Anaphylaxis associated with intracavernous penile injection of prostaglandin E1 in combination with papaverine and phentolamine / Anafilaxia associada à injeção intracavernosa peniana de prostaglandina E1 em combinação com papaverina e fentolamina

Total radical prostatectomy for advanced prostate cancer may lead to sexual impotence, since it is associated with severe erectile dysfunction. A widely recommended treatment for this disabling condition is intracavernous penile injection of a mixture of prostaglandin E1, papaverine, and phentolamine. To our knowledge, we present the first case of anaphylaxis associated with intracavernous penile injection of prostaglandin E1 in combination with papaverine and phentolamine.

A prostatectomia radical total para câncer de próstata avançado pode levar à impotência sexual, associada a uma disfunção erétil grave. Um tratamento amplamente recomendado para esta condição incapacitante é a injeção intracavernosa no pênis de uma mistura de prostaglandina E1, papaverina e fentolamina. Até onde sabemos, estamos apresentando o primeiro caso de anafilaxia associada à injeção intracavernosa peniana de prostaglandina E1 em combinação com papaverina e fentolamina.

Efficacy comparison between Milrinone and Papaverine on the spasm of internal mammary artery during off-pump coronary artery bypass grafting / 中华胸心血管外科杂志

Objective:To compare the efficacy of Milrinone and Papaverine in relieving the spasm of internal mammary artery (LIMA) during off-pump coronary artery bypass grafting (OPCABG).Methods:Between April 2018 to December 2018, 200 patients who suffered obvious angina pectoris and three-vessel disease documented by coronary angiography, undergoing OPCABG at Beijing Anzhen Hospital, Capital Medical University were recruited in this study, including 103 males and 97 females, aged 46-74 years, with an average of (59.12±0.49) years old. For all patients, the LIMA was anastomosed to left anterior descending artery(LAD). According to different methods relieving LIMA spasm, all patients randomly divided into 4 groups (n=50): Papaverine surface infiltration group (group Ⅰ), Papaverine injection group (group Ⅱ), Milrinone surface infiltration group (group Ⅲ) and Milrinone injection group (group Ⅳ). The blood flow (ml/min) of the free LIMA, the blood flow of the LIMA-LAD after bypass, anastomotic time of obtuse marginal artery, the use of vasoactive drugs, the outcomes of perioperative period and 1 year after operation were compared in the four groups.Results:There was no significant difference between group Ⅲ and group Ⅰ in the blood flow of free LIMA and LIMA-LAD[(45.50±1.43)ml/min vs. (47.42±1.61)ml/min、(28.60±0.89)ml/min vs. (28.40±0.96)ml/min, all P>0.05]. The blood flow of free LIMA and the LIMA-LAD in group Ⅱ were significantly higher than those in group Ⅰ[(60.36±1.28)ml/min vs. (47.42±1.61)ml/min, (42.40±1.25)ml/min vs. (28.40±0.96)ml/min, all P<0.05]. The blood flow of free LIMA and LIMA-LAD in group Ⅳ were significantly higher than those in group Ⅲ[(70.86±2.00) ml/min vs. (45.50±1.43) ml/min, (59.46±1.25) ml/min vs. (28.60±0.89) ml/min, all P<0.05]. The blood flow of free LIMA and LIMA-LAD in group Ⅳ were significantly higher than those in group Ⅱ[(70.86±2.00) ml/min vs. (60.36±1.28) ml/min, (59.46±1.25) ml/min vs. (42.40±1.25)ml/min, all P<0.05]. The anastomotic time of obtuse marginal artery[(7.14±0.72)min vs. (8.30±0.93)min, (8.10±0.89)min, (8.14±0.90)min, P<0.05], the dopamine dose[(3.76±0.40)μg·kg -1·min -1 vs. (5.02±0.52)μg·kg -1·min -1, (4.84±0.48)μg·kg -1·min -1, (4.90±0.49)μg·kg -1·min -1,P<0.05] and the esmolol usage (32% vs. 60%, 58%, 58%, P<0.05) during the operation in group Ⅳ were significantly reduced compared with the other three groups. The V3 ST depression on the postoperative first day[(0.34±0.18)mv vs. (0.71±0.22)mv, (0.68±0.20)mv, (0.69±0.22) mv, P<0.05], and the TNI on the postoperative third day[(0.24±0.08)ng/ml vs. (0.56±0.15)ng/ml, (0.54±0.11)ng/ml, (0.53±0.12) ng/ml, P<0.05] were significantly lower in group Ⅳ than those in the other three groups. However, there was no significant difference about the first-year patency of LIMA-LAD among four groups. Conclusion:For relieving spasm of LIMA, the Milrinone injection was better than that of Papaverine, which could shorten the anastomotic time of obtuse marginal artery, maintain intraoperative hemodynamics stability, reduce myocardial damage during OPCABG.

