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Biomedical subjects

P Horan

Publications and source records attributed to P Horan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of calcium and calcium chelator on the response of the bladder to in vitro ischaemia.

OBJECTIVE: To examine the effect of different concentrations of calcium on the contractile responses of isolated strips of rabbit bladder detrusor to various forms of stimulation after 2 h incubation in the presence of substrate and oxygen depletion (in vitro ischaemia), followed by 1 h of recovery. The resultant contractile responses were correlated with the level of lipid peroxidation as determined by malonedialdehyde (MDA) concentration. MATERIALS AND METHODS: Isolated strips of rabbit bladder detrusor smooth muscle were incubated in Tyrode's solution containing different concentrations of calcium (0-5.4 mmol/L). The effect of 2 h of incubation in oxygen- and substrate-free medium (in vitro ischaemia), followed by a 1-h incubation in the presence of oxygen and substrate, on the contractile responses to field stimulation, carbachol and KCl were determined. The effects of repetitive stimulation (15 s of stimulation at 32 Hz applied every 5 min during the 2-h experimental period) were also assessed. RESULTS: The contractile responses to all stimuli increased as the extracellular calcium concentration was increased from 0.6 to 5.4 mmol/L. A 2 h exposure to in vitro ischaemia, followed by a return to normal solution, resulted in a diminished response to all stimuli. This contractile dysfunction was least in the presence of calcium chelator (EGTA) and greatest in the presence of 5.4 mmol/L calcium. Repetitive stimulation during in vitro ischaemia also exacerbated the contractile dysfunction. Lipid peroxidation increased during in vitro ischaemia in proportion to the calcium concentration and was enhanced by repetitive stimulation during this period. Regardless of the incubation conditions, the reduction in the contractile response was significantly greater for field-stimulated tissues than for those stimulated with carbachol or KCl. CONCLUSIONS: These results show that the magnitude of contractile dysfunction induced by incubation in the presence of substrate and oxygen depletion is reduced in the presence of low calcium concentrations, increased in the presence of high calcium levels and increased in the presence of repetitive stimulation. In addition, the level of lipid peroxidation after the recovery period was proportional to the magnitude of contractile dysfunction present.

Animals↗
PubMed1998

Physiological effects of macrocycle 1 on the rabbit corpus cavernosum.

When the penis is in the flaccid state, the corpus cavernosum smooth muscle is under adrenergic control in order to maintain the sinusoids in a contracted condition (primarily via alpha-adrenergic stimulation). Penile erection is mediated by relaxation of corporal smooth muscle through a variety of direct and indirect mechanisms. Pharmacological agents that either inhibit alpha-adrenergic transmission or facilitate corporal smooth muscle relaxation will be beneficial for penile erection. Preliminary studies on macrocycle 1, a novel bioactive agent, demonstrated that this compound inhibits receptor-stimulated contraction without significantly altering field-stimulated contraction. The current study was designed to determine the physiological effects of macrocycle 1 on the response of the rabbit corpus cavernosum to various forms of stimulation. Sexually mature male New Zealand White rabbits were used in this study. The corpus cavernosum was dissected sharply from the removed penis and two longitudinal strips were prepared for isometric tension studies. Each strip was prestimulated with 200 mumol/l phenylephrine to produce a maximal contraction. The influences of macrocycle 1 (15.6, 62.5, 250, 1,000 mumol/l) on both the contractile response to phenylephrine and the relaxant effects of field stimulation, carbachol, ATP and nitroprusside were determined. The results demonstrated that although basal tension was not altered, the contractile response to phenylephrine was decreased by 5, 18, 47 and 57%, respectively, by the different concentrations of macrocycle 1. The degree of relaxation induced by field stimulation of various frequencies was significantly enhanced by macrocycle 1 in a concentration-dependent manner. Similarly, the degrees of relaxation induced by bethanechol, ATP and nitroprusside were all significantly enhanced in a concentration-dependent manner. The conclusion from this study is that macrocycle 1 significantly inhibits phenylephrine-stimulated contraction and significantly enhances field-stimulated and pharmacologically induced relaxation. Although the mechanisms of action are not clear, its physiological effects on the rabbit corpus cavernosum implicate a potential for the treatment of erectile dysfunction.

