Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PAPAVERINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1984

Lack of a causal relationship between the vasodilator effect of papaverine and cyclic AMP production in the dog basilar artery.

The effects of papaverine and isoprenaline on smooth muscle cells of the dog basilar artery were investigated using radioimmunoassay, electrophysiological and isometric tension recording methods. For comparative purposes, the actions of these drugs on the guinea-pig basilar artery were also examined. Papaverine and isoprenaline (1 microM and 10 microM) increased the amount of cyclic AMP in both dog and guinea-pig basilar arteries. Papaverine (up to 100 microM) and isoprenaline (up to 1 microM) had no effect on the membrane potential and membrane resistance measured by recording the amplitudes of the electrotonic potentials in smooth muscle cells of the dog and guinea-pig basilar arteries. The action potential evoked by outward current pulses after pretreatment with tetraethylammonium chloride (5-10 mM) was inhibited by papaverine (greater than 1 microM) but not by isoprenaline (up to 10 microM) in smooth muscle cells of the dog and guinea-pig basilar arteries. In the dog basilar artery, papaverine (greater than 1 microM) consistently inhibited the contractions evoked by excess concentrations of [K]o (greater than 20.2 mM) or 5-hydroxytryptamine (10 nM-10 microM), dose-dependently. Isoprenaline (1 microM) had only slight effects on the contraction evoked by low concentrations of 5-hydroxytryptamine (10 nM). In the Ca2+-free solution containing EGTA (2 mM), the contraction evoked by 5-hydroxytryptamine (10 microM) or caffeine (10 mM) was dose-dependently inhibited by papaverine (greater than 1 microM). However, isoprenaline (1 microM) had no effect on these contractions. These results indicate that the vasodilator actions of papaverine on the dog basilar artery are mainly due to inhibition of the voltage-dependent influx of Ca2+ and also to inhibition of the receptor-activated release of Ca2+ stored in the cell. Since isoprenaline increased the cyclic AMP to the same extent as papaverine but had no effect on the electrical and mechanical responses, the inhibitory actions of papaverine on this tissue may not be causally related to the increased levels of cyclic AMP induced by inhibition of phosphodiesterase.

Animals↗
PubMed1984

Inhibition by papaverine of calcium movements and tension in the smooth muscles of rat vas deferens and urinary bladder.

Papaverine, up to 150 micron, was without effect on resting tension of vas deferens and urinary bladder smooth muscle strips, but caused a dose-dependent inhibition of the phasic component of the 100 mM-K contracture. At 150 micron, papaverine caused an 80 and 60% inhibition of phasic tension in vas deferens and urinary bladder muscle respectively. Papaverine caused a marked dose-dependent reduction in the tonic component of 100 mM-K contractures in both preparations. At 150 micron, papaverine often relaxed preparations below initial starting tension. Addition of 150 micron-papaverine to incubation media caused a fall of 25-30% in 45Ca uptake by both preparations. Papaverine at 150 micron caused a small fall in resting 45Ca efflux from vas deferens and a larger fall in efflux from bladder muscle. However, this papaverine concentration caused a large inhibition of the 45Ca uptake by and 45Ca efflux from both preparations when stimulated by high-K depolarization. Papaverine at 150 micron was without significant effect on Ca binding by either microsomes or mitochondria isolated from both vas deferens and urinary bladder smooth muscle. The main site of papaverine action appears to be on the Ca-influx mechanism responsible for regulating Ca entry during prolonged K depolarization.

Animals↗
PubMed1991

Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism.

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.

Adenosine↗
PubMed1982

Mechanism of relaxant action of papaverine. Effect on caffeine-induced contraction of guinea pig taenia coli.

