Showing papers on "Blockade published in 1990"

Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade.

Abstract: Study Objective:To determine whether beta-adrenergic blockade augments cocaine-induced coronary artery vasoconstriction. Design:Randomized, double-blind, placebo-controlled trial. Setting:...

5-HT2 receptor blockade by ICI 169,369 and other 5-HT2 antagonists modulates the effects of D-2 dopamine receptor blockade.

Abstract: The effects of D-2 dopamine (DA) receptor blockade were modulated by ICI 169,369, a selective 5-hydroxytryptamine (5-HT)2 receptor antagonist, and by other 5-HT2 antagonists. Specifically, it appears that blockade of 5-HT2 receptors can attenuate the effects of D-2 receptor blockade on rat striatal dopaminergic transmission. Thus, the blockade of D-2 receptors by haloperidol results in a compensatory increase in rat striatal DA metabolism, which is enhanced by ICI 169,369. By itself, ICI 169,369 did not significantly alter DA metabolism. Conversely, several compounds which possess appreciable activity at 5-HT2 sites in ex vivo binding assays, but possess little activity at D-2 sites (i.e., pirenperone, setoperone, fluperlapine and clozapine), all produced large increases in striatal DA metabolism. Therefore, these data suggest that the 5-HT2 component of these compounds, by enhancing DA metabolism, may act to attenuate the blockade of striatal D-2 receptors by these compounds. Consistent with this hypothesis, the chronic blockade of D-2 receptors by haloperidol increases the number of striatal D-2 DA receptors, and these increases are attenuated by the coadministration of ICI 169,369. Likewise, pirenperone and clozapine, at doses which acutely produced elevations in DA metabolism which were similar to those produced by haloperidol, failed to increase the number of D-2 receptors in striatum. Interestingly, 5-HT2 receptor blockade did not appear to potently modulate the effects of D-2 receptor blockade in the olfactory tubercle, a brain region which is innervated by mesolimbic DA-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Kupffer cell blockade increases mortality during intra-abdominal sepsis despite improving systemic immunity.

Abstract: • The effect of Kupffer cell (KC) blockade on systemic immunity during intra-abdominal sepsis was evaluated. Gadolinium chloride, a rare earth metal, reduced KC phagocytosis by 75% when it was given to BALB/c mice for 2 days. Thereafter, control mice and mice with KC blockade underwent either a sham operation or a cecal ligation and puncture. As indicators of systemic cell-mediated immunity, delayed-type hypersensitivity responses to soluble antigen and cellular alloantigen were measured 24 hours after the abdominal operations. The activation of KCs was assessed by their in vitro interleukin 1 production. Control septic mice were profoundly immunosuppressed and demonstrated marked KC activation. Septic mice with KC blockade, however, demonstrated less systemic immune hyporesponsiveness and significantly reduced KC activation, but died more rapidly. We concluded that despite apparent improvement in systemic immunity by KC blockade during intra-abdominal sepsis, the resulting impairment in functional phagocytic integrity predisposes to significantly higher mortality. (Arch Surg.1990;125:36-41)

Beta Blockade to Decrease Silent Myocardial Ischemia During Peripheral Vascular Surgery

Abstract: The incidence and duration of intraoperative silent myocardial ischemia have been shown to be significantly correlated with the incidence of perioperative myocardial infarction in patients undergoing peripheral vascular surgery. To assess the effectiveness of intraoperative beta blockade in limiting such silent myocardial ischemia, a group of 48 patients was treated with oral metoprolol immediately prior to peripheral vascular surgery. The total duration of intraoperative silent myocardial ischemia, the percentage of intraoperative time silent myocardial ischemia was present, the number of intraoperative episodes of silent myocardial ischemia, and the intraoperative heart rate in the treated patients were compared with those in 152 similar but untreated peripheral vascular surgery patients. The patients treated with oral metoprolol had significantly less intraoperative silent ischemia with respect to relative duration and frequency of episodes, a significantly lower intraoperative heart rate, and less intraoperative silent myocardial ischemia in terms of total absolute duration. These results suggest that beta-adrenergic activation may play a major role in the pathogenesis of silent myocardial ischemia during peripheral vascular surgery.

Baroreceptor reflex impairment and mild hypertension in rats with dietary-induced obesity.

