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1.
Dopexamine hydrochloride is a novel compound with properties of DA1-dopaminergic and beta 2-adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of dopexamine (0.5 to 6 micrograms/kg/min) with those of dobutamine (5 to 25 micrograms/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (dopexamine 87 +/- 17 to 100 +/- 14; dobutamine 91 +/- 18 to 103 +/- 17 min-1), cardiac index increased (dopexamine 1.7 +/- 0.5 to 2.8 +/- 1.1; dobutamine 1.8 +/- 0.5 to 3.0 +/- 1.1 l.min-1.m-2) and systemic vascular resistance decreased (dopexamine 1553 +/- 221 to 1117 +/- 432; dobutamine 1721 +/- 347 to 1280 +/- 433 dyne.s.cm-5). Neither drug affected pulmonary artery wedge pressure (dopexamine 24 +/- 6 to 22 +/- 6; dobutamine 25 +/- 9 to 24 +/- 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (dopexamine 20 +/- 9, dobutamine 27 +/- 15 g.m.m-2, P less than 0.05) and cardiac power output (dopexamine 0.71 +/- 0.36, dobutamine 0.93 +/- 0.46 W, P less than 0.05). These haemodynamic effects, due largely to vasodilatation but with some contributory positive inotropy, indicate that dopexamine will be useful in the acute treatment of congestive heart failure. 相似文献
2.
Changes in regional blood flow distribution induced by infusions of dopexamine hydrochloride or dobutamine in anesthetized dogs 总被引:1,自引:0,他引:1
Systemic blood flow distribution was determined using radionuclide-labeled microspheres in anesthetized dogs during infusions of dopexamine hydrochloride or dobutamine. Three doses of the drugs were administered intravenously, in the form of 22-minute infusions (3 X 10(-9), 10(-8), 3 X 10(-8) mol/kg/min [1.3 to 12.9 micrograms/kg/min] dopexamine hydrochloride and 10(-8), 3 X 10(-8), 10(-7) mol/kg/min [3.4 to 34.0 micrograms/kg/min] dobutamine). Both drugs induced dose-dependent acceleration of the heart rate. Blood pressure was maintained during infusions of dobutamine, while dopexamine hydrochloride induced arterial hypotension. As a result, the increments in heart rate-blood pressure product were smaller with dopexamine hydrochloride than with dobutamine. Dopexamine hydrochloride induced blood flow increments in the heart, several sections of the gastrointestinal tract, kidney and skeletal muscle. Quantitatively, these changes were different from those induced by dobutamine in only 3 organs. The myocardial blood flow increments during infusions of dopexamine hydrochloride were smaller than those of dobutamine, whereas in the stomach and in skeletal muscle, the flow increments induced by dopexamine hydrochloride were significantly greater than those induced by dobutamine. The findings suggest that dopexamine hydrochloride, by virtue of its agonist activity at beta 2-adrenergic and DA1- and DA2-dopaminergic receptors, is a powerful vasodilator. 相似文献
3.
Inotropic, vascular and neuroendocrine effects of dopexamine hydrochloride and comparison with dobutamine 总被引:1,自引:0,他引:1
Dopexamine hydrochloride is a novel beta 2- and dopaminergic-receptor agonist proposed for intravenous therapy in patients with congestive heart failure. To gain a clearer knowledge of its efficacy relative to other agents, intravenous infusions of dopexamine hydrochloride (4 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) were administered to 10 patients with congestive heart failure (ejection fraction less than 0.4). Both agents increased stroke volume and cardiac indexes to a similar degree, and both decreased systemic vascular resistance, with a trend toward a greater decrease with dopexamine hydrochloride. Although dobutamine had no significant effect on left ventricular systolic pressure, dopexamine hydrochloride caused a decrease from 121 +/- 8 to 110 +/- 7 mm Hg (p less than 0.01). Both dobutamine and dopexamine hydrochloride increased peak rate of left ventricular pressure development (dP/dt), and there was a trend to a greater increase with dobutamine (control 1,043 +/- 102 mm Hg/s; dobutamine 1,340 +/- 142 mm Hg/s; dopexamine hydrochloride 1,213 +/- 120 mm Hg/s, p = 0.067 vs dobutamine). Plasma norepinephrine levels increased only with dopexamine hydrochloride (+49%, p less than 0.05). Plasma renin activity increased with both agents (dobutamine +38%, p less than 0.06; dopexamine hydrochloride +41%, p less than 0.05). Dobutamine and dopexamine hydrochloride, therefore, improve cardiac function by way of both vasodilator and inotropic mechanisms. At the doses administered, dopexamine hydrochloride relies on a greater systemic vasodilator effect than dobutamine to achieve and increase in left ventricular performance. Increased levels of endogenous catecholamines may contribute to the increased inotropic state with dopexamine hydrochloride. 相似文献
4.