The mode of action of papaverine on smooth muscle relaxation was examined through analyzing its effects on caffeine-induced contraction of guinea pig taenia coli, which might be due to calcium ion mobilized from intracellular store sites. Caffeine contraction induced in normal solution at 32 degrees C was decreased in the presence of papaverine but increased after the removal of papaverine, and it was also increased when the muscle was preincubated with papaverine and then washed out. These papaverine actions were inhibited at low temperature. Caffeine contraction induced in Ca-free, depolarizing solution was also enhanced by treatment with papaverine during Ca-loading. Cyclic AMP and its dibutyryl derivative produced a similar effect on the caffeine contraction induced in normal or Ca-free, depolarizing solution as those of papaverine. In addition, a good correlation was observed between the papaverine-induced increases in caffeine response and in tissue cyclic AMP level. From these results, it is considered that papaverine increases cyclic AMP of the taenia coli, and this increased cyclic AMP stimulates accumulation of calcium ion into its storage sites from where calcium ion was released by caffeine, finally leading to smooth muscle relaxation.

Animals↗
PubMed2000

Inhibitory mechanism of papaverine on the smooth muscle of guinea pig urinary bladder.

In guinea pig urinary bladder, the hyperosmotic 65 mM KCI (H-65K+)- or carbachol (CCh)-induced contraction was inhibited by an addition of papaverine in a concentration-dependent manner. The cAMP content of the muscle in the presence of H-65K+ or CCh was increased by papaverine only at the higher concentration of 100 microM, but cGMP content was not affected by papaverine. Forskolin, compared with papaverine, increased cAMP content in a concentration-dependent manner, and nitroprusside did not significantly increase cGMP content. In a fura 2 loaded muscle, papaverine did not affect an increase of [Ca2+]i level by high K+ or CCh. The increase of oxidized flavoprotein (FPox) fluorescence and muscle contraction in the presence of H-65K+ or CCh was decreased by papaverine (1 - 100 microM), and the increase of pyridine nucleotide (PNred) fluorescence was not affected by papaverine. In summary, it was concluded that papaverine induced relaxation by inhibiting mitochondrial respiration in guinea pig urinary bladder as well as ileum. Moreover, it is proposed that the mechanism of papaverine-induced relaxation in the smooth muscle, which shows predominantly a metabolic dependency on its contraction, is an inhibition of mitochondrial respiration.

Animals↗
PubMed1991

[The meanings of the papaverine test].

Intracavernous administration of papaverine is now commonly employed for diagnosis and therapy of impotence. To assess the pharmacokinetics of papaverine, we recorded its concentration in peripheral blood and also in cavernous blood after intravenous and intracavernous injection of 40 mg of papaverine. Peripheral blood was sampled serially after injection. Plasma was immediately extracted and then kept at at -40 degrees C until analysis. High pressure liquid chromatography was used to record the concentration of papaverine. The maximum serum concentration of papaverine measured after intracavernous injection was 7.7 ng/ml, which was considerably lower than the average serum concentration of 24.0 ng/ml after intravenous injection. Peak serum concentration was reached 1 min after intravenous injection and 10 min after intracavernous injection. It is clear that the corpus cavernosum constitutes a separate pharmacokinetic compartment. Therefore there was no significant difference between the papaverine concentration in peripheral blood of patients who showed full erection after intracavernous injection and that of patients who did not achieve erection. The concentration of papaverine in the intracavernous blood of a fully erected penis was only about 1 microgram/ml after 20 min. This concentration is similar to that in cavernous blood of those who showed excessively persistent erection. Our results imply that papaverine administered into the cavernous space relaxes smooth muscle, and is then washed out to general circulation, and the concentration in the cavernous space reaches a low level of about 1 microgram/ml. The low concentration level is maintained for several hours during erection. Therefore, we presume that papaverine acts on both the inflow system and smooth muscle of cavernous tissue in the phase of producing erections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

[Experimental study on enhancement of tissue expansion with papaverine cream].