Effect of papaverine on left internal mammary artery flow: topical spraying versus perivascular injection method

Abstract Objective: To analyze two techniques of papaverine application, topical spray on the harvested left internal mammary artery (LIMA) and perivascular injection, to find out their ability to improve LIMA flow. Methods: Forty patients were randomized into two groups. In Group 1, papaverine was sprayed on the harvested pedunculated LIMA. In Group 2, papaverine was delivered into the perivascular plane. Drug dosage was the same for both groups. LIMA flow was measured 20 minutes after applying papaverine. Blood flow was recorded for 20 seconds and flow per minute was calculated. The systemic mean pressures were maintained at 70 mmHg during blood collection. The data collected was statistically evaluated and interpreted. Results: The LIMA blood flow before papaverine application in the Group 1 was 51.9±13.40 ml/min and in Group 2 it was 55.1±15.70 ml/min. Statistically, LIMA flows were identical in both groups before papaverine application. The LIMA blood flow, post papaverine application, in Group 1 was 87.20±13.46 ml/min and in Group 2 it was 104.7±20.19 ml/min. The Group 2 flows were statistically higher than Group 1 flows. Conclusion: Papaverine delivery to LIMA by the perivascular injection method provided statistically significant higher flows when compared to the topical spray method. Hence, the perivascular delivery of papaverine is more efficient than the spray method in improving LIMA blood flow.

Effect of local papaverine on arteriovenous fistula maturation in patients with end-stage renal disease / Efeito da papaverina local na maturação de fístulas arteriovenosas em pacientes com doença renal terminal

Abstract Background: Arteriovenous fistula (AVF) maturation is one of the main concerns in patients with end-stage renal disease (ESRD) and finding a strategy for increasing success rate and accelerating fistula maturation is valuable. The aim of this study was to evaluate the effects of papaverine injection on AVF maturation and success rate. Method: This study was a randomized clinical trial that involved 110 patients with ESRD that were referred for AVF construction. Patients were allocated in papaverine group and control group with block randomization according to age and sex. In the case group, papaverine (0.1 or 0.2 cc) was injected locally within the subadventitia of artery and vein after proximal and distal control during AVF construction and in the control group, AVF construction was done routinely without papaverine injection. Results: Maturation time in case and control groups was 37.94 ± 11.49 and 44.23 ± 9.57 days, respectively (p=0.004). Hematoma was not seen in the case group but occurred in one patient in the control group. One patient of the case group developed venous hypertension. Four functional fistulas, 1 (1.8%) in the case group and 3 (5.5%) in the control group, failed to mature (p=0.618). Maturation rate did not differ between the two groups statistically (p=0.101). Conclusion: Local papaverine injection increased vessel diameter and blood flow, increasing shearing stress in both arterial and venous segment of recently created AVF. In this way, papaverine probably can decrease AVF maturation time without an increase in complications.

Resumo Introdução: A maturação da fístula arteriovenosa (FAV) é uma das principais preocupações em pacientes com doença renal terminal (DRT). Assim, é importante identificar estratégias para aumentar as taxas de sucesso e acelerar a maturação da fístula. O objetivo do presente estudo foi avaliar os efeitos da infiltração de papaverina sobre a maturação da FAV e suas taxas de sucesso. Método: O presente ensaio clínico randomizado incluiu 110 pacientes com DRT encaminhados para colocação de FAV. Os pacientes foram randomizados em bloco em função de idade e sexo e alocados nos grupos caso ou controle. Os indivíduos no grupo caso receberam infiltração local de papaverina (0,1 ou 0,2 ml) no plano da sub-adventícia da artéria e veia após o controle proximal e distal durante a construção da FAV. No grupo controle, a construção da FAV foi realizada rotineiramente sem infiltração de papaverina. Resultados: Os tempos de maturação dos grupos caso e controle foram 37,94 ± 11,49 e 44,23 ± 9,57 dias, respectivamente (p = 0,004). Foi observado hematoma em apenas um paciente do grupo controle. Um paciente do grupo caso desenvolveu hipertensão venosa. Quatro fístulas funcionais, uma (1,8%) no grupo caso e três (5,5%) no grupo controle, não amadureceram (p = 0,618). A taxa de maturação não diferiu estatisticamente entre os dois grupos (p = 0,101). Conclusão: A infiltração local de papaverina aumentou o diâmetro do vaso e o fluxo sanguíneo, elevando a tensão de cisalhamento nos segmentos arterial e venoso da FAV recentemente criada. Desta forma, a papaverina provavelmente consegue reduzir o tempo de maturação da FAV sem aumentar as complicações.