Adenosine Triphosphate↗
PubMed1998

Digital analysis of the pharmacological effects of in vitro ischemia on rabbit corpus cavernosum.

PURPOSE: Regulation of corporal smooth muscle tone is essential for the initiation of penile erection. In recent years, in vitro isometric tension studies using isolated corpus cavernosal tissue have been used extensively to investigate the mechanisms regulating corporal smooth muscle tone and tension. In the present study, we utilized digital analysis of contractile data generated from investigation of contractile and relaxation responses of isolated rabbit corpus cavenosum to various forms of stimulation. Digital analysis of the contractile and relaxation data allows quantitation of both maximal and mean rates of tension change, and time elapsed to maximal response. Rates of tension changes may provide additional important information regarding cellular events that mediate corporal tone and tension changes. METHODS: Sexually mature male New Zealand White rabbits were used. Each corpus cavernosum was dissected sharply from the removed penis, then two longitudinal strips were prepared for isometric tension studies and placed in individual baths. Tension was monitored continually using an 8-channel Grass Polygraph. The Grass PolyVIEW system simultaneously converted analog signals to digital information and stored data using a 486 PC computer. Each corporal strip was prestimulated with 300 mumol/l phenylephrine to produce a maximal contraction, then field stimulation (FS), carbachol and nitroprusside were applied consecutively to determine relaxation effects. This procedure was repeated after strips were deprived of glucose and oxygen (in vitro ischemia) for 1 h. The following parameters were quantitated for all responses: maximal tension change; maximal and mean rates of tension change, and time to maximal response. RESULTS: Effects of 1-hour in vitro ischemia on rabbit corporal tissue were as follows: (1) an 85% decrease in contractile response to phenylephrine, and (2) a marked increase in rate of contractile response to phenylephrine. Phenylephrine precontracted strips exhibited: (3) no change in relaxant response to FS; (4) increased relaxant responses to carbachol and nitroprusside; (5) no change in rates of relaxation in response to FS; (6) increased rates of relaxation in response to carbachol and nitroprusside, (7) no change in elapsed time to maximal relaxation in response to FS, and (8) decreased elapsed time to maximal relaxation in response to carbachol and nitroprusside. CONCLUSION: Digital analysis of the data generated facilitates recording, reviewing and analyzing of in vitro isometric tension studies on rabbit corpus cavernosum. Digital analysis allows quantification of additional parameters that have important implications for determination of mechanisms by which specific pathological processes occur.

Animals↗
PubMed1998

Effect of repetitive stimulation on the contractile response of rabbit urinary bladder subjected to in vitro hypoxia or in vitro ischemia followed by reoxygenation.

