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Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 163 records · Page 9Linked to original sources

Importance of effective, early and sustained reperfusion during acute myocardial infarction.

The determinants of myocardial salvage after thrombolytic therapy during acute myocardial infarction (AMI) have not been clearly defined. In 1984, a prospective randomized trial was undertaken to define the relations between delay to treatment and effectiveness of perfusion to salvage of myocardium. Patients presenting within 2 hours of symptom onset received intravenous streptokinase immediately (group 1, 20 patients) or 5 hours after symptom onset (group 2, 16 patients). Effective perfusion (less than or equal to 90% residual stenosis with rapid distal runoff) occurred in 63% of patients in both groups. Five patients, all in group 1, had recurrent AMI; 4 of the 5 had effective perfusion. There was no group difference in left ventricular ejection fraction at baseline or before discharge. However, group 1 patients with effective perfusion tended to have a greater predischarge mean ejection fraction than those in group 1 with ineffective perfusion (53 +/- 13 vs 44 +/- 16%, p less than 0.10) and had a greater mean value than those in group 2 with ineffective perfusion (53 +/- 13 vs 38 +/- 17%, p less than 0.03). The ejection fraction did not change significantly between admission and discharge in either group, but it increased significantly in group 1 patients with effective perfusion and no recurrent AMI (delta EF = +6 +/- 8%, p less than 0.04). Group 1 patients with ineffective perfusion had a significant decrease in ejection fraction (delta EF = -4 +/- 4%, p less than 0.04). In group 2 patients the ejection fraction did not change, regardless of the state of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Initiation and duration of myogenic precursor cell replication in transplants of intact skeletal muscles: an autoradiographic study in mice.

Skeletal muscle fibers are capable of regeneration following ischemia, traumatic injury, or transplantation. Although the time course of the regenerative process has been studied in detail histologically, little is known about the time of activation of myogenic precursor cells which are primarily responsible for muscle regeneration. This study was designed to determine the initiation, peak proliferative activity, and cessation times of muscle precursor replication in small skeletal muscle transplants. Forty-eight young male BALB/c mice had the extensor digitorum longus muscles of both hind legs autotransplanted to a different site in the same leg. At various time intervals after transplantation (from 24 hours to 14 days), mice were injected once with a small dose of tritiated thymidine in order to label proliferating myogenic precursor cells. The transplants were allowed to regenerate for 14 days, before being removed, processed for autoradiography, and analysed by light microscopy. The presence of labelled myotube nuclei in regenerated transplants showed that myogenic precursors had been replicating at the time of tritiated thymidine injection. Myogenic precursor replication was initiated late on the second day (42-48 hours) after transplantation, peaked after 6 days, and was complete within 10 days.

Animals↗

A component analysis of the effects of DPAT on male rat sexual behavior.

Male rat sexual behavior was examined in a variety of tests following a single acute IP injection of the serotonin1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT). The objective was to determine the effects of 5-HT1A receptor stimulation on the components of sexual behavior (arousal/motivation, erection and ejaculation) using this prototypical 5-HT1A ligand. In the ex copula genital reflex test, DPAT dramatically inhibited ejaculation and the display of penile erections. When examined in the mating behavior test, DPAT caused a significant reduction in intromission frequency (IF), ejaculation latency (EL), intercopulatory intervals (ICI) and postejaculatory interval (PEI). The decrease in IF and EL indicated a lowering of the behavioral-ejaculatory threshold, while the reduction in ICI and PEI indicated a stimulation of two aspects of sexual arousal. Further tests, however, revealed complexities. Using the mounting test (with genital anesthesia) as an assessment of sexual arousal, no effect of DPAT was found. Collection and examination of the coagulated ejaculates resulting from mating (copulatory plugs) provided evidence of an impairment in ejaculation, as a result of DPAT treatment. The data suggests that 5-HT1A receptor stimulation lowers the behavioral-ejaculatory threshold despite inhibition of ejaculation in and ex copula; as well as stimulating specific aspects of sexual arousal. It remains to be determined whether the effects on arousal were either due to nonselectivity as currently believed or because 5-HT1A receptor stimulation affects alpha 2-adrenoceptor activity by some as yet undefined mechanism; and as a result modulates sexual arousal.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Pericardial pressure attenuates release of atriopeptin in volume-expanded dogs.