Effect of papaverine on wound healing of full-thickness skin defect after skin stretching / 中华创伤杂志

Objective@#To investigate the effect of papaverine on wound healing of full-thickness skin defect after skin stretching in swine.@*Methods@#Eight Bama pigs were prepared. Standard full-thickness skin defect for 7 cm×7 cm was produced in the middle part of each pig's forelimb, and skin traction was used to close the wound. According to random number table method, the pigs were divided into experiment group and control group, with four pigs in each group. Percutaneous oxygen partial pressure (TcPO2) was compared preoperatively and postoperatively. Wound healing clinical score was evaluated four and 10 days after operation. Weidner counting method was employed to determine the microvascular density (MVD) of the wound edge tissue 0 and 10 days after operation. Immunohistochemistry was used to observe the expression of hypoxia inducible factor 1-α (HIF- 1α) and vascular endothelial growth factor (VEGF) 0, 4 and 10 days after operation.@*Results@#There was no statistically significant difference in TcPO2 between the experiment group [(55.1±5.4)mmHg] and the control group [(54.7±5.9)mmHg] before skin stretching (P>0.05), while statistically significant difference was found after stretching [(22.7±3.3)mmHg vs. (16.4±3.4)mmHg] (P<0.01). There was no statistically significant difference in clinical wound healing scores between the control group and experiment group 4 days after skin stretching [(2.6±0.7)points vs. (2.1±0.4)points] (P>0.05), but better result was found in experiment group compared with the control group in 10 days [(1.3±0.5)points vs. (4.6±0.7)points] (P<0.01). MVD of skin tissue showed no statistically significant difference between the control group (8.5±1.3) and the experiment group (9.3±1.2) immediately after skin stretching (P>0.05), while the MVD of wound skin tissue in the experiment group (29.5±4.8) was significantly higher than that in the control group (21.1±3.4) 10 days after skin stretching (P<0.01). After skin stretching, the HIF-1 alpha expression in experiment group was significantly higher than the control group 4 days after skin stretching [(50.0±7.0) vs. (38.6±7.0)] (P<0.01), but no statistical significance was found between that at 0 day and 10 days(P>0.05). The expression of VEGF in the wound skin tissues of the experiment group was significantly higher than that of the control group [(49.9±10.8) vs. (39.2±6.3)] at 4 days after skin stretching (P<0.05), while no statistically significance was found at 0 and 10 days (P>0.05).@*Conclusion@#For full-thickness skin defect after skin stretching in pigs, papaverine can alleviate small vessel spasm, improve skin edge oxygen supply, and promote the growth of microvessels, thus promoting the healing, which might be associated with the increase of HIF-1ɑ and VEGF expression.

Effect of papaverine on wound healing of full-thickness skin defect after skin stretching / 中华创伤杂志

