload. The prototype worked at the roller speeds of 50, 100, and 150 rpm with flow rates of 1.7, 3.7, and 5.4 L/min, respectively. Next the prototype was connected to a Donovan type mock circulatory system and worked at roller speeds of 88-214 rpm with flow rates of 3.0-8.4 L/min against mean afterloads of 82-120 mm Hg.