Efficacy of combined administration of intracoronary papaverine plus intravenous adenosine 5'-triphosphate in assessment of fractional flow reserve.

BACKGROUND: Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Intravenous adenosine and adenosine 5'-triphosphate (ATP) have been used to achieve maximal hyperemia. However, they may not induce maximal hyperemia in all patients. The present study evaluated the combined effect of intracoronary papaverine and intravenous ATP on FFR measurements. METHODS: FFR measurements with administration of intracoronary papaverine (12mg in the left coronary artery and 8mg in the right coronary artery), intravenous ATP (140µg/kg/min), and combined administration of intracoronary papaverine and intravenous ATP were performed in 51 patients with 57 intermediate lesions. RESULTS: The mean FFR after intravenous ATP was higher compared to intracoronary papaverine and intravenous ATP plus intracoronary papaverine (0.76±0.13 vs. 0.75±0.13 vs. 0.75±0.13, p=0.01). FFR-positive lesions (FFR ≤0.80) were observed more frequently with intravenous ATP plus intracoronary papaverine compared to intravenous ATP (64.9% vs. 47.4%, p=0.02). Of 32 and 25 FFR-negative lesions with intravenous ATP and intracoronary papaverine, 11 (34%) and 7 (28%) had positive FFR after administration of intravenous ATP plus intracoronary papaverine. No ventricular tachycardia or ventricular fibrillation was observed after administration of intracoronary papaverine. CONCLUSIONS: Maximal hyperemia may not be induced with intravenous ATP in all lesions. When sufficient hyperemia is doubtful during intravenous infusion of ATP, additional intracoronary administration of papaverine may be a possible option.

Assessment of lower limb flow and adequate intra-arterial papaverine doses to achieve maximal hyperemia in elder subjects.

Previous studies reported that invasive physiological assessment for significance of the lesions in the patients with claudication under the condition of pharmacological hyperemia was important to identify the patients who will benefit from revascularization. However, the maximal hyperemic response in lower limb and the method to induce maximum dilatation of vascular bed in lower limb were not well established. The aim of this study was to investigate the range of maximal hyperemic response in lower limb of the normal subjects and to identify the ideal lower limb vasodilatory stimulation. Twelve limbs without stenotic lesions from 12 subjects (average age: 72 ± 6 years) were analyzed. Thermodilution-derived mean transit time (Tmn) was obtained at baseline and during pharmacological hyperemia with incremental dose of intra-arterial papaverine (10, 20, 30, and 40 mg) using a 0.014-inch pressure/temperature sensor-tipped wire in the superficial femoral artery (SFA). Percent increase in blood flow (%IBF) of lower limb was defined as the ratio between baseline Tmn and hyperemic Tmn. Mean ankle brachial index score of the subjects was 1.14 ± 0.09. The %IBF values were enhanced by papaverine in a dose-dependent manner. A dose of 30 mg of intra-arterial papaverine was sufficient to achieve maximum hyperemia (%IBF: range 219-769 %). In conclusion, the increase in blood flow of lower limb during maximal hyperemia varied between individuals and maximal hyperemia can be achieved with 30 mg of papaverine for the SFA lesion.

Invasive assessment of the coronary microcirculation using the index of microcirculatory resistance: description and validation of an animal model.

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-µm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Erectile dysfunction in spinal cord injury: a cost-utility analysis.

