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PubMed2006

Effects of papaverine and carbon dioxide alone or in combination on the blood flow of internal thoracic artery.

OBJECTIVE: The internal thoracic artery is frequently used as an arterial graft for coronary bypass. Spasms of internal thoracic artery may contribute to early myocardial ischemia. To prevent vasospasm and increase the blood flow, some vasodilatory agents (such as carbon dioxide or papaverine) are used. The aim of the study was to evaluate the combined effects of carbon dioxide and papaverine versus either alone on the blood flow of the internal thoracic artery. METHODS: One hundred patients undergoing coronary artery bypass grafting (28 women and 72 men) with similar characteristics were randomly divided into four groups. We used the classic technique without any vasodilatory management before surgery in group 1, papaverine injection into the endothoracic fascia in group 2, and carbodissection technique in groups 3 and 4. Initial free flows of the internal thoracic arteries were measured after cutting of the vessel. After the first measurement, the ITA pedicles were washed with papaverine solution and wrapped with gauze in the first and fourth groups. Blood flow measurements were repeated 15 minutes later in all groups. RESULTS: When vasodilatory management was applied during excision, the blood flows were significantly increased relative to group 1. The mean blood flows reached a significantly higher level in groups 1, 2, 3, and 4 at the second measurements. In groups 2 and 3, the increase at the first measurements compared to the first group's level was continuously high, but no additional increase was observed between the first and second measurements. In groups 1 and 4, regardless of whether a previous vasodilatory management was present, the increases measured at repeated measurements were significant versus each group's first measurements (P < .05). CONCLUSIONS: Vasodilatory management, such as injection of papaverine into endothoracic fascia or carbon dioxide insufflation applied during excision, increased the free blood flows of internal thoracic artery pedicles. Exogenously applied papaverine produces an additional and continuous vasodilatation regardless of whether a vasodilatory intervention was previously applied.

Aged↗

PubMed2006

Flow measurement before and after papaverine injection in above-knee prosthetic femoropopliteal bypass.

OBJECTIVE: To investigate the value of intraoperative blood flow measurements on early and long-term patency of above-knee prosthetic femoropopliteal bypass. METHODS: Flow was measured with a transit time flowmeter before (basal flow) and after an intragraft injection of papaverine (papaverine flow) in 87 operations (86 patients) between January 1990 and December 2001. Sixty-one grafts were of polyester, and 26 were of polytetrafluoroethylene. The operations were done under epidural anesthesia. The preoperative angiographic run-off score and clinical risk factors were recorded. Patency rates were analyzed with the product limit method and compared with the log-rank test. Variables found to be near significantly related to patency rates (P < .1) were included in a multivariate analysis performed with the Cox proportional hazard model. RESULTS: Basal flow measurements were not related to patency. The 2- and 5-year patency rates for grafts with a papaverine flow < or = 500 mL/min were 48% and 18% compared with 66% and 52% for grafts with a papaverine flow > or = 500 mL/min. These differences were statistically significant (P = .012, hazard ratio, 2.6). Two- and 5-year patency rates for smokers vs nonsmokers were 44% and 18% vs 69% and 54%. The patency rates for patients with poor vs good run-off were 42% and 27% vs 66% and 31%. Smoking (P = .008, hazard ratio, 2.75) and poor run-off score (P = .009, hazard ratio, 2.38) were found to be independent risk factors for reduced patency rates. Poor run-off score did not correlate with low values of measured basal or papaverine flow. CONCLUSIONS: Papaverine flow of < or = 500 mL/min is associated with reduced mid- and long-term patency rates. Additional antithrombotic medication and frequent follow-up for these grafts should be considered. The inferior patency rates of smokers and patients with poor run-off indicate that prosthetic bypass is less suitable for these groups of patients.

Angiography↗

PubMed2003

Detrimental effects of papaverine on the human internal thoracic artery.

