Objective To compare milrinone （MIN）, Phenoxybenzamine （PHE），and mixture of nitroglycerin and verapamil(NVC) for the prevention and treatment of human radial artery spasm. Methods Residuary radial arteries from 30 patients undergoing coronary artery bypass grafting （CABG） using autologous radial artery from March to September of 2012 in General Hospital of Shenyang Military District were collected. All the artery specimens were cut into 60 vessel rings of 3 mm in width and hanged in the Organ-Bath. Using a random number table，all the vessel rings were divided into 4 groups：PHE group，NVC group，MIN group and blank group （control group）. Firstly，20 vessel rings were used for spasm relaxation experiment with 5 rings in each group. Phenylephrine was added into the Organ-Bath to reach final concentration of 10-3 mol/L in order to cause vessel rings spasm. PHE of 1 mmol/L，NVC of both 30 μmol/L，MIN of 30 μmol/L and Krebs-Ringer’s solution were added respectively into above groups to compare the relaxant effect of these vasodilators on radial artery spasm. Secondly，the other 40 vessel rings were used for spasm prevention experiment with 10 rings in each group. All the 40 vessel rings were dipped in above 4 groups. After 30 minutes，phenylephrine was added to the Organ-Bath to reach final concentration of 10-3 mol/L. Time-dependent constriction of the vessel rings were compared to examine the prevention effect of these vasodilators on radial artery spasm. Results In the spasm relaxation experiment, vessel ring spasm relaxed most quickly in NVC group （P＜ 0.01）. Vessel rings in MIN group relaxed more slowly but steadily （P＜ 0.05）. Vessel rings in PHE group relaxed most slowly （P＜0.01）. And there was no relaxation in the control group. In the spasm prevention experiment，vessel rings in the control group contracted （spasm） 100% immediately after phenylephrine administration. Vessel rings in MIN group contracted immediately after phenylephrine administration too，but slower than the control group（P＜0.01）. Vessel rings in NVC group did not contract right after phenylephrine administration，but the sedentary tension of these vessel rings gradually increased 120 minutes after phenylephrine administration，and vessel ring contraction reached 46.89% 240 minutes after phenylephrine administration. There was no vessel ring contraction in PHE group. Conclusions All the vasodilators in our experiment are effective for the prevention and treatment of radial artery spasm to different degree，but each medication has its own characteristics，vasodilatation result and time-dependent effect. NVC is most effective to dilate radial artery which has been in spasm state, while radial artery pretreated by PHE is least to become spasm after being stimulated.
Abstract: Objective To compare the effects of nitroglycerine (NTG)， Verapamil(VP), papaverine(PA) and the mixed solution of Verapamil and nitroglycerine (VG) on relaxing function of human radial arteries. Methods The radial arteries of thirty patients were used during the operation of coronary artery bypass grafting (CABG). A short segment (1.0-1.5cm) of radial arteris were taken from the distal end of radial arteries of each patient and were cut into vascular rings, which were mounted in the organ bath chamber and then subject to a series of tests for vascular smooth muscle viability and endothelial integrity. The effects of five storage solutions on the relaxing function were evaluated by “OrganBath” technique. The five solutions included: (1) Ringer’ s solution (control group); (2) VP solution (VP group); (3) NTG solution (NTG group); (4) PA solution (PA group); (5) VG solution (VG group). First, challenged with phenylephrine (10-5mol/L), vasorelaxant effect of these drugs (effect onset and efficacy) was observed at different time point and resting tension was recorded. Second, after 30min preincubation with either verapamil, papaverine, phenoxybenzamine or VG mixture, potassium chloride (final concentration of 60mmol/L) was added in the organ bath chamber and then vasoconstriction was observed subsequently. Finally, after 30min pretreatment of different antispasmodic agent in the same way as described above, the vascular rings were mounted in organ bath chamber and challenged with phenylephrine(10-5mol/L). Vascular spasticity and vosospasm duration were observed at different time point which might provide guidance for optimal timing of clinical application. Results The radial arteries in VG, VP, NTG and PA solutions were relaxed in 11 min after vasospasm and there was no difference between them (Pgt;0.05). But during the initial three minutes，the relaxation effect of VG and NTG was significantly better than other two groups. Relaxation curve showed that the ability of vasodilatation of VG, NTG, VP and PA decreased in order. In the experiment about antivasospasm pretreatment of radial arteries, there was no difference between VG and VP group (Pgt;0.05 ), whose effects were better than NTG and PA group(Plt;0.05 ). After cold storage for 24h, VG and VP still could prevent vasospasm. But NTG and PA hardly had any function and there was no difference compared with the control group (Pgt;0.05 ). Conclusion Although in the final all these drugs could prevent and relieve vasospasm of radial arteries in the different level, it appeared that a combination of verapamil and nitroglycenn is more fit for treating radial artery during CABG operation than other drugs.
