Comparison of the apoptotic effects of topically applied papaverine, diltiazem, and nitroprusside to internal thoracic artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

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.

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.

Effects of papaverine and sodium nitroprusside solution as topical vasodilators for internal mammary artery

To compare the effects of topical sodium nitroprusside [SNP] and papaverine solutions to treat left internal mammary artery spasm. Randomized Control Trial [RCT]. AFIC / NIHD Rawalpindi from Jan 2009 to March 2009. Fifty consecutive patients undergoing elective coronary artery bypass graft surgery [CABG] were randomly assigned to two groups: group N [n=25, Sodium Nitroprusside solution], and group P [n=25, Papaverine]. In each patient, pedicled left internal mammary artery was harvested, five minutes after heparin administration, left internal mammary artery was divided distally; flow per minute was calculated after measuring the free flow for over 15 seconds; this is named [Flow 1.]Then, the pedicled left internal mammary artery was sprayed with the randomized solution, and covered with the test solution soaked sponge. The second flow measurement [Flow 2] was done before commencing cardiopulmonary bypass. A third flow measurement [Flow 3] was recorded just before left internal mammary artery to left anterior descending coronary artery anastomosis, while the patient was on cardio pulmonary bypass. Analysis of variance was applied to detect differences among groups; paired-sample t test was used for left internal mammary artery topical free flow in both groups. Mean left internal mammary artery free flows were as follows: group N, flowl=32.72 +/- 27.67 ml/min, versus group P flowl=23.44 +/- 15.16 ml/min [p<0.148], group N flow2=63.92 +/- 33.40 ml/min versus group P flow2=38.88 +/- 24.54 ml/min [p<0.004], and group N flow3=62.44 +/- 38.38 ml/min versus group P flow3=49.52 +/- 30.29 ml/min [p <.170]. Topical free flow difference amongst the two groups was statistically significant in the flow2 [p< 0.004]; whereas topical mean free flow difference was statistically significant when the groups were individually compared group N flowl:flow2, flow 1: flow 3and flow 2: flow 3 group N [p<.000, .000, .846] and group P [p<.001, .000, .001] respectively. Sodium nitroprusside [SNP] and papaverine solutions are able to treat vascular spasm and increase the flow of left internal mammary artery, when they are used topically. However sodium nitroprusside allows early and better relief of vascular spasm

Comparação do efeito da nimodipina e da papaverina como vasodilatadores sobre o fluxo na artéria torácica interna esquerda / Comparison of the effects on the flow in the left internal thoracic artery using nimodipine and papaverine as vasodilators

OBJETIVO: O objetivo do presente estudo é comparar o fluxo da artéria torácica interna esquerda sob o efeito local farmacológico por embebição e o efeito intraluminal de bloqueador do canal de cálcio com um grupo controle com papaverina. MÉTODO: Foi realizado estudo prospectivo de 73 pacientes submetidos a revascularização do miocárdio, no período de quatro meses, nos quais se utilizou a artéria torácica interna esquerda como parte do grupo de enxertos, operados no período de julho de 2004 e novembro de 2004, para análise de fluxo comparativo entre dois fármacos. Os pacientes foram aleatorizados para receberem os vasodilatadores nimodipina ou papaverina. Foram determinados dois fluxos: o fluxo no Tempo 1, o qual representou o período de ação farmacológica por embebição (extraluminal), e o fluxo no Tempo 2, este representou a ação farmacológica intraluminal. A comparação das médias de fluxo entre os dois grupos de fármacos foi realizada através do teste não paramétrico de Mann-Whitney. RESULTADOS: Não há evidências de que os fluxos médios dos dois fármacos sejam diferentes no Tempo 1 (p=0,534). Os fluxos médios dos dois fármacos são semelhantes no Tempo 2 (p=0,063). CONCLUSÃO: Não há evidências de que os fluxos médios dos dois fármacos sejam diferentes sob ação por embebição (extraluminal), assim como os fluxos médios dos dois fármacos são semelhantes quando por ação farmacológica intraluminal, tornando a nimodipina uma opção como vasodilatador de ação local comparável à papaverina.

OBJECTIVE: To compare the flow of the left internal thoracic artery under a local pharmacological effect caused by the topical action on the arterial pedicle and the intraluminal effect of a calcium channel blocker with a control group using papaverine. METHODS: Over a period from July to November 2004, a prospective study was performed involving 73 patients who were submitted to coronary artery bypass surgery utilizing the left internal thoracic artery as one of a group of grafts. A comparative analysis of the flow was made when using two different pharmacological agents. The patients were randomized to receive either nimodipine or papaverine as vasodilators. Two types of flow were determined: the flow at Time 1 representing the period of topical action of the drug on the arterial pedicle (extraluminal) and the flow at Time 2 representing the intraluminal action of the drug. A comparison of the means of the two types of flow between the two groups of pharmacological agents was carried out using the non-parametric Mann-Whitney test. RESULTS: There is no evidence that the mean flow using the two pharmacological agents is different at Time 1 (p = 0.534) or at Time 2 (p = 0.063). CONCLUSIONS: There is no evidence that the mean flow varies due to the topical action of one or other drug or that the mean flow is different due to the intraluminal action, proving that nimodipine as a locally acting vasodilator is similar to papaverine.