OBJECTIVE: We sought to determine the effects of papaverine on human and canine internal thoracic artery function and structure. METHODS: Vascular function was assessed with wire myography, and apoptosis was examined with confocal microscopy in arteries stained with ApopTag. RESULTS: Acetylcholine-induced endothelium-dependent relaxation in phenylephrine-precontracted arteries was significantly impaired by papaverine treatment in both human and canine internal thoracic arteries (maximal relaxation: 68.35% +/- 7.13% vs 47.5% +/- 9.32% in human arteries and 74.8% +/- 5.5% vs 34.3% +/- 8.5% in canine arteries) but not by incubation with acidified saline solution (pH 3.9, which is equivalent to the pH of 10(-2) mol/L papaverine solution) in canine internal thoracic arteries. Contraction of human internal thoracic arteries to phenylephrine or to U46619 was not significantly affected by papaverine treatment and neither was the contraction of canine internal thoracic arteries to phenylephrine. Total apoptotic endothelial and smooth muscle cells were significantly greater in papaverine-treated human and canine internal thoracic arteries. CONCLUSIONS: Papaverine impairs endothelial function and triggers apoptosis of endothelial and smooth muscle cells of human and canine internal thoracic arteries. The long-term consequence of this impairment on vascular function is not known. Until this question is answered, it will be prudent to use other vasodilators that are less damaging to the internal thoracic artery for cardiac surgery.

Animals↗

PubMed1998

Vasoactive cocktails for erectile dysfunction: chemical stability of PGE1, papaverine and phentolamine.

PURPOSE: Vasoactive cocktails are widely used in diagnosing and treating erectile dysfunction, especially in poor responders to prostaglandin E1 (PGE1). However, very little information as to their chemical interactions and stability is available, despite the huge amount of published work regarding their clinical efficacy. Obviously, medical and legal problems are involved. MATERIALS AND METHODS: We analyzed four kinds of vasoactive cocktails, composed of papaverine, phentolamine and PGE1 in different combinations, using High Performance Liquid Chromatography analysis after 5 to 60 days of storage at temperatures between 2 and 8C. SPSS MANOVA analysis and a t-test for paired samples were used for statistical purposes. RESULTS: Papaverine and phentolamine concentrations showed no significant variations during the 2 month study, ranging from a minimum of 96.75+/-1.20 to a maximum of 103.00+/-0.20% of the starting values. In the same period, PGE1 showed an accelerated degradation profile, reaching concentration values, after 60 days, of 76.00+/-2.28% and 70.20+/-2.02% when added to phentolamine or papaverine respectively and 70.00+/-2.40% with both. CONCLUSIONS: Papaverine and phentolamine are characterized by chemical stability when blended together or with PGE1. Papaverine and/or phentolamine increase the naturally occurring degradation of PGE1 in physiological solution. This effect is most evident in the first 10 days. Papaverine has the greatest deteriorating effect on PGE1. A safe and proper use of these cocktails should take into account the variations of PGE1 concentration.

Adrenergic alpha-Antagonists↗

PubMed1990

Prostaglandin E1 therapy for impotence, comparison with papaverine.

The efficacy of prostaglandin E1 as a pharmacological treatment of erectile dysfunction (impotence) was compared with the standard treatment, papaverine, in a single blind, crossover trial. A total of 129 impotent men received intracavernous injections of either prostaglandin E1 (5 micrograms) or papaverine (18 mg.) 1 month apart. Observations by 1 observer recorded 10 to 20 minutes after injection demonstrated that prostaglandin E1 generated a better erection in 72 men (55.8%) compared to papaverine. Papaverine was more effective than prostaglandin E1 in 23 men (17.8%, chi-square 6.26, p less than 0.025). Subjective assessment by the patients who detected a difference showed that 71 (55%) preferred prostaglandin E1 and 35 (27%) preferred papaverine (chi-square 11.56, p less than 0.001). A total of 34 men achieved full erections with prostaglandin E1 compared to 17 who used papaverine.

Adult↗

PubMed1986

Is intracavernous injection of papaverine a reliable screening test for vascular impotence?