PURPOSE: We studied the effects of hypoxia followed by reoxygenation and an in vitro model of ischemia (hypoxia + substrate [glucose] deprivation) followed by reperfusion (reoxygenation + substrate replacement) on the contractile response of rabbit urinary bladder strips to nonrepetitive and repetitive field stimulation (FS), and correlated the results with the rate of lipid peroxidation. We view repetitive FS as a model for hyperreflexia. METHODS: The effects of repetitive and nonrepetitive FS on the contractile responses of isolated strips of rabbit bladder to FS, carbachol, and KCl were determined in the presence of 3 different incubation media: O2 + glucose (normal physiological medium); N2 + glucose (in vitro hypoxia), and N2 - glucose (in vitro ischemia). Then, all strips were incubated for 1 h in normal physiological medium ('reperfusion') followed by a final stimulation; the resultant contractile responses were correlated with the level of lipid peroxidation as determined by malonedialdehyde (MDA) concentration. RESULTS: Repetitive stimulation, a model of hyperreflexia, significantly increased the rate of development of contractile dysfunction in bladder tissue strips incubated in all 3 media as compared to nonrepetitive stimulation, which caused no degradation of the contractile response in normal physiological medium. The rate of development of contractile dysfunction was significantly greater in bladder tissue strips incubated in the in vitro ischemia medium (N2 - glucose) than in strips incubated in the hypoxia medium (N2 + glucose); which, in turn, was significantly greater than in those incubated in the normal physiological medium (O2 + glucose). Repetitive stimulation ('hyperreflexia') during all 3 incubation conditions resulted in increased [MDA] after reoxygenation or 'reperfusion'. Incubation in in vitro ischemia buffer (N2 - glucose) followed by 1 h reoxygenation + substrate replacement stimulated lipid peroxidation to a significantly greater extent than did incubation in hypoxia buffer (N2 + glucose) followed by 1 h of reoxygenation; the level of lipid peroxidation, [MDA], paralleled the magnitude of the contractile dysfunctions present. Independent of the incubation medium, the magnitude of FS-induced contractile dysfunction after reoxygenation or 'reperfusion' was significantly greater than the magnitude of dysfunction in response to carbachol or KCl. CONCLUSIONS: The results demonstrate that the rate of contractile failure induced by in vitro ischemia is greater than that induced by in vitro hypoxia, and that the contractile response to FS is significantly more sensitive to both hypoxia and in vitro ischemia than is the contractile response to either carbachol or KCl. Repetitive stimulation ('hyperreflexia') increases the rate of contractile failure under all conditions tested, and the magnitude of the contractile failure may be due, in part, to the generation of free radicals and subsequent stimulation of lipid peroxidation upon reoxygenation or 'reperfusion'.

Animals↗
PubMed1998

Effects of atropine, isoproterenol and propranolol on the rabbit bladder contraction induced by intra-arterial administration of acetylcholine and ATP.

INTRODUCTION: In the rabbit, both cholinergic and purinergic nerves mediate bladder contraction. Acetylcholine is the neurohumoral transmitter for the cholinergic nerves, and ATP is the neurohumoral transmitter for purinergic innervation. Beta-adrenergic stimulation mediates relaxation of the bladder. In the current study, we investigated the effects of atropine, isoproterenol and propranolol on the bladder contraction induced by intra-arterial administration of acetylcholine and ATP. METHODS: Mature male New Zealand White rabbits were used in this study. A polyethylene catheter with an outer diameter of 0.043 inches was inserted through the rabbit's right femoral artery until it reached the lower abdominal aorta. An 8 F catheter was inserted through the urethral orifice into the bladder and secured by tying a 2-0 silk ligature around the bladder neck. The catheter was connected to an infusion pump and a pressure transducer by a 3-way valve. After 15 ml. of saline was infused into the bladder, an intra-arterial administration of acetylcholine and ATP was infused and the change of intravesical pressure was quantitated and recorded with a Grass model 7D polygraph. The procedure was repeated after a 5-minute pretreatment with atropine, isoproterenol or propranolol. RESULTS: The results are summarized as follows: 1) Baseline intravesical pressure was not altered by pretreatment with atropine. Pretreatment with atropine shifted the dose-response curve of acetylcholine to the right and the maximal response was reduced by 9%, 49% and 77% respectively with pretreatment with atropine 10(-8), 10(-7) and 10(-6) mole/kg. The dose-response curve of ATP was not significantly affected by pretreatment with atropine. 2) Baseline intravesical pressure was lowered by pretreatment with isoproterenol. Pretreatment with isoproterenol shifted both dose-response curves of acetylcholine and ATP rightward. The maximal response of acetylcholine was reduced by 10%, 26% and 37% respectively, and the maximal response of ATP was reduced by 6%, 31% and 43% respectively by pretreatment with isoproterenol 10(-8), 10(-7) and 10(-6) mole/kg. 3) Baseline intravesical pressure was not changed by pretreatment with propranolol. Both dose-response curves of acetylcholine and ATP were not significantly affected by pretreatment with propranolol. SUMMARY: In conclusion, pretreatment with atropine inhibited acetylcholine-induced bladder contraction, but had no effect on ATP-induced contraction. Pretreatment with isoproterenol significantly inhibited both contractile stimulation by acetylcholine and ATP. Pretreatment with beta-adrenergic antagonist had no effect on the bladder contraction induced either by acetylcholine or by ATP. Thus, although beta-adrenergic stimulation is capable of significantly inhibiting the contractile responses to both cholinergic and purinergic stimulation, under normal conditions, sympathetic nerves do not modulate either cholinergic or purinergic stimulation.