Abstract: Cardiovascular dysfunction associated with obesity was assessed by comparing rats that had been maintained on a regular or high fat diet since weaning. Rats on the high fat diet not only gained weight faster than age-matched controls but also had higher systolic and mean pressures. Development of mild hypertension in obese rats was first detected by indirect tail-cuff measurement and confirmed later by recording intra-arterial pressures directly from indwelling femoral catheters. To assess baroreceptor reflex sensitivity, reflex heart rate responses were elicited by lowering blood pressure with sodium nitroprusside or elevating it with phenylephrine. Initial tests showed that, although reflex tachycardia during depressor responses to sodium nitroprusside did not differ between groups, reflex bradycardia during pressor responses to phenylephrine was weaker in obese than in control rats. Underlying autonomic mechanisms were then examined by repetition of baroreceptor reflex tests after cholinergic blockade with methylatropine or beta-adrenergic blockade with propranolol. Reflex tachycardia was equally inhibited in both groups by either antagonist. By contrast, reflex bradycardia was reduced more in obese than in control rats by beta-adrenergic blockade but was equally reduced by cholinergic blockade. Because residual responses after beta-adrenergic blockade would represent remaining parasympathetic mediation, these results indicate that reflex bradycardia was selectively impaired because of deficient parasympathetic mediation. Considered collectively, our results suggest that impaired parasympathetic mediation of reflex bradycardia could either result from or contribute to the blood pressure elevation in obese rats.

Time course of the alteration in dorsal horn substance P levels following formalin: blockade by naloxone.

Abstract: Substance P (SP) found in the dorsal horn of the spinal cord has been proposed as a mediator of nociception. Formalin injected into the hind paw of a rat as a nociceptive stimulus has been shown to increase the amount of immunoreactive SP in the dorsal horn, perhaps by decreasing SP release from primary afferent neurons. These SP changes may be due to the actions of endogenous opiates which can block SP release from primary afferent neurons. In order to determine the time course of SP changes in the dorsal horn and their modulation by naloxone, anesthetized rats pretreated subcutaneously with naloxone or saline were injected in the right hind paw with 0.4 ml of either sahne or 5% formalin. After various time intervals, the animals were perfused and the lumbar enlargement of the spinal cord removed. Immunohistochemical staining and manual photometry were used to quantitate SP-like immunoreactivity (SPLI) in the dorsal horn. The results show that saline injection produced an increase in SPLI lasting 20 min, while formalin produced a biphasic effect with early (0–20 min) and late (20–60 min) increases in SPLI. Naloxone pretreatment 30 min prior to hind paw injection partially blocked the initial SPLI increase due to saline or formahn. However, this was not the case if naloxone was injected 2 min following hind paw injection. The formalin-induced late SPLI increase was blocked by naloxone only if it was administered prior to the formalin. This blockade of SPLI increases in the dorsal horn by naloxone implies that endogenous opioid systems play a role in the control of SP levels in the dorsal horn during nociception.

Reversal of intense neuromuscular blockade following infusion of atracurium.

Abstract: In order to evaluate reversal time from very intense neuromuscular blockade caused by a continuous infusion of atracurium, the time course of neostigmine induced reversal from different levels of neuromuscular blockade was evaluated using the post-tetanic count (PTC) and the train-of-four (TOF) in 30 patients anesthetized with nitrous oxide, fentanyl, and thiopental. Reversal time (time from administration of neostigmine at different PTC levels to a TOF ratio of 0.7) was found to depend upon the degree of blockade at the time of reversal. Median reversal time from a PTC of 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, and greater than 13 (but less than 10% twitch height) to a TOF ratio of 0.7 was 31, 23, 19, 18, 14, and 13 min, respectively. Spontaneous recovery from PTC level of 1-2, when atracurium infusion was stopped, to a PTC level at which antagonism was induced and reversal time were both correlated to the square root of the PTC. Total recovery time (spontaneous recovery plus reversal time) was not shortened by an early injection of neostigmine. It is concluded that neostigmine administration during intense neuromuscular blockade following atracurium infusion does not shorten total recovery time and offers no clinical advantages.

Effects of epidural anesthesia on sympathetic nerve discharge to the skin.