BACKGROUND: There is a high incidence of erectile dysfunction after spinal cord injury. This can have a profound effect on quality of life. Treatment options for erectile dysfunction include sildenafil, intracavernous injections of papaverine/alprostadil (Caverject), alprostadil/papaverine/phentolamine ("Triple Mix"), transurethral suppository (MUSE), surgically implanted prosthetic device and vacuum erection devices. However, physical impairments and accessibility may preclude patient self-utilization of non-oral treatments. METHODS: The costs and utilities of oral and non-oral erectile dysfunction treatments in a spinal cord injury population were examined in a cost-utility analysis conducted from a government payer perspective. Subjects with spinal cord injury (n=59) reported health preferences using the standard gamble technique. RESULTS: There was a higher health preference for oral therapy. The cost-effectiveness results indicated that sildenafil was the dominant economic strategy when compared with surgically implanted prosthetic devices, MUSE(R) and Caverject. The incremental cost-utility ratios comparing sildenafil with triple mix and vacuum erection devices favoured sildenafil, with ratios less than CAN$20,000 per quality adjusted life year gained. CONCLUSION: Based on this study, we conclude that sildenafil is a cost-effective treatment for erectile dysfunction in the spinal cord injury population.

Clinical and duplex US assessment of effects of sildenafil on cavernosal arteries of the penis: comparison with intracavernosal injection of vasoactive agents--initial experience.

PURPOSE: To prospectively evaluate the clinical response and hemodynamic changes in cavernosal arteries after oral administration of sildenafil without and with audiovisual sexual stimulation and to compare those responses with responses from intracavernosal injections of vasoactive agents. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Thirteen consecutive patients (age range, 22-77 years; mean, 60.4 years) with erectile dysfunction were evaluated with clinical assessment and cavernosal duplex ultrasonography (US). The patients were examined at two sessions 3 weeks apart. First, each patient received 100 mg of sildenafil citrate orally and was examined 60 minutes later without any sexual stimulation. Each patient then underwent repeat clinical and duplex US assessment after audiovisual sexual stimulation. Three weeks later, the patients underwent identical clinical evaluation and duplex US after intracavernosal injection of a commercially available combination of papaverine, prostaglandin E1, and phentolamine. Clinical and duplex US data (ie, peak systolic velocity [PSV]) were examined by using the Wilcoxon signed rank test for matched pairs. RESULTS: At rest, the overall mean cavernosal artery PSV was 1.08 cm/sec and remained unchanged after intake of sildenafil without any audiovisual stimulation, with no clinical evidence of erection. With the addition of audiovisual sexual stimulation, eight (62%) of 13 patients had penile congestion or erection, and six (46%) had a PSV greater than 25 cm/sec. With intracavernosal injection of the combination of three drugs, all 13 patients achieved congestion or erection, and 10 (77%) had a PSV greater than 25 cm/sec. Both clinical and duplex US responses to intracavernosal injection were significantly greater than they were to sildenafil with audiovisual sexual stimulation (P = .04 and .003, respectively). CONCLUSION: Oral sildenafil with audiovisual sexual stimulation led to a significant clinical response and increment in blood flow in the cavernosal arteries. However, more patients responded to intracavernosal injection of the combination of three drugs than to sildenafil, and the clinical response was significantly better.

Clinical and sonographic assessment of the side effects of intracavernous injection of vasoactive substances.

The objective of this study is to evaluate the side effects of intracavernous vasoactive agents on clinical and sonographic basis. Two groups of patients were included, group I included 168 ED patients trained on self-injection therapy using one of the three protocols. Protocol A: papaverine; protocol B: PGE1; and protocol C: trimix (papaverine, phentolamine and PGE1). Patients were followed up clinically, sonographically and by laboratory investigations for 6 months to evaluate the occurrence of side effects. Group II included 21 patients presenting to our department for the first time with a complication of intracavernous injection pharmacotherapy (ICI) initiated elsewhere. In all, 168 patients of group I completed the study. Patients on papaverine had the highest incidence of complications concerning prolonged erection, subcutaneous hematoma and penile fibrosis. Postinjection penile pain was observed more with groups B and C than group A. No systemic side effects were reported. Duplex ultrasound was beneficial in detecting mild clinically impalpable fibrosis. In total, 10 patients of group II presented with prolonged erection, seven with penile fibrosis, three with cavernositis and one with intracavernous needle breakage. We conclude that although ICI therapy is an effective second-line treatment option, patients on a self-injection program should be followed up both clinically and sonographically both at the initiation phase and on regular follow-up visits.