Objective To investigate the effect of papaverine on wound healing of full-thickness skin defect after skin stretching in swine. Methods Eight Bama pigs were prepared. Standard full-thickness skin defect for 7 cm × 7 cm was produced in the middle part of each pig 's forelimb, and skin traction was used to close the wound. According to random number table method, the pigs were divided into experiment group and control group, with four pigs in each group. Percutaneous oxygen partial pressure ( TcPO2 ) was compared preoperatively and postoperatively. Wound healing clinical score was evaluated four and 10 days after operation. Weidner counting method was employed to determine the microvascular density (MVD) of the wound edge tissue 0 and 10 days after operation. Immunohistochemistry was used to observe the expression of hypoxia inducible factor 1-α ( HIF- 1α) and vascular endothelial growth factor (VEGF) 0, 4 and 10 days after operation. Results There was no statistically significant difference in TcPO2 between the experiment group [(55. 1 ± 5. 4)mmHg] and the control group [(54. 7 ± 5.9)mmHg] before skin stretching (P>0.05), while statistically significant difference was found after stretching[(22.7±3.3)mmHg vs. (16.4±3.4)mmHg] (P <0.01). There was no statistically significant difference in clinical wound healing scores between the control group and experiment group 4 days after skin stretching [(2.6 ±0.7)points vs. (2.1 ±0.4)points] (P>0.05), but better result was found in experiment group compared with the control group in 10 days [(1. 3 ± 0. 5)points vs. (4. 6 ± 0. 7)points] (P<0. 01). MVD of skin tissue showed no statistically significant difference between the control group (8. 5 ± 1. 3) and the experiment group (9. 3 ± 1. 2) immediately after skin stretching ( P>0. 05), while the MVD of wound skin tissue in the experiment group (29. 5 ± 4. 8) was significantly higher than that in the control group (21. 1 ± 3. 4) 10 days after skin stretching (P<0. 01). After skin stretching, the HIF-1 alpha expression in experiment group was significantly higher than the control group 4 days after skin stretching [(50. 0 ± 7. 0) vs. (38. 6 ± 7. 0)] (P < 0. 01), but no statistical significance was found between that at 0 day and 10 days(P>0. 05). The expression of VEGF in the wound skin tissues of the experiment group was significantly higher than that of the control group [(49. 9 ± 10.8) vs. (39.2 ±6.3)] at 4 days after skin stretching (P<0.05), while no statistically significance was found at 0 and 10 days (P>0. 05). Conclusion For full-thickness skin defect after skin stretching in pigs, papaverine can alleviate small vessel spasm, improve skin edge oxygen supply, and promote the growth of microvessels, thus promoting the healing, which might be associated with the increase of HIF-1ɑand VEGF expression.

Vasodilatory efficacy and impact of papaverine on endothelium in radial artery predilatation for cabg surgery: in search for optimal concentration

Abstract Objective: The aim of this study was to compare the efficacy of two different papaverine concentrations (0.5 mg/ml and 2 mg/ml) for vasospasm prevention and their impact on endothelium integrity. Methods: We have studied distal segments of radial arteries obtained by no-touch technique from coronary artery bypass graft (CABG) patients (n=10). The vasodilatory effect of papaverine (concentrations of 0.5 mg/ml and 2 mg/ml) was assessed in vitro, in isometric tension studies using ex vivo myography (organ bath technique) and arterial rings precontracted with potassium chloride (KCl) and phenylephrine. The impact of papaverine on endothelial integrity was studied by measurement of the percentage of vessel's circumference revealing CD34 endothelial marker. Results: 2 mg/ml papaverine concentration showed stronger vasodilatatory effect than 0.5 mg/ml, but it caused significantly higher endothelial damage. Response to KCl was 7.35±3.33 mN for vessels protected with papaverine 0.5 mg/ml and 2.66±1.96 mN when papaverine in concentration of 2 mg/ml was used. The histological examination revealed a significant difference in the presence of undamaged endothelium between vessels incubated in papaverine 0.5 mg/ml (72.86±9.3%) and 2 mg/ml (50.23±13.42%), P=0.002. Conclusion: Papaverine 2 mg/ml caused the higher endothelial damage. Concentration of 0.5 mg/ml caused better preservation of the endothelial lining.

The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury

ABSTRACT Objective: To investigate the effect of papaverine and alprostadil on testicular torsion-detorsion injury in rats. Materials and Methods: A total of 40 male Wistar-Albino rats were used in this study. Four hours of right testicular torsion was applied to each group, excluding sham oper- ated group. The torsion-detorsion (T/D), T/D + papaverine and T/D + alprostadil groups received saline, papaverine and alprostadil at the same time as surgical detorsion, respectively. At 14 days after the surgical detorsion, ischaemic changes and the degree of damage were evaluated with Cosentino scoring and the Johnson tubular biopsy score (JTBS). Results: JTBS was determined as 8.8±2.7 in the Sham group, 5.08±1.9 in the T/D+papaverine group, 5.29±2.3 in the T/D +alprostadil group and 2.86±1.9 in the TD group. The JTBS was determined to be statistically significantly high in both the T/D + papaverine group and the T/D + alprostadil group compared to the T/D group (p=0.01, p=0.009). In the T/D + papaverine group, 3 (43%) testes were classified as Cosentino 2, 3 (43%) as Cosentino 3 and 1 (14%) as Cosentino 4. In the T/D +alprostadil group, 5 (50 %) testes were classified as Cosentino 2, 3 (30 %) as Cosentino 3 and 2 (20%) as Cosentino 4. Conclusion: The present study indicated that spermatic cord administration of alprostadil and papaverine showed a protective effect against ischemia/reperfusion injury after right-side testes torsion and histological changes were decreased after testicular ischemia reperfusion injury.

