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PubMed2000

Comparison of oral and intracavernosal vasoactive agents in penile erection.

This discussion summarizes the potential differences in physiologically and pharmacologically induced erections and highlights the possible differences in the pathways facilitated by oral versus intracavernosal agents in penile erection. Oral agents act in conjunction with sexual stimulation either increasing corporal smooth muscle relaxation or attenuating smooth muscle contraction. However, their efficacy is dependent on sexual stimulation. Intracavernosal administration of phosphodiesterase type 5 inhibitor (sildenafil) or short-acting alpha adrenergic receptor antagonist (phentolamine), in the absence of sexual stimulation, does not initiate penile erection. In contrast, intracavernosal administration of PGE1 or papaverine induces erection independent of sexual stimulation. Thus, oral agents are not direct mediators of smooth muscle relaxation and act to facilitate relaxation in response to sexual stimulation, while intracavernosal agents directly mediate smooth muscle relaxation, independent of sexual stimulation. Although, considerable advances have been made in elucidating the physiology and pharmacology of erectile function, details of the signal transduction pathways affected by these agents in the penile corpus cavernosum are yet to be fully investigated. International Journal of Impotence Research (2000) 12, Suppl 1, S81-S88

Journal Article↗
PubMed2002

[Methylene blue: an effective therapeutic alternative for priapism induced by intracavernous injection of vasoactive agents].

OBJECTIVE: Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. Etiologies of this condition are numerous. Recent advances in the understanding of erectile physiology have improved the prompt diagnosis and treatment of priapism. Treatment of priapism varies from a conservative medical to a drastic surgical approach. Normally, priapism is effectively treated with intracavernous vasoconstrictive agents or surgical shunting. Recent findings indicate methylene blue (MB), a guanylate cyclase inhibitor, to be a potential inhibitor of endothelial-mediated cavernous relaxation. This prompted us to assess the feasibility, the use and the effectiveness of MB in the treatment of priapism. METHODS: 25 patients were treated for priapism. Etiologies were: 22 drug-mediated (PGE1 or papaverine/phentolamine mixture) after corpus cavernosum injection therapy (CCIT), 1 leukemia-induced and 2 idiopathic high-flow priapism. Patient ages ranged from 13 to 72 years. The average duration of priapism was 5 hours and 22 minutes after CCIT. MB was administered after blood aspiration of the corpora cavernosa. 5 ml of MB was injected intracavernously (i.c.) and left for 5 min. MB was then aspirated and the penis compressed for an additional 5 min. RESULTS: All patients with CCIT-induced priapism were cured with MB alone. The 3 patients who did not respond to MB underwent i.c. phenylephrine administration and finally, if necessary, embolization of the pudendal artery. Etiology and duration of priapism were the strongest predictors for success with intracavernously administered MB. The primary side effects were a transient burning sensation and blue discoloration of the penis on injection of MB. The initial baseline erectile status was restored in all patients cured by MB. CONCLUSIONS: These results confirm that MB is a safe and highly effective treatment agent for short-term pharmacologically-induced priapism. Furthermore, MB demonstrates distinct advantages over a-adrenergic agents for intracavernous use, such as lower costs, absence of systemic or local toxic side effects and shorter treatment time leading to faster detumescence. For this reason, MB is a suitable and safe substance for alternative routine intracavernous therapy in males with pharmacologically-induced priapism.

Adolescent↗
PubMed1976

Coronary circulation in experimental traumatic shock, and effect of some vasoactive agents on its parameters.

On 35 heparinized cats with experimental traumatic shock induced according to Cannon, changes in the coronary blood flow, produced by intravenous injections of noradrenaline, angiotensin, hydrocortisone, histamine, and serotonin, were studied. Traumatic shock was characterized by decreases in the coronary blood flow and organic oxygen uptake, despite a simultaneous decrease in the regional vascular resistance. Injections of noradrenaline (14-18 mug/kg) and angiotensin (29 mug/kg) induced, both in the initial normal state and in shock, increases in the coronary blood flow rate and in the regional oxygen uptake; an injection of hydrocortisone (7.1 mg/ml) produced similar effects in the normal state, but did not elevate the oxygen uptake in shock; an injection of histamine (32 mug/kg) had no effect on the coronary blood flow rate, but reduced the regional oxygen uptake both in the normal state and in shock; an injection of serotonin (30 mug/kg) exerted no major effects on the blood flow. The results obtained might serve as guidelines for pharmacological regulation of coronary circulation in shock.

Angiotensin II↗
PubMed2004

Beneficial effects of early initiation of vasoactive agents in patients with acute decompensated heart failure.