The incidence and management of priapism in Western Australia: a 16 year audit.

The objective of the study was to conduct a retrospective audit of patients who presented with priapism in Western Australia during the years 1985-2000. We searched the records of the teaching hospitals in metropolitan Perth and those of the Keogh Institute for Medical Research for the diagnostic code for priapism. A total of 82 episodes of priapism in 63 patients occurred over this 16 year period. In all, 62 episodes occurred after intracavernosal injections (ICI) and 20 were due to other causes. Treatment of priapism included simple aspiration of blood, intracavernosal injection of alpha-adrenergic agents and surgical shunt procedures. Priapism occurring outside the setting of ICI was more likely to require surgery; seven of 20 episodes. After ICI therapy, eight of 62 episodes required shunts. The use of prostaglandin E1 as the drug of choice in ICI therapy in 1989 led to a fall in the incidence of ICI-induced priapism. Priapism is a major side effect of ICI therapy and an uncommon, although important, side effect of other conditions. The incidence of priapism has fallen with the introduction of prostaglandin E1 monotherapy as the favoured drug for ICI therapy of erectile failure.

[Erectile disorders: the reality]. / Erectiestoornissen: de actuele situatie.

The grouping together of erectile dysfunction and erectile disorder (i.e. dysfunction with distress) has led to the presentation of incredibly high prevalences (up to 52%). When limited to erectile disorder, two Dutch open population studies, among men aged 40-79 years, show remarkably similar and more realistic prevalences, namely 3 to 10%. Although the 'Leiden Impotence Screening Test' appears to reliably exclude somatic aetiological factors, it would be preferable if the general physician posed such diagnostic questions. It is hoped that the availability of pharmacotherapeutic treatments (notably sildenafil) will not tempt the general physician to join the patient in his inclination to 'somatise' his erectile disorder. Both intracavernosal self-injection therapy and the implantation of an erectile prosthesis give rise to a large proportion of dissatisfied men. In the Netherlands to date, the number of continuation prescriptions for sildenafil equals the number of first prescriptions, which suggests that many men also stop with this therapy. In the Netherlands, health insurance companies only reimburse self-injections and prosthesis implantations. It can be argued that all cost-effective treatments for erectile disorder, including psychosexual therapy, should be reimbursed, or none at all.

Cost utility analysis of sildenafil compared with papaverine-phentolamine injections.

OBJECTIVE: To compare the cost effectiveness of sildenafil and papaverine-phentolamine injections for treating erectile dysfunction. DESIGN: Cost utility analysis comparing treatment with sildenafil (allowing a switch to injection therapy) and treatment with papaverine-phentolamine (no switch allowed). Costs and effects were estimated from the societal perspective. Using time trade-off, a sample of the general public (n=169) valued health states relating to erectile dysfunction. These values were used to estimated health related quality of life by converting the clinical outcomes of a trial into quality adjusted life years (QALYs). PARTICIPANTS: 169 residents of Rotterdam. MAIN OUTCOME MEASURES: Cost per quality adjusted life year. RESULTS: Participants thought that erectile dysfunction limits quality of life considerably: the mean utility gain attributable to sildenafil is 0.11. Overall, treatment with sildenafil gained more QALYs, but the total costs were higher. The incremental cost effectiveness ratio for the introduction of sildenafil was pound sterling 3639 in the first year and fell in following years. Doubling the frequency of use of sildenafil almost doubled the cost per additional QALY. CONCLUSIONS: Treatment with sildenafil is cost effective. When considering funding sildenafil, healthcare systems should take into account that the frequency of use affects cost effectiveness.

Assessment of coronary artery stenosis during PTCA by measurement of the trans-stenotic pressure gradient. Comparison with quantitative coronary angiography.