Avoiding liver injury with papaverine and ascorbic acid due to infrarenal cross-clamping: an experimental study

Abstract Objective: Ischemia-reperfusion injury after acute ischemia treatment is a serious condition with high mortality and morbidity. Ischemia-reperfusion injury may result in organ failure particularly in kidney, lung, liver, and heart. In our study, we investigated the effects of papaverine and vitamin C on ischemia-reperfusion injury developed in the rat liver after occlusion-reperfusion of rat aorta. Methods: 32 Sprague-Dawley female rats were randomized into four groups (n=8). Ischemia was induced with infrarenal aortic cross-clamping for 60 minutes; then the clamp was removed and reperfusion was allowed for 120 minutes. While the control group and the ischemia-reperfusion group did not receive any supplementary agent, two other groups received vitamin C and papaverine hydrochloride (papaverine HCL). Liver tissues were evaluated under the light microscope. Histopathological examination was assessed by Suzuki's criteria and results were compared between groups. Results: In ischemia-reperfusion group, severe congestion, severe cytoplasmic vacuolization, and parenchymal necrosis over 60% (score 4) were observed. In vitamin C group, mild congestion, mild cytoplasmic vacuolization and parenchymal necrosis below 30% (score 2) were found. In papaverine group, moderate congestion, moderate cytoplasmic vacuolization and parenchymal necrosis below 60% (score 3) were observed. Conclusion: An ischemia of 60 minutes induced on lower extremities causes damaging effects on hepatic tissue. Vitamin C and papaverine are helpful in reducing liver injury after acute ischemia reperfusion and may partially avoid related negative conditions.

Clinical Observation of the Application of Alprostadil Combined with Papaverine in Uremic Hemodialysis Patients after Initial Arteriovenous Fistula / 中国药房

OBJECTIVE:To observe the effects of alprostadil combined with papaverine on blood coagulation indexes and complications in uremic hemodialysis patients after initial arteriovenous fistula.METHODS:One hundred and eighteen uremic hemodialysis patients undergoing initial arteriovenous fistula in our hospital during Feb.-Jun.2015 were divided into control group and observation group according to random number table,with 59 cases in each group.Both groups received local irradiation with hemodialysis internal fistula repair instrument 30 min,tid,from 3 days before surgery to 10 days after surgery.Control group was treated with Alprostadil injection 10 μg,iv,qd,immediately after surgery.Observation group was additionally treated with Papaverine in jection 30 mg,iv,qd,on the basis of control group.Both groups received treatment for 10 d.The orificium fistulae blood flow,hemodialysis blood flow and the time of initial hemodialysis were compared between 2 group.The plasma prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fib),platelet count (PLT) and C-reactive protein (CRP) levels were observed in 2 groups before and after surgery.The occarrence of postoperative complications was observed.RESULTS:The orificium fistulae blood flow and hemodialysis blood flow of observation group were significantly higher than those of control group,and ini tial hemodialysis time was significantly shorter than control group,with statistical significance (P＜0.05).Before surgery,there was no statistical significance in PT,APTT,Fib,PLT and CRP between 2 groups (P＞0.05).After surgery,APTT and CRP of 2 groups were increased significantly,Fib was decreased significantly;the above indexes of observation group was significantly better than that of control group,with statistical significance (P＜0.05).There was no statistical significance in PT,PLT between 2 groups (P＞0.05).There was no statistical significance in the incidence of internal fistula infection and postoperative wound bleeding volume＞ 10 mL between 2 groups (P＞0.05).The incidence of internal fistula occlusion and orificium fistulae thrombus in observation group were significantly lower than control group,with statistical significance (P＜0.05).CONCLUSIONS:The application of alprostadil combined papaverine on uremic hemodialysis patients after initial arteriovenous fistula can effectively prevent inflammation reaction,fistula thrombus formation and fistula occlusion,and improve the maturation of fistula.

