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PubMed1979

[Comparative studies on the chemical modifications of Ehrlich ascites tumor cell membranes by hydrophobic drugs (cepharanthine, papaverine and cholesterol) (author's transl)].

Comparative studies were done on the actions of hydrophobic drugs (cepharanthine, papaverine and cholesterol) regarding chemical modifications of Ehrlich ascites tumor cell membranes. Changes in membrane potential monitored by using cyanine dye (diS-C3-(5)) were induced by cepharanthine and papaverine, but not by cholesterol. Increase in membrane permeability of K+ ions induced with lysolecithin was strongly inhibited in the order of papaverine, cholesterol and cepharanthine. Oxygen uptake by the cells was also strongly inhibited by papaverine, but the inhibitory effect by cepharanthine was little and cholesterol had no effect. Membrane fluidity was decreased in the order of cholesterol, cepharanthine and papaverine. From these results, it was suggested that papaverine maintained the compartmentation of K+ ion and membrane fluidity by regulating the intracellular mitochondrial metabolism or by inhibiting the membrane bound ATPase nucleotidase activity. The membrane stabilizing effect of cepharanthine and cholesterol probably was due to decrease in the membrane fluidity because of the hydrophobic association to the lipid bilayer of the cell membranes.

Alkaloids↗
PubMed2005

Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage that has become refractory to maximal medical management can be treated with selective intra-arterial papaverine infusions. Papaverine is a potent vasodilator of the proximal, intermediate, and distal cerebral arteries and can improve cerebral blood flow (CBF). When infused intra-arterially using endovascular microcatheter techniques, papaverine can effectively increase angiographic vessel diameter, decrease prolonged cerebral circulation time, and improve cerebral oxygenation. However, one of the major disadvantages of papaverine is its transient nature, which can result in recurrent and/or persistent angiographic and clinical vasospasm that may require multiple repeated infusions, despite a successful response to the initial treatment. Intra-arterial papaverine can be used alone or in combination with balloon angioplasty. This article reviews the mechanism of action, technique of administration, effects on CBF, clinical results, and complications of intra-arterial papaverine for the treatment of cerebral vasospasm.

Brain↗
PubMed1997

Distribution of intraarterially administered papaverine in endovascular treatment of delayed cerebral vasospasm.

The distribution of selectively administered papaverine was determined in nine patients with delayed cerebral vasospasm in the territories of the anterior (ACA) and/or middle cerebral arteries (MCA) secondary to aneurysmal subarachnoid hemorrhage by simultaneous infusion with technetium-99m-hexamethyl-propyleneamine oxime (99mTc-HMPAO). Four of the nine patients had a ruptured anterior communicating artery aneurysm, four had an internal carotid artery aneurysm, and the remaining one had a MCA aneurysm. Trapping of anterior communicating artery was carried out in one case and clipping of aneurysms in other eight cases. Neurological deterioration with hemiparesis, paraparesis, and/or somnolence appeared between postsurgical Days 8 and 13 due to delayed cerebral vasospasm in all patients. Intraarterial infusion of 40 mg of papaverine containing 37 MBq of 99mTc-HMPAO was performed from the C1 segment in seven of the nine patients and from the C4 segment in the other two patients. 99mTc-HMPAO was distributed in the territories of the ACA and MCA in the two patients who were treated with intraarterial infusion of papaverine from the C4 segment, but was distributed only to the territory of the ACA in four patients who were treated with intraarterial infusion of papaverine from the C1 segment at 1 ml/min. In contrast, 99mTc-HMPAO was distributed in the territories of the ACA and MCA in the three patients who were treated with papaverine from the C1 segment at 2 ml/min, although most 99mTc-HMPAO was distributed in the territory of the ACA. Vasospasm of the ACA can be treated by intraarterial infusion of papaverine from the C1 segment at 1 ml/min when selective catheterization to the ACA is difficult to perform.

Adult↗
PubMed1996

Superselective intraarterial papaverine administration: effect on regional cerebral blood flow in patients with arteriovenous malformations.