Abstract: Direct intraneural recordings of skin sympathetic activity (SSA) were performed to determine the magnitude of blockade of sympathetic fibers to the lower extremities during epidural anesthesia. Lumbar epidural catheters were inserted in nine volunteers. Multiunit postganglionic sympathetic activity was recorded in a skin fascicle of the peroneal nerve before and after injection of 4 ml of mepivacaine 2% epidurally, followed by an additional 12-16 ml after 5 min. Arousal stimuli such as sudden loud noises and noxious electrical skin stimulation were used to elicit transient sympathetic activation. Epidural anesthesia with upper level of sensory blockade at T4-T8 (n = 7) completely blocked spontaneous SSA and no detectable skin sympathetic activity could be provoked by arousal stimuli later than 14 min after the test dose. Sympathetic blockade was accompanied by marked increases in foot skin blood flow and loss of skin resistance responses to arousal. Epidural anesthesia with sensory blockade up to T10-11 (n = 2) only produced a partial sympathetic blockade. The result shows that epidural anesthesia with sensory blockade at T8 or above is equally as effective as injections of local anesthetics directly at postganglionic nerve fibers or ganglionic blockade in producing a complete sympathetic blockade of intraneurally recorded SSA. This neural blockade was paralleled by skin vasodilatation and a loss of sudomotor responses in the foot.

Treatment of painful neuromas with neurolytic blockade.

Abstract: In 10 patients with intractable pain from neuromas that developed after amputations or other surgery, 20 neuromas were treated with neurolytic blockade. In all cases surgical treatment had been unsuccessful. The blockades were performed with phenol-glycerol. Nine patients became asymptomatic, with no relapse occurring thus far during an observation period of 8–22 months. In 1 patient with 3 neuromas, only one neuroma was completely asymptomatic after a single blockade. This treatment may offer an alternative when surgical treatment has not been successful.

Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs.

Abstract: To study the effect of selective alpha 1- or alpha 2-adrenergic blockade on the myocardial contractile and chronotropic response to exercise, 29 dogs were chronically instrumented with a sonomicrometer for measuring myocardial wall thickness and a micromanometer for measuring left ventricular pressure. During treadmill exercise, either the selective alpha 1-blocker prazosin (80 micrograms/kg, n = 12) or the alpha 2-blocker idazoxan (80 micrograms/kg, n = 8) was infused into the left atrium beginning 2-3 minutes after the onset of exercise. alpha 1-Adrenoceptor blockade, like alpha 2-adrenoceptor blockade, was found to cause significant increases in systolic wall thickening, thickening velocity, heart rate, and left ventricular contractility, indicating an increase in inotropic state that was comparable to that with alpha 2-adrenoceptor blockade. Preventing the decrease in aortic blood pressure after selective alpha 1-blockade by using either systemic angiotensin II infusion (n = 6) or inflation of an intra-aortic balloon (n = 6) did not prevent the observed increases in wall thickening, heart rate, and left ventricular contractility. In four of the dogs treated with prazosin, the norepinephrine concentration in the coronary sinus was found to more than double after alpha 1-blockade. beta-Adrenergic blockade (propranolol, 1.0 mg/kg) prevented the increased contractile and chronotropic state caused by alpha 1- or alpha 2-blockade. Selective alpha-adrenergic blockade during adrenergic activation by intravenous norepinephrine infusion, in contrast to exercise, had no effect on wall thickening, heart rate, or left ventricular contractility. These data indicate that selective alpha 1-adrenergic blockade, like selective alpha 2-adrenergic blockade, causes a significant augmentation of heart rate and left ventricular contractility in the dog during dynamic exercise. These data are consistent with the hypothesis that this occurs through a presynaptic disinhibition of neural norepinephrine release mediated by a prejunctional alpha 1-adrenoceptor.

Relative roles of the sympathetic and parasympathetic systems in the 4-s exercise test.

Abstract: To evaluate the relative influence of the two branches of the autonomic nervous system on the 4-s exercise test which measures heart rate acceleration at the onset of exercise, 6 healthy male subjects performed the 4-s test under sympathetic blockade with propranolol, parasympathetic blockade with atropine and dual blockade. The magnitude of the 4-s test results (means +/- SD) was significantly different only between the conditions with and without atropine (1.04 +/- 0.03 vs 1.53 +/- 0.33, respectively), with no differences between the control (1.60 +/- 0.25) and the test under sympathetic blockade (1.51 +/- 0.33). These results support the conclusion that the 4-s exercise test is a specific method for the evaluation of parasympathetic activity.