Papaverine treats vasospasm caused by PICC intubation with B-mode ultrasonography / 现代临床护理

Objective To study the effect of papaverine on vasospasm caused by PICC intubation with B-mode ultrasonography. Method Three mg papaverine were injected into the median cubital vein for at least 2 minutes in 15 patients with vasospasm. Results The vasospasm in the 15 patients was relieved 36~270 s seconds after injection. The followed intubation was all successful. There was no abnormality in their liver function and heart rate, or abnormal bleeding, or other serious complications. Conclusion Papaverine can relieve vasospasm caused by PICC intubation, so it can allow another intubation. It also can avoid delayed intubation reduce patients′pain and cost and reduce psychological pressure of the nursing practitioner.

The combined application of low molecular dextran, papaverine and low molecular weight heparin sodium to improve testicle survival rate after the reduction of testicular torsion in rabbits / 中华泌尿外科杂志

Objective To observe the effect of drug combinations on the blood flow after reduction of the testicular torsion in rabbits.Methods From October 2014 to June 2015,36 male rabbits (weighing 1.8-2.4 kg,10-14 months of age) were randomly divided into experimental group and control group,18 in each group.Produced by surgical testicular torsion model (720° counterclockwise rotation of the left side testicle),every rabbit was accepted surgery reset after 9 hours and found all twisted testicles were dark.After fomentation with warm salt water,all the testicles were observed no significant improvement in colors,and no fresh blood flow after opening tunica albuginea,then all the testicles were retained and fixed.Low molecular dextran(5 ml/kg,ear marginal vein injection,1/d),papaverine(1.5 mg/kg,intramuscular,3/d) and low molecular weight heparin sodium (200 IU/kg,subcutaneous,l/d) were applied to promote testicular revascularization for 5 days in experimental group,and penicillin (40 000 U/kg,intramuscular,1/d) for 7 days.Control group was only given penicillin (40 000 U/kg,intramuscular,1/d) to prevent wound infection.Then Color Doppler ultrasound was used to observe the testicular blood flow siganals that were divided into 0,1,2,3 classes.Class 2 and class 3 could be considered as testicular survival.After each scrotum was opened,according to color,texture of testicle and whether the fresh blood flowing out when tunica albuginea was opened,to determine whether the testicle was alive.The testicle was ruddy,flexible,and fresh blood was observed,which could prove testicular survival.Results In experimental group,the testicular blood flow siganals:0 class 4 cases,1 class 3 cases,2 class 4 cases,3 class 7 cases.In control group,the testicular blood flow siganals:0 class 9 cases,1 class 2 cases,2 class 4 cases,3 class 3 cases.Surgical exploration found 11 cases of testicular survival in experimental group and 7 cases in control group,which was significantly difference (P ＜ 0.05).Conclusions The combined application of low molecular dextran,papaverine,low molecular weight heparin sodium can promote the recovery of testicular blood after reduction of testicular torsion,and improve testicular survival rate.

Improved Preservation of Saphenous Venous Conduits by the Use of Papaverine mixed heparinized blood Solution during Harvesting.

Background: High-pressure distension during harvesting damages the saphenous vein (SV) and may contribute to subsequent coronary artery bypass graft (CABG) occlusion. Application of vasodilator agents to the SV during harvesting may reduce the need for high-pressure distension and improve graft quality. We tested the effects of a vasodilator solution containing the conventional agent papaverine (Pap) mixed with heparinized blood on the pressure necessary to overcome SV spasm and on the structure. Methods: 150 patients undergoing CABG were nonrandomly allocated to receive an application of either intraluminal papaverine (Pap) mixed with heparinized blood(Group-A), or intraluminal heparin mixed normal saline(group-B) to the SV for distension during harvesting. The peak pressures required to distend the vein were recorded. Samples of SV were taken for microscopical analysis just before we performed the anastomosis. Results: The results for mean peak pressures (mm Hg) were: Normal saline 131.77±20.6 (range 85 to199 mmHg); and Papaverine mixed blood solution, 56.4±2.1 (range 40 to 90 mmHg); P<0.001, (Pap mixed blood solution versus normal saline); The results of histological study for endothelial injury were: Normal saline, 52.5 %; Papaverine mixed blood solution , 20%; (P<.02, untreated versus Pap mixed blood solution). Conclusions: Intraluminal use of Papaverine mixed heparinized blood solution during vein harvesting requires low distension pressure and improves endothelial coverage compared with the use of heparin mixed normal saline.