In this study the authors determined the effect of papaverine on regional cerebral blood flow (rCBF) in the angiographically normal arteriolar beds of patients with arteriovenous malformations (AVMs) who underwent transfemoral superselective angiography. Middle cerebral artery (MCA) branch vessels were catheterized during 10 procedures performed in nine patients. The mean (+/- standard deviation) largest AVM diameter was 4.4 +/- 1 cm. Regional CBF was measured by recording the washout of a bolus of xenon-133 injected through the microcatheter. In a dose-ranging study. rCBF and MCA pressure in two patients were repeatedly measured after 3-minute infusions of papaverine at 0.07, 0.7, and 7 mg/minute. In a single-dose study, an additional eight patients received only the highest dose of papaverine administered over a 3-minute period. In the dose-ranging study, CBF increased from baseline in a dose-dependent fashion. In the single-dose study, papaverine increased in rCBF 103%, from 48 +/- 11 to 95 +/- 23 ml/100 g/minute at an MCA pressure of 55 +/- 23 mm Hg. Increase in rCBF was linearly related (y = 2.2x - 17, r2 = 0.84; p = 0.001) to baseline MCA pressure (range 22-84 mm Hg). Papaverine increases rCBF in a direct proportion to baseline MCA pressure, even at low baseline pressures. Selective infusion of vasodilators should be investigated in acute cerebral hypotension to facilitate either primary or collateral recruitment of CBF by aiding spontaneous autoregulatory vasodilation. In addition, rCBF monitoring may be useful in determining the most effective intraarterial dose of papaverine while minimizing complications due to hyperemia.

Adult↗
PubMed1993

[Mechanisms of relaxing action of papaverine on isolated canine corpus cavernosum].

The mechanisms of relaxing effect of papaverine on the phenylephrine (10(-6) M)- or the high K+ (30 mM)-induced contracture were studied on the isolated canine corpus cavernosum. Rod shaped preparation of the corpus cavernosum without the tunica albuginea was mounted in a tissue bath, immersed in Tyrode solution and the isometric tension was recorded. Cumulative applications of papaverine (10(-6) approximately 3 x 10(-5) M) relaxed the phenylephrine (10(-6) M)- or the high K+ (30 mM)-induced contracture with a dose-dependent manner. A pretreatment with papaverine (10(-5) approximately 10(-4) M) dose-dependently reduced the magnitude of the phenylephrine (10(-6) M)-induced contracture, more prominently in the tonic than in the phasic component, while reduced that of the high K+ (30 mM)-induced contracture in both components. The relaxing effect of papaverine (5 x 10(-6) M) on the high K+ (30 mM)-induced contracture was antagonized by an increase in extracellular Ca++ concentration. A reintroduction of Ca++ after perfusion of Ca++ free and high K+ (30 mM) solution containing 1 mM EGTA failed to bring about normal contractile activity in the presence of papaverine (10(-4) M), Papaverine, even if its high concentration (10(-4) M), could not completely abolish the transient phasic contraction evoked norepinephrine (10(-5) M) which was abolished by ryanodine (3 x 10(-6) M), in Ca++ free solution. Isoproterenol (10(-8) approximately 10(-6) M) or dibutyryl cyclic-AMP (10(-5) approximately 10(-3) M) relaxed the phenylephrine (10(-6) M)- and the high K+ (30 mM)-induced contracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Role of xanthine oxidase and xanthine dehydrogenase systems in thymocyte apoptosis, induced by papaverine].