Fisiología coronaria y su utilidad para el cardiólogo intervencionista: Medición invasiva de la presión y flujo coronarios / Coronary physiology and its usefulness for the interventionist cardiologist: Invasive measurement of coronary flow-pressure

Una de las más importantes limitaciones de la angiografía coronaria es su incapacidad para determinar el impacto fisiológico de las estenosis coronarias moderadas. La medición de la presión y del flujo sanguíneo coronario nos brinda información valiosa que complementa la evaluación anatómica y facilitan la toma de decisiones en el laboratorio de cateterismo cardíaco. En esta revisión se discuten los conceptos fundamentales de la fisiología coronaria, así como la metodología y aplicación clínica de las técnicas de medición de presión y flujo coronarios.

One of the most important limitations of coronary angiography is the inability to characterize the physiological significance of an intermediate coronary stenosis. Measuring coronary blood flow and pressure provides unique information that complements anatomic evaluation and facilitates decision-making in the cardiac catheterization unit. This review discusses the fundamental concepts of coronary physiology, methodology, and clinical applications of coronary and flow measurements.

Nonspecific blockade of vascular free radical signals by methylated arginine analogues

Methylated arginine analogues are often used as probes of the effect of nitric oxide; however, their specificity is unclear and seems to be frequently overestimated. This study analyzed the effects of N G -methyl-L-arginine (L-NMMA) on the endothelium-dependent release of vascular superoxide radicals triggered by increased flow. Plasma ascorbyl radical signals measured by direct electron paramagnetic resonance spectroscopy in 25 rabbits increased by 3.8 ñ 0.7 nmol/l vs baseline (28.7 ñ 1.4 nmol/l, P<0.001) in response to papaverine-induced flow increases of 121 ñ 12 por cento. In contrast, after similar papaverine-induced flow increases simultaneously with L-NMMA infusions, ascorbyl levels were not significantly changed compared to baseline. Similar results were obtained in isolated rabbit aortas perfused ex vivo with the spin trap Ó-phenyl-N- tert -butylnitrone (N = 22). However, in both preparations, this complete blockade was not reversed by co-infusion of excess L-arginine and was also obtained by N-methyl-D-arginine, thus indicating that it is not related to nitric oxide synthase. L-arginine alone was ineffective, as previously demonstrated for N G -methyl-L-arginine ester (L-NAME). In vitro , neither L-arginine nor its analogues scavenged superoxide radicals. This nonspecific activity of methylated arginine analogues underscores the need for careful controls in order to assess nitric oxide effects, particularly those related to interactions with active oxygen species

Pharmacologically induced penile erections in the assessment and treatment of erectile impotence: a preliminary study of 100 patients.

OBJECTIVE: To assess and compare the immediate and subsequent response to pharmacologically induced penile erections, using intracavernosal injections of papaverine. DESIGN: Preliminary, prospective study. SETTING: Male sexual dysfunction clinic at the National Hospital of Sri Lanka. PATIENTS: 100 consecutive patients receiving 20 mg papaverine hydrochloride intracavernosally as the first dose. MAIN OUTCOME MEASURES: Assessment of the quality of the erection following the initial injection and determination of the optimum dose to achieve a normal erection; number who elected self-injection at home. RESULTS: Mean age of the 100 impotent men was 36.6 years and the mean duration of erectile dysfunction 43.9 months. Of men in the third decade 87.5% had a normal erection but only one-third of patients over 50 years showed a normal response. 16 patients had a reasonably well established organic problem. 42% of patients had normal nocturnal or early morning erections. The drop-out rate after the initial injection was 17%, 19% of men had a normal erection with 20 mg papaverine and 67% had a normal response to 20 to 80 mg papaverine. Seven patients continued on the self-injection program. Prolonged erections were experienced by 6% of men (1.9% of injections). CONCLUSIONS: Intracavernosal injection of papaverine hydrochloride is effective in a dose of 20 to 80 mg.

