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PubMed2000

Mechanism of relaxant response to papaverine on the smooth muscle of non-pregnant rat uterus.

In the present paper, we examined a mechanism of the papaverine induced relaxation in the smooth muscle of non-pregnant rat uterus. The hyperosmotic 65 mM KCl (H-65K+)-or oxytocin-induced contraction in the uterus was inhibited by an addition of papaverine in a concentration-dependent manner. Papaverine did not increase both cAMP and cGMP contents in the uterus in the presence of H-65K+ or oxytocin. In fura 2 loaded muscles, papaverine did not affect an increase of [Ca2+]i level by high K+ or oxytocin. In permeabilized muscles, papaverine had no effect on the Ca2+-induced contraction. H-65K+ and oxytocin increased the rate of oxygen consumption 1.8 and 1.5 times higher than that in the resting condition, respectively. The increase of oxygen consumption in the H-65K+ or oxytocin was significantly inhibited by papaverine (1-100 microM). These results suggested that papaverine inhibits smooth muscle contraction mainly by inhibition of mitochondrial respiration in rat uterus as well as guinea pig ileum, which shows a highly spontaneous activity and a highly metabolic dependency of a contraction.

Animals↗
PubMed1992

Treatment of cerebral vasospasm with intra-arterial papaverine.

Cerebral vasospasm continues to be the leading treatable cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. In this preliminary anecdotal series of 12 patients who were candidates for balloon angioplasty, vasospasm was treated instead with intra-arterial papaverine. Eight patients had marked angiographic reversal of the arterial narrowing following papaverine infusion, four of whom showed dramatic reversal of profound neurological deficits. Two patients deteriorated clinically 5 days after the initially successful papaverine infusions. In both, repeat angiography demonstrated severe recurrent vasospasm, which was partially reversed with a second intra-arterial papaverine treatment. Two patients developed focal neurological deficits during papaverine infusion, which resolved spontaneously over several hours after cessation of the intra-arterial infusion. Arterial narrowing in the posterior circulation and middle cerebral artery distribution appeared to be more responsive to papaverine infusion than was spasm in the anterior cerebral arteries. The infusion of 300 mg of papaverine over 1 hour seemed to be an adequate and safe dose to effect these angiographic and clinical improvements.

Adult↗
PubMed1998

Increase in diameters of vasospastic intracranial arteries by intraarterial papaverine administration.

OBJECT: This study was conducted to determine if there is a change in intracranial arterial diameters after papaverine infusion for vasospasm and to determine whether the change occurs in proximal, intermediate, and distal arteries. METHODS: The authors measured arterial diameters retrospectively in all patients who received intraarterial papaverine for treatment of vasospasm between November 1992 and August 1995. Patients who received papaverine in the same session with or following angioplasty were excluded. Measurements were made in a blinded manner with the aid of a magnification loupe at 12 predetermined sites on each angiogram before and after papaverine infusion. Eighty-one treatments in 34 patients were included. Angiograms obtained at the time of presentation with subarachnoid hemorrhage (SAH) were examined in 26 of the 34 patients. Nine carotid territories visualized by repeated angiography on the day after infusion were examined to determine the duration of the papaverine effect. CONCLUSIONS: In all treatment groups an increase was found in the average arterial diameters ranging from 2.8 to 73.9%, with a mean increase of 26.5%. Increases in diameter were observed in proximal, intermediate, and distal arteries. The timing of treatments ranged from Day 3 to Day 19 post-SAH, and there was no relationship between timing and arterial responsiveness (r = -0.06). There was a moderately good correlation between the degree of vasospasm in an artery and its responsiveness to papaverine (r = -0.54, -0.66, and -0.66, for proximal, intermediate, and distal arteries, respectively). The effect of papaverine did not persist until the following day in patients in whom repeated angiography was performed.

Angiography, Digital Subtraction↗
PubMed2001

Effect of papaverine applications on blood flow of the internal mammary artery.

