Biomedical subjects

K M Azadzoi

Publications and source records attributed to K M Azadzoi.

28 records · Page 2Linked to original sources

PubMed1996

Study of etiologic relationship of arterial atherosclerosis to corporal veno-occlusive dysfunction in the rabbit.

PURPOSE: The aim of this study was to explore the possible etiologic relationship of hypercholesterolemia and atherosclerosis to corporal veno-occlusive dysfunction. MATERIALS AND METHODS: In the New Zealand White rabbit, the competence of the corporal veno-occlusive mechanism was examined at various intervals after exposure to control diet, high cholesterol diet, or aortoiliac atherosclerosis. RESULTS: Initially, all animals showed normal erectile function and corporal veno-occlusion. After 8 weeks and 16 weeks, the control animals preserved normal erection and corporal veno-occlusion, while most of the hypercholesterolemic and atherosclerotic animals developed corporal veno-occlusive dysfunction. The incidence of corporal veno-occlusive dysfunction in the hypercholesterolemia and atherosclerotic animals increased with time. CONCLUSIONS: This study suggests that a close relationship exists between prolonged atherosclerotic occlusion of major penile arteries and the development of corporal veno-occlusive dysfunction. Ischemia-induced corporal veno-occlusive dysfunction may be the result of alterations in corporal smooth muscle relaxation or changes in the structure and fibroelastic properties of erectile tissue.

Animals↗

PubMed1995

Hemodynamics of penile erection: III. Measurement of deep intracavernosal and subtunical blood flow and oxygen tension.

Previous studies have shown that intracavernosal blood flow increases during penile erection, but little is known about intracavernosal hemodynamics. Using a previously developed canine model of erection, we measured intracavernosal blood flow and oxygen tension at 2 sites within the corpus cavernosum: directly beneath the tunica albuginea and deep within the cavernous tissue. We chose to measure oxygen tension as an indicator of arterial blood flow. Penile erection was induced by pelvic nerve stimulation as well as by injection of papaverine and phentolamine. In the flaccid penis, blood flow measured directly under the tunica albuginea was significantly higher than deep intracavernosal blood flow. Subtunical oxygen tension in the flaccid penis was consistent with a largely arterial circulation. These observations provide physiological evidence of an important subtunical circulation that carries most of the intracavernosal blood flow when the penis is flaccid. With pelvic nerve stimulation, deep intracavernosal blood flow increased significantly followed by an increase in oxygen tension. Oxygen tension deep within the corpus cavernosum increased during penile erection from a level consistent with venous blood to a level consistent with arterial blood. Injection of papaverine and phentolamine caused a significant increase in intracavernosal pressure and a significant decrease in subtunical blood flow but did not cause statistically significant change in intracavernosal blood flow or oxygen tension. In contrast to nerve-induced erection, pharmacologically induced erection appears to depend more on intracavernosal shunting of blood than on increased total arterial blood flow to the penis. Hypogastric nerve stimulation during established erection caused detumescence by contracting cavernosal smooth muscle, reducing deep cavernosal blood flow and reestablishing blood flow through the subtunical space. Our observations suggest that the subtunical space contains an important circulation that may play a role in the hemodynamics of the flaccid, as well as the erect, penis.

Animals↗

PubMed1994

Effects of intra-abdominal pressure on renal tissue perfusion during laparoscopy.

An animal model was established to study the effects of elevated intra-abdominal pressure (IAP) on systemic and renal hemodynamics during laparoscopy. In a pilot study in five dogs, we simultaneously recorded carotid artery blood flow (CABF), carotid artery blood pressure (CABP), inferior vena caval pressure (IVCP), renal parenchymal blood flow, and IAP. The renal parenchymal blood flow was measured by a laser Doppler flowmetry (LDF) needle probe and the renal artery blood flow by an ultrasonic Doppler probe, both placed through laparotomy. The reliability and reproducibility of these two measurements at different renal perfusion pressures were documented. The established method was then used to assess the effects of increased IAP on renal hemodynamics during laparoscopy in six pigs. Pneumoperitoneum was achieved by insufflating the abdominal cavity with air. The LDF needle probe was inserted into the renal parenchyma laparoscopically. An increase in IAP from 0 to 40 mm Hg did not influence CABP. However, significant decreases in CABF were seen from 190.8 +/- 59.5 mL/min at 0 mm Hg IAP to 169 +/- 43.6 mL/min at 15 mm Hg. The CABF decreased in a linear fashion as IAP was increasing (correlation coefficient R = 0.976). Renal cortical blood flow (RCBF) decreased from 50.1 +/- 17.7 mL/min per 100 g at 0 mm Hg to IAP to 21.2 +/- 9.6 mL/min per 100 g of tissue at 15 mm Hg. There was an exponential correlation between IAP and RCBF (R = 0.897).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1992