It has been established that papaverine as well as other xenobiotics (dexamethasone and nitrosodimethylamine) [figure: see text] provoked the thymocyte death like apoptosis. The increase of the quantity of double-strand, single-strand DNA breaks and low molecular weight fragments of DNA preceded cell death. In papaverine-induced process of thymocyte apoptosis the total activity of xanthine oxidase in thymocytes strongly elevated long before their death, the conversion of xanthine dehydrogenase (D-form) to xanthinoxidase (O-form) and accumulation of O-form in the cultural medium took place. Direct stimulating effect of papaverine on O-form of enzyme in thymocyte lysate was revealed. The used digitonin thymocytes were divided into cytoplasmic and structural component fractions. It was shown that about 80% of total xanthinoxidase activity was concentrated in cytoplasma while only 20% of its activity was found in structural components. More higher ratio of xanthinoxidase/xanthindehydrogenase (XO/XDH) was observed and papaverine-induced changes of these enzyme forms activities were expressed more brightly in the structural components, than in the thymocyte cytoplasma. During the process of developing thymocytes apoptosis caused by papaverine the reaction of lipid peroxidation was intensified. XO-hypoxanthin system displaying prooxidant influence on cells increased the cytotoxic effect of papaverine but the presence of allopurinol or catalase and superoxidedismutase decreased it. Besides, cytotoxic action on thymocytes of allopurinol itself as well as hypoxanthin itself was revealed.

Animals↗
PubMed1992

The effect of ambient temperature on papaverine-induced relaxations in canine saphenous veins.

This study was designed to measure the effect of ambient temperature (25 degrees C) on papaverine-induced relaxations in canine saphenous veins. Segments of vein were suspended in water-jacketed tissue baths at 37 degrees C, and isometric tension was recorded. After equilibration, veins were preconstricted by a median effective dose of norepinephrine 2 x 10(-6) mol/L at either 25 degrees C or 37 degrees C. Consequent dose-dependent relaxations showed that papaverine (10(-7) to 10(-3) mol/L was three times more potent as a dilator at 37 degrees C than at 25 degrees C, with half-maximal relaxations occurring at 2.2 x 10(-5) mol/L and 6.4 x 10(-5) mol/L, respectively. A 10(-4) mol/L dose of papaverine completely relaxed veins at 37 degrees C, whereas veins at 25 degrees C never fully relaxed even at ten times the standard concentration. In addition, the time for half-maximal relaxation with a 10(-4) mol/L dose of papaverine averaged 40 minutes at 25 degrees C compared with 22 minutes at 37 degrees C; this is indicative of a reduced relaxation rate at the lower temperature. These data show that papaverine is a slower and less potent dilator of canine saphenous veins at 25 degrees C than at 37 degrees C. This may have implications for the use of papaverine in the operating room, where it is usually applied at ambient temperature to reduce vasospasm of the saphenous vein during coronary artery bypass procedures.

Animals↗
PubMed1975

Actions of various methylxanthines and papaverine on the synthesis of corticosterone in vitro.

Actions of various methylxanthines (theophylline, theobromine, caffeine) and papaverine, i.e. drugs which are known to inhibit phosphodiesterase (PDE), were studied on the basal and stimulated synthesis of corticosterone in vitro by using rat adrenal slices. When slices were incubated with methylxanthines, the synthesis of corticosterone was slightly increased. The order of potency, expressed as the efficacy (intrinsic activity) was: theophylline greater than caffeine greather than theobromine. Papaverine did not stimulate the synthesis. The synthesis stimulated by ACTH or the dibutyryl derivative of c-AMP (DBA) was reduced by all of the inhibitors of phosphodiesterase. The molar concentration of the inhibitors which reduced the stimulated steroidogenesis by 50% was lowest for papaverine, higher for theobromine and theophylline and highest for caffeine. Papaverine was active in concentrations of about 10(-5)M, while the methylxanthines were effective in concentrations of 10(-3)--10(-2)M. When the PDE-inhibitors were added to the incubate simultaneously with the stimulant (ACTH or DBA), there was a delay of 60 min before the synthesis was completely blocked. When the stimulant was added 30 min before the administration of an inhibitor, the inhibitory action was no more evident. The inhibitory action of theophylline, but not that of papaverine, was reversed by washing adrenal slices free from the inhibitor, before adding the stimulant. The type of inhibition for papaverine as well as for methylxanthines in antagonizing both the ACTH- and DBA-stimulated synthesis of corticosterone was not competitive but of a mixed type.

Adrenal Glands↗
PubMed1986

[Diagnosis and therapy of erectile impotence with special reference to papaverine].