The hemodynamic dose-response effects of intravenous dopexamine hydrochloride (0.5 to 2.0 micrograms/kg/min) have been compared with dopamine (2.5 to 10 micrograms/kg/min) in 12 patients with ischemic left ventricular dysfunction in an open randomized crossover study. Both drugs increased cardiac output and decreased systemic vascular resistance. Dopexamine hydrochloride appeared to increase heart rate more than dopamine although this did not reach statistical significance. Dopexamine hydrochloride produced small increases in systolic and decreases in diastolic blood pressure, whereas dopamine had a biphasic effect resulting in a decrease in mean blood pressure at low doses and an increase at the highest dose studied. With increasing dosage, there was a trend toward more vasodilator activity with dopexamine hydrochloride than with dopamine. Dopexamine hydrochloride produced fewer adverse effects than dopamine. 相似文献
5.
B.D. Prendergast P. MacCarthy J.F. Wilson A.M. Shah 《Basic research in cardiology》1998,93(4):276-284
Nitric oxide (NO) exerts several effects on myocardial contraction, including enhancement of relaxation and diastolic function,
modulation of β-adrenergic inotropic responses, and inotropic effects in the absence of agonist pre-stimulation. Different
effects have been observed in different species and preparations, and it is unclear whether they are species- or preparation-specific,
or whether they represent a range of responses that can manifest in most mammalian species. We therefore examined the effects
of NO on the inotropic response to β-adrenergic stimulation in the isolated guinea-pig heart, a species in which we have previously
shown that NO enhances basal left ventricular (LV) relaxation and modulates the Frank-Starling response. Isolated ejecting
hearts were perfused with Krebs buffer at constant paced heart rate (1 μM indomethacin, 37°C, constant loading conditions),
and high fidelity LV pressure was monitored by an apical 2F Millar catheter. All hearts were initially treated with dobutamine
(0.1 μM) and then, once the peak inotropic and chronotropic response had been established, with either (a) no further treatment
(n=6), (b) the NO donor sodium nitroprusside (1 μM, n=6; 10 μM, n=6), or (c) the specific agonist for NO release, substance
P (0.1 μM, n=6). Dobutamine (0.1 μM) produced a rapid positive inotropic and chronotropic response, associated with a fall
in LV end-diastolic pressure (LVEDP) and a rise in coronary flow. The positive inotropic effect of dobutamine declined over
20–28 minutes, while the chronotropic response persisted over this period. Low dose sodium nitroprusside (1 μM) delayed the
decline in the inotropic response to dobutamine and exaggerated the fall in LVEDP. Similar effects were observed with substance
P (0.1 μM). In contrast, a higher dose of sodium nitroprusside (10 μM) did not alter the response to dobutamine. These data
indicate that “low dose” NO augments the inotropic response to β-adrenergic stimulation in the isolated ejecting guinea-pig
heart, in addition to its previously reported effects on basal LV relaxation in the same preparation.
Received: 3 September 1997, Returned for revision: 30 September 1997, Revision received: 16 December 1997, Accepted: 19 January
1998 相似文献
6.
Dopexamine hydrochloride is a new intravenous, short-acting agent with agonist activity at beta 2-adrenergic and DA1-dopaminergic receptors. The effects of dopexamine hydrochloride infusion on systemic and coronary hemodynamics, myocardial metabolism and the neuroendocrine system were evaluated in 10 patients with chronic severe congestive heart failure at baseline, at rates of 1, 2, 4 and 6 micrograms/kg/min at 15-minute intervals, and after a 1-hour infusion of the "optimal" dose. Right atrial pressure was reduced by 25% (p less than 0.01), pulmonary capillary wedge pressure by 26% (p less than 0.05), systemic vascular resistance by 44% (p less than 0.001) and pulmonary vascular resistance by 34% (p less than 0.01) after the optimal dose. Heart rate increased by 17% (p less than 0.01), rate-pressure product by 17% (p less than 0.01) and stroke volume index by 31% (p less than 0.001). There was no change in mean arterial pressure, myocardial oxygen consumption, coronary sinus blood flow, myocardial oxygen extraction or norepinephrine balance. None of the patients demonstrated net myocardial lactate production. These findings suggest that dopexamine hydrochloride improves systemic hemodynamics and cardiac performance without adversely affecting myocardial energetics or norepinephrine balance. Thus, dopexamine hydrochloride may be a useful agent for the short-term treatment of congestive heart failure. 相似文献
7.