Systemic effects of three β-blocker eyedrops: Comparison in healthy volunteers of β1- and β2-adrenoreceptor inhibition

Abstract: The β1- and β2-adrenoreceptor blockade by means of the systemic diffusion of three β-blocker eyedrops—timolol, carteolol, and betaxolol—was evaluated in a randomized, single-blind, three-way crossover study in 18 volunteers. The blockade was evaluated by analyzing the variations of the β1- and β2-blockade effects of isoproterenol before and after instillation of one drop in each eye. The β1-blockade effect was judged on the variation of heart rate, and the β2-blockade effect was judged on the change in peripheral blood flow measured by veno-occlusive plethysmography. Comparison of the blockade by these drops showed that carteolol and timolol totally inhibited the β1 and β2 effects of a dose of isoproterenol able to increase heart rate by 50% (placebo eyedrops were used as a control). Betaxolol differ significantly because it allowed the same effects with the same dose of isoproterenol. Intensity of the blockade was measured by comparison of the effective doses of isoproterenol. Carteolol and timolol were shown to be four times more inhibitory. Clinical Pharmacology and Therapeutics (1990) 47, 578–583; doi:10.1038/clpt.1990.78

Hormonal therapy of prostatic carcinoma. Defining the challenge.

Abstract: Prostate cancer is the most common neoplasm in the American male. More than 50% of patients present with locally advanced or metastatic disease and are not curable with local therapies such as radical prostatectomy or radiation therapy. This cancer is hormonally dependent, and methods that interrupt the hypothalamus-pituitary-testicular axis have been used to treat and control the disease effectively. The role of neutralizing the adrenal androgens is controversial. Combined androgen blockade refers to treatment modalities that lower circulating serum testosterone such as bilateral orchiectomy or an LH-RH agonist and combining it with an antiandrogen. The issue at hand is to review current clinical trials addressing the concept of combined androgen blockade and to determine the feasibility of a meta-analysis.

Heart rate and arterial blood pressureat the onsetof staticexerciseinman with complete neural blockade

Abstract: SUMMARY 1.We tested the'muscle-heart reflex' hypothesis fortheimmediate increases in heart rateandbloodpressure attheonset ofstatic exercise inmanbyperforming complete blockade ofafferent nerves fromtheworking muscles. Brief (5s)maximal static hand-grip contractions wereperformed without performing aValsalva-like manoeuvre andwithnoincrease incentral venouspressure bothbefore andafter combined axillary andradial blockade withlidocaine. Muscle strength wasreduced tonearzero. Theeffectiveness oftheafferent neural blockade wasevaluated by recording theheart rateandblood pressure responses andrating theperceived pain during acoldpressor test oftheblocked andcontralateral unblocked hand. 2.Thecoldpressor testincreased blood pressure buthadnoeffect onheart rate. Afferent neural blockade eliminated theincrease inblood pressure andtheperceived painassociated withthecoldpressor test. Maximal hand-grip contractions resulted inimmediate andsimilar increases inheart rateandblood pressure before andafter afferent neural blockade ofthearm. 3.Theresults ofthis study suggest thattheimmediate increases inheart rateand blood pressure attheonsetofstatic exercise inmanoccurwhenthe'muscle-heart reflex' isinoperable.

Heart rate and arterial blood pressure at the onset of static exercise in man with complete neural blockade.

Abstract: 1. We tested the 'muscle-heart reflex' hypothesis for the immediate increases in heart rate and blood pressure at the onset of static exercise in man by performing complete blockade of afferent nerves from the working muscles. Brief (5 s) maximal static hand-grip contractions were performed without performing a Valsalva-like manoeuvre and with no increase in central venous pressure both before and after combined axillary and radial blockade with lidocaine. Muscle strength was reduced to near zero. The effectiveness of the afferent neural blockade was evaluated by recording the heart rate and blood pressure responses and rating the perceived pain during a cold pressor test of the blocked and contralateral unblocked hand. 2. The cold pressor test increased blood pressure but had no effect on heart rate. Afferent neural blockade eliminated the increase in blood pressure and the perceived pain associated with the cold pressor test. Maximal hand-grip contractions resulted in immediate and similar increases in heart rate and blood pressure before and after afferent neural blockade of the arm. 3. The results of this study suggest that the immediate increases in heart rate and blood pressure at the onset of static exercise in man occur when the 'muscle-heart reflex' is inoperable.

Long-term continuous axillary plexus blockade using 0.25% bupivacaine. A study of three cases.

Abstract: Three patients, presenting with various traumatic, vasospastic and chronic neuromuscular disorders of the upper body, received continuous axillary block ranging from 4 to 16 days. Intermittent injections of 0.25% bupivacaine were used to provide analgesia, sympathetic blockade and muscle relaxation. No systemic or neurological side-effects were recorded. Nerve function recovered promptly after stopping the injections. It is concluded that continuous brachial plexus blockade is a clinically safe and effective technique for the relief of acute traumatic pain and vasospastic disorders of the upper limb. The technique, its merits and possible complications are discussed.