OBJECTIVE: To evaluate the effect of external use of papaverine cream on enhancement of tissue expansion. METHODS: 8 mini pigs were randomly divided into 4 groups. During inflation, papaverine was given externally in group A, through a delivery system in group B, though intramuscular injection in group C. Papaverine was not given in group D. The time of inflation, the expansion rate, the surviving length of expanded flaps and the papaverine concentration in the fibrous capsule in each group were examined. Histologic and electroscope examinations of the expanded tissue were made. RESULTS: The average inflation time was 28.9 +/- 4.5 days in group A, 34.0 +/- 2.6 days in group B, 37.6 +/- 4.8 days in group C and 38.5 +/- 3.5 days in group D. There was significant difference between each group(P < 0.05). The average surviving length of expanded flaps in group A was 13.67 +/- 1.28 cm, 11.07 +/- 0.88 cm in group B, 10.79 +/- 0.49 cm in group C, and 9.49 +/- 0.77 cm in group D. There was significant difference between each group (P < 0.01). Histologic examinations of the expanded tissue suggested that there were no significant differences in thickness of epidermis, derma and fibrous capsule among the four groups. Electroscope examinations of the myofibroblast in fibrous capsule showed that there were smaller nuclei, fewer microfilaments and fewer mitochondrias and rougher endoplastic reticulume in group A than those in other groups. The concentration of papaverine in fibrous capsule of group A was 3.5 +/- 1.2 micrograms/g. Papaverine was detected neither in the skin of other groups nor in the blood of all groups. CONCLUSIONS: 1. Papaverine cream can permeate through skin and maintain high concentration and continuous effect in local tissue. 2. External use of papaverine cream can inhabit the function of myofibroblast in fibrous capsule, increase inflation rate, accelerate expansion process, and improve microcirculation of the expanded skin with a result of prolongation of surviving length of expanded flaps. 3. The technique of enhancing tissue expansion with external use of papaverine has the advantages of convenient delivery, cheapness, no more injury and infection, and no side effects etc. It is a safe, effective, simple, and reliable method for accelerating tissue expansion.

Animals↗
PubMed1992

On the mechanism of papaverine inhibition of the voltage-dependent Ca++ current in isolated smooth muscle cells from the guinea pig trachea.

The effects of papaverine, a smooth muscle relaxant agent, on the voltage-dependent Ca++ current were examined in isolated smooth muscle cells from the guinea pig trachea. The tight-seal whole cell voltage clamp technique was used. Papaverine (1-100 microM) inhibited the Ba++ inward current (IBa) through the voltage-dependent L-type Ca++ channel in a concentration-dependent fashion. The inhibitory effect of papaverine on IBa appeared to have both tonic and use-dependent components. In addition to the reduction of the maximal conductance of IBa, papaverine (20 microM) shifted the quasi-steady-state inactivation curve of IBa to more negative membrane potentials by approximately 10 mV. These effects of papaverine on IBa were completely reversible. Although it has been suggested that papaverine inhibited phosphodiesterase to increase intracellular cyclic AMP, phosphodiesterase inhibitors (theophylline, 500 microM, and 3-isobutyl-1-methylxanthine, 500 microM), isoproterenol (2 microM) and dibutyryl cyclic AMP (1 mM) did not affect IBa. Thus, papaverine inhibits IBa in a way independent of intracellular cyclic AMP. Papaverine also had inhibitory effects on other membrane currents (i.e., the voltage-dependent transient outward K+ current and the Ca(++)-activated oscillatory K+ current), which may result in an enhancement of the excitability of the cells. These results suggest that inhibition of the voltage-dependent L-type Ca++ channel is involved in the papaverine-induced relaxation of the tracheal smooth muscle.

Animals↗
PubMed1984

Influence of papaverine on spontaneous activity of isolated right atria from small mammals.