Objective To investigate the therapeutic effects of subconjunctival verapamil on outcome in an experimental model of traumatic proliferative vitreoretinopathy. Methods An experimental model of traumatic proliferative vitreoretinopathy was induced in pigme nt rabbits,which then were selected randomly to receive either subconjunctival verapamil injection treatment or a placebo injection(control)daily for 3 weeks.Animals were examined by indirect ophthalmoscopy at weekly intervals for 5 weeks. Eyes were enucleated for light microscopy 5 weeks later. Results Fifty-six percent(18 of 32)of the rabbits receiving subconjunctival verapamil injection had developed tractional retinal detachment,whereas eighty-one percent(26 of 32)of control animals had developed tractional retinal detachment(chi;2=4.655,P=0.031).The results of clinical examination and light microscopy didn't show evidence of toxicity between the verapamil treated animals and control animals. Conclusion Subconjunctival verapamil decreased the incidence of tractional retinal detachment due to traumatic proliferative vetreoretinopathy in this rabbit model.Verapamil at the dose used in this model has no evident toxicity on rabbit eyes.Further studies are needed to determine the doseresponse and efficacy of the drug. (Chin J Ocul Fundus Dis,1999,15:69-71)
OBJECTlVE:To evaluate the value of inhibiting effect of the verapamil(Ver)on human selcral fibroblast (HSF). METHODS:The rate al inhibition of Ver,5-Fu,heparin(Hep)and dexamethasone(Dex)to cultured HSF was respectively determined by MTT method and enzyme linked immunosorbent assay. In addition,the rate of inhibition of Ver associated with 5-Fu Hep and Dex to cultured HSF was respectively determined. RESULTS:The rate of cellular proliferation of cultured HSF was found to be significantly reduced(Plt;0.05),when the concentration of Ver was 20mg/L,and further reduced when 5-Fu,Hep or Dex was added even in smaller dose (5~10mg/L)of Ver. CONCLUSION: Tbe effect of inhibition of cellular proliferation of 5-Fu, Hep and Dex in eye could be enbenced by Ver. （Chin J Ocul Fundus Dis,1996,12: 98-100）
【Abstract】 Objective To investigate the effect of verapamil on apoptosis, calcium and expressions of bcl-2 and c-myc of pancreatic cells in ischemia-reperfusion rat model. Methods Wistar rats were randomly divided into three groups: control group （n=10）; ischemia-reperfusion group （n=10）; verapamil treatment group （n=10）. The anterior mesenteric artery and the celiac artery of rats in both ischemia-reperfusion group and verapamil treatment group were occluded for 15 min followed by 12-hour reperfusion. Verapamil （1 mg／kg） was injected via caudal vein to the rats in verapamil treatment group 15 min before occlusion and 1 hour after the initiation of reperfusion, respectively; and ischemia-reperfusion group was given the same volume of salient twice intravenously. Pancreatic tissues were collected from the dead rats after twelve hours since the reperfusion. The pathologic characters of pancreatic tissue were observed under light microscope; The level of calcium in the tissue was measured by atomic absorption spectrometer; TUNEL was used to detect apoptosis of pancreatic cells; and the expressions of c-myc and bcl-2 in the cells were also analyzed by immunohistochemistry technique and flow cytometry. Results The pathologic change in verapamil treatment group was less conspicuous than that of ischemia-reperfusion group. Both the calcium level and the number of apoptotic cells in verapamil treatment group were less than those of ischemia-reperfusion group 〔（411.1±55.8） μg/g dry weight vs （470.9±31.9） μg/g dry weight, P＜0.05 and （9.5±2.9）% vs （18.4±3.1）% 〕, P＜0.05. After taking verapamil, the number of apoptotic cells decreased, whereas the expressions of bcl-2 and c-myc increased. The fluorescent indexes of bcl-2 and c-myc in verapamil treatment group were significantly higher than those of ischemia-reperfusion group (1.72±0.11 vs 1.41±0.07, P＜0.05; 1.76±0.19 vs 1.55±0.13, P＜0.05. Conclusion Ischemia-reperfusion injury can induce apoptosis of pancreatic cells. Verapamil could protect the injured pancreatic tissue by reducing the level of calcium, stimulating the expressions of bcl-2 and c-myc and inhibiting apoptosis of pancreatic cells.