Dopamine1-receptor blockade inhibits ANP-induced phosphaturia and calciuria in rats

Abstract: Atrial natriuretic peptide (ANP) is known to enhance the excretion of Pi and Ca, solutes reabsorbed primarily by the proximal tubule. Previous studies have shown that proximal tubule Na transport is inhibited by dopamine (DA), and that the natriuretic action of ANP is blunted by DA-receptor blockade. However, alterations in Na reabsorption cannot localize ANP or DA action to a specific nephron site. Therefore, the possibility that DA mediates the apparent proximal tubule effects of ANP was investigated with the use of Pi and Ca as proximal tubule markers. ANP was infused into normal rats in the presence and absence of specific DA-receptor antagonists, and Na, Pi, and Ca excretion rates were determined. ANP enhanced Na, Pi, and Ca excretion at doses that failed to alter glomerular filtration rate and mean arterial pressure (MAP). DA1-receptor blockade significantly blunted the influence of ANP on urinary Na, Pi, and Ca excretion, whereas DA2-receptor blockade was without effect. MAP and inulin and p-aminohippurate (PAH) clearances remained stable during DA-receptor blockade. Because endogenous ANP levels are elevated in rats with remnant kidneys, and because blockade of endogenous ANP reduces Pi and Ca as well as Na excretion in this model, the effect of DA1-receptor blockade on solute excretion was also examined in rats with 5/6 nephrectomy. DA1-receptor blockade significantly reduced absolute and fractional Na, Pi, and Ca excretion in rats with 5/6 nephrectomy, in the absence of measurable changes in MAP, inulin, or PAH clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide infusion causes vasoconstriction after autonomic blockade in conscious dogs

Abstract: Many studies have shown that atrial natriuretic peptide (ANP) reduces mean arterial pressure (MAP) in conscious animals by lowering cardiac output (CO) with no change or even increased total peripheral resistance (TPR). Because ANP is thought to be a vasodilator, the lack of fall in TPR in conscious animals is generally considered to be due to autonomic reflex increases in vascular resistance. In the present study in conscious, trained, chronically instrumented dogs (n = 7), we measured hemodynamic and renal excretory responses to 30-min infusions of alpha-human ANP (alpha hANP; 25, 50, and 100 ng.kg-1.min-1) in the presence and absence of autonomic nervous system blockade using the ganglion blocking agent pentolinium. In the absence of blockade, MAP and CO fell, whereas TPR rose with alpha hANP infusions, but these changes did not reach significance. There were significant increases in renal vascular resistance (RVR; 16-25%) and mesenteric vascular resistance (MVR; 14-40%). During autonomic nervous system blockade, alpha hANP caused dose-related reductions in MAP (7-12%), due to falls in CO (13-34%). Remarkably, the absence of autonomic reflex responses exposed substantial dose-related increases in TPR (5-33%). Autonomic blockade did not alter the ANP-induced increases in MVR but did abolish the rises in RVR. In summary, ANP caused vasoconstriction in mesenteric vasculature and substantial vasoconstriction in other nonrenal areas, independent of autonomic reflexes.

Effects of selective beta-adrenoceptor blockade on anxiety associated with flight phobia:

Abstract: The present study is aimed at studying the effects of selective beta-adrenoceptor blockade on anxiety in subjects with flight phobia. Using an incomplete block design subjects received a beta-1 (atenolol 2 x 50 mg), a beta-2 (ICI 118 551 3 x 50 mg) selective blocking drug, or placebo on three occasions over a 16 h period under double-blind conditions prior to a 1/2 h flight. The same procedure was repeated 4 weeks later. Thirty-four subjects completed this double-blind, two-period crossover study. Self-reporting by the Alderley Park State Anxiety Questionnaire, Global Flight Anxiety and Treatment Preference showed a moderate but significant effect of atenolol in alleviating especially somatic symptoms of flight anxiety in addition to an overall effect in the treatment of this entity (p<0.01). ICI 118 551 was ineffective in alleviating any of the important symptoms of flight phobia. These results may imply that the effect of beta-adrenoceptor blockade in reducing phobic anxiety may be more a result of beta-1 than of beta-2 blockade. Beta-1 adrenoceptor blockade may be an alternative treatment of flight phobia, particularly when the symptoms are of somatic character and when intellectual performance is expected shortly after the flight.