Early diagnosis and treatment of acute decompensated heart failure (ADHF) results in improved clinical outcomes, reduced resource utilization, improved quality of life, and lower treatment costs. Currently, heart failure results in nearly 1 million hospitalizations annually in the United States, and 50% of hospitalized patients are readmitted within 6 months of initial discharge. The costs associated with resource utilization are substantial. Despite the personal and societal burden of this condition, until recently, very little progress had been made in optimizing treatment of ADHF. Nesiritide, a human recombinant B-type natriuretic peptide, is a safe, effective vasodilator that can be easily used early in the emergency department to improve outcomes in ADHF.

Cardiotonic Agents↗
PubMed2006

[Vasoactive agents and prostanoids in the therapy of PAD: facts, questions, disproven assumptions].

In the view of the AkdA (Drug Committee of the German Medical Profession), the efficacy in intermittent claudication is currently proven only for Naftidrofuryl, whereas in the opinion of the DGA (German Society of Angiology) also that of prostaglandin E(1) is proven. Both drugs are indicated if neither walking exercise nor vascular or endovascular reconstruction are feasible. In critical limb ischaemia (Fontaine stage III/IV), the efficacy of prostaglandin E(1) and iloprost is proven according to both the treatment recommendations of the DGA and the ACC/AHA Guidelines. The AkdA also agrees with the administration of prostanoids, even though it considers their efficacy not sufficiently proven in accordance with CPMP criteria. Here, prostaglandin E(1) is approved for the treatment of Fontaine's stage III/IV regardless of its etiology, whereas iloprost is approved only for the treatment of thrombo-angiitis obliterans.

Arterial Occlusive Diseases↗
PubMed1989

Motility, haemodynamics and responsibility to vasoactive agents after revascularization of autotransplanted small intestine segments in the dog.

Functional and haemodynamic changes occurring after revascularization of an autotransplanted small intestine segment were studied in acute experiments performed in 10 dogs under pentobarbital anaesthesia. Intestinal motility and mesenteric blood flow of the segment were measured with intraluminal pressurized balloon and electromagnetic flowmeter, respectively. The time-course of observations was divided, according to the findings, into three main periods (phases 1 to 3). In the initial phase (1) the bowel exhibited very slight spontaneous motility which was found to increase moderately but significantly after denervation and isolation of the graft still left in situ before transplantation (phase 2). After declamping of anastomoses of the retransplanted graft (which was protected by cooling to 4 degrees C after being removed from the body) a short period (approximately 2 min) of reactive hyperaemic flow increase was observed in association of vigorous bowel movements lasting for a more prolonged (approximately 15 min) period of time (phase 3a and 3b). Reactivity of the retransplanted vasculature as compared to the denervated control revealed a marked relative shift in adrenergic balance, tested by dopamine, to the vasoconstrictor range, but it showed no change in responses to general haemodynamic or haemorheologic interventions, tested by veratrine and pentoxifylline, respectively. However, the basic levels of blood supply (controlled also by thermography) and systemic blood pressure remained unaltered after transplantation. Regarding the critical role of functional changes immediately after transplantation in determining the survival of bowel grafts, these observations may contribute to a more effective monitoring of surgical interventions.

Animals↗
PubMed1989

Effects of vasoactive agents on isolated human umbilical arteries in preeclamptic women treated with magnesium sulfate: a preliminary report.

Increased vascular reactivity has been noted in preeclampsia. It is uncertain whether this increased reactivity extends to the umbilical circulation. Helical strips of human umbilical arteries from 12 preeclamptic and 17 control patients were set up isometrically in physiological solution. Four preeclamptics who had not received magnesium were included. The resting tensions of the strips, amplitudes, frequencies, and times of onset of spontaneous contractions during the incubation period were noted and did not differ between the groups. When logarithmic dose contractile-response curves were made for serotonin, bradykinin, and KCl for each group, differences were noted only for KCl. The threshold dose for KCl was higher in tissues from the preeclamptic group (8.52 +/- 0.96 mM) compared to the controls (4.09 +/- 0.59 mM) regardless of magnesium therapy. Also, the ED50 for KCl was higher for preeclamptics given magnesium (12.45 +/- 1.21 mM) compared to controls (9.17 +/- 1.05 mM). There were no significant differences between maximal tensions obtained, but a trend was noted for preeclamptics who did not receive magnesium to develop less tension than either controls or preeclamptics who did receive magnesium, regardless of the agonist tested. Relaxation times differed only for KCl, where there was a shortening of the time for the preeclamptics (8.76 +/- 0.64 min) compared to controls (14.53 +/- 2.46 min). These results do not support other studies in which an increased peripheral vascular reactivity in preeclamptics was noted. An explanation for the decreased reactivity to KCl awaits further investigation.

Adult↗