Effect of Landiolol Hydrochloride on Hemodynamics in a Histamine-Induced Shock Model.

BACKGROUND AND OBJECTIVE: Anaphylactic shock is a serious adverse drug reaction that can occur in response to contrast media used during coronary computed tomography angiography. The imaging quality of coronary computed tomography angiography is improved by ß-blockers, which decrease heart rate. In this study, we sought to analyze anaphylactic shock treatment in patients receiving short-acting ß1-blockers. METHODS: We examined the influence of epinephrine and glucagon on hemodynamics during ß-blocker treatment, using a dog histamine shock model; the ß1-blocker landiolol hydrochloride was used. The effects of these drugs were assessed by recording changes relative to established baselines. RESULTS: Histamine and landiolol decreased mean blood pressure. Histamine exerted no apparent effect on heart rate, whereas landiolol decreased heart rate. Further, landiolol reduced histamine-mediated increases in the force of cardiac contraction. Increasing the doses of epinephrine and glucagon ameliorated anaphylactic shock-induced deterioration in hemodynamic parameters in subjects receiving landiolol. CONCLUSIONS: In patients receiving landiolol for coronary computed tomography angiography, deterioration in hemodynamic parameters due to anaphylactic shock can be mitigated by increasing the doses of epinephrine and glucagon. Clinicians should thus prepare appropriate amounts of epinephrine and glucagon prior to coronary computed tomography angiography.

Intermittent minodronic acid treatment with sufficient bone resorption inhibition prevents reduction in bone mass and strength in ovariectomized rats with established osteopenia comparable with daily treatment.

This study examined and compared the effects of four-week intermittent and daily administrations of minodronic acid, a highly potent nitrogen-containing bisphosphonate, on bone mineral density (BMD), bone strength, bone turnover, and histomorphometry on established osteopenia in ovariectomized (OVX) rats. Fourteen-week-old female F344 rats were OVX or sham-operated. At 12 weeks post surgery, minodronic acid was orally administered once every 4 weeks at 0.2, 1, and 5 mg/kg and once daily at 0.006, 0.03, and 0.15 mg/kg for 12 months. The total dosing amount was comparable between the two dosing regimens. The levels of urinary deoxypyridinoline and serum osteocalcin were measured to assess bone turnover. BMD as assessed via dual-energy X-ray absorptiometry, bone structure and dynamical changes in vertebral trabecula and biomechanical properties were measured ex vivo at 12 months to assess bone content and material properties. Minodronic acid dose-dependently ameliorated the decrease in BMD of lumbar vertebrae and the femur in both treatment regimens similarly. Minodronic acid suppressed elevated urinary levels of deoxypyridinoline, a bone resorption marker, and reduced the serum levels of osteocalcin, a bone formation marker. In the mechanical test at 12 months of treatment, minodronic acid dose-dependently ameliorated the reduction in bone strength in femur and vertebral body. There is no significant difference in parameters between the two regimens except maximal load of lower doses in lumbar vertebral body and absorption energy of middle doses in femur. With these parameters with significant differences, values of the intermittent regimen were significantly lower than that of daily repeated regimen. Bone histomorphometric analysis of the lumbar vertebral body showed that minodronic acid significantly ameliorated the decrease in bone mass, trabecular thickness and number, and the increase in trabecular separation, bone resorption indices (Oc.S/BS and N.Oc/BS), and bone formation indices (BFR/BS, MAR and OV/BV) in both regimens. Minodronic acid suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, thereby improving the deterioration of bone quality under osteoporotic disease conditions regardless of the regimen. In conclusion, a four-week intermittent treatment of minodronic acid suppressed increased bone resorption as daily treatment when considering the total administered dose in OVX rats with established osteopenia. The improvement of microarchitectural destruction in low dose of intermittent treatment was weaker than that observed in a daily repeated regimen; however the effects of high and middle doses of intermittent treatment were equivalent to that observed in daily repeated regimen accompanied by sufficient bone resorption inhibition in rats. These findings suggest that minodronic acid at an appropriate dose in an intermittent regimen may be as clinically useful in osteoporosis therapy as in daily treatment.

The effect of continuous arterial infusion of gabexate mesilate (FOY-007) on experimental acute pancreatitis.

The effectiveness of continuous arterial infusion of Gabexate Mesilate (FOY-007) on experimental acute pancreatitis was investigated. Acute necrotizing pancreatitis was induced by an injection of 10% Na-taurocholate (1ml/kg) into the main pancreatic duct of mongrel dogs. Animals were divided into three groups; Group A: non-treated control, Group B: after the induction of pancreatitis, injected with FOY-007 intravenously (5mg/kg/hr), Group C: after the induction of pancreatitis, injected with FOY-007 via the celiac artery. The changes in the values of amylase and lipase in serum and ascites etc. were examined. A histological examination was done and the FOY-007 concentration of the pancreas was measured. In both groups B and C, the serum levels of amylase and lipase reached significantly to low levels compared with those in group A. The extents of pancreatic parenchyma necrosis in each group were 36.1, 25.3 and 19.5%, respectively, and were significantly improved in group C. In addition, the FOY-007 levels in pancreas specimens in the intraarterial infusion group exceeded those in the intravenous infusion group by 32 times. The results suggest that continuous FOY-007 arterial infusion therapy is useful as a local treatment for severe acute pancreatitis.