The effects of papaverine and verapamil were studied in spontaneously beating right atria of guinea pigs, rabbits and rats and on segments of sinoatrial node tissue from rabbits. Papaverine (10(-4)M) produced a significant negative chronotropic effect in guinea pigs and rats, with a lesser effect in rabbits. Papaverine antagonized the positive chronotropic response to transmural nerve stimulation (TNS) of the sinoatrial node of rabbit atria in a concentration-dependent manner. The chronotropic response to 5 X 10(-7)M norepinephrine was enhanced in the presence of 10(-6)M papaverine, but was noncompetitively antagonized at concentrations above 10(-5)M. The negative chronotropic response to TNS was unaltered by papaverine except at concentrations at or above 5 X 10(-5)M; however, the negative chronotropic response to 5 X 10(-6)M methacholine was not altered by 10(-4)M papaverine. A local anesthetic (lidocaine) inhibited both the positive and negative chronotropic TNS response at a concentration that had no effect on the response to exogenous norepinephrine. Verapamil (10(-7) to 10(-6)M) had no significant effect on either the positive or negative chronotropic response to TNS. The effects of papaverine on TNS are attributed to the influence of at least three actions: 1) phosphodiesterase inhibition, 2) local anesthetic activity and 3) physiological antagonism of norepinephrine. The effects of 2 X 10(-4)M papaverine on action potentials of rabbit sinoatrial node cells were studied. Papaverine decreased the maximum diastolic potential, increased the action potential overshoot and transformed the normal ramp configuration of slow diastolic depolarization into a concave shape.

Action Potentials↗
PubMed1998

Papaverine solutions cause loss of viability of endothelial cells.

OBJECTIVE: The optimal composition of the solution used for irrigation of saphenous veins used for cardiac surgery may influence ultimate graft patency due to potential injurious effects on the vein endothelium of some of the solution constituents. EXPERIMENTAL DESIGN: The viability of cultured saphenous vein endothelial cells was assessed after incubation of saphenous vein endothelial cells with solutions containing saline, saline with papaverine (0.15 M NaCl, 32.5 mg/mL papaverine), culture medium and buffered saline solution (Plasma-Lyte-A). RESULTS: Cell viability was significantly decreased after one hour incubation with solutions containing saline with papaverine (24.4+/-9.4%) as compared to culture medium and buffered saline solutions (medium 100%, Plasma-Lyte-A 86.8+/-6.90%). Loss of viability was directly related to the length of exposure of the cultured cells to papaverine. Morphologic changes of cells incubated with saline: papaverine were also seen including cell retraction and nuclear pyknosis. The cells exposed to medium recovered 100% viability whereas by 4 hours only 22% of the saline: papaverine cells were viable, and by 3 days this viability had fallen to 7.7%. CONCLUSIONS: Loss of viability was shown in cultured saphenous vein endothelial cells exposed to saline solutions containing papaverine, whereas no difference was found between culture medium, saline and balanced salt solutions. Cell death was directly related to the length of exposure of the cells to papaverine. Further, after short- and long-term recovery periods, there was little recovery of cell viability. Although papaverine is a potent vasodilator, exposure to this compound may compromise long-term viability of graft endothelial cells.

Cell Death↗
PubMed1998

Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm.

PURPOSE: Intraarterial papaverine infusions are performed to reverse cerebral arterial vasospasm resulting from subarachnoid hemorrhage, but such infusions may lead to increases in intracranial pressure (ICP). This study was undertaken to determine when ICP monitoring is indicated during papaverine treatment. METHODS: Seventy-eight vessels were treated in 51 sessions in 28 patients with symptomatic vasospasm. ICP, papaverine doses, and infusion rates were recorded during treatment sessions. The procedural data, Hunt and Hess scores, Fisher grades, Glasgow Coma Scale scores, and ages for all subjects were reviewed and analyzed retrospectively. RESULTS: Baseline ICP ranged from 0 to 34 mm Hg. With typical papaverine doses of 300 mg per territory and infusion times ranging from 5 to 60 minutes per vessel, ICP increases above baseline during papaverine infusion ranged from 0 to 60 mm Hg. Significant (> or = 20 mm Hg) ICP increases during therapy were observed even in patients with low baseline ICP and with papaverine infused at the slowest rate. Patients with a baseline ICP of more than 15 mm Hg were much more likely to have significant ICP increases than were patients with a baseline ICP of 0 to 15 mm Hg. Hunt and Hess scores, Fisher grades, age, and Glasgow Coma Scale scores on admission and immediately before treatment did not correlate with ICP increases during papaverine infusion. Patients with ICP increases of more than 10 mm Hg during therapy were more likely to experience adverse clinical events than were patients with ICP increases of < or = 10 mm Hg. Reduction in the rate of papaverine infusion, or termination of infusion, resulted in reversal of drug-induced ICP elevation. CONCLUSION: ICP monitoring during intraarterial papaverine infusions for cerebral vasospasm is recommended for all patients and is particularly important for patients with elevated baseline ICP. Continuous ICP monitoring facilitates safe and time-efficient drug delivery.