Acetylcholine↗
PubMed1997

Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit.

Tadenan (Debat Laboratories, France) is a plant extract used in Europe for the treatment of micturition disorders associated with benign prostatic hypertrophy (BPH). Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction observed after 2 weeks of partial outlet obstruction. The specific aim of the present study was to determine the effect of Tadenan therapy following the creation of partial outlet obstruction. Two sets of experiments were performed: one with mild and the other with severe outlet obstruction. For both sets of experiments, male New Zealand rabbits (3-5 kg) were separated into 3 groups of 5 rabbits each. Each rabbit in groups 1 and 2 was obstructed using standard methodology. Rabbits in group 3 served as controls and did not receive any surgery. After 2 weeks, each rabbit in group 1 received Tadenan orally at 100 mg/kg/day for 3 weeks; each rabbit in group 2 received vehicle (peanut oil). After 3 weeks of treatment (5 weeks after partial outlet obstruction), rabbits were anesthetized and cystometries were performed. Immediately after cystometry, the rabbits were euthanized, the bladder rapidly removed, and 4 longitudinal strips prepared and mounted in individual baths for contractile studies. The contractile responses to field stimulation, carbachol, adenosine-5'-triphosphate (ATP), and potassium chloride (KCl) were determined, as follows: (1) Bladder mass approximately doubled in the mildly obstructed groups. Bladder mass increased significantly (3-5-fold) in the severely obstructed groups. (2) Cystometrograms from the mildly obstructed rabbits treated with peanut oil showed low compliance, whereas those of the mildly obstructed rabbits treated with Tadenan showed normal compliance. The cystometrograms of all severely obstructed rabbits showed low compliance. (3) Mild obstruction caused small but significant decreases in the contractile response to field stimulation that were reversed by Tadenan treatment. No changes were noted in response to bethanechol, ATP, and KCl stimulation. (4) Severe obstruction caused significant decreases in the response of bladder strips to field stimulation and bethanechol. Following Tadenan therapy, there was a significant improvement in the response to high-frequency field stimulation and a substantial improvement in the response to bethanechol (response equal to control). No changes were noted in response to ATP and KCl stimulation. In conclusion, Tadenan treatment reversed the bladder dysfunctions induced by mild partial outlet obstruction, and resulted in improved bladder function in the severe model of outlet obstruction. These studies are consistent with previous studies showing that Tadenan pretreatment protects the bladder against the development of contractile dysfunctions.

Animals↗
PubMed1996

Physiological effects of a novel bioactive agent.

Urinary bladder smooth muscle contraction can be evaluated using field stimulation (neurohumoral transmission), carbachol (muscarinic stimulation), and KCl (direct membrane depolarization). We recently evaluated the activity of a novel organic chemical, macrocycle-1, on the contractile responses of the bladder to field stimulation, carbachol, and KCl. Isolated strips of rabbit bladder were mounted in individual baths containing 7.5 ml Tyrode's solution. The response to FS (1-32 Hz), carbachol (1 mumol/l), and KCl (120 mmol/l) were determined in the presence and absence of 3 different concentrations of macrocycle-1. Maximal tension, the rate of tension generation, the time to maximal tension, and the rate of decay following maximal tension were determined. The results can be summarized as follows: (1) In the absence of macrocycle-1, maximal tension and the maximal and mean rate of tension generation increased with frequency, whereas the time to maximal tension was constant. The rate of decay of tension following maximum tension was greater for 8, 16 and 32 Hz as compared to 1 or 2 Hz. (2) The maximal response to KCl was lower than either FS or carbachol. The maximal rates of tension generation for carbachol and KCl were lower than that of FS; and the rate of tension generation for KCl was lower than that of carbachol. The time to maximal stimulation for KCl was greater than that of either carbachol or FS. (3) Macrocycle-1 had a greater inhibitory effect on KCl stimulation than on carbachol stimulation; and a greater inhibitory effect on KCl and carbachol stimulation than on FS. (4) The rate of tension generation was more sensitive to macrocycle-1 inhibition than was the maximal tension responses to all methods of stimulation. Our current hypothesis is that macrocycle-1 is acting as an intracellular calcium buffer whose affinity constant and association rate does not interfere with rapid intracellular release mechanisms (FS) while it inhibits slow intracellular calcium release mechanisms (carbachol and KCl).