The Effect of Papaverine on the Calcium-dependent K+ Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Papaverine has been used in treating vasospasm following subarachnoid hemorrhage(SAH). However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. RESULTS: Papaverine of 100 microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by BKCa(large conductance calcium dependent potassium channels)blocker, IBX(iberiotoxin), and calcium chealator, BAPTA(1, 2-bis(o-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid), in whole cell mode. CONCLUSION: These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.

Experimental and clinical study on effect of endovascular dilation on symptomatic cerebral vasospasm / 中国脑血管病杂志

Objective To undertake animal experimentation and clinical study on the safety and efficacy of percutaneous transluminal angioplasty (PTA) and intraarterial papaverine (IAP) infusion for treatment of refractory symptomatic cerebral vasospasm (CVS). Methods In the experimental study, vasospasm was induced in rabbits by double injections of blood into the cisterna magna, IAP infusion was given on either the 4th day or the 7th day after occurrence of subarachnoid hemorrhage (SAH), and then neurological observation, angiography, light and electron microscopy were done. In the clinical study, since September 1996, 22 patients with refractory symptomatic CVS involving 50 vascular territories received dilation therapy by PTA and IAP within 24 hours of clinical neurological deterioration. Results In the experimental study, all the rabbits except two in the 'the 4th day' group showed angiographic dilation in all of the spastic basilar arteries, and neurological improvement; in the ' the 7th day' group angiographic dilation appeared in 4 (57. 1% ) out of 7 rabbits. After 24 hours, 1 rabbit in each group had recurrence of neurological deficits and angiographic constriction. In the clinical study after aneurysm clipping or endovascular coil embolization was done, within 72 hours of SAH all patients underwent endovascular treatment: PTA alone in 3 cases, IAP alone in 14 cases, PTA and IAP in the remaining 5 cases. All vessel segments were dilated satisfactorily after endovascular treatment. Clinical improvement was significant in 13 cases,moderate in 7, minimal or none in 2; 2 cases died on the 7th day after endovascular dilation treatment. Conclusion Endovascular dilating techniques, namely, PTA, IAP and a combination of PTA and IAP, are safe and effective for treatment of symptomatic CVS refractory to medical therapy.

Study on preparation of papaverine-gelatin microspheres and its release in vitro / 医学研究生学报

Objective To sustain drug concentration of papaverine in subarachnoid for treatment of vasospasm following subarachnoid hemorrhage and confirm whether controlled releasing system is appropriate for the prevention of vasospasm following subarachnoid hemorrhage.To prepare appropriate gelatin microspheres by optimizing experiment conditions,load them with papaverine and observe its release characteristics in vitro.Methods Degradable gelatin was used as a carrier with liquid paraffin as oil phase and Span-80 as emulsifier.Orthogonal experimental design was introduced to optimize the preparation conditions of the blank gelatin microspheres.Furthermore,papaverine gelatin microspheres were prepared using improved emulsified cold-condensation method.Results After optimizing,microspheres with good shape,smooth surface and narrow size distribution were prepared.The amount of drug carried by microspheres was 28%.Studies on the release in vitro showed that newly no initial burst release could be seen,the drug could be released slowly in two weeks.Conclusion The preparation procedure established was stable and practical,and the microspheres obtained showed good sustained-release characteristics.

Chemical Stability of Lyophilized Papaverine/Phentolamine/Alprostadil (Standro(R)) / 대한남성과학회지

PURPOSE: To investigate the chemical stability of papaverine/phentolamine/alprostadil (Standro(R)) used for intracaver nous injection in patients with erectile dysfunction. MATERIALS AND METHODS: Samples of lyophilized Standro(R) were stored at room temperature (25+/-2 degrees C) or in the refrigerator (4+/-2 degrees C). The pH and concentration of papaverine HCl, phentolamine mesylate, and alprostadil were measured at intervals by high-performance liquid chromatography. RESULTS: At 24 months, the concentrations of papaverine, phentolamine, and alprostadil stored in the refrigerator and at room temperature were 99.7%, 98.9%, and 98.7% and 98.4%, 96.3%, and 93.3% of the original concentrations, respectively. When the product was stored in solution in the refrigerator for 19 weeks, the concentrations of the three drugs were 98.7%, 97.2%, and 88.0%, respectively. In 5 days at room temperature, the concentration of alprostadil dropped to 86.4%, which is below the minimum concentration for the product specified by the Korean Food and Drug Administration, although the concentrations of papaverine and phentolamine remained stable (99.6%, 98.4%). The pH of the three agents did not change significantly regardless of the storage conditions (temperature, duration, lyophilized or dissolved). CONCLUSIONS: Lyophilized papaverine/phentolamine/alprostadil (Standro(R)) is chemically stable for at least 2 years at room temperature, although solutions need to be kept in the refrigerator and become less effective with prolongation of storage.