The introduction of intracorporeal papaverin injections has significantly changed the investigation and treatment of erectile dysfunction. Papaverin acts on the smooth (vascular) muscle cell and induces erection. A good response to papaverin injection excludes major vascular disturbances within the penis. The interpretation of a negative result is more difficult. Depending on the Doppler blood-flow measurements, further radiological investigations (dynamic cavernosography or selective angiography of the pudendal arteries) may be needed. Treatment of impotence with papaverin is most successful in patients with psychogenic disturbances, which are often coincident with minor vascular pathology. Autoinjection is easily learned for long-term treatment by patients with moderate vascular disorders or neurogenic dysfunction. Major vascular disturbances, e.g. occlusion of the penile arteries or marked venous shunt, require surgery by a trained urologist. Papaverin may cause side effects, especially priapism, which may lead to definitive impotence. Careful investigation of erectile disturbances and search for the appropriate papaverin dosage are therefore crucial.

Erectile Dysfunction↗
PubMed1986

[Efficacy of intracisternal papaverine on symptomatic vasospasm].

This study reports the effect of intracisternal administration of papaverine in 15 patients with vasospasm due to rupture of aneurysm. All patients had undergone clipping of aneurysm and had neurological deterioration and decreasing level of consciousness. Bolus injection of 40 mg of 1% papaverine hydrochloride was started on day 6.3 +/- 1.7 and continued for 4.4 +/- 1.6 days. In seven cases serial angiogram after initial dose revealed dilatation of IC and/or anterior, middle cerebral arteries at 30 min and further dilatation up to 85% increase in diameter at 60 min, which continued at least 90 min. Arteries with marked vasospasm responded more to papaverine than those with less vasospasm. There was a close correlation between degree of vasospasm and vasodilatation effect (r = 0.88, p less than 0.01). In all but two cases vasodilatation tended to become prominent by repeat doses, twice a day, for two to seven days (r = 0.87, p less than 0.01). Vasodilatation was observed only in IC and proximal trunks of ACA and MCA where papaverine could make direct contact, but not in the distal branches beyond A3 or M3. Neurological examination showed improvement of paresis or level of consciousness in 7 cases but no effect in 6 cases. Intracerebral hematoma occurred in two cases (one by high concentration 4% papaverine) during the treatment. Therefore intracisternal papaverine is the treatment of choice in cases with symptomatic vasospasm with some cautions on concentration to be administered.

Cerebral Angiography↗
PubMedDate not supplied

Papaverine hydrochloride as an adjunct to asanguinous cardioplegia, is it beneficial?

Papaverine hydrochloride was added to a standard asanguinous cardioplegic solution to study its effect on cardioplegic distribution by evaluating coronary resistance, myocardial temperature, and postoperative enzyme changes. Seventeen patients were randomized into a control group (8 patients) and a papaverine group (9 patients). All patients received 300 cc of a standard asanguinous cardioplegic solution into the aortic root after systemic cooling to 28 degrees C and measurement of septal temperature (To). The duration of infusion (t1), root pressure (p1), and septal temperature (T1) were recorded. All patients received a subsequent infusion of 200 cc of cardioplegia to which had been added either 10 cc normal saline (control group) or 1 mg papaverine hydrochloride in 10 cc normal saline (papaverine group). Time of infusion, root pressure, and septal temperature (t2, p2, T2) were recorded. Coronary resistance was calculated. Postoperative CPK and CPK-MB were recorded and compared. Mean high CPK in the papaverine group was 163 units and 182 units in the control group. There was no statistically significant difference in any parameter between groups. This study, in contradistinction to experience with animal research models, failed to demonstrate any significant value in adding papaverine hydrochloride to standard cardioplegic solutions.

Body Temperature↗
PubMed1981

Effects of papaverine on Ca++-dependent action potentials in guinea-pig myocardium depolarized by potassium.