The role of the pericardium in the release of atriopeptin (AP) was examined, utilizing two separate protocols, in alpha-chloralose-anesthetized dogs. Protocol I consisted of an experimental group (9 dogs), in which the pericardium was incised to allow instrumentation and reapproximated, and a control group (6 dogs), in which the pericardium was left undisturbed. In the experimental group, mean right atrial pressure (Pra) was elevated from a control value of 1.8 +/- 0.9 mmHg (mean +/- SD) to 8.3 +/- 0.8 mmHg for 40 min by volume expansion with isoncotic, lactated Ringer solution. After this period of volume expansion, the pericardium was removed while holding Pra at 8 mmHg. During volume expansion, arterial blood samples for AP analysis were taken at 5, 10, 15, 20, 30, and 40 min, pre- and postpericardiectomy. A similar protocol was followed in the control group. At a Pra of 8 mmHg prepericardiectomy, the plasma AP concentration was 76 +/- 17 pM/l and 74 +/- 38 pM/l in the experimental and control groups, respectively. However, after pericardiectomy, AP levels increased significantly in both the experimental group (136 +/- 41 pM/l; P less than 0.001) and the control group (107 +/- 53 pM/l; P less than 0.025). In protocol II (6 dogs), the pericardium was removed before volume expansion, and Pra was elevated by 2- to 3-mmHg increments and maintained for periods of 13 min at each pressure. AP concentration did not increase until Pra reached 3-4 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of volume loading during experimental acute pulmonary embolism.

Volume loading is used to treat hemodynamically compromised patients with acute pulmonary embolism despite data to suggest that volume loading after embolism might cause a leftward shift of the ventricular septum with a subsequent decrease in left ventricular (LV) end-diastolic volume and stroke work. We studied 10 closed-chest, anesthetized, and ventilated dogs to assess the effects of volume loading after pulmonary embolism caused by autologous clot. LV, right ventricular, and right atrial pressures as well as LV anteroposterior, septum-to-right ventricular, and septum-to-LV free wall diameters (sonomicrometry) were measured. Pericardial pressure was measured with flat, liquid-containing balloons. The effects of volume loading were assessed before embolism, after one episode of embolization, and after repeated embolizations. The LV area index (as a reflection of LV volume) increased during volume loading before embolism (2,870 +/- 430 to 3,080 +/- 520 mm2; p less than 0.05), did not change significantly during infusion of fluid after one embolization (2,850 +/- 470 to 2,860 +/- 500 mm2; p = NS), and decreased significantly during volume expansion after repeated embolizations (2,760 +/- 440 to 2,660 +/- 420 mm2; p less than 0.01). An index of LV stroke work increased (188 +/- 85 to 260 +/- 101 mm Hg x mm2; p less than 0.05), did not change significantly (188 +/- 39 to 203 +/- 52 mm Hg x mm2; p = NS), and decreased markedly (133 +/- 64 to 45 +/- 27 mm Hg x mm2; p less than 0.001) before embolism, after one embolization, and after repeated embolizations, respectively. The decrease in LV area index during volume loading after repeated embolizations was associated with an increase in septum-to-right ventricular free wall diameter (31 +/- 8 to 34 +/- 8 mm; p = 0.001) and a decrease in the septum-to-LV free wall diameter (44 +/- 5 to 42 +/- 5 mm; p less than 0.001), whereas the LV anteroposterior diameter did not change (62 +/- 5 to 63 +/- 5 mm; p = NS). This is compatible with a leftward septal shift being partially responsible for the decrease in LV end-diastolic volume; such a shift would be expected with the observed decrease in transseptal end-diastolic pressure gradient (-3 +/- 2 to -5 +/- 2 mm Hg; p = 0.001). In addition, after repeated embolizations, LV transmural pressure decreased in response to the volume load reflecting a marked increase in pericardial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Volume-pressure analysis of reflex changes in forearm venous function. A method by mental arithmetic stress and radionuclide plethysmography.