The aim of this prospective study was to compare the effect of different papaverine applications on the free blood flow in the internal mammary artery (IMA) prepared for coronary artery bypass grafting (CABG). The patients were divided into three groups: group I (n=50; intraluminal papaverine application), group II (n=50; topical papaverine application), and group III (n=50; periarterial papaverine application). The free flow from the distal cut end of the IMA was measured under controlled hemodynamic conditions (Flow 1). Just before the establishment of cardiopulmonary bypass, the flows of the IMA were measured again (Flow 2). The mean blood flow in the IMA was 60.7+/-6.0 ml/min before papaverine application. After papaverine application, the mean blood flow in group I was 129.3+/-10.0 ml/min, in group II, it was 87.7+/-3.8 ml/min, and in group III, it was 130.6+/-9.2 ml/min (p<0.0001). Proportional increases in blood flow observed in group I (106.3%) and group III (116.2%) were higher than in group II (44.2%) (p<0.0001). Consequently, to relieve perioperative spasm of the IMA, application of papaverine injected into the periarterial tissues of its pedicle was considered to be a safe and effective alternative to topical or intraluminal application.

Adult↗
PubMed1992

Papaverine inhibits human platelet aggregation induced by ADP.

1. The in vitro and ex vivo effect of therapeutic levels of papaverine on human platelet aggregation induced by 3-5 microM adenosine-5'-diphosphate (ADP) was evaluated in platelet-rich plasma (PRP) by photometric and impedance aggregometry, and in whole blood by impedance aggregometry. 2. Platelet aggregation induced by 3-5 microM ADP in whole blood was significantly inhibited by 5.32 and 10.64 microM papaverine in vitro. This effect was also observed in PRP enriched with erythrocytes but not in PRP alone or enriched with leukocytes. 3. Papaverine (5.32 microM) significantly enhanced the antiplatelet activity of adenosine (0.75 microM) in human whole blood, an effect that was not observed in PRP. 4. A single oral dose of 100 mg papaverine hydrochloride, given to eight healthy human volunteers 1 h before the platelet aggregation evaluation, significantly inhibited the platelet aggregation induced by 3-5 microM ADP in whole blood. This effect was not observed in PRP. 5. Oral administration of the same dose at 8-h intervals (10 times) to seven additional healthy human volunteers led to a significant negative correlation (r = -0.55, P < 0.01) between the slope of platelet aggregation in whole blood and plasma papaverine levels (0.12-0.75 microM). 6. Papaverine and adenosine, alone or together, had no in vitro effect on whole blood platelet aggregation of male Wistar rats measured by impedance aggregometry. 7. These results suggest that papaverine inhibits human platelet aggregation in whole blood by an interaction with red blood cells.

Adenosine Diphosphate↗
PubMed1987

Stability of papaverine hydrochloride and phentolamine mesylate in injectable mixtures.

The stability of papaverine hydrochloride and phentolamine mesylate combined in a single vial was studied. Injectable mixtures (10 mL) of papaverine hydrochloride 300 mg and phentolamine mesylate 5 mg (from two sources) were prepared by adding the contents of one vial of lyophilized phentolamine mesylate to the contents of one vial of papaverine hydrochloride injection. The vials were stored at 5 degrees C and 25 degrees C. Duplicate aliquots of the mixtures were obtained, and the concentrations of papaverine hydrochloride and phentolamine mesylate remaining at time 0 and after 1, 2, 5, 10, 20, and 30 days were determined in triplicate by a stability-indicating high-performance liquid chromatographic assay. The concentration of papaverine hydrochloride stored in the vials remained constant (less than 1% loss) over the 30-day period at both 5 degrees C and 25 degrees C. Phentolamine mesylate was less stable than papaverine but still retained more than 97% of its original concentration after 30 days at 5 degrees C and more than 95% of its original concentration at 25 degrees C. Papaverine hydrochloride and phentolamine mesylate are stable in injectable mixtures when stored for up to 30 days at 5 degrees C or 25 degrees C.

Chromatography, High Pressure Liquid↗
PubMed1989

Investigation on the effect of dipyridamole and papaverine on regional blood flow and cardiac hemodynamics in anesthetized dogs.