Ventricular and atrial tissues isolated from guinea-pig hearts were depolarized by exposure to 22 mM K+ to study the effects of papaverine on the Ca++-mediated slow inward current (Isi). Papaverine at 5 x 10(-6) to 5 x 10(-5) M caused a concentration-dependent decrease in the threshold current required to excite the field-stimulated tissues and an enhancement of action potential amplitude, action potential duration and maximum rate of depolarization of the Ca++-dependent action potentials. In ventricular preparations, 5 x 10(-5) and 10(-4) M papaverine invariably induced rhythmic spontaneous activity that was abolished by verapamil. It is proposed that the membranal electrical effects of papaverine in the K+-depolarized myocardium are caused by an enhancement of Isi and a decrease in K+ conductance. However, at the highest concentration studied (10(-4) M), papaverine inhibited Isi in atrial tissue, demonstrating that papaverine exerts another action on Isi opposite to that observed at lower concentrations.

Action Potentials↗
PubMed1977

Effects of D 600 and papaverine on the inotropic response to isoprenaline on left guinea-pig atria under the graded influence of changes of frequency and temperature.

Isolated left guinea-pig atria were used to examine the influence of D 600 and papaverine on baseline contractile function and inotropic response to isoprenaline, under variable conditions of temperature (27 degrees to 42 degrees C) and rate of beat (0.125 to 4 Hz). The inotropic stimuli, caused by increasing the frequency of stimulation and decreasing the temperature, could not overcome the depressive action of D 600 on basal systolic tension. In addition the inotropic effects evoked by papaverine at low rates of beat and high temperatures were converted into cardiodepressive effects at high stimulation rates and low temperatures. The inotropic response to isoprenaline appeared to be by far more resistant to the depressive actions of D 600 and papaverine than the baseline contractile function. Only at a stimulation frequency of 2 Hz, high concentrations of D 600 (3 X 10(-7)M) and papaverine(3 X 10(-5)M) reduced the response caused by isoprenaline. At a stimulation frequency of 0.5 Hz, however, D 600 left the inotropic responses to isoprenaline unchanged, whereas papaverine potentiated these responses. It appears from the present results that the frequency of stimulation and the temperature greatly modify the cardiodepressive actions evoked by D 600 and papaverine.

Animals↗
PubMed1994

Effect of mode of application of papaverine on the contractile response of the internal mammary artery.

A study was performed to investigate the duration of action of papaverine applied either intraluminally or in a combined intraluminal and extraluminal fashion in vitro, and how the reactivity of the internal mammary artery (IMA) to a range of vasoconstrictors is affected. Segments of IMA exposed to only intraluminal papaverine (10(-4) mol/l) for 15 min recovered their contractile response to 90 mmol/l potassium chloride to pretreatment levels within 2 h. In contrast, combined intraluminal and extraluminal administration of papaverine resulted in a significant depression of the contractile response to 90 mmol/l potassium chloride (P < 0.001), which persisted for at least 5 h. Responses to 5-hydroxytryptamine, noradrenaline, the thromboxane mimetic U46619, histamine and dopamine were not significantly different between control tissues and those that had received intraluminal papaverine. The duration of action of papaverine is affected by its route of delivery and there are no significant short-term effects on the contractile mechanisms in the arterial wall after intraluminal administration.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Changes in epicardial coronary arterial diameter following intracoronary papaverine in man.

The effect of intracoronary papaverine administration on epicardial coronary arterial diameter was examined in 18 male patients. Coronary-artery cineangiograms were acquired with a power injector before intervention, 20 sec after intracoronary saline (control), and 20 sec after administration of papaverine into either the left (12 mg) or right (8 mg) coronary artery. Absolute coronary arterial diameter of a normal-appearing segment was quantified using a previously validated, fully automated digital edge detection program with an ADAC digital radiographic unit. Baseline coronary arterial diameter of 3.1 +/- 0.8 mm did not significantly change after saline administration (3.1 +/- 0.9 mm) but did significantly increase (p less than .001) to 3.4 +/- 0.9 mm after papaverine administration. No significant percent change in diameter occurred in either the left anterior descending (-.5 +/- 1.7%), left circumflex (-.2 +/- 1.1%), or right (-3.0 +/- 3.8%) coronary arteries with saline, but significant (p less than .001) increases occurred with papaverine (7.2 +/- 4.1%, 7.0 +/- 4.5%, 6.8 +/- 2.7%, respectively). The response of 7 coronary arteries examined immediately proximal to a significant lesion was not significantly different from the response of the remaining 11 coronary arteries. In conclusion, intracoronary papaverine causes a significant increase in coronary arterial diameter. This has clinical implications for assessing coronary flow reserve with devices that defect flow velocity.