To determine whether intracavernous injection of papaverine can discriminate vascular versus psychogenic impotence 80 mg. papaverine were injected intracorporeally into 27 impotent patients without any hormonal or neurological abnormality. The patients also underwent dynamic cavernosography, the artificial erection test and selective internal iliac arteriography. In addition, 21 of the patients underwent nocturnal penile tumescence monitoring. The response to intracavernous papaverine injection was noted as positive (fully rigid erection), intermediate or negative (soft or absent erection). Among 14 patients with severe arterial lesions and/or severe venous leakage the response was negative in 11 and positive in none. Among the remaining 13 patients (moderate or absent vascular abnormalities) the response was positive in 4 but negative in 4. Of 15 patients with an abnormal nocturnal penile tumescence test the response to intracavernous papaverine injection was negative in 12 and positive in none. However, of 6 patients with a normal nocturnal penile tumescence test the response was positive in only 1. Over-all, the results of the intracavernous papaverine injection test are correlated only fairly with those of the nocturnal penile tumescence test and the vascular investigations. This test could be useful to save some nocturnal penile tumescence tests in cases of suspected vascular impotence. However, the safety of this procedure must be confirmed in larger series. Indeed, 1 of our patients suffered priapism after a second intracavernous papaverine injection performed for a therapeutic purpose.

Adult↗

PubMed2001

Intra-arterial papaverine-induced seizures: case report and review of the literature.

BACKGROUND: Microcatheter-guided intra-arterial (IA) papaverine infusion in conjunction with balloon angioplasty is an available therapy for patients with symptomatic vasospasm after subarachnoid hemorrhage (SAH) that is refractory to hypertensive, hypervolemic therapy. However, side effects and complications have been reported in association with its use. CASE DESCRIPTION: We report on a patient who developed symptomatic vasospasm after subarachnoid hemorrhage due to rupture of a left terminal internal carotid artery (ICA) saccular aneurysm. Seven days after the hemorrhage and 4 days after surgical clipping, the patient developed aphasia and right hemiparesis due to vasospasm, which was refractory to maximal medical treatment with volume and blood pressure elevation. Cerebral angiography identified severe narrowing of distal ICA and proximal middle cerebral artery segments bilaterally. These findings partially resolved after balloon angioplasty. However, after 300 mg of IA papaverine, the patient developed generalized convulsions. This occurred despite therapeutic serum levels of phenytoin. Twenty-four hours later, after brief neurologic improvement, recurrent neurologic deficits prompted repeat papaverine administration. Seizures again occurred after the administration of 240 mg of IA papaverine and prevented administration of the full dose. The patient did not develop further seizures and her neurologic deficits continue to resolve. CONCLUSIONS: IA papaverine-induced seizures are infrequently reported. This potential complication should be considered when papaverine administration is entertained in the treatment of anterior circulation refractory symptomatic vasospasm after SAH.

Adult↗

PubMed1997

Comparison of transdermal nitroglycerin and intracavernous injection of papaverine in the treatment of erectile dysfunction in patients with spinal cord lesions.

This study was done to evaluate the effectiveness of transdermal nitroglycerin in the treatment of erectile dysfunction in males with spinal cord lesions as compared to the treatment with intracavernous injection of papaverine. The study design used was an open, randomized, cross over trial of intracavernous injection papaverine versus transdermal nitroglycerin. Twenty eight male patients with spinal cord lesions with erectile dysfunction were included in the study, and were subjected to intracavernous injection of papaverine and transdermal nitroglycerin with an interval of 2 weeks as the wash out period. Objectively, the times taken for the onset and the duration of erection were noted. The length of the penis and its circumference at its base were measured at intervals until the erection subsided. The volume of the penis at the onset and at the peak of erection was calculated. Twenty six patients (ie 93%) who received an injection of papaverine, and 17 (ie 61%) of the patients who received nitroglycerin showed a complete response. The difference was statistically significant (P = 0.004). Nine (32%) patients had complications with the injection of papaverine. The only complication noted with the application of a nitroglycerin patch was mild headache, experienced by six (21%) patients. It was concluded from the study that intracavernous injection of papaverine is more effective than transdermal nitroglycerin in the treatment of erectile dysfunction in patients with spinal cord lesions.

Administration, Cutaneous↗

PubMed1999

The effect of papaverine on morphologic differentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells.