R A Foulds 《The American journal of cardiology》1988,62(5):41C-45C
A clinical development program was initiated to identify the hemodynamic profile of activity of dopexamine hydrochloride. Studies in healthy subjects confirmed the cardiovascular activity of dopexamine hydrochloride and demonstrated its potency. Doses of 0.5 to 8 micrograms/kg/min doubled cardiac output without change in mean blood pressure, although pulse pressure did widen. In patients with stable chronic cardiac failure (mainly New York Heart Association class III), dopexamine hydrochloride (4 micrograms/kg/min) increased stroke volume 47 +/- 9%, cardiac index 64 +/- 10% and heart rate 11.7 +/- 3%. Systemic vascular resistance decreased by 42 +/- 5%. At higher doses, cardiac index increased further, but chronotropic effects became more prominent. Subsequent studies in patients recovering from cardiac surgery and studies of longer duration in patients with chronic congestive heart failure have demonstrated a similar hemodynamic profile that is sustained throughout the infusion. The renal vasodilator effects have been confirmed in both healthy subjects and patients. With all catecholamines the balance of chronotropic to inotropic or vasodilator effect is critical. Dopexamine hydrochloride (1 to 4 micrograms/kg/min) increases cardiac index by over 40% at clinically insignificant (10%) increases of heart rate. 相似文献
8.
TENG J.-K.; KWAN C.-M.; LIN L.-J.; TSAI L.-M.; CHENG J.-T.; CHANG W.-C.; CHEN J.-H. 《European heart journal》1993,14(10):1349-1353
(±)-Dobutamine is a positive inotropic drug usually usedto improve ventricular function in patients with congestiveheart failure (CHF). However, it has been found that haemodynamicresponses to dobutamine become blunted during continuous treatment.In this study we determined the time-dependent changes of ß-adrenergicreceptors in CHF patients treated with dobutamine. Seven CHFpatients received a continuous intravenous infusion of dobutamine(5 µg.kg1. min1) for 96 h. Blood sampleswere obtained before and every 24 h after starting the therapy.The density of ß-adrenergic receptors on mononuclearleukocytes and the plasma concentrations of norepinephrine andepinephrine were determined. During dobutamine treatment thereceptor density (fmol.mg1, mean±SEM) graduallydecreased from 42.8±4.4 (baseline) to 31.4±3.3(P<0.05), 25.2±4.0 (P<0.01), 18.8±5.5 (P<0.01)and 13.4±3.4 (P<0.01) at 24, 48, 72 and 96 h, respectively.However, the plasma concentrations of norepinephrine and epinephrinewere not significantly changed during the 96 h period of treatment.Thus, the ß-adrenergic receptors down-regulated asearly as 24 h after the dobutamine treatment was begun in CHFpatients. This receptor down-regulation was not associated withchanges of plasma catechol-amine concentrations, but was relatedrather to the development of drug tolerance to dobutamine. 相似文献
9.
D N Hunter H Gray Y Mudaliar C Morgan T W Evans 《International journal of cardiology》1989,23(3):365-371
We studied the effects of dopexamine hydrochloride in 14 patients following cardiopulmonary bypass for coronary revascularisation (12 patients) or valve replacement (2 patients). The drug was administered by intravenous infusion at rates of 1, 2, 4 and 6 micrograms/kilogram/minute for a period of 10 minutes at each dose. Measurements of heart rate, blood pressure, right atrial pressure, pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output (thermodilution method) were made at the end of each period. There were significant increases in heart rate (P less than 0.05), cardiac index (P less than 0.05) and systolic blood pressure (P less than 0.05). There were significant falls in systemic vascular resistance (P less than 0.05) and pulmonary vascular resistance (P less than 0.05). There were no significant changes in pulmonary arterial or wedge pressure. No serious adverse effects were observed. Dopexamine hydrochloride appears to be a useful supportive agent in patients following cardiopulmonary bypass, although further trials need to be carried out in order to establish precise therapeutic indications for its use. 相似文献
10.