Aged↗
PubMed1984

Papaverine enhances the effect of adenosine in guinea-pig atria.

Papaverine, while enhancing the force of contraction of guinea-pig atria, remarkably and dose-dependently enhanced the negative inotropic response of the atria to adenosine. It also enhanced the actions of ATP and other adenine nucleotides, but not those of 2-chloroadenosine and ACh. At similar concentrations, papaverine inhibited the uptake of adenosine by the atrial tissue during incubation with adenosine. Adenosine in the medium was degraded to inactive inosine during incubation with the atrial tissue, and papaverine reduced its degradation. The enhancing effect of papaverine on the action of adenosine on guinea-pig atria was like those of dipyridamole, 6-(2-hydroxy-5-nitrobenzyl)thioguanosine and cinepazide. The effect seemed to be due mainly to inhibition of adenosine uptake into the tissue. Inhibition of adenosine degradation may also have contributed to the action of papaverine, but this action was probably much less important than inhibition of adenosine uptake.

Adenine Nucleotides↗
PubMed1986

Effects of papaverine on calcium efflux and contractility in superfused rat left atria.

The effects of papaverine upon force of contraction, maximal rate of contraction, maximal rate of relaxation and 45Ca efflux were studied in isolated superfused rat left atria electrically driven at 1 Hz. Papaverine (3 X 10(-5) mol/l, increased developed tension (from 5.35 +/- 1.17 mN to 7.18 +/- 1.51 mN) by 1.8 +/- 0.41 mN (+33%, p less than 0.01) and maximal rate of contraction (+T) by 34.5 +/- 13% (p less than 0.05). In all experimental conditions tested, papaverine increased the rate of 45Ca efflux. The amount by which papaverine increased 45Ca efflux was 175 +/- 41 nmoles . g wet wt-1 and 304 +/- 76 nmoles . g wet wt-1, in the presence and in the absence of caffeine, respectively. The plot of changes in 45Ca efflux versus changes in developed tension fitted to a straight line (r = +0.56, n = 17, p less than 0.05), with a slope and intercept of 42 nmoles Ca . mN-1 . g wet wt-1 and -0.47 mN respectively, suggesting an association between the changes induced by papaverine in force development and increased 45Ca efflux.

Animals↗
PubMedDate not supplied

The use of papaverine in arterial sheaths to prevent loss of femoral artery pulse in pediatric cardiac catheterization.

This study evaluated the efficacy of intraarterial papaverine infusion after pediatric cardiac catheterization in reducing the incidence of lost pulse. This study was conducted at a teaching pediatric hospital and was designed as a randomized, prospective, double-blind, placebo-controlled study. Patients were children 5 years old or less undergoing antegrade and retrograde heart catheterization. The intervention used was an intraarterial infusion of placebo or 1.5 mg/kg papaverine after catheterization. Bilateral femoral artery ultrasound study was performed pre- and postcatheterization, including two-dimensional, color, spectral, and pulsatility index analysis. Outcome measures included clinical loss of pulse, ultrasound findings, plus other clinical factors. Fifty-six patients participated in the study (28 per group). Six patients clinically lost the pulse in the catheterized arteries [four in the papaverine and two in the placebo groups (p > 0.64)]. Clinical loss of pulse correlated with diminished pulsatility index (p < 0.035). The use of papaverine did not prevent decreased pulse or pulsatility index (p > 0.79). Increased arterial time was the only clinical factor associated with lost pulse (p < 0.0004). Pulsatility index <3.34 correlated with loss of pulse in the catheterized artery. The results indicated that intraarterial papaverine infusion after femoral artery catheterization does not prevent loss of pulse in the catheterized artery, and decreased pulsatility index correlates with diminished pulse and represents a good noninvasive method of evaluating femoral artery patency and flow.

Cardiac Catheterization↗