A fibreoptic pressure sensor mounted on an 0.018 inch guidewire (Pressure Guide, RadiMedical Systems, Uppsala, Sweden) was used to measure the trans-stenotic pressure gradient in 20 patients admitted for percutaneous transluminal coronary angioplasty (PTCA) of a single, discrete stenosis. Pressure measurements were made both at rest and during maximal vasodilatation induced by intracoronary injection of papaverine. From the ratio of distal coronary pressure divided by the proximal pressure, the relative coronary flow reserve was calculated. The aim of the study was to compare the different pressure-derived parameters by correlating them to stenosis geometry estimated by quantitative coronary angiography. There was a moderate correlation between baseline pressure gradient and percent area stenosis; r = 0.64, P < 0.001 and minimal cross-sectional area; r = 0.45, P < 0.005. A higher correlation was found between hyperaemic pressure gradient and area stenosis (r = 0.80, P < 0.001) and minimal cross-sectional areas, respectively (r = 0.55, P < 0.005). The best correlation was found between relative coronary flow reserve and area stenosis (r = 0.86, P < 0.001) and minimal cross-sectional area (r = 0.70, P < 0.001). In conclusion, pressure measurement using a pressure guidewire is useful as a complement to angiography in evaluation of coronary stenoses during PTCA. Pressures should be measured during maximal vasodilatation. Relative coronary flow reserve calculated from the pressure measurements provides additional information about the fraction of normal maximal flow possible in the presence of a stenosis.

The clinical assessment of erectile dysfunction: a comparison of nocturnal penile tumescence monitoring and intracavernosal injections.

One hundred and fifty-nine men with erectile dysfunction were assessed with Rigiscan monitoring of nocturnal penile tumescence (NPT) and response to intracavernosal injections (ICI) of papaverine or prostaglandin E1. A satisfactory NPT, suggestive of psychogenic causation, was recorded in 58%, whereas 15% had clearly impaired NPT. There was a significant association between presence of vascular disease, diabetes and impairment of NPT. For ICI, only 32% showed a satisfactory response, with 48% clearly impaired. Of the 92 men with satisfactory NPT, 40% HAD clearly impaired and 41% satisfactory ICI response. Of the 51 men with satisfactory ICI response, 8% had clearly impaired and 74.5% satisfactory NPT. There was no association between ICI response and history of vascular disease. We conclude that monitoring of NPT by Rigiscan, and without sleep monitoring, is a valuable diagnostic procedure. In contrast, because of the high proportion of false negative results. ICI monitoring is of very limited diagnostic value. The explanation for false negative ICI responses, however, could prove to be of considerable theoretical and clinical importance.

Experience with triple-drug therapy in a pharmacological erection program.

A group of 170 impotent men achieved usable erections during a 26-month period with a combination of papaverine, phentolamine and prostaglandin E1 (triple-drug therapy) injected intracorporeally. Of the patients 146 elected to enter a pharmacological erection program using this combination. Patient age ranged from 24 to 85 years and the average duration on the program was 11.2 months. Average injection volume was 0.36 cc per injection (range 0.1 to 1). Among those patients managed by our nurse clinician, only 3 episodes of priapism were encountered (1.7%). Scarring was documented in 7 of 170 patients (4.2%) 1 week to 21 months after starting the injections. Pain was encountered in 6 of 170 patients (3.5%). A superior dose response coupled with a low incidence of priapism, pain and scarring have led us to use triple-drug therapy as our agent of choice in the pharmacological management of erectile dysfunction.

Assessment of penile blood flow by duplex ultrasonography in 44 men with normal erectile potency in different phases of erection.

Duplex ultrasonography is important in the diagnosis of vasculogenic erectile dysfunction. We measured the ultrasonographic parameters of cavernous blood flow in different phases of penile erection. We examined 44 volunteers with normal erectile potency. Doppler spectra of the cavernous artery were obtained in a time-dependent manner after intracavernous administration of papaverine. Following intracavernous pharmacological stimulation, the Doppler spectrum alters according to a specific pattern indicating the different hemodynamic phases of erection. Peak flow velocity and acceleration time, measured in the early post-injection phase, may be used to grade arterial inflow. The difference between resistance index in the pre-injection and late post-injection phases may be used to estimate veno-occlusive function. References values are defined.