Role of cavernosometry and cavernosography in the diagnosis of vasogenic impotence

This study included eighty-six men with ages ranging between twenty- three and sixty-seven years. They were divided into two groups, eight healthy volunteers and seventy-eight patients with clinical suspicious of vasogenic impotence. The work aimed to study the role of cavernosometry and cavernosography after intracorporeal injection of papaverine in the diagnosis of vasogenic impotence

Tratamento contemporâneo de disfunçäo erétil através de injeçäo intracavernosa / Contemporary treatment of erectile dysfunction through intracavernous injection

Desde 1970 o tratamento da impotência sexual tem sofrido inúmeras modificaçoes. Isto se deu graças ao profundo conhecimento adquirido, através de inúmeras pesquisas, da fisiofarmacologia envolvida na ereçao. A descoberta de que substâncias vasoativas injetadas dentro dos corpos cavernosos poderiam produzir uma ereçao fisiológica trouxe nova luz ao tratamento de tal moléstia. Esta nova modalidade terapêutica, doravante denominada auto-injeçao intracavernosa, é sem dúvida o tratamento de primeira escolha para o paciente com disfunçao erétil de qualquer etiologia em 1994. Neste artigo os autores descrevem as principais drogas utilizadas nesta modalidade terapêutica, assim como o seu mecanismo de açao e complicaçoes.

Positive lusitropic effect and diminished myofibrillar sensitivity to calcium produced by cAMP on toad (Bufo Arenarum Hensel) ventricle

En tiritas intactas de ventrículo de sapo, se estudió el efecto relajante o lusitrópico positivo de diferentes intervenciones qu aumentan el AMPc intracelular. El isoproterenol aumentó la tensión desarrollada (DT), la velocidad máxima de contracción (+T), y la velocidad máxima de relajación (-T aumentó proporcionalmente más que +T a concentraciones de isoproterenol desde 10-8 a 10-4M, por lo que la relación +T/-T disminuyó significativamente. Una dosis única de isoproterenol (3x10**-8M) aumentó significativamente los niveles de AMPc desde 0.174 ñ 0.022 a 0.329 ñ pmoles/mg peso húmedo y produjo un aumento en la contractilidad de 69 ñ 13% y una disminución de +T/-T de 18.5 ñ 4.55%. La administración de 10**-3M de dibutiril AMPc(dAMPc) aumentó significativamente DT y +T y disminuyó significativamente la relación +T/-T. Efectos similares produjo la administración de milrinona, un inhibidor específico de la fosfodiesterasa de AMPc. La papaverina, un inhibidor inespecífico de fosfodiesterasas, no produjo aumentos en +T, pero aumentó significativamente -T. En trabéculas desprovistas químicamente de membrana, la sensibilidad al calcio de las proteínas contráctiles aumentó significativamente por la administración de 10**-5M del inhibidor de fosfodiesterasa 3-isobutil-1-metil-xantina (IBMX). La administración de 10**-3M de dAMPc no afectó la sensibilidad al calcio de las trabéculas desprovistas de membrana. Sin embargo la misma concentración de dAMPc produjo una disminución en la sensibilidad al calcio de las proteínas contráctiles cuando se administró en presencia de IBMX o de papavarina. Los resultados indicarían que el efecto relajante del isoproterenol es mediado en el ventrículo de sapo por un aumento en los niveles de AMPc intracelular. Estos resultados sugieren además que la disminución de la sensibilidad al calcio de los miofilamentos podría ser un mecanismo por el que el AMPc produce su efecto relajante

Estudo hemodinâmico do corpo cavernoso / Hemodynamic study of the corpus cavernosum

Procedeu-se à avaliaçäo da ereçäo após a injeçäo de cloridrato de papaverina no corpo cavernoso. Estudou-se o total de 178 pacientes desde abril de l984 a agosto de l985. Os resultados mostraram três grupos de pacientes: grupo I - 85 pacientes que responderam positivamente; grupo II - 59 pacientes que responderam positivamente após infusäo salina; grupo III - 34 pacientes com resposta negativa, mesmo após infusäo de altos fluxos de soro fisiológico. Compararam-se estes resultados com doppler e avaliaçöes psicológicas, neurológica e urológica, além da tumescência peniana noturna, o que nos levou às conclusöes: pacientes do grupo I têm o sistema vascular íntegro; a impotência é provavelmente psicogênica; pacientes do grupo II devem ter uma doença arterial do eixo hipogástrico-peniano; pacientes do grupo III com fluxo de saída aumentado provavelmente por defeitos da albugínea

Arteriografia peniana sob vasodilataçäo / Penile arteriography under vasodilatation

A arteriografia peniana é um exame de execuçäo e de interpretaçäo difícil. As artérias do pênis, especialmente as artérias profundas, recebem pouco fluxo durante o estado flácido, sendo o contraste levado principalmente para as artérias de irrigaçäo muscular do períneo. Dez pacientes foram submetidos a arteriografia peniana antes e depois de injeçäo intracavernosa de papaverina. Em oito deles, houve uma visível melhora da qualidade do exame, com melhor visibilizaçäo da artéria profunda. Em conclusäo, a arteriografia peniana deve ser feita sempre com vasodilataçäo provocada