Vasodilating effects of dipyridamole were compared with those of papaverine in anesthetized open-chest dogs. Dipyridamole i.v. produced a significant fall in aortic blood pressure and significant increases in aortic and coronary blood flows. Vertebral blood flow did not alter, but renal blood flow was transiently decreased. Left ventricular dP/dt, heart rate and left ventricular enddiastolic pressure were hardly affected by dipyridamole. Papaverine i.v. significantly increased aortic, vertebral and coronary blood flows, left ventricular dP/dt and heart rate and significantly decreased aortic blood pressure and left ventricular enddiastolic pressure. Renal blood flow was instantly decreased by papaverine. Percent change in each vascular resistance showed decreases in total peripheral, vertebral and coronary vascular resistances in response to both drugs, and the decrease in coronary vascular resistance was the most remarkable. Renal vascular resistance was increased by dipyridamole, while it was decreased by papaverine. Percent change in double product (heart rate x systolic arterial blood pressure) showed a monophasic decrease pattern with dipyridamole and a biphasic pattern with an initial, transient decrease followed by an increase with papaverine. The present results indicate that dipyridamole and papaverine produce marked coronary vasodilatation, and that papaverine is different from dipyridamole in cardiotonic properties.

Anesthesia↗
PubMed1986

Effects of papaverine and theophylline on renal adenosine transport.

We have studied the effects of papaverine and theophylline on the transport of adenosine by the isolated perfused rat kidney and by isolated renal luminal (L) and antiluminal (AL) membrane vesicles. In filtering isolated kidneys perfused with 0.1 mM adenosine, 1 mM papaverine inhibited adenosine removal from the perfusate by 40% and elevated the fractional excretion of adenosine from 0.4 +/- 0.1 to 0.7 +/- 0.0. Theophylline (10 mM) inhibited 0.1 mM adenosine removal in the filtering kidney by 18% and decreased the fractional excretion of adenosine to 0.2 +/- 0.1. In nonfiltering isolated kidneys perfused with 0.1 mM adenosine, 1 mM papaverine or 10 mM theophylline inhibited the rate of adenosine removal from the perfusate by 41 or 19%, respectively. Papaverine (50 or 100 microM) was a potent cis inhibitor of the initial (15 sec) rate of 1 microM [3H]adenosine influx into L and AL membrane vesicles. The influx of 1 microM [3H]adenosine was inhibited partially by 50 microM and inhibited completely by 100 microM papaverine. Papaverine at 10 microM trans stimulated the efflux of 50 microM [3H]adenosine preloaded into AL vesicles. However, theophylline (up to 100 microM) had no effect on the influx of 1 microM [3H]adenosine into L and AL vesicles. The data suggest that papaverine is a potent, direct inhibitor of adenosine transport across both L and AL membranes whereas it is likely that theophylline increases net adenosine influx across the L membrane and decreases adenosine influx across the AL membrane by indirect metabolic effects.

Adenosine↗
PubMed1988

[Value of prostaglandin El in the diagnosis of erectile dysfunction in comparison with papaverine and papaverine/phentolamine in 61 patients with erectile dysfunction].

In 61 patients with erectile dysfunction a comparative study with intracavernous injection of prostaglandin E1 (PGE1), papaverine and a mixture of papaverine and phentolamine was performed. All patients underwent comprehensive multidisciplinary examinations, including bulbocavernosus reflex (BCR) latencies and somatosensory evoked potentials, penile Doppler sonography, dynamic or pharmaco-cavernosonography, and for 11 patients nocturnal penile tumescence (NPT) was also recorded with the Rigiscan. This diagnostic approach suggested that in 24 (39.3%) of the 61 pts the etiology was psychogenic and in the remaining 37 (60.7%) it was organogenic. PGE1 had a much higher erectile potency than papaverine and a somewhat higher potency than the mixture of papaverine and phentolamine. Complete erection was achieved in 41 of the 61 patients (67.2%) with PGE1, as against 20 of the 61 patients (32.8%) with papaverine alone and 20 of the 61 (32.8%) with papaverine/phentolamine. Whereas 7 of 61 patients (11.5%) had priapism of more than 6 h duration and requiring therapy after injection of papaverine or papaverine/phentolamine, no priapism occurred after PGE1. Thus, compared with papaverine and phentolamine, PGE1 offers important advantages in the diagnosis and perhaps also in the therapy of erectile dysfunction.