The hemodynamic effects of dopexamine hydrochloride and dobutamine were compared during dose-response infusions of dopexamine (1.0 to 4.0 micrograms/kg/min) and dobutamine (2.5 to 10.0 micrograms/kg/min) and during 48-hr infusions at doses producing initial matched increases in cardiac output. Thirty-three patients with severe, stable, chronic congestive heart failure (CHF) (New York Heart Association class III to IV) participated. Both drugs produced an increase in cardiac index, brought about by increased stroke volume index and heart rate, and systemic vasodilatation. The relative contribution of these mechanisms differed, dopexamine proving the more potent vasodilator. The effects of dopexamine were maintained without variation during the 48-hr infusion, apart from a reduction in the increase in heart rate. The effects of dobutamine, while remaining above control at most time-points during the 48-hr infusion, attenuated toward control values. Dopexamine also appeared to promote increased urine output and creatinine clearance during the 48-hr infusion. Both drugs were well tolerated. Dopexamine elicited larger peak hemodynamic effects at dosages that had equivalent effects on cardiac output, and favorable renal responses, and demonstrated no long-term attenuation of effect. 相似文献
11.
Studies in our laboratory have confirmed that dopexamine hydrochloride is a potent beta 2-adrenoceptor and DA1-dopamine receptor agonist. We examined the effects of dopexamine hydrochloride on both cardiac contractile force, determined by use of a Walton-Brodie strain-gauge arch sutured to the right ventricle, and heart rate in anesthetized dogs. Dopexamine hydrochloride increased cardiac contractile force and heart rate and decreased blood pressure. After administration of the ganglionic blocking agents, hexamethonium and atropine, or the selective beta 1-adrenoceptor antagonist, atenolol, the positive inotropic and chronotropic effects of dopexamine hydrochloride were reduced or eliminated, demonstrating that the drug had little or no direct beta 1-adrenoceptor action and that a myocardial beta 2-adrenoceptor action was not involved in its cardiac effects. During these investigations, dopexamine hydrochloride was found to be an inhibitor of norepinephrine uptake, potentiating the cardiac effects of both exogenously administered norepinephrine and norepinephrine released from sympathetic nerves. These results led to the following conclusions: Dopexamine hydrochloride stimulates the heart by 2 mechanisms--(1) baroreceptor-mediated release of norepinephrine resulting from hypotension produced by beta 2 adrenoceptor and DA1 dopamine receptor-mediated vasodilatation, and (2) potentiation of the released norepinephrine due to prevention of norepinephrine uptake by sympathetic nerves. The latter mechanism may be involved in the cardiac stimulation observed in patients with congestive heart failure and shock, since excessive sympathetic activity and elevated catecholamine levels are present in these conditions. 相似文献
12.
Summary Dopexamine is a newly developed sympathetic catecholamine which combines dopaminergic (DA-1) andβ
2-adrenergic agonist activity with only minorβ
1-adrenergic action. Thereby, this compound exerts systemic and preferential renal vasodilation, causing afterload reduction,
increases in cardiac output, and improved renal perfusion in animals and normal volunteers. Short-term administration of dopexamine
in congestive heart failure established benefical effects in central hemodynamics, that is, reduction of systemic and pulmonary
vascular resistance, combined with a decrease in LV-filling pressures and increased renal blood flow. The effect on central
hemodynamics are comparable to sodium nitroprusside. With higher doses, however, heart rate may increase substantially with
dopexamine along with increased myocardial oxygen consumption. Experiences with prolonged administration of this drug are
scarce and have, so far, yielded conflicting results. Thus, dopexamine appears to be a promising agent in the short-term management
of congestive heart failure. However, its ultimate value for prolonged administration remains to be established. 相似文献
13.