Age Factors↗
PubMed1992

Papaverine inhibits transcytotic vesicle transport and lipid excretion into bile in isolated perfused rat liver.

Papaverine is a nonspecific smooth muscle relaxant and a phosphodiesterase inhibitor. Its effects on biliary excretion of lipids and horseradish peroxidase were investigated in a single-pass isolated perfused rat liver model. A constant infusion of papaverine (1.6 mumol/min; 40 mumol/L) significantly increased bile flow (microliters per minute per gram of liver) before (2.03 +/- 0.09 vs. 1.0 +/- 0.06) and after sodium taurocholate infusion (2.77 +/- 0.10 vs. 1.88 +/- 0.11). However, papaverine significantly and reversibly reduced biliary excretion of phospholipids and cholesterol (nanomoles per minute per gram of liver) after a 1.0 mumol/min sodium taurocholate infusion, from 7.45 +/- 0.83 and 1.42 +/- 0.15 to 1.75 +/- 0.18 and 0.39 +/- 0.06, respectively (p less than 0.01), whereas secretion of bile acids was unaffected. When a 1-min pulse of horseradish peroxidase (25 mg) was infused in isolated perfused rat liver after a continuous infusion of N6,O-2'-dibutyryladenosine 3',5'-cyclic monophosphate (0.25 mumol/min; 6.25 mumol/L), horseradish peroxidase appeared in bile in an early (4 to 6 min) and late (20 to 25 min) peak. Papaverine significantly reduced the late peak, from 1.211 +/- 0.264 to 0.498 +/- 0.107 (p less than 0.01). Papaverine had no significant effects on either cyclic AMP or cyclic GMP in the liver and bile, although it has been reported that papaverine is a phosphodiesterase inhibitor. These findings indicate that papaverine inhibits biliary excretion of lipids but not bile acids, and they suggest that papaverine has an inhibitory effect on transcytotic vesicle transport independent of an increase of cyclic nucleotides in hepatocytes.

Animals↗
PubMed1992

Contraction and relaxation of human internal mammary artery after intraluminal administration of papaverine.

The internal mammary artery has become the conduit of choice for coronary artery bypass grafting. Intraluminal papaverine treatment during operation reduces vasospasm and facilitates anastomosis. However, it has been suggested that papaverine may cause intimal damage, and accordingly we have investigated endothelial damage by comparing the responsiveness of internal mammary arteries before and after intraluminal exposure to papaverine (15 mg/mL). Control and papaverine-treated segments of internal mammary artery were obtained from 13 patients undergoing coronary artery bypass grafting and mounted as ring preparations in an organ bath. Cumulative dose contractions to noradrenaline were performed, and the dose producing a half maximal response was determined. Relaxation studies of submaximally contracted arteries were performed using the endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator sodium nitroprusside. In the human internal mammary artery the use of intraluminal papaverine increased the lumen size by 20% (p less than 0.05), and the contractions elicited by noradrenaline were significantly less in the papaverine group than in the control group (p less than 0.05). Endothelium-dependent relaxation to acetylcholine or bradykinin was not affected by papaverine treatment. Endothelium-independent relaxation was the same in both groups, with almost 100% relaxation achieved by sodium nitroprusside. These results indicate that intraluminal papaverine treatment during coronary artery bypass grafting causes a reduction of smooth muscle contraction and does not impair endothelium-dependent relaxation.