Objective To probe the change of the structure and function of the small bowel by injection of different drugs (verapamil, energy compounds or normal saline) via the superior mesenteric artery (SMA) injections.Methods The model of the small intestine ischemia/reperfusion (I/R) injury was made in grey rabbits. Free calcium concentration in mitochondria of the small intestine was determined, and the ultrastructural change was also observed by electron microscopy at the very time of occlusion, 60 minutes after occlusion and 30 minutes after reperfusion. Results The free calcium concentration in mitochondria was more declined in verapamil group (2.976±0.410 nmol/mg.prot) than in N.S. group (4.234±0.542 nmol/mg.prot), Ｐ＜0.01, at 60 minutes after occlusion. At 30 minutes after reperfusion, free calcium concentration in mitochondria was more decreased in energy compunds group (2.401±0.323 nmol/mg.prot) and verapamil group (3.847±0.610 nmol/mg.prot) than in the N.S. group (5.981±1.031 nmol/mg.prot). Conclusion Verapamil and energy compouds have protective effects on the functions and ultrastructures of the I/R of small intestine.
Objective To evaluate the activity of the pancreatic tissue phospholipase A2 (PLA2) in acute pancreatitis (AP) and the therapeutic effects of verapamil in rats. MethodsThe model of rat AP induced by a closed duodenal loop technique was established to observe the changes of PLA2 activity in AP group and treated group. The pancreatic histology was examined by light and electron microscopy. Results At 16 and 24 hours after induction of AP in rats, significant inhibition of the pancreatic tissue PLA2 activity was shown in the treated group as compared with AP group, with 32.34±3.87u, 35.26±4.52u and 44.83±5.31u, 47.77±5.86u respectively. The treated animals also showed a decrease in the severity of pancreatic hemorrhage, necrosis and damage to the cellular ultrastructures. Conclusion There exists high activity of PLA2 in rats AP. Calcium channel blocker, verapamil might take therapeutic effects on AP by inhibiting activity of PLA2.
ObjectiveIn order to evaluate that whether the P-glycoprotein-inhibitor verapamil (VPM) could effect the distribution of antiepileptic drug phenytoin (PHT) in a rat model of mesial temporal lobe epilepsy (MTLE).MethodsThe rat models of MTLE were induced by li-pilocarpine and were randomly divided into two groups (PHT group and VPM+PHT treatment group) to compare the PHT distribution in brain, liver and kidney. Brain dialysate samples were collected by microdialysis technology. And the analysis of samples for PHT concentration was performed by high performance liquid chromatography (HPLC). The comparisons were carried out by t test (or Wilcoxon test).ResultsIn VPM+PHT treatment group, 4 out of 9 rats were dead within 30 minutes after drug administration. The significantly decreased area under the curve (AUC) ratio of brain/plasma in VPM+PHT group was 0.11±0.06 when compared with PHT group 0.21±0.02 (t=3.237, P=0.025), while there were no significant differences in ratios of liver/plasma ［PHT (1.12±0.37) vs. VPM+PHT (0.99±0.27), Z=−0.490, P=0.624］ and kidney/plasma ［PHT (0.74±0.16) vs. VPM+PHT (0.49±0.26), t=1.872, P=0.103］ between two groups.ConclusionsThe P-glycoprotein-inhibitor VPM significantly decreased PHT level in brain of rat with MTLE.