Mental arithmetic stress is known to cause forearm arterial dilation, but the venous responses, including possible changes in the volume-pressure relation, have not been defined. Hence, 10 apparently normal subjects, eight men and two women, mean age 46 +/- 9 years, were studied before and during mental arithmetic stress. Changes in forearm venous volume were estimated with 99mTc blood pool scintigraphy. Group variability of this measurement technique was 1.8 +/- 2.3%. A brachial blood pressure cuff was used to obtain venous occluding pressures of 0, 10, 20, and 30 mm Hg. Mental arithmetic stress increased group systolic and diastolic blood pressure from 126 +/- 12 to 152 +/- 20 mm Hg and from 83 +/- 8 to 93 +/- 15 mm Hg, respectively (p less than 0.001). Heart rate increased from a mean of 75 +/- 15 to 85 +/- 17 beats/min (p less than 0.01). There was no evidence of interaction between or nonlinearity of the volume-pressure plots. Linear regression then yielded the equations V = 99.8 + 0.96P before and V = 86.3 + 0.96P during mental arithmetic stress, which represents a 13.5 +/- 1.6% decrease in forearm vascular volume (p less than 0.001). We conclude that 1) a linear relation exists between forearm venous volume and pressure at physiologic pressures before and during mental arithmetic stress; 2) mental arithmetic stress causes forearm venoconstriction; and 3) such venoconstriction takes place by a parallel shift in the volume-pressure relation (i.e., a shift in unstressed venous volume).

Adult↗

Beta-endorphin levels in the human menstrual cycle.

To examine the fluctuation in plasma beta-Endorphin (beta-EP) concentration throughout the menstrual cycle, 8 healthy females with normal cycles were studied. After an overnight fast, the subject's blood samples were drawn between 8 and 10 a.m. They gave blood at 2 or 4 day intervals through three menstrual cycles. Using the LH surge as day 0, the mean beta-EP concentrations were higher on days -10, -9, -8 (6.5 +/- 2.6, 6.9 +/- 3.8 and 6.7 +/- 2.7 pmol/l, follicular phase), on days -1, 0, +1 (9.2 +/- 3.3, 9.1 +/- 5.2 and 8.8 +/- 3.3 pmol/l, periovulatory phase), and on days +9 and +12 (8.6 +/- 2.5 and 8.8 +/- 3.8 pmol/l, luteal phase). Most beta-EP levels were low during menstruation. The rise and fall in beta-EP and its relation to temporal LH and FSH secretion are discussed. The findings show that three beta-EP rises take place during the menstrual cycle and that beta-EP may be involved in the regulation of ovulation.

Adult↗

Usefulness of early positive technetium-99m stannous pyrophosphate scan in predicting reperfusion after thrombolytic therapy for acute myocardial infarction.

To test the hypothesis that scans with technetium-99m pyrophosphate (Tc-99m-PPi) are positive when performed early after successful thrombolytic therapy for acute myocardial infarction (AMI), 16 consecutive patients with AMI who received thrombolytic therapy within 5 hours after the onset of chest pain were studied. Patients were included if chest pain lasted for greater than 30 minutes, was unresponsive to sublingual nitroglycerin and was associated with at least 0.2 mV ST-segment elevation in at least 2 contiguous electrocardiographic leads. All patients received 1.5 million IU of streptokinase intravenously, a mean of 195 +/- 99 minutes after onset of chest pain. Tc-99m-PPi scans and coronary cineangiograms were recorded 491 +/- 156 minutes and 518 +/- 202 minutes, respectively, after the onset of symptoms. Effective reperfusion was present in 10 patients, 6 of whom had positive Tc-99m-PPi scans (sensitivity of 60% to detect reperfusion). Of the 6 patients without effective reperfusion, 3 had positive Tc-99m-PPi scans (specificity of 50%, p greater than 0.05). Analysis of the data using various definitions of effective reperfusion or artery patency yielded similar results. Thus, our findings indicate that early AMI scanning with Tc-99m-PPi does not accurately detect the presence or absence of reperfusion in patients with AMI after treatment with intravenous streptokinase. At this time, coronary cineangiography is the only reliable method to detect reperfusion promptly after thrombolytic therapy.

Aged↗

Localized septal hypertrophy: part of the spectrum of hypertrophic cardiomyopathy or an incidental echocardiographic finding?