Erectile response to visual erotic stimuli before and after intracavernosal papaverine, and its relationship to nocturnal penile tumescence and psychometric assessment.

Three methods of assessing erectile capacity--nocturnal penile tumescence (NPT), response to visual erotic stimuli (VES) and to intracavernosal papaverine (ICI)--have been assessed in 42 men presenting with erectile dysfunction. There was some overlap but also important differences between the 3 measures. Subjects were divided into "high" and "low" NPT groups. The "high" group produced greater erectile responses to both VES and ICI. The combination of VES and ICI was the best discriminator of the two NPT groups, and may be of diagnostic value, particularly in younger men, reducing the need for repeated injections and higher doses of papaverine. In the "low" NPT group, presumed predominantly organic, the ICI response correlated better than the VES response with NPT. In the "high" NPT group, the opposite applied, suggesting that in "psychogenic" cases, response to ICI may be modified by psychological mechanisms which could be of aetiological importance and which deserve further study. These three methods should be regarded as measuring different aspects of erectile function and not as alternative diagnostic procedures. More research is required before their respective diagnostic values are established.

Diagnosis and treatment of impotence.

Among the common procedures used in the diagnosis of impotence, neither nocturnal penile tumescence testing nor inhome monitoring devices designed to measure tumescence or rigidity is regarded as reliable for evaluating impotence. Plethysmography as a nonspecific test of vascular competence is increasingly being supplanted by Doppler ultrasound as a safe and effective diagnostic modality. Arteriography, cavernosography, and cavernosometry are established techniques for evaluating penile vasculature. Intracavernosal injection of smooth muscle relaxing drugs, endocrine assays, and electrophysiological testing are widely used for the diagnosis of impotence. Excluding implanted devices, and intracavernosal injections. Aortoiliac reconstruction, endarterectomy, or arterial dilatations are regarded as safe and effective for the treatment of proximal occlusive lesions, and venous leakage surgery is regarded as investigational. Intracavernosal injections are widely employed in clinical environments and for self-injection at home. However, this currently represents the use of FDA-approved drugs for an unlabeled indication. The use of external vacuum devices has achieved widespread use and is regarded as being safe and effective for the treatment of impotence.

Impotence. Assessment in the private-practice office.

Impotence can have a psychogenic or organic basis, or a combination of both. Many times the partial erection or inability to maintain the erection is at least somewhat the result of the aging process. Once the cause has been established, through careful history taking and appropriate testing, the physician, along with the patient and his partner, can choose the most desirable treatment method. With patience and realistic expectations, the patient can usually achieve a satisfactory resolution of the problem.

Value and limitations of intracoronary adenosine for the assessment of coronary flow reserve.

An ideal coronary vasodilator for studying coronary flow reserve should rapidly produce a maximal hyperemic response, be short acting to permit repeated measurements, and not alter systemic hemodynamics. We measured with a Doppler tip balloon catheter, in 12 patients before and/or after percutaneous transluminal coronary angioplasty the hyperemic response following 12.5 mg intracoronary papaverine and following gradually incremental bolus injections of intracoronary adenosine, starting from 0.05 mg until a maximal hyperemic response or side effects. The mean dose (+/- SD) of adenosine needed to produce maximal hyperemia was 0.23 (+/- 0.20 mg). Coronary blood flow velocity after adenosine increased to 1.6 +/- 0.3 times resting coronary blood flow velocity, comparable in magnitude to the hyperemia following intracoronary papaverine. The time from injection to peak effect after adenosine was 7.4 (SD +/- 2.2) sec and after papaverine 26 (SD +/- 7) sec. Adenosine resulted in a bradyarrhythmia in three patients. Intracoronary adenosine is a potent and very short acting vasodilator for studying coronary flow reserve, but the side effects and unpredictability of the dosage needed to produce maximal hyperemia may limit its applicability.