BACKGROUND: Intracellular cyclic adenosine monophosphate (AMP) level changes are thought to play an important role in inhibiting cell proliferation and inducing differentiation in several types of cells. It has been reported that cyclic AMP analogs induce terminal differentiation in human prostate cancer cells. Consequently, phosphodiesterase inhibitors may be useful in delineating the role of cyclic AMP in the differentiation of these cells. Therefore, the effect of phosphodiesterase inhibitors on morphologic differentiation, proliferation and invasive potential of human prostate cancer cells was investigated. METHODS: Three human prostate cancer cell lines PC-3, DU145 and LNCaP were treated with one of the phosphodiesterase inhibitors, papaverine, 3-isobutyl-1-methylxanthine (IBMX) or theophylline, for 6 days. Morphologic changes of these cells induced by phosphodiesterase inhibitors were observed by microscopy. Intracellular cyclic AMP levels in LNCaP cells were measured by radioimmunoassay using a cyclic AMP assay kit. The effect of papaverine on the proliferation and invasive potential of LNCaP cells were measured by cell counting and the Matrigel invasion chamber assay. RESULTS: Of the three agents, examined papaverine (10(-5) mol/L) is the most effective inducer of morphologic change and also raised intracellular cyclic AMP levels in LNCaP cells. However, unlike LNCaP cells, PC-3 and DU145 cells treated with phosphodiesterase inhibitors, including papaverine, showed little change in morphology. Additionally, proliferation and invasive potential of LNCaP cells were significantly inhibited by papaverine. CONCLUSION: The results suggest that papaverine induces terminal differentiation in LNCaP cells, which is correlated with an intracellular cyclic AMP-mediated pathway.

1-Methyl-3-isobutylxanthine↗

PubMed2006

Buffered papaverine facilitates passage of intratympanic dexamethasone to the inner ear.

CONCLUSION: We conclude that when papaverine is intratympanically administered together with dexamethasone after buffering, passage of dexamethasone to the inner ear is increased. OBJECTIVE: To determine the influences of papaverine and buffered papaverine on passage of dexamethasone administered intratympanically to the inner ear. MATERIALS AND METHODS: Twenty-seven Vienna white rabbits were divided into five groups: eight received intratympanic dexamethasone (4 mg/ml) (group 1), seven received intratympanic papaverine (10 mg/ml) + dexamethasone (2 mg/ml) (group 2), six received buffered (with sodium bicarbonate 8.4%) intratympanic papaverine (7.5 mg/ml) + dexamethasone (1.5 mg/ml) (group 3), three had basal cortisol levels in venous blood and perilymph measured (group 4), and three received intravenous papaverine + dexamethasone (group 5). At 1 h after the administration of the drugs, dexamethasone levels in ipsilateral and contralateral perilymph and venous blood were measured by radioimmunoassay. RESULTS: Animals in group 3 demonstrated the highest levels of ipsilateral perilymph dexamethasone. Ipsilateral perilymph levels were significantly higher in groups 1 and 3 than they were in the other groups (p<0.05). Although the perilymph levels observed in animals in group 2 were slightly higher than those in group 4, no significant difference existed (p = 0.160).

Animals↗

PubMed1999

Clinical evaluation of the effect of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

The clinical efficacy of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for treatment of vasospasm following subarachnoid hemorrhage was investigated. Between 1990 and 1993, 84 patients were treated for cerebral vasospasm in National Defense Medical College Hospital. Angioplasty was performed for asymptomatic vasospasm in 18 patients and for symptomatic vasospasm in 12 patients. Intra-arterial papaverine infusion was performed for asymptomatic vasospasm in 10 patients and for symptomatic vasospasm in four patients. The other 40 patients were treated with standard conservative therapy including hypervolemic and hypertensive hemodilution. The outcomes of these patients were analyzed using the Glasgow Outcome Scale. The outcome tended to be better for patients treated with angioplasty, but not for those treated with papaverine infusion, than for those treated conservatively. Recurrence of vasospasm was more frequent after papaverine infusion than after angioplasty. Undesirable complications such as abrupt development of unconsciousness were experienced during papaverine infusion but not during angioplasty. We conclude that percutaneous transluminal angioplasty is superior to intra-arterial papaverine infusion for prevention and treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

Angioplasty, Balloon↗

PubMed1997

Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery.

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.

Administration, Topical↗

PubMed1987

Inhibitory effect of papaverine on HVJ (Sendai virus) replication in rat glioma C6 cells.