In a prospective study of the results of 5582 consecutive two-dimensional echocardiographic examinations, hypertrophy of a localized region of the basal ventricular septum was identified in 26 patients. Proven diagnoses were coronary disease in five patients, coronary plus valvular disease in three, valvular disease in seven, and miscellaneous in four. Localized septal hypertrophy was the only cardiac diagnosis in seven patients. The ratio of the thickness of the hypertrophied area to that of the adjacent septum was greater than or equal to 1.7 (mean 1.93 +/- 0.19) in all patients. The ration of the length of the hypertrophied portion (mean 0.34 +/- 06) to the length (apex to base) of the septum was less than 0.39 in all but one patient. Although the mitral valve tended to be more anterior than expected in 20, other features of hypertrophic cardiomyopathy were generally lacking. Of four patients undergoing left ventricular angiography, the bulge was identified in only one in whom cranial-caudal angulation was added to the 60-degree left anterior oblique view. An autopsy was performed in one patient; the hypertrophy was identified, although results of microscopic examination showed no fiber disarray. These data suggest that, in most instances, localized septal hypertrophy is an incidental echocardiographic finding. The diagnosis of hypertrophic cardiomyopathy should generally not be made on the basis of this feature alone.

Aged↗

Increased pulmonary vascular capacitance with beta-adrenergic receptor stimulation: an experimental study of the effect of isoproterenol on the pulmonary vascular volume-pressure relationship.

The present study is an investigation of the effect of beta-adrenergic receptor stimulation by isoproterenol on pulmonary vascular capacitance. The experiments were done in six intact-chest, anaesthetized dogs in which pulmonary and cardiac blood volumes were assessed by blood pool scintigraphy. Isoproterenol (0.150 microgram.kg-1.min-1) significantly (p less than 0.005) lowered pulmonary capillary wedge pressure (PPCW) and pulmonary artery pressure (PPA) but did not significantly change pulmonary blood volume (PBV). Left ventricular end-diastolic pressure and total cardiac volume both significantly (p less than 0.005) decreased. Pulmonary vascular volume-pressure (V-P) relationships before and during isoproterenol were described by means of blood transfusions and hemorrhage. In individual dogs the PBV-PPCW and the PBV-(PPCW + PPA)/2 relationships were significantly shifted upward by isoproterenol (p less than 0.05 or less); slope changes were variable. Pooled data from all dogs also showed a significant (p less than 0.001) upward shift in the pulmonary vascular V-P relationship regardless of which measure of distending pressure was used. These results suggest that beta-receptor stimulation by isoproterenol increases pulmonary vascular capacitance by increasing the unstressed volume.

Adrenergic beta-Agonists↗

Acute changes in forearm venous volume and tone using radionuclide plethysmography.

In this investigation blood pool scintigraphy was validated as a method to study acute changes in human forearm veins. Changes in regional forearm vascular volume (capacity) and the occluding pressure-volume (P-V) relationship induced by sublingual nifedipine (NIF) and nitroglycerin (GTN) were recorded in 16 patients with simultaneous data collection by the radionuclide and the mercury-in-rubber strain-gauge techniques. The standard error of estimate (Syx) between successive control measurements using the radionuclide method was 3.1% compared with 3.2% for the strain-gauge method. The venous P-V curves were highly reproducible using both techniques. Strain gauge and radionuclide measurements of acute changes in forearm venous volume correlated well (r = 0.86; Syx = 7%, n = 156). After 20 mg of NIF or 0.6 mg of GTN, mean heart rate increased from 71 +/- 10 to 77 +/- 9 and from 68 +/- 10 to 75 +/- 11 beats/min, respectively, and group systolic blood pressure decreased from 128 +/- 22 to 120 +/- 19 and from 136 +/- 18 to 126 +/- 23 mmHg, respectively (P less than 0.05). At venous occluding pressures of 0 and 30 mmHg, the forearm vascular volume did not change after NIF (2 +/- 4 and -1 +/- 4%; P greater than 0.05), whereas it increased after GTN (8 +/- 5 and 12 +/- 7%; P less than 0.001). The forearm venous P-V relationship did not change after NIF, whereas a significant rightward shift (venodilation, with an increase in unstressed volume) occurred after GTN.(ABSTRACT TRUNCATED AT 250 WORDS)

Forearm↗

Ventricular interaction during experimental acute pulmonary embolism.