Diabetes mellitus impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle.

The effect of alloxan-induced diabetes on the reactivity of corporeal nerves, endothelium and smooth muscle was studied in the New Zealand white rabbit. Fifteen rabbits were randomly divided into treated (n = 6) and control (n = 9) groups. The treated group was maintained for 6 weeks. Two control groups were studied. One control group (n = 3) was maintained for 6 weeks as littermate controls for diabetic group. The second control group (n = 6) was not maintained but was weight matched with the 6 week diabetic group. The reactivity of corpus cavernosum tissue from the diabetic animals and the control animals was studied in organ chambers. When tissue contraction was produced with phenylephrine for the study of relaxation to various stimuli, the tension induced was similar in the diabetic and the control groups. Relaxation of corpus cavernosum tissue to electrical stimulation of autonomic nerves as well as relaxation to the endothelium-dependent vasodilator acetylcholine were comparably unaffected in the weight matched and littermate control groups while significantly inhibited in the diabetic group. Treatment of the corporeal tissue with the cyclooxgenase inhibitor indomethacin enhanced the relaxation to electrical stimulation and to acetylcholine in the control and in the diabetic groups but did not improve the significant difference in relaxation between the two groups. Relaxation of corporeal tissue to endothelium-independent vasodilators, papaverine and nitroprusside was similar in the control groups and the diabetic groups. It is concluded that diabetes impairs neurogenic and endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. These findings are comparable to those described in corpus cavernosum tissue from diabetic men, showing the validity of this experimental animal model. The mechanism for the nerve or endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the ability of the corporeal smooth muscle to relax via a cGMP-dependent mechanism. Since nitric oxide has been shown to act as the nonadrenergic noncholinergic neurotransmitter as well as endothelium-derived relaxing factor (EDRF) of the trabecular smooth muscle, it is possible that impairment of neurogenic and endothelium-dependent relaxation due to diabetes is mediated by alteration in the synthesis or availability of nitric oxide in corporeal tissue.

Acetylcholine↗

PubMed1992

Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone.

Relaxation of penile corpus cavernosum smooth muscle is controlled by nerve and endothelium derived substances. In this study, endothelium-dependent relaxation of corporal smooth muscle was characterized and the role of arachidonic acid products of cyclooxygenase in endothelium-dependent relaxation was examined. Endothelium removal from rabbit corpora was performed by infusion with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate and was confirmed by transmission electron microscopy. Strips of human and rabbit corporal tissues were studied in the organ chambers for isometric tension measurement. The accumulation of cyclic guanosine monophosphate (cGMP) and the release of eicosanoids from corporal tissue was measured by radioimmunoassay and correlated to smooth muscle relaxation. Our study showed that relaxation of corpus cavernosum tissue to acetylcholine, bradykinin and substance P was endothelium-dependent; potentiated by indomethacin; and inhibited by NG-monomethyl-L-arginine, methylene blue or LY83583. Relaxation to papaverine and sodium nitroprusside was endothelium-independent, and unaffected by NG-monomethyl-L-arginine. Relaxation to vasoactive intestinal polypeptide was partially endothelium-dependent; potentiated by indomethacin; attenuated by NG-monomethyl-L-arginine or methylene blue. The tissue level of cGMP was enhanced by acetylcholine and nitric oxide. Methylene blue inhibited both basal and drug-stimulated levels of cGMP. The release of eicosanoids was enhanced by acetylcholine and blocked by indomethacin. In conclusion, nitric oxide or a closely related substance accounts for the activity of endothelium-derived relaxing factor in the corporal tissue. Inhibition of the release of eicosanoids potentiates the relaxing effect of nitric oxide. Nitric oxide increases tissue cGMP which appears to modulate corporal smooth muscle relaxation.