Animals↗
PubMed1992

Antinociceptive interactions of opioid delta receptor agonists with morphine in mice: supra- and sub-additivity.

In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the delta agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu4]deltorphin (DELT) or [Met5]enkephalin (MET) were examined using the mouse warm water tail flick test. When morphine was coadministered with DPDPE or DELT in a 4:1 and 9:1 mixture, respectively, a synergistic antinociceptive effect was observed. In contrast, when morphine was coadministered with MET in a 1:2 fixed ratio mixture, a subadditive interaction occurred. These results demonstrate both positive and negative modulatory interactions of delta agonists with morphine in an antinociceptive endpoint and that these interactions can be either supra- or subadditive. The data support the concept of a functional interaction between opioid mu and delta receptors and a potential regulatory role for the endogenous ligands of the opioid delta receptor.

Analgesics↗
PubMed1992

Extremely long-lasting antagonistic actions of nor-binaltorphimine (nor-BNI) in the mouse tail-flick test.

The duration of antagonistic action of nor-binaltorphimine (nor-BNI), a kappa antagonist, of antinociception resulting from selective opioid agonists, was examined using the mouse tail-flick assay as the endpoint. Nor-BNI (1 nmol, i.c.v. at -20 min) antagonized equiantinociceptive doses of the opioid kappa agonists (5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl) benzeneacetamide (U69,593) (70 nmol i.c.v.) or bremazocine (25 nmol i.c.v.), but did not antagonize antinociception produced by the mu opioid-selective [D-Ala2, NMePhe4, Gly-ol]enkephalin or the delta opioid-selective [D-Pen2, D-Pen5]enkephalin. Pretreatment with nor-BNI (1 nmol i.c.v.) antagonized the antinociceptive effects of U69,593 and bremazocine for up to 28 days. At all pretreatment times, the antinociceptive dose-response lines for these kappa agonists were displaced to the right to various degrees in a parallel fashion; an increasing rightward displacement of the U69,593 and bremazocine antinociceptive dose-response lines was observed at 1 and 3 days after a single nor-BNI pretreatment, with a gradual return toward the control level at later times after pretreatment. Increasing the dose of nor-BNI to 10 nmol produced only a transient blockade of equiantinociceptive doses of the mu selective agonist [D-Ala2, NMePhe4, Gly-ol]enkephalin and the delta selective agonist [D-Pen2, D-Pen5]enkephalin (at 20-30 min post-nor-BNI pretreatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

The physical dependence liability of butorphanol: a comparative study with morphine.

In these studies, the physical dependence liability of butorphanol, a mixed 'agonist/antagonist' opioid analgesic, was compared to that of morphine. Male, Sprague-Dawley rats received i.c.v. infusions of saline (1 microliter/h), or an equimolar dose of butorphanol or morphine (52.3 nmol/h) for 3 days. The physical dependence liabilities of these two compounds were then compared by assessing both behavioral withdrawal signs and weight loss following naloxone-precipitated withdrawal. Body weight loss was also evaluated following abrupt (cessation of infusion) withdrawal from butorphanol or morphine. In animals receiving i.c.v. infusions of butorphanol or morphine, naloxone administration (5 mg/kg s.c.) induced an equivalent degree of body weight loss compared to saline-treated animals. In addition, the ED50 of naloxone to produce wet shakes, escape behavior, teeth chattering, urination and defecation was equivalent in rats receiving butorphanol or morphine. Infusions of butorphanol or morphine also produced an equivalent degree of weight loss in animals undergoing abrupt withdrawal. These results demonstrate then that a substantial degree of physical dependence had developed in rats which received a large dose of butorphanol.