The replication of HVJ (Sendai virus) in C6 rat glial cells was found to be inhibited by treatment of the cells with papaverine, an inhibitor of cAMP phosphodiesterase, but not with cAMP or dibutyryl cAMP. In addition, cyclic GMP which often manifests a reciprocal relationship to cAMP did not counteract the inhibition of HVJ yield by papaverine. Both viral genome replication and transcription were suppressed slightly by treatment of the cells with papaverine. In the cells cultured in the presence of papaverine, the synthesis of viral proteins and their phosphorylation occurred at normal rates. Membrane immunofluorescence and cell surface immunoprecipitation showed that the viral glycoproteins HN and F0 were expressed on the cell surface of the papaverine-treated cells. Moreover, all the viral structural proteins were associated with plasma membrane isolated from the treated cells. These results indicate that papaverine treatment suppresses some part of the process of virus budding at the plasma membrane.

Animals↗

PubMed1994

Different pharmacological characteristics of structurally similar benzylisoquinoline analogs, papaverine, higenamine, and GS 389, on isolated rat aorta and heart.

In the present study, we compared the pharmacological properties of structurally similar benzylisoquinoline compounds, papaverine, higenamine, and GS 389, using isolated rat aorta and atrial preparations. The three benzylisoquinoline compounds, concentration dependently, relaxed phenylephrine (3 microM) induced contraction of rat aortic rings, with the rank order of potency being higenamine > papaverine > GS 389. They also relaxed high K+ (60 mM) induced contraction, with the rank order of potency being papaverine > GS 389 >> higenamine. The relaxation was not modified by the presence of endothelium. To assess whether these compounds directly interfere with Ca2+ influx, the effects of these compounds on Ca(2+)-induced contraction in Ca(2+)-free media were examined. Among the three compounds, papaverine most strongly inhibited Ca(2+)-induced contraction of both K+ stimulated and phenylephrine-stimulated aorta. Higenamine was least potent in inhibition of Ca(2+)-induced contraction in high K+ depolarized aorta. In atrial tissues, lower concentrations of papaverine increased spontaneous beats and isometric tension, whereas above 30 microM its action was reversed. GS 389 decreased heart rate without affecting the contractility. On the other hand, higenamine concentration dependently increased both heart rate and isometric tension, as well as cyclic AMP levels in atrial tissues as a result of beta-receptor activation. Cyclic AMP and cyclic GMP dependent phosphodiesterases from rat atrial and ventricular tissue homogenates were inhibited by papaverine and GS 389, but not by higenamine. These results suggest that calcium antagonistic action of these compounds is at least in part responsible for vasodilation action, but not for cardiac action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

PubMed2005

Effectiveness of vardenafil versus papaverine in penile Doppler ultrasonography.

PURPOSE: To evaluate erectile dysfunction, penile color Doppler ultrasound is currently considered the best method. But intracavernous injection is invasive and has adverse effects, such as prolonged erection and risk of priapism. In our study we want to evaluate whether vardenafil can be used instead of papaverine in penile Doppler ultrasonography. MATERIALS AND METHODS: A total of 24 patients with erectile dysfunction underwent color Doppler ultrasound before and after intracavernous injection of 60 mg papaverine with genital and audiovisual sexual stimulation. Peak flow and end diastolic velocity were measured in the recorded waveforms obtained 0, 1, 5, 10 and 20 min after injection. The patients also underwent color Doppler ultrasound after a 10-mg oral dose of vardenafil with genital and audiovisual sexual stimulation and at least 5 days after the prior examination. The same parameters were measured at 30, 45, 60, 75 and 90 min after the drug administration. We compared the results with the values obtained after papaverine injection. RESULTS: After oral vardenafil mean peak flow velocity significantly increased starting at 30 min and achieving a maximum value at 60 min. There were no significant differences in the 2 methods in mean peak velocity 1, 5, 10 and 20 min after papaverine injection, and 30, 45, 60, 75 and 90 min after oral vardenafil administration. Although papaverine injection is the gold standard for penile color Doppler ultrasound, it has severe adverse effects such as prolonged erection which we observed in 3 patients (12.5%) and required pharmacological detumescence. After vardenafil no severe adverse effects were observed. CONCLUSIONS: Vardenafil administration achieved increased peak flow velocity comparable to that after intracavernous papaverine injection. With no prolonged erection vardenafil is a safer alternative compared to more invasive intracavernous injection and is also an alternative for patients who fear injections.

Adult↗

PubMed1991

Effect of papaverine on endothelial cell harvest from canine external jugular veins.