Acetylcholine↗

PubMed1992

Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model.

An animal model was developed to study the pathophysiology of erectile dysfunction due to atherosclerotic vascular disease. Thirty one New Zealand white male rabbits were divided into control (n = 5) and treatment groups (n = 26). The control group was placed on a regular diet while the treatment group underwent balloon de-endothelialization of the aorto-iliac arteries and received 1.6% cholesterol and 4% triglyceride diet for eight weeks. After eight weeks in the control animals (n = 5), blood levels of cholesterol, triglycerides and low density lipoproteins, radiologic studies as well as hemodynamic parameters of erectile function were all normal. In the surviving treatment animals (n = 21) after the same time period, a significant increase in blood levels of cholesterol, triglyceride and low density lipoprotein were observed. In addition, 62% of these animals developed hypertension which was not observed in the control group. Angiographically, 10 animals (48%) demonstrated severe atherosclerotic lesions (75% to 100% occlusion of common or internal iliac arteries on one side and over 50% occlusion of the opposite side), five (24%) had moderate lesions (50 to 75% luminal occlusion of right and left common iliac or internal iliac arteries) and 6 revealed minimal lesions (less than 50% occlusion of the right and left common iliac or internal iliac arteries). Of the 15 animals with 50% or greater luminal occlusion of the iliohypogastric arteries, erectile dysfunction was found in 93% of cases. Due to the development of erectile dysfunction in 33% of animals with minimal occlusive lesions, it appears that factors, other than large vessel luminal occlusion, may exist in this animal model which adversely influence erectile function. This model may therefore be of further benefit in the study of other factors associated with atherosclerosis and impotence, such as the possible concomitant hypercholesterolemic and atherosclerotic-induced alterations in the local reactivity of corpus cavernosum smooth muscle and lacunar space endothelial cells.

Animals↗

PubMed1991

Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle.

The majority of cases of impotence are associated with vascular risk factors such as diabetes, hypercholesterolemia, hypertension and smoking. These factors induce impairment of endothelium-dependent relaxation of blood vessels in man and in experimental animals. In this study the effects of hypercholesterolemia on the reactivity of rabbit corpus cavernosum smooth muscle strips to endothelium-dependent and endothelium-independent agents were investigated. New Zealand White rabbits (n = 14) were randomly divided into control and treatment groups. The control group (n = 7) received a regular diet while the treatment group (n = 7) was fed a diet of 0.5% cholesterol and 4% peanut oil for 10 weeks. Animals were then sacrificed and the corporal tissue studied in organ chambers for isometric tension measurement. Tissue was contracted with phenylephrine and concentration-dependent relaxation to acetylcholine, in the presence and absence of indomethacin, and to nitroprusside were examined. Blood level of cholesterol in the cholesterol-fed group was significantly higher compared to the control group. Contractions to phenylephrine were similar in both groups. Hypercholesterolemia, however, inhibited relaxation to acetylcholine but did not alter relaxation to nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent, direct smooth muscle dilator. Indomethacin enhanced the relaxations to acetylcholine in both control and cholesterol-fed groups but did not correct the difference in the relaxation to acetylcholine between both groups. It is concluded that hypercholesterolemia impairs endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. The mechanism for the endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the cGMP-dependent relaxation of corporal smooth muscle. Impairment of endothelium-dependent relaxation of corporal smooth muscle may contribute to the pathophysiology of impotence associated with hypercholesterolemia in man.

Acetylcholine↗

PubMed1991

Pathophysiology of prolonged penile erection associated with trazodone use.