Adult↗
PubMed1979

Comparative study of the clinical effect of vincamine versus papaverine given parenterally in the acute phase of stroke.

The efficacy of the "oxygenator", vincamine was assessed in comparison to a classic vasodilator, papaverine, after parenteral administration during the first days of an acute thrombo-embolic stroke. All 263 patients admitted to this open trial had a thrombo-embolism of the A. carotis or one of its cerebral branches within the previous 24 h. Patients demonstrating minimal neurological deficit or requiring admission to an intensive care unit, or patients with a suspected hemorrhagic syndrome were excluded. Each patient received i.v. infusions (15 mg X 6) of 6 vials of vincamine per 24 h, or 6 vials of papaverine (40 mg X 6) per 24 h, occasionally in combination with acetylsalicylic acid (ASA), dipyridamol and hydrocortisone. An initial 3-h control was followed by regular surveillance for 5 days, paying special regard to consciousness and motricity. The administration of vincamine alone had a significantly more favourable effect than papaverine alone on consciousness (p less than 0.001). Furthermore, vincamine associated with other drugs was significantly superior (p less than 0.01) to papaverine given in association. A similar tendency was noted for motor recuperation after vincamine compared to papaverine (p less than 0.001). Vincamine and papaverine were well tolerated during the 5-days observation period, only one side effect after vincamine and four after papaverine being noted.

Adult↗
PubMed1981

Action potential, membrane currents and force of contraction in cat ventricular heart muscle treated with papaverine.

The effects of papaverine on force of contraction, action potential configuration and membrane currents were studied in ventricular heart muscle from cats. The force of contraction was variably affected by different concentrations of papaverine. At 2 X 10(-5) M papaverine, the following results were obtained. The action potential duration was prolonged at all voltage levels. The steady-state outward current and the outward tail currents after 800 msec-depolarizing voltage clamp steps were reduced. The slow inward current was slightly enhanced or reduced. Both the slow inward current and the force of contraction were greatly increased in the presence of both papaverine and isoprenaline (3 X 10(-9) M); isoprenaline (3 X 10(-9) M) alone had no significant effects either on the slow inward current or on the force of contraction. It is concluded that the predominant membrane effect of papaverine on the heart is to reduce the potassium conductance. The inhibition of papaverine on the phosphodiesterase activity does not change considerably either the slow inward current or the force of contraction. An adrenergic stimulus, however, is greatly increased in the presence of papaverine.

Action Potentials↗
PubMed1976

A comparative study between the cardiovascular effects of cetiedil, a new vasodilator, and papaverine and aminophylline.

The cardiovascular effects of progressively increasing infusions of papaverine hydrochloride, aminophylline and cetiedil, a new vasodilator, were studied and compared in the anesthetized intact dog preparations. Papaverine and aminophylline had qualitatively the same effects on the various parameters, but in general the maximal effects of papaverine were of a greater order of magnitude. Cetiedil exhibited a different pattern of cardiovascular activity characterized by initial decrease in mean pulmonary arterial flow of 16% accompanied by an increase in systemic vascular resistance of 28% and in pulmonary vascular resistance of 19%, a stage of restoration of mean pulmonary arterial flow to control level accompanied by decrease in dp/dt of 25% and increase in pulmonary vascular resistance of 27% and a final stage of decrease in mean pulmonary arterial flow, representing toxic effects and accompanied by decrease in mean aortic pressure of 26%, dp/dt of 54% and heart rate of 27%, and an increase in pulmonary vascular resistance of 84%. These results indicate that cetiedil is devoid of cardiac stimulant activity. In another group of experiments devoted to measurement of vascular resistance of the hind limb, the results indicate that cetiedil, like papaverine and aminophylline, increased femoral blood flow through a decrease in resistance of the hind limb vasculature. This increase in flow could have been brought about only by redistribution of the cardiac output through differential effects on different vascular beds, since unlike papaverine and aminophylline, cetiedil does not increase cardiac output. The lesser maximal increase in femoral blood flow following cetiedil as compared to that following papaverine is probably referable to the relatively limited capacity of redistribution of the cardiac output to augment femoral blood flow. Superimposition of cetiedil and aminophylline on maximal effects of papaverine led to an additional decrease in mean femoral perfusion pressure, probably implying differences in basic mechanisms by which the three agents bring about their smooth muscle relaxant action.