Endothelial cell seeding procedures have been developed to line prosthetic bypass grafts used in peripheral vascular disease; however, because of current inefficient cell harvest techniques a high ratio of vein-to-graft area is necessary. This study was done to determine if the use of papaverine, a smooth muscle cell relaxant, would affect the number or viability of endothelial cells harvested from canine external jugular veins. Using a 0.12 mg/ml solution of papaverine in tissue culture medium to bathe the veins during dissection and excision, the viable cell yield was 2.20 +/- 1.16 (cells x 10(4)/cm2). A control group of veins using standard dissection technique gave a yield of 0.97 +/- 0.40 (p = 0.025). A second group of veins dissected while bathed in tissue culture medium alone gave a yield of 1.82 +/- 0.75, compared to a yield of 2.73 +/- 0.45 for papaverine harvested veins (p = 0.009). Percent cell viability was not significantly different for any of the groups: 73, 70, and 76% for papaverine, control and media only veins, respectively. The papaverine-harvested cells and those harvested with medium alone grew to 95% confluence in tissue culture in 9.8 +/- 1.1 and 9.9 +/- 0.9 days, respectively. Compared to conventional surgical techniques, use of papaverine more than doubled the endothelial cell yield from excised vein segments without adversely affecting viability or rate of growth in cell culture.

Animals↗

PubMed2004

Neurotoxicity of intra-arterial papaverine preserved with chlorobutanol used for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Papaverine is used to vasodilate cerebral arteries undergoing vasospasm from subarachnoid hemorrhage. However, papaverine inhibits cellular respiration in vitro and could cause neurotoxicity in humans. METHODS: We studied 5 consecutive patients with cerebral vasospasm who were treated with intra-arterial papaverine preserved with chlorobutanol and imaged with MRI fluid-attenuated inversion recovery and diffusion-weighted imaging after treatment. One patient had histological analysis of the brain at autopsy. RESULTS: All 5 patients exhibited marked neurological decline immediately after treatment, and this was sustained through hospital discharge. In all cases, MRI images showed selective gray matter-only signal changes within the vascular territory treated with papaverine. Histological analysis of 1 case brought to autopsy showed selective injury to islands of neurons with relative sparing of white matter. CONCLUSIONS: Intra-arterial delivery of papaverine preserved with chlorobutanol into vasospastic anterior cerebral arteries may result in marked neurological deterioration with selective gray matter changes on MRI imaging. This effect is consistent with a permanent toxic effect to human brain. It is unclear whether this toxicity is caused by papaverine or chlorobutanol, and its use in the treatment of cerebral vasospasm should be reserved for cases without alternatives.

Aged↗

PubMed1983

Beneficial effect of papaverine plus raubasine in peripheral arterial insufficiency.

It has been demonstrated that, in most arteriopathic patients, vasodilators induce the vascular steal phenomenon, i.e. the shunting of blood from the ischemic to the normally perfused areas. It is conceivable, therefore, that vasoconstrictors may improve in the opposite way, reducing the blood flow to the normal zones and increasing it to the ischemic. A "reverse vascular steal" caused by the simultaneous IV injection of a vasodilator and a beta-blocker has been previously shown; however, the chronic treatment of arteriopathic patients with beta-adrenoceptor blocking drugs often results in increased evidence of peripheral arterial insufficiency; therefore, the combination of a vasodilating drug with a beta-blocker is limited in the clinical practice. The aim of this study was to investigate the efficacy of the combination of the vasodilator papaverine hydrochloride with a drug having vasoconstrictive action without the undesirable side effects of beta-blockers. Accordingly, raubasine (40 mg) was given p.o. associated with papaverine (300 mg) in 10 arteriopathic patients, who presented a significant reduction of blood flow in the affected limb after the administration of 300 mg p.o. of papaverine alone. The measurements of blood flow were performed by impedance plethysmographic recordings to evaluate papaverine plasma concentrations. Data obtained by this study indicate that papaverine alone induces a significant reduction of blood flow starting from the time of its maximal plasma concentration. Raubasine alone does not induce any change in blood flow, while the combination of the 2 drugs significantly increases the blood supply to the affected limb. These favorable results, probably related to the ability of raubasine to induce a reverse vascular steal, suggest that the combination of this drug with a vasodilator such as papaverine may represent a new approach in the treatment of peripheral arterial insufficiency.

Aged↗