Acetylcholine↗
PubMed1991

Global and regional ventricular function following intracoronary application of papaverine.

Intracoronary injection of papaverine is used to determine coronary flow reserve in patients. The present study was to investigate the effect of papaverine on the performance of myocardium with reduced flow reserve. In nine anaesthetized open-chest dogs a bypass from the aorta to the left circumflex coronary artery (LCX) was established. Left ventricular end-diastolic and aortic pressure, dP/dt, stroke volume, LCX blood flow, and ECG were monitored. The performance of a segment of subendocardial wall supplied by the LCX was assessed by sonomicrometry. Peak reactive hyperaemia after 15s bypass occlusion was 1.44 +/- 0.09 times the baseline flow (41 ml/min), indicating reduced coronary flow reserve. Papaverine was injected into the bypass (0.3, 0.6, 1.2, 2.5, 5.0 mg/ml, 1 ml in 15s). The maximum LCX flow following PAPA 0.3 mg was comparable to peak reactive hyperaemia, but 10-15% higher after injection of 0.6-5.0 mg papaverine. Systolic shortening of the myocardium (control: 17.5% of end-diastolic length) became reduced in a dose-dependent fashion (5-25%) for about 1 min following papaverine injection. Stroke volume (control: 0.94 +/- 0.12 ml/kg) was reduced by about 8%, left ventricular end-diastolic pressure (control: 6.2 +/- 0.8 mmHg) increased by 15%, and dP/dtmin (control: 1850 +/- 150 mmHg/s) was curtailed by 15-25%. The ECG showed a transient T inversion and S-T depression following papaverine administration and in one experiment ventricular fibrillation occurred after the injection of 2.5 mg papaverine. The observed effects of intracoronary papaverine are consistent with the theory of transient subendocardial ischaemia arising from a redistribution of blood flow from the subendocardial to the subepicardial layers, because of greater vasodilatory capacity in the latter than in the former.

Animals↗
PubMed1996

Effect of normothermic papaverine to relieve intraoperative spasm of the internal thoracic artery.

BACKGROUND: After mobilization, vasospasm often reduces flow through the internal thoracic artery. An established method of relaxing the artery and increasing flow is to use papaverine at ambient temperature (20 degrees to 22 degrees C) as a topical vasodilator. However, the pharmacologic actions of papaverine generally have been assessed at 37 degrees C. METHODS: In 60 patients in whom the left internal thoracic artery was used for myocardial revascularization, we investigated the effects of normal saline solution at 20 degrees C (group I), papaverine at 20 degrees C (group II), and papaverine at 37 degrees C (group III). Under controlled hemodynamic conditions, free flow was measured before any pharmacologic intervention and a median of 16 minutes after the pedicle had been sprayed with one of the agents. RESULTS: Normal saline solution at 20 degrees C produced a small increase in flow from 37.5 +/- 8.1 mL/min to 50 +/- 10.2 mL/min. A significant increase occurred with papaverine at 20 degrees C, from 38.05 +/- 6.5 mL/min to 78.75 +/- 21.2 mL/min (p < 0.0001). Papaverine at 37 degrees C, however, produced an increase in flow from 36.9 +/- 12.6 mL/min to 103.3 +/- 44.6 mL/min (p < 0.0001) and proved to be more effective than papaverine at room temperature (p = 0.0174). CONCLUSIONS: We recommend topical use of papaverine at 37 degrees C to relieve intraoperative spasm of the internal thoracic artery.

Administration, Topical↗
PubMed1998

The difference in the inhibitory mechanisms of papaverine on vascular and intestinal smooth muscles.