Aminophylline↗
PubMed1995

Evaluation of impotent men with intracorporeal injection of papaverine and colour Doppler ultrasound.

Fifty impotent patients have been evaluated with intracorporeal injection of papaverine and colour Doppler ultrasound. The papaverine tests were negative in 34 of 50 patients. Nineteen of 34 patients with negative papaverine results showed normal colour Doppler findings. In 14 of 16 patients with positive papaverine results the colour Doppler analysis revealed normal structure and functions. Correlation between intracorporeal papaverine injection and colour Doppler ultrasound results was found in 59% (p < 0.01). We concluded that intracorporeal papaverine injection is an effective, simple diagnostic test for beginning evaluation of impotent men. However, this screening test should be supported by colour Doppler ultrasound.

Adult↗
PubMed1987

Superiority of intracoronary papaverine to radiographic contrast for measuring coronary flow reserve in patients with ischemic heart disease.

Measurement of coronary flow reserve has been suggested as an adjunct to anatomic assessment of coronary stenoses in patients with ischemic heart disease. We compared papaverine hydrochloride and radiographic contrast to determine which agent was superior for the determination of coronary flow reserve. Coronary flow reserve was determined during cardiac catheterization by means of digital coronary angiography and parametric imaging. Two groups of patients were studied. Among patients in group 1, coronary flow reserve was determined by means of both papaverine and contrast. In group 1 patients with normal coronary arteries, papaverine-induced flow reserve was greater than contrast-induced reserve in all but one vascular region (n = 9, 4.98 +/- 1.15 vs 3.56 +/- 0.89; p = 0.29). Group 1 patients with coronary disease also demonstrated significantly greater flow reserve with papaverine (n = 25, 2.57 +/- 0.20 vs 1.83 +/- 0.11, p less than 0.01). Group 2 included patients with single-vessel coronary artery stenoses. These patients were studied by means of either papaverine or contrast to determine coronary flow reserve for both the stenotic "ischemic" region and an adjacent nonstenotic, "nonischemic" region. Those patients in group 2 who were studied by means of contrast had a modest difference between flow reserve values in the nonischemic and those in the ischemic regions (n = 15, 1.78 +/- 0.10 vs 1.26 +/- 0.09; p less than .0001) with considerable overlap. Patients studied by means of papaverine had a much greater separation in flow reserve between nonischemic and ischemic regions (n = 22, 2.78 +/- 0.19 vs 1.46 +/- 0.14; p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1975

The absence of stimulation of lipolysis by papaverine, a strong inhibitor of phosphodiesterase.

Quantitative studies of the action of theophylline and papaverine were performed in rat epididymal fat pads, both on the lipolytic effect and on the activity of phosphodiesterase, adenylate cyclase and protein kinase. Papaverine, a stronger inhibitor of phosphodiesterase than theophylline, did not produce lipolysis. The maximum lipolytic effect (glycerol release) of theophylline was much higher than that of epinephrine and nearly approached the effect exerted by dibutyryl cyclic AMP. While theophylline potentiated or was without any effect on lipolysis produced by epinephrine and dibutyryl cyclic AMP, papaverine at concentration 10- minus 3 M reduced the effect of both drugs as well as of theophylline by 90 per cent. These concentrations of papaverine also strongly inhibited the activity of adenylate cyclase. Neither papaverine nor theophylline prevented the activation of protein kinase by cyclic AMP. The data suggest that the lack of a lipolytic effect of papaverine migth be caused by a combination of its inhibitory effect on adenylate cyclase and direct inhibition of activation of triglyceride lipase.