Treatment with the antidepressant trazodone has been associated with the occurrence of prolonged penile erection and priapism. To evaluate the effect of trazodone on erection we monitored the periodic physiological sleep-related erections in 6 healthy volunteers in a double-blind crossover study comparing the effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In addition, to determine the effects of trazodone on the neurovascular control of penile smooth muscle we performed in vitro studies on corpus cavernosum tissue obtained from patients undergoing penile prosthesis implantation. Trazodone significantly increased the total interval of nocturnal erectile activity, while trimipramine had no effect. During the high dose treatment (nights 4 and 5) the average duration of erectile activity per night with placebo was 158 +/- 41 minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for night 5. During trazodone treatment the erectile activity per night was significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86 during night 5 (p less than 0.01). Analysis of the erectile activity in relation to the rapid eye movement sleep period during which erectile activity usually occurs revealed that the detumescence phase of erection, under sympathetic control, was significantly prolonged an average of 2.4 times by trazodone compared to placebo (p less than 0.05). In vitro, trazodone at concentrations comparable to those reached in plasma significantly impaired corporeal smooth muscle contractions elicited by electrical stimulation of adrenergic nerves and antagonized contractions induced by exogenous norepinephrine. We conclude that trazodone can enhance penile erection in man and propose a mechanism related to the alpha-adrenoceptor blocking properties of trazodone by interference with the sympathetic control of penile detumescence.

Adolescent↗

PubMed1991

A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle.

This study was initiated to characterize nonadrenergic-noncholinergic (NANC) inhibitory neurotransmission in penile corpus cavernosum. Using organ baths, isometric tension measurements were made in strips of human and rabbit corpus cavernosum. In examining endothelium-mediated responses, cumulative additions of exogenous acetylcholine elicited dose-dependent relaxations which were significantly reduced or completely inhibited in tissues treated with NG-monomethyl L-arginine (L-NMMA; an inhibitor of nitric oxide synthesis), oxyhemoglobin (a nitric oxide scavenger), or methylene blue (a guanylate cyclase blocker). Tissues exposed to hypoxic conditions (PO2 = 5-10 mmHg) also did not respond to exogenous acetylcholine. Mechanical removal of the endothelium in human corporal strips or in situ treatment of rabbit corpora with detergent blocked the relaxation to acetylcholine. Transmural electrical stimulation of corporal tissue strips denuded of functional endothelium, in the presence of adrenergic blockade with bretylium and muscarinic receptor blockade with atropine, caused frequency-dependent relaxation. This neurogenic relaxation was reduced or prevented by L-NMMA, oxyhemoglobin, methylene blue, and hypoxia. The effects of L-NMMA were reversed by L-arginine and the effects of hypoxia were readily reversed by normoxic conditions. Authentic, exogenous nitric oxide relaxed corporal strips which were contracted with adrenergic agonists and this effect was significantly inhibited by oxyhemoglobin. It is concluded that (a) endothelium-mediated responses of corpus cavernosum smooth muscle are mediated by a diffusible nitric oxide-like substance; (b) NANC neurogenic inhibitory responses do not require functional endothelium, and (c) nitric oxide, or a closely related substance, may act as an inhibitory neurotransmitter in penile corpus cavernosum smooth muscle.

Acetylcholine↗

PubMed1990

Effects of intracavernosal trazodone hydrochloride: animal and human studies.

Trazodone hydrochloride is an oral antidepressant agent which has been associated with the improvement of erections in impotent men and the development of prolonged erections or priapism in potent men. An in vivo study in animal and human subjects was performed to gain experience with the effect of intracavernosal trazodone. In the anesthetized New Zealand White rabbit, intracavernosal trazodone or its major metabolite m-chlorophenylpiperazine (m-CPP) produced full penile erection in 76% and 84% of animals studied respectively with doses ranging from one to 15 mg. On the other hand, intracavernosal administration of five mg. papaverine resulted in a prolonged erection in 90% of animals studied. In 13 selected volunteer patients, intracavernosal trazodone caused tumescence but not full penile erection with corporal body pressures of 28.2 +/- 5.8 mm. Hg. Intracavernosal papaverine or papaverine and phentolamine in these subjects resulted in significantly higher corporal body pressures of 58 +/- 18 mm. Hg (p less than .05). Intracavernosal administration of alpha adrenoceptor agonists but not normal saline resulted in complete detumescence of trazodone- or m-CPP-induced prolonged erection in the animal studies. Intracavernosal trazodone results in erectile activity that appears in part based on its local alpha blocking activity but like other intracavernosal alpha-blocking agents is not as effective in initiating penile erections as are intracavernosal agents that directly induce smooth muscle relaxation.

Adrenergic alpha-Antagonists↗