Papaverine (0.3-100 microM) more potently inhibited phenylephrine (1 microM)-induced contraction than 65 mM K+-induced contraction of the aorta, while it equally inhibited contractions induced by 65 mM K+ and carbachol (1 microM) in ileal smooth muscle. In phenylephrine-treated aorta, papaverine (1-10 microM) increased the cAMP and cGMP content. However, in carbachol-treated ileum, 30 microM papaverine partially increased the cAMP content while it maximally relaxed the preparation. In fura2-loaded aorta, papaverine (0.3-10 microM) inhibited both the contraction and the increase in intracellular Ca2+ level ([Ca2+]i) induced by phenylephrine in parallel. However, papaverine inhibited carbachol-induced contraction with only a small decrease in [Ca2+]i. Papaverine (1-30 microM) inhibited the carbachol-induced increase in oxidized flavoproteins, an indicator of increased mitochondrial oxidative phosphorylation, in ileal smooth muscle whereas it did not change the phenylephrine-induced increase in the aorta. These results suggest that papaverine inhibits smooth muscle contraction mainly by the accumulation of cAMP and/or cGMP due to the inhibition of phosphodiesterase in the aorta whereas, in ileal smooth muscle, papaverine inhibits smooth muscle contraction mainly by the inhibition of mitochondrial respiration.

Animals↗
PubMed1995

Dilation of the internal mammary artery by external and intraluminal papaverine application.

Three methods for prevention of perioperative spasm of the internal mammary artery were compared in 78 patients undergoing coronary artery bypass grafting. In group 1, internal mammary artery pedicles were divided distally, clamped, and placed under the upper sternum submerged in papaverine solution (1.5 mg/ml). In group 2, as in group 1 but before clamping, 2 ml of heparinized blood with 1.5 mg/ml papaverine added was injected into the vessel lumen. In group 3 treatment was as in group 2, but heparinized blood with papaverine was injected a second time just before extracorporeal bypass was begun. In a univariate analysis free flow from dilated internal mammary arteries was not significantly different among the groups (group 1, 58 ml/min; group 2, 82 ml/min; group 3, 68 ml/min; p < 0.1). When free flow from dilated internal mammary arteries was the dependent variable in a regression analysis, the use of intraluminal papaverine, high blood pressure during flow measurement, and high initial blood flow were predictors of high flow (all p < 0.01). Morphometric measurements on the resected distal portion of the dilated internal mammary arteries disclosed less folding of the internal elastic lamina and a larger luminal area in groups 2 and 3 compared with respective findings in group 1 (1.21 mm2 and 1.42 mm2 versus 0.77 mm2; p < 0.02). Mechanical vessel wall injury occurred in 8 of 52 internal mammary arteries treated with intraluminal papaverine. Intraluminal papaverine solution injected once or twice in addition to external papaverine exposure therefore provides a better blood flow rate and distal dilation than mere submersion in papaverine solution, but at a considerable risk of mechanical wall injury.

Adult↗
PubMed1991

Inhibition of wound contraction by papaverine: in vitro analysis with a submucosal tissue model.

We studied the effect of topical application of papaverine, a smooth-muscle relaxant, on the contraction of open, dorsal skin wounds in rats. Wound contraction was inhibited significantly in papaverine-applied wounds compared with saline-dressed control wounds. The in vitro effect of papaverine on wound contraction was studied by using human oral fibroblasts cultured three-dimensionally in the hydrated collagen gels containing papaverine. Papaverine inhibited collagen gel contraction in a dose-dependent manner. Any change in actin filament organization in fibroblasts cultured three-dimensionally in the collagen gels was observed by staining the filaments with fluorescent dye-conjugated phalloidin. In the control cultures, well-organized stress fibers were formed in the cell projections; in papaverine-treated fibroblasts, during the early stages of the treatment, the stress fibers were disrupted and actin filament aggregation was observed. In addition, papaverine induced a delay in the formation of the processes in fibroblasts cultured in collagen gels. These results indicate that wound contraction inhibition by papaverine is mediated by its effects on the organization of actin filaments of fibroblasts.

Actins↗