Adenylyl Cyclases↗
PubMed1995

Papaverine injures the endothelium of the internal mammary artery.

Intraluminal injection of papaverine may be employed to dilate the internal mammary artery for use as a coronary artery bypass graft. The biochemical and morphological consequences of exposing the endothelium of the internal mammary artery to papaverine have been investigated. Biochemical injury was assessed by measuring changes in basal and vortex-stimulated prostaglandin I2 production, and morphological damage by scanning electron microscopy. Segments of internal mammary artery from 10 patients were placed in one of three solutions; papaverine (1.5 mg/ml of normal saline), normal saline acidified to the pH of the papaverine solution, and normal saline alone. Basal production of prostaglandin I2 was similar in the three groups but vortex-stimulated production was significantly lower in segments stored in papaverine (18.3 pg/mg) and acidified saline (19.1 pg/mg) compared with that of saline alone (43.6 pg/mg). No consistent morphological difference was found by scanning electron microscopy. It was concluded that the low pH of the papaverine solution injured the endothelium of the internal mammary artery.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Dilation of the internal mammary artery by external papaverine application to the pedicle--an improved method.

Spasm of the internal mammary artery (IMA) during coronary bypass grafting may cause inadequate graft flow and makes accurate placement of sutures difficult. In addition, IMAs with poor intraoperative flow rates are more likely to occlude. In this study three methods for spasm prevention were compared in 51 patients undergoing coronary bypass surgery. In group 1, IMA pedicles were covered with a sponge soaked with papaverine solution (0.8 mg/ml of papaverine in 0.9% saline) and left intact distally, thus allowing continuous blood flow until used for bypass. In group 2, the IMAs were divided and clamped distally and the pedicle tucked into a papaverine-soaked sponge. In group 3, the IMAs were also divided distally, clamped, and placed under the upper sternum submerged in papaverine solution (0.8 mg/ml) inside a surgical glove. Free flow from the IMA was higher in group 3 than in groups 1 and 2 (60 ml/min vs. 44 and 30, respectively, P < 0.03). Morphometric measurements disclosed a larger luminal area and less folding of the internal elastic lamina in group 3 compared with groups 1 and 2 (0.73 mm2 vs 0.33 and 0.37, respectively, P < 0.03). Submersion in papaverine solution thus provides better procurement of IMA grafts than storage of the pedicle in a papaverine-soaked sponge.

Adult↗
PubMed2004

Papaverine delivery to the internal mammary artery pedicle effectively treats spasm.

BACKGROUND: Left internal mammary artery spasm is well recognized during coronary artery bypass operations. Papaverine has been used by many surgeons to maximize mammary artery flow perioperatively, but the best delivery method is not known. We analyzed two techniques used at our institution. METHODS: Fifty-eight patients were randomized into three groups to compare papaverine's ability to prevent spasm and to treat established spasm. Group 1 was control and no treatment was employed. In group 2, papaverine was injected with a blunt needle through the endothoracic fascia parallel to the mammary artery before harvest to assess spasm prevention. In group 3, papaverine was delivered perivascular in an identical manner to group 2 but after the mammary artery was dissected from the chest wall. This group was an evaluation of spasm treatment. Drug dosage was the same for both groups and routine bypass grafting was performed. Before anastomosing the mammary artery to the left anterior descending artery, blood flow was recorded for 15 seconds and flow per minute calculated. Cardiopulmonary bypass pressures were maintained at 70 mm Hg during collection. RESULTS: Mean blood flows were: group 1 = 86.2 mL/min, group 2 = 122.5 mL/min, and group 3 = 139.7 mL/min. Left internal mammary artery flow in group 3 was statistically different from control (p = 0.0457). Group 2 flow approached but did not reach statistical significance (p = 0.0874). Mammary artery dissection times for the three groups were not different. CONCLUSIONS: Papaverine delivery to the left internal mammary artery after dissection treats spasm effectively, improves blood flow at the time of its anastamosis to the left anterior descending artery, and avoids any risk of intimal injury. Injection of papaverine before mammary artery harvest does not shorten dissection time, and flow is not statistically improved.

Arterial Occlusive Diseases↗