Elementary inquiry into the mechanism of annexation of bradykinin and papaverine on BTB opening / 中国药理学通报

Aim To investigate whether the annexation of bradykinin and papaverine had some synergetic effects on the opening of blood-tumor barrier,and find out the action of cytokine in this mechanism.Methods 160 female rats were divided into 8 groups:sham operated group;model group,PA group,BK group,PA+BK group,1/2PA+BK group,1/2BK+PA group and 1/2PA+1/2BK group.20 rats were needed in each group.The C6 brain tumor model was built.The drug was pumped into rat's brain via the carotid artery.The opening of the tight junction was detected by electron microscop.And the permeability of the blood-tumor barrier was tested by Evans blue.The expression of IL-1? was tested by Western blot and the expression of IL-1? on/around the capillary in the brain of the cerebral glioma rats was tested by SABC immunochemistry.Results In contrast to sham operated group/model group,the expression of IL-1? in PA group,BK group and PA+BK group increased obviously(P

Multicenter Study on the Efficacy and Safety of Intracavernous 'TM' (Standro(R)) for the Treatment of Erectile Dysfunction in Korean / 대한비뇨기과학회지

PURPOSE: To evaluate the efficacy and safety of an intracavernous injection of lyophilized papaverine/phentolamine/alprostadil (Standro(R)) for the treatment of erectile dysfunction (ED) in Koreans. MATERIALS AND METHODS: 249 men (>20 years old), with ED (>6 month duration), were enrolled from 14 clinical centers. The intracavernous 'TMs' were titrated in a stepwise fashion at the clinic, from 0.05-0.25ml (17.64mg papaverine, 0.6mg phentolamine, and 6mug alprostadil per ml), with increment of 0.02-0.05ml, according to the etiology and severity of the ED and the patients' ages. RESULTS: Of the 249 men, 238 completed the dose titration, and progressed to home treatment of 3 months duration. Of these 238, 193 (psychogenic 13.0%, organic 75.5%, mixed 11.5%) completed the home treatment (4 or more self-injections), with the other 45 dropping out (lost to follow-up in 24, patient refusal in 9, no chance to have intercourse in 7 and omitted recording of patient diary in 2). The success rate per trial (a total number of sufficient erection for vaginal intromission/a total number of injections) and per patient (number of patients who had one or more sufficient erections for vaginal intromission/the enrolled patients at beginning or 193 patients), and the satisfaction rate per patient (number of patients who had both patient and partner satisfaction with erection/193 patients) were 74.1, or 91.2 and 75.1%, respectively. The adverse reactions were prolonged erections in 3, urethral pain in 1 and penile skin edema in 2. Three patients complained of penile pain during an erection, but there was no dropout due to the pain. No significant changes in laboratory tests were found after the home treatment. CONCLUSIONS: A 'TM' seems to be effective and safe for an intracavernous injection for the treatment of men with erectile dysfunction.

The Effect of Papaverine on L-Type Ca2+ Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Papaverine has been used to manage vasospasm after subarachnoid hemorrhage. However, its mechanism for cerebrovascular smooth muscle are still not clear. This study was undertaken to investigate the effect of papaverine on L-type Ca2+ channels directly by using patch clamp techniques in freshly isolated single smooth muscle cells from rat basilar artery. METHODS: Whole-cell patch clamp technique was used for measuring the amplitude of L-type Ca2+ current. Papaverine was added to the bath solution. RESULTS: Patch clamp studies revealed a whole-cell current which resembles the L-type Ca2+ current reported by others. The amplitude of this current was decreased by nimodipidine and increased by Bay K 8644. Papaverine 100 micro M reduced the amplitude of the L-type Ca2+ channel current. CONCLUSION: We can conclude that papaverine may relax cerebral vessel through decreasing level of intracellular calcium, [Ca2+]i, by inhibition of L-type Ca2+ channel.