The short- and long-term hemodynamic effects of intravenous dopexamine hydrochloride (Dopacard) were studied in 12 patients with low cardiac output left ventricular heart failure. In the short-term study, a dose of 4 micrograms/kg/min produced a 60% increase in cardiac output (p less than 0.001), a 30% increase in stroke volume (p less than 0.01), a 23% increase in heart rate (p less than 0.01) and a 39% decrease in systemic vascular resistance (p less than 0.001). In the long-term study, there was a sustained hemodynamic benefit after 8 hours of dopexamine hydrochloride infusion (mean dose 3.5 micrograms/kg/min). There was a 32% increase in cardiac output (p less than 0.001), an 18% increase in stroke volume (p less than 0.05), a 12% increase in heart rate (p less than 0.001) and a 30% decrease in systemic vascular resistance (p less than 0.01). After 48 hours of dopexamine hydrochloride infusion (mean dose 3.8 micrograms/kg/min), the hemodynamic effect was significant only for cardiac output (+20%, p less than 0.05) and for systemic vascular resistance (-26%, p less than 0.01). Thus, dopexamine hydrochloride has beneficial short-term hemodynamic effects in patients with low-output left ventricular heart failure and the benefit appears to diminish with long-term infusion. 相似文献
14.
Neil J. Weissman Stefan M. Nidorf Arthur E. Weyman Michael H. Picard 《Clinical cardiology》1995,18(1):17-20
The purpose of this study was to determine whether it is possible to prevent or delay the onset of midventricular cavity obliteration during a dobutamine stress test with standard hydration. Left ventricular (LV) intracavitary obstruction has been reported as the mechanism for hypotension seen in approximately 20% of patients undergoing dobutamine stress echocardiography. In addition, it has been proposed that administration of a normal saline bolus prior to dobutamine infusion may avert the dynamic ventricular obstruction. We performed a standard graded dobutamine stress echocardiogram before and after fluid loading with 10 ml/kg of normal saline in 10 mongrel dogs. Measurements were made of left atrial pressure, aortic pressure, and the area of the LV cavity at the papillary muscle level throughout each infusion. Although hydration produced an increase in baseline left atrial pressure (5.7 ± 3.2 to 8.1 ± 2.7 mmHg, p < 0.01) and systolic blood pressure (128 ± 18 to 139 ± 22 mmHg, p=0.03), there was no significant change in pre-dobutamine heart rate or systolic area. With dobutamine infusion, there was a similar change in heart rate, systolic blood pressure, diastolic area, and systolic area (SA) at each dose of dobutamine regardless of hydration status. In addition, the dose at which cavity obliteration occurred was not altered by hydration (p = NS). Although all dogs developed cavity obliteration (SA<1.0 cm2) with dobutamine infusion, none experienced hypotension. In this canine model, cavity obliteration does not lead to systemic hypotension and cannot be prevented or delayed by volume loading. 相似文献
15.
Left ventricular filling pattern in {beta}-thalassaemia major -- a Doppler echocardiographic study 总被引:3,自引:0,他引:3
KREMASTINOS D. T.; RENTOUKAS E.; MAVROGENI S.; KYRIAKIDES Z. S.; POLITIS C.; TOUTOUZAS P. 《European heart journal》1993,14(3):351-357
The pattern of left ventricular filling was assessed by Dopplerechocardiography in 38 adult ß-thalassaemia majorpatients; 28 with normal (age 25.2±5.3 years) and 10with abnormal (age 24.5±8.8 years) left ventricular systolicfunction. The findings were compared with those obtained from38 age and sex matched normal individuals. In patients with normal left ventricular systolic function,peak flow velocity in early diastole was higher than in thecontrols (94±16 vs 79±12 cm. s1 P <0.001).The peak flow velocity in late diastole was also greater (60±18vs 46±9cm. s1 P <0.001) but the ratio betweenthe early and late (atrial) peaks was approximately the samein both groups (1.74±0.72 vs 1.70±0.30 There wasno difference in deceleration time and rate between the twogroups (152±32 vs 151±21 ms and 504±93vs 508±115 cm. s2 respectively). None of the patientshad atrial predominant left ventricular inflow pattern. In patients with congestive heart failure the peak flow velocityin early diastole was greater than in the controls (96±10vs 79±2 cm. s1 P < 0.001) while in late diastoleit was smaller (39±6 vs 44±2 cm. s1 P <0.05).The ratio between the early and late peaks was greater in thepatients than in the controls (2.5±0.35 vs 1.8±0.08,P <0.001). The deceleration time and rate were not significantlydifferent in the two groups (153±33 vs 152±17msand 617±219 vs 550±56 cm. s2 respectively),until the end stage of congestive heart failure. Thus, leftventricular filling pattern in ß-thalassaemia majorpatients with normal left ventricular systolic function, issimilar to that seen in conditions of an increased preload.Patterns compatible with abnormally prolonged relaxation orrestriction do not appear. 相似文献
16.