Animals↗
PubMed1991

Differential antagonism of U69,593- and bremazocine-induced antinociception by (-)-UPHIT: evidence of kappa opioid receptor multiplicity in mice.

The effect of pretreatment with the kappa receptor nonequilibrium antagonist, (-)-UPHIT (1S,2S-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-(1-pyrrol idinyl) cyclohexyl]benzeneacetamide), on U69,593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5) dec-8-yl)benzeneacetamide]- and bremazocine-induced antinociception was examined in mice. Both U69,593 and bremazocine produced antinociception in the warm water tail-flick test after i.c.v. administration. Pretreatment with the kappa antagonist, nor-binaltorphimine, at doses shown not to affect [D-Ala2, NMePhe4, Gly-ol]enkephalin- (mu-agonist) or [D-Pen2, D-Pen5]enkephalin (delta-agonist)-induced antinociception, significantly attenuated the effects of U69,593 and bremazocine, suggesting actions of these agonists at kappa receptors. Furthermore, beta-funaltrxamine (mu antagonist) and ICI 174,864 [N,N,-diallyl-Tyr-(alpha-aminoisobutyric acid)2-Phe-Leu-OH] (delta antagonist), had no effect on U69,593 or bremazocine in this test providing further evidence of kappa receptor-mediated activity. Pretreatment with (-)-UPHIT produced no effect alone and a long-lasting (up to 48 hr) antagonism of U69,593, but not bremazocine, antinociception. The antagonist actions of (-)-UPHIT did not alter the antinociceptive effects of [D-Ala2, NMePhe4, Gly-ol]enkephalin or [D-Pen2, D-Pen5]enkephalin. These data suggest that (-)-UPHIT is a selective, long-lasting kappa antagonist which can differentially antagonize the antinociception produced by these two kappa agonists. These data provide evidence in vivo supportive of kappa receptor subtypes in the mouse, and suggest that (-)-UPHIT may be a useful probe for the exploration of kappa receptor heterogeneity.

Analgesics↗
PubMed1989

Butorphanol precipitates abstinence in morphine dependent rats.

Butorphanol precipitated a withdrawal syndrome in rats receiving continuous intracerebroventricular infusions of morphine for three days. However, the potency of butorphanol to induce defecation, urination, teeth chattering and escape behavior was one to two orders of magnitude less on a molar basis than that of naloxone. Wet shake behavior, a prominent feature of naloxone precipitated withdrawal, was absent in morphine dependent animals challenged with butorphanol. These data indicate qualitative as well as quantitative differences in the withdrawal syndromes induced by butorphanol and naloxone.

Animals↗
PubMed1989

Beneficial hemodynamic effects of milrinone and enalapril in conscious rats with healed myocardial infarction.

Milrinone and enalapril, which inhibit PDE-III and ACE, respectively, are able to prolong survival of myocardially infarcted (MI) rats. This study sought to identify oral hemodynamic effects of these agents which could underlie such efficacy in this heart failure model. Four weeks after ligation of the left main coronary artery, basal left ventricular (LV) systolic pressure and dP/dtmax, heart rate and mean blood pressure of the MI rats were significantly less than that of sham-operated controls, and LV end-diastolic pressure (LVEDP) was markedly elevated. Milrinone, at 2.0 mg/kg, reduced LVEDP and renal blood flow of these 4-week MI rats by an average of 39 and 18%, respectively (P less than 0.05) within 1 h. At 4.0 mg/kg, it reduced LVEDP by 46% and raised heart rate by 16% (P less than 0.05). Enalapril (1.0 mg/kg) increased small intestine blood flow of these compromised rats by 16% (P less than 0.05), and tended to reduce LVEDP (-28%) within 1.5 h. Treatment with milrinone (2.0 mg/kg) plus enalapril (1.0 mg/kg) promoted LV dP/dtmax, coronary blood flow, and heart rate by 48, 40 and 13%, and reduced LVEDP by 40% (P less than 0.05 for all effects). Thus these agents can reduce LVEDP and redistribute cardiac output of MI rats. Furthermore, the combination of enalapril and milrinone can restore LVEDP and LV dP/dtmax of MI rats to near normal and promote coronary blood flow without compromising cardiac output or renal blood flow. Such effects, it timely or sustained, may prolong survival.