Although stroke volume may decrease markedly after acute pulmonary embolism, left ventricular end-diastolic pressure (LVEDP) usually changes very little, which suggests that compliance or contractility or both are reduced. To test the hypothesis that the altered LV function during pulmonary embolism is primarily due to reduced preload mediated by increased pericardial constraint, hemodynamics and chamber dimensions (measured by sonomicrometry) were assessed in seven anesthetized dogs during control volume loading, after pulmonary embolism (with autologous blood clot), and after repeated pulmonary embolism in the volume-loaded state. The correlation between LVEDP and an index of LVED volume (LVED area index) throughout a wide range of LVEDP before and after embolism was poor (mean r = 0.42; range, 0-0.82). However, the correlation between transmural LVEDP (LVEDP-directly measured pericardial pressure) and LVED area index (mean r = 0.78; range, 0.61-0.94) was significantly higher (p = 0.03). Similarly, an index of stroke work (LV area stroke work) correlated less well (p less than 0.01) with LVEDP (mean r = 0.43; range, 0.07-0.77) than with transmural LVEDP (mean r = 0.82; range, 0.68-0.92). LV area stroke work also correlated well with the LV area index (mean r = 0.84; range, 0.70-0.95). These data indicate that neither compliance nor contractility is substantially altered during acute pulmonary embolism. The altered LV performance is due to reduced LV preload as reflected by a decrease in transmural LVEDP. This study also demonstrates that LVEDP is a poor index of LV preload during pulmonary embolism, whereas transmural LVEDP accurately reflects LVED dimensions.

Acute Disease↗

Stereoselectivity of tocainide pharmacodynamics in vivo and in vitro.

Racemic tocainide [R,S-T], which is used in the treatment of ventricular arrhythmias, consists of an R(-)-enantiomer [R-T] and an S(+)-enantiomer [S-T]. The present experiments examined these substances for pharmacodynamic differences. The ability of various doses of R-T, S-T, and R,S-T to both induce ataxia (A) and protect against chloroform-induced ventricular arrhythmias (P) in mice were compared at 20 min after subcutaneous treatment. For A effects, the ED50S (95% Fieller Limits) of R-T, S-T, and R,S-T were 125 (78-802), 125 (84-283), and 90 (61-149) mg/kg, respectively. For P effects, the ED50S were 40 (11-71), 116 (82-204), and 86 (55-187) mg/kg. The ratios of A/P, a measure of the margin of safety, were 3.1, 1.1, and 1.0. Effects upon intracardiac conduction in isolated rabbit hearts also exhibited, qualitatively, similar patterns of selectivity. At 1 X 10(-4) M intraatrial, His-Purkinje, intraventricular conduction times, and the QT interval were prolonged with the following order of potency: R-T greater than R,S-T greater than S-T; A-V nodal conduction was unchanged. R-T also evoked the greatest decrease in contractility. With respect to separation of antiarrhythmic action and the production of ataxia, R-T has a greater margin of safety than either S-T or R,S-T.

Animals↗

The pathogenesis of acute left ventricular failure. The role of the pericardium.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Animals↗

Left ventricular external constraint: relationship between pericardial, pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs.

Left ventricular (LV) diastolic filling is limited by the constraining effects exerted by the pericardium (PE) and the lung/chest wall. The aim of the present study was to assess the validity of various estimates of external cardiac constraint, compared to pericardial surface pressure (Ppe) measured lateral to the LV myocardium. In nine anesthetized dogs we measured Ppe, pleural surface pressure (Ppt) (lateral to the pericardium) and esophageal pressure (Pes) under conditions of volume loading and positive end-expiratory pressure (PEEP). We measured Ppe and Ppl with flat, liquid-containing silastic rubber balloons and Pes with an air-containing cylindrical balloon. After instrumentation, the chest was resealed and continuous suction (-5 mm Hg, 1 mm Hg = 0.133 kPa) was maintained. Volume loading with incremental intravenous infusions of saline was used to increase LV end-diastolic pressure to 20-25 mm Hg. PEEP of 0, 10 and 20 mm Hg were applied at baseline and after each increment of volume loading. At low volume, increases in PEEP caused simultaneous increases in LV end-diastolic pressure (P less than 0.01) and in Ppe (P less than 0.0001) but a reduction in transmural LV pressure (P less than 0.0005). Ppl and Pes both increased with PEEP (P less than 0.001 and P less than 0.01, respectively). However, Ppe always exceeded Ppl, while Pes remained at only approximately 1/3 Ppl throughout. Volume loading caused a significant increase in Ppe (P less than 0.0001) and a smaller, but significant increase in Ppl (P less than 0.05). Pes remained unchanged during volume loading. Thus external cardiac constraint increased markedly during volume loading and PEEP as evidenced by a marked elevation of Ppe. Both Ppl and Pes markedly underestimated this increase. Therefore, calculation of transmural LV pressure by subtracting pleural or esophageal pressure from intracavitary pressure can lead to overestimation of LV preload. The decrease in cardiac output during PEEP occurs secondary to decreased preload, i.e. decreased transmural pressure and end-diastolic dimension. Analysis of performance using cardiac function curves does not suggest a change in contractility with PEEP.