BORGES A. C.; PlNGITORE A.; CORDOVIL A.; SlCARI R.; BAUMANN G.; PlCANO E. 《European heart journal》1995,16(11):1726-1730
Background: Pathophysiological data and pragmatic clinical experiencewith stress echocardiography suggest that inotropic stimulationwith simultaneous changes in heart rate and loading conditionscan affect the function of various myocardial regions asymmetrically,inducing heterogeneity in wall motion and thickening, possiblymimicking ischaemic regional hypokinesis or lackof hyperkinesis during stress. Objectives: To describe, in a quantitative fashion, the physiologicalcontractile response of different left ventricular regions followingdobutamine infusion. Methods: Two hundred and twenty-three in-hospital patients undergoingdobutamine stress echocardiography and coronary angiographywere initially considered. Of these 223 patients, 18 had angiographicallynormal coronary arteries, normal resting function, negativeergonovine and exercise stress tests, and negative dobutaminestress echo-cardiograms; of the 18, only in 11 patients (sixfemales, age=56 ± 10 years) was it possible to obtainquantitative measurements of the middle segments of the inferior,anterior, lateral, and septa! walls. Two-dimensional echocardio-graphicmeasurements of wall thickness were obtained at the end-diastolic(onset of Q wave) and end-systolic phases, both at baseline(rest) and at the peak of the dobutamine infusion (40 fig. min1.kg1plus atropine). Results: Dobutamine increased heart rate (rest-69 ±9vs dobutamine=138 ± 13 beats. min1; P<0.01),whereas systolic blood pressure did not change significantly(rest-136 ± 75 vs dobutamine.150 ± 25 mmHg, P=ns).During stress, % systolic thickening decreased in the inferiorwall (rest = 73 ± 24 vs dobutamine ± 50 ±9%; P<0.01), whereas it tended to increase to a variableextent in the other regions, i.e. septal (rest=46± 17vs dobutamine=68 ± 13%, P<0.01), anterior (rest 62± 19 vs dobutamine=69 ± 11%, P=ns), and lateralwall (rest=48± 16 vs dobu-tamine=61 ± 18%, P=ns).The decrease in % systolic thickening of the inferior wall wasinversely correlated with the increase in end-diastolic wallthickness (r= 0.75; P<0.01), but neither with heartrate (r=0.15; P=ns) nor with systolic blood pressure changes(r=0.05; P=ns). Conclusions: Heterogeneity of left ventricular wall thickeningcan be induced or magnified by dobutamine infusion even in subjectswithout coronary artery disease, with the inferior wall showinga lack of hyperkinesis, up to relative hypokinesis, in comparisonwith other myocardial regions. Caution in aggressive dobutaminestress echocardiography reading, especially in the inferiorwall, might be warranted. 相似文献
17.
OBJECTIVE: To investigate the role of endothelial vasodilating factors in adaptation of myocardial blood flow to increased metabolic demands. DESIGN: Alterations in the effects of endothelium dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators and the beta 1 receptor agonist dobutamine were studied after inhibition of endothelium derived relaxing factor (EDRF) with L-NG-nitro-arginine methyl ester (L-NAME), prostanoid synthesis with indomethacin, and ATP sensitive potassium channels with glibenclamide. EXPERIMENTAL ANIMALS: Female Wistar rats, in situ perfused heart. MAIN OUTCOME MEASURES: Myocardial blood flow (H2 clearance); systolic fractional thickening (pulsed Doppler); mean arterial blood pressure. RESULTS: L-NAME reduced myocardial blood flow by 58 (12)% (mean (SD), P < 0.001) and systolic thickening fraction (FT) by 36 (9)% (P < 0.05). These effects were significantly reversed by administration of L-arginine but not D-arginine. Pretreatment with L-NAME inhibited the increase in myocardial blood flow caused by acetylcholine (control: +42 (9)%; L-NAME: -29 (7)%, P < 0.001) but did not affect the increase in myocardial blood flow caused by sodium nitroprusside (control: +44 (5)%; L-NAME: +34 (10)%, NS). Pretreatment with L-NAME did not change the effect of dobutamine on myocardial blood flow (+61 (3)%) and FT (+32 (8)%) compared with baseline values (P < 0.001). Neither pretreatment with indomethacin nor with glibenclamide reduced the dobutamine induced increase in myocardial blood flow. CONCLUSIONS: Inhibition of EDRF, prostanoid synthesis, and ATP sensitive potassium channels did not reduce the vasodilator reserve during increased metabolic demands induced by beta 1 adrenergic stimulation. Therefore, adaptation of myocardial blood flow to increased metabolic demands is independent of endothelial relaxing factors in the rat heart. 相似文献
18.