Administration, Oral↗
PubMed1989

Beneficial hemodynamic effects of milrinone in conscious rabbits with chronic aortic regurgitation.

Aortic regurgitation (AR) was induced in rabbits by aortic valve puncture. Two years later, echocardiography [two-dimensional (2-D) and M-mode; Doppler] was used to monitor acute left ventricular (LV) effects of milrinone. At that time, two of eight AR survivors had hindlimb edema and/or ascites. Baseline LV diameter and wall thickness of AR rabbits was 125-145% for that of sham-operated subjects; mean stroke volume and total LV output (TLVO) were approximately 2.5 x normal; regurgitant fraction was 0.57; and effective (forward) cardiac output (CO) was normal. Basal LV fractional shortening (FS) and mean circumferential fiber shortening velocity (Vcf) were not significantly depressed. Milrinone (10 micrograms/kg/min. i.v.) decreased mean LV stroke volume and TLVO by 25-33% (p less than 0.05). However, forward CO was maintained as regurgitant stroke volume fell an average of 52%. Milrinone significantly reduced aortic mean reverse/mean forward blood flow velocity ratio (-16%) and LV end-diastolic (ED) chamber diameter (-7%), consistent with reduced regurgitation. Mean Vcf was 39% greater than that seen after saline infusion (p less than 0.05). Thus, milrinone promoted Vcf and maintained forward CO in rabbits with chronic compensated AR while appreciably reducing LV regurgitation, chamber size, and total output. These beneficial effects may reflect vasodilating and positive inotropic activities confirmed in normal rabbits.

Animals↗
PubMed1989

Time course of hemodynamic changes in rats with healed severe myocardial infarction.

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10-16/group) or sham operation (control; n = 9-14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11-38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

Animals↗
PubMed1985

Normal human blood density gradient lymphocyte subset analysis: I. An interlaboratory flow cytometric comparison of 85 normal adults.

An interlaboratory flow cytometric comparison of several commercially available human lymphocyte subset reagents was undertaken in three different laboratories. Fresh Hypaque-Ficoll purified blood mononuclear cells were stained at 4 degrees C or 22 degrees C. Direct or indirect surface immunofluorescence was carried out at all sites using an EPICS V flow cytometer. Fullbright, 10-micron fluorescent polystyrene microspheres were used for optical alignment and standardization. A log integral fluorescent histogram gated on forward and right angle scatter was collected on 1-2 X 10(4) cells for each reagent and the proportion, of positive cell determined for each reagent. With the exception of one reagent, anti-B1, which showed an approximately twofold variation, all three laboratories showed remarkable agreement. Thus there was no significant difference noted for the following reagents: OKT4, CCT4, Leu 3a, Leu 2a, OKT8, or CCT8. We attribute these findings to the availability of quality reagents, precision instrumentation, and a standard lymphocyte preparation.

Adult↗
PubMed1984

Removal of HLA-A,B antigens from platelets.

Recent evidence suggests that HLA-A,B antigens present on human platelets, are acquired from plasma. Using hypertonic acid chloroquine (200 mg/ml, pH 5.0, 1 hr, 4 degrees C), we demonstrate elution of most or all HLA-A2 and HLA-B7,40 immunoreactive material from platelets. Corresponding antigens on human lymphocytes were not affected by this treatment. These findings are consistent with the hypothesis that HLA-A,B antigens are adsorbed onto platelet surfaces.

Antibodies, Monoclonal↗