Animals↗

Treatment of menopausal hot flashes with transdermal administration of clonidine.

A randomized prospective double-blind study was performed to evaluate the efficacy of a transdermal therapeutic system delivering clonidine in the treatment of menopausal hot flashes. Frequency, severity and duration of the flushing attacks before and during the 8-week treatment period were evaluated. The reduction in the number of hot flashes was highly significant in patients receiving the clonidine transdermal therapeutic system. On subjective comparison of flushing attacks before and during treatment, of the 15 patients who received the clonidine transdermal therapeutic system, 80% reported fewer hot flashes; 73% a decrease in severity; and 67% a decrease in duration. Among the 14 patients who were treated with placebo only, 36% reported fewer hot flashes; 29% a decrease in severity; and 21%, shorter duration (frequency, p less than 0.04; severity, p less than 0.04; and duration, p less than 0.03). Reported side effects were minimal, and no significant effect was observed on blood pressure or pulse rate. Transdermal clonidine therapy had no effect on the pulsatile luteinizing hormone secretion.

Administration, Cutaneous↗

Alpha 2-adrenoceptor antagonists and male sexual behavior: I. Mating behavior.

Three alpha 2-adrenoceptor antagonists yohimbine, idazoxan, and imiloxan were compared by examining the effects of a single injection on male rat copulatory behavior. Dose ranges were: yohimbine: 0.25-8.0 mg/kg; idazoxan: 0.25-8.0 mg/kg; imiloxan: 12.5-50.0 mg/kg. Yohimbine and idazoxan administration produced significant increases in the number of animals copulating to ejaculation and all three drugs increased the rate of copulation as evidenced by reductions in ejaculation latency and intercopulatory interval. Only yohimbine significantly reduced mount latency and postejaculatory interval, but yohimbine and imiloxan significantly reduced intromission latency and idazoxan showed a similar trend. The highest yohimbine dose suppressed sexual activity. A time-course experiment with yohimbine (2.0 mg/kg) and idazoxan (4.0 mg/kg) showed stimulation at 75 min and a trend at 5. To further explore the arousal-stimulating capacity of the two more effective drugs, a mounting test with genital anesthetization was used. Yohimbine but not idazoxan showed marked increases in mounting at 1.0-4.0 mg/kg. Both drugs had a suppressive effect at the highest doses. These data support the involvement of alpha 2-adrenoceptors in the regulation of male sexual behavior, specifically by facilitating sexual arousal, with no effects on ejaculatory threshold, as measured by intromission frequency. Yohimbine is the most globally effective agent and it is likely that factors other than yohimbine's alpha 2-antagonism may play a role in its unique, consistent and broad behavioral effects.

Adrenergic alpha-Antagonists↗

Alpha 2-adrenoceptor antagonists and male sexual behavior: II. Erectile and ejaculatory reflexes.

Three alpha 2-adrenoceptor antagonists, yohimbine, idazoxan, and imiloxan, all shown to have stimulatory effects on sexual arousal/motivation, were studied to identify their possible effects on the other two major components of male copulatory behavior: erection and ejaculation. Genital reflex ex copula tests were used in order to assess these two responses without the confounding factors of mating behavior. Dose ranges were yohimbine: 0.25-4.0 mg/kg; idazoxan: 1.0-8.0 mg/kg; and imiloxan: 12.5-50.0 mg/kg. Lower doses of two of the drugs significantly enhanced the frequency of erections, while the third (yohimbine) showed a strong trend in that direction. At higher doses, all three alpha 2-antagonists produced significant reductions in the number of rats showing penile reflexes, including both erections and ejaculations. In those rats which did show penile reflexes, higher doses of yohimbine (4.0 mg/kg) inhibited the frequency of erections, while the higher dose of idazoxan showed a trend towards such inhibition. Thus, profound, largely inhibitory effects of these agents were demonstrated at dose ranges which have been shown to enhance sexual arousal. These data indicate that within the nervous system alpha 2-adrenoceptor antagonists can modulate erectile and ejaculatory mechanisms quite independently from effects on arousal/motivation.

Adrenergic alpha-Antagonists↗