Al-Khalili F; Landgren B.-M; Eksborg S; Franco-Cereceda A; Schenck-Gustafsson K 《European heart journal》1998,19(7):1019-1026
Background A variety of vascular effects have been ascribed to 17ß-oestradiol.These effects may partially explain the reduced incidence ofcardiovascular disease found in post-menopausal women on oestrogenreplacement therapy. Objectives To evaluate the effects of 2mg sublingual 17ß-oestradiolon exercise capacity, exercise-induced myocardial ischaemiaand circulating levels of endothelin-1 in post-menopausal womenwith stable coronary artery disease. Methods Twelve post-menopausal women, mean age 61 (range 5272)years, with angiographically verified significant coronary arterydisease, were randomly assigned to 2mg of sublingual 17ß-oestradiol,2·5mg of buccal nitroglycerine and to placebo in a double-blindcross-over study design with at least 2 days between each ofthe study arms. Antianginal medications, with the exceptionof beta-blockers, were discontinued before investigation. Allstudy patients underwent a maximal bicycle exercise test 30minafter drug intake. Blood was withdrawn immediately before andup to 8h after medication for analyses of circulating levelsof oestradiol and endothelin-1. Results The mean serum levels of oestradiol increased from a controllevel of 72±28pmol.l1to 3557± 1631pmol.l1after30min and to 5028±3971pmol.l1after 60min witha gradual decline thereafter. Sublingual 17ß-oestradioldid not induce any improvement in exercise duration when comparedwith nitroglycerin and placebo (500±112s, 505±107s,498±157s), and did not influence time to onset of ST-segmentdepression (358±89s, 436±93s, 384±116s).The plasma levels of endothelin-1 did not change after administrationof 17ß-oestradiol, nitroglycerin or placebo. Conclusions No effects on exercise capacity, exercise-induced acute ischaemia,or plasma levels of endothelin-1 were found after a single doseof 2mg 17ß-oestradiol in post-menopausal women withdocumented coronary artery disease. 相似文献
19.
Dopexamine hydrochloride, a dopamine analog with specific beta 2 adrenergic and DA1 dopaminergic receptor activity, was evaluated in a prospective study including 20 patients undergoing coronary artery bypass grafting. Shortly after admission to the intensive care unit, increasing doses of dopexamine hydrochloride (1.0, 2.0, 4.0, 6.0, 8.0 and 10.0 micrograms/kg/min) were administered as continuous infusion at 20-minute intervals. Hemodynamic monitoring revealed that dopexamine hydrochloride causes a significant decrease in systemic vascular resistance and a significant increase in cardiac output and heart rate, even at lower dose levels (1.0 micrograms/kg/min). At higher dose levels (greater than or equal to 2.0 micrograms/kg/min), adverse effects such as systolic hypertension and tachycardia were observed. Shunt fraction increased significantly during dopexamine hydrochloride administration, probably due to the increase in cardiac output. It is concluded that dopexamine hydrochloride is a potent vasodilating agent at lower dose levels and is of potential benefit to patients with compromised myocardial function after coronary artery bypass grafting. Higher dose levels may cause unwanted side effects, which might be explained by various mechanisms such as norepinephrine uptake inhibition. 相似文献
20.
The effects of low-dose (10(-9) and 3 x 10(-9) mole/kg/min) infusions of dopexamine HCl, a new synthetic catecholamine with beta 2-adrenergic and DA1-dopaminergic agonostic actions, was tested in anesthetized dogs, with and without acute ligation of the left anterior descending coronary artery. The infusions caused diastolic arterial blood pressure to fall by 12 +/- 4 and 23 +/- 5 mmHg, respectively. Microsphere-estimated collateral blood flow to the ischemic myocardium did not change significantly during the drug infusions. The findings suggest that low doses of dopexamine HCl do not cause coronary "steal" from acutely ischemic myocardium. 相似文献