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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group. At rest, following a control saline period, four doses of the drug (log cumulative dosage: 1.25, 2.5, 5.0, and 10.0 mg) were administered by i.v. infusion over a total period of 40 min; haemodynamic indices were recorded during the 3-5 min following each 5 min infusion. The exercise effects of the drug, in each posture, were determined by comparison of a control predrug exercise with observations at the same workload following the maximal cumulative dose. Nicardipine reduced resting mean blood pressure (MBP) and systemic vascular resistance index (SVRI) in both postures, the decrease being more pronounced when upright (MBP, -12%, -18%; p less than 0.01: SVRI, -30%, -46%; p less than 0.01). The increases in cardiac index (CI) and stroke volume index (SVI) were higher when upright (29 and 54% vs. 10 and 27%; p less than 0.01). Pulmonary artery occluded pressure (PAOP) increased by 29% when upright, without change when supine. On exercise, the effects for HR, MBP, CI, SI, and SVRI responses were independent of posture; however, a qualitative difference was apparent for PAOP (-17% vs. +14%; p less than 0.05). Thus, although the actions of nicardipine were qualitatively similar, quantitative differences related to posture were confirmed. These differences appeared to relate to posture-related baseline haemodynamic differences between the groups but with similar postnicardipine absolute values.
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PMID:How does posture influence the haemodynamic assessment of a cardiovascular drug? Experience with nicardipine. 169 70

The dihydropyridine derivatives constitute a distinct subcategory of calcium channel blockers that have marked peripheral vascular effects with minimal or no electrophysiologic actions when administered to intact animals or humans. These dihydropyridine derivatives are structurally similar to nifedipine, the most widely studied dihydropyridine. The derivatives have varying affinities for different regional circulations, and there may be an important relationship between structure and activity of these compounds with respect to the predilection of the site of their action in vascular tissue. It is possible that such differences may be of clinical significance. As a class, the dihydropyridines exert reasonably distinct hemodynamic changes that may be of particular importance in the treatment of hypertension, cardiac failure, and regurgitant valvular lesions. Nicardipine hydrochloride is a newer agent that has undergone extensive evaluation in recent years. Pharmacologically and electrophysiologically, it resembles other dihydropyridines. Unlike nifedipine, however, it can be administered by both the intravenous and oral routes. There are additional differences between its properties and those of other calcium channel blockers. For example, nicardipine appears to produce a greater increase in coronary sinus blood flow than other calcium channel blockers. The clinical significance of this finding is unclear. In addition, nicardipine appears to increase myocardial contractility, even in patients with severe congestive cardiac failure. Nicardipine produces a dose-dependent decrease in blood pressure and systemic vascular resistance with increases in heart rate, left ventricular dP/dt, LV ejection fraction, cardiac output, and stroke work index, but no significant change in LV end-diastolic pressure. Clearly, the drug has negligible venodilator actions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology, pharmacokinetics, and hemodynamic effects of nicardipine. 196 96

Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.
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PMID:Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest. 202 76

1. Effects of consecutive administration of YM-09730-5, (3S)-1-benzyl-3-pyrrolidinyl-methyl (4S)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxy lat e hydrochloride, a new calcium antagonist, for 9 wk on blood pressure and urinary excretion of electrolytes were studied in stroke-prone spontaneously hypertensive (SHRSP) rats. 2. YM-09730-5 (1 and 3 mg/kg per day, p.o.) prevented development of hypertension and produced a significant reduction in blood pressure from the first week of the experiment. Nicardipine (15 mg/kg per day, p.o.) produced almost the same degree of antihypertensive effect as YM-09730-5 at a dose of 3 mg/kg. 3. YM-09730-5 produced significant diuresis and increased urinary excretion of electrolytes throughout the experiment. 4. Chronic administration of YM-09730-5 (3 mg/kg) reduced the severity of glomerular lesions in the kidney and vasculitis in the mesenteric artery. 5. These results demonstrate that YM-09730-5 is a potential antihypertensive drug with a potency about 5 times higher than that of nicardipine.
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PMID:Antihypertensive and diuretic effects of YM-09730-5, a new calcium antagonist, in stroke-prone spontaneously hypertensive rats. 205 18

We evaluated the effect of nicardipine, a calcium channel blocker, on somatosensory evoked potentials (SEP) in 26 patients with acute cerebral infarction. Post treatment, 58% (15/26) of the N20 and P25 latencies were prolonged in the affected hemispheres; 8% (2/26) were shortened; and 35% (9/26) did not change. The mean N20 and P25 latencies were significantly prolonged two hours post treatment in the affected hemisphere (N20, P less than 0.01, P25 P less than 0.01). Nicardipine (Ni) had no effect on SEP components in the intact hemispheres. Seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure (BP) after taking nicardipine, but there were no undesirable side effects or worsening of neurological signs. Our study demonstrates that nicardipine prolongs the latencies of short-latency components of SEP in the affected hemisphere after acute ischaemic stroke and also decreases BP. These observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone.
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PMID:Effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction. 226 63

Nicardipine is a second-generation dihydropyridine calcium antagonist with relative coronary and cerebrovascular selectivity. To study the effects of nicardipine on systolic and diastolic myocardial function, we used three experimental models. In isolated feline papillary muscle, nicardipine produced a dose-dependent calcium antagonistic effect manifested by depressed indexes of contraction and relaxation. In an autoregulating blood-perfused isolated rabbit heart preparation, nicardipine markedly increased coronary blood flow and slightly decreased systolic pressure at a given end-diastolic pressure. The systolic pressure and +dP/dt versus volume curves, however, were shifted to the left during nicardipine administration, indicating improved systolic function. This increase was accompanied by decreased volume elastance and is probably due, at least in part, to the coronary turgor effect. In humans at rest, intravenous nicardipine administration produced pronounced coronary and systemic vasodilation with improved left ventricular systolic performance and enhanced relaxation accompanied by reflex sympathetic activation. With exercise to ischemia, nicardipine preserved the salutary effects on left ventricular function seen at rest and significantly blunted the increase in left ventricular end-diastolic pressure observed in the control setting. Administration of intracoronary nicardipine to patients produced a slight and transient depression of systolic and diastolic left ventricular function that was accompanied by a pronounced coronary vasodilator response and later by improved ventricular function. This improvement was manifested by decreased end-systolic volume and increased +dP/dt without changes in heart rate, arterial pressure, end-diastolic pressure, or end-diastolic volume. Global diastolic function indexes, including the time constant for isovolumic relaxation, peak filling rate normalized for stroke volume, and volume elastance, were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nicardipine on myocardial function in vitro and in vivo. 229 78

To define the short-term effects of intravenous nicardipine on exercise- and pacing-induced myocardial ischemia, 15 men with coronary artery disease were studied. Nicardipine was administered as a 2 mg bolus followed by an infusion, titrated to maintain a 10 to 20 mm Hg decrease in systolic arterial pressure. At rest, nicardipine significantly decreased systemic and coronary vascular resistances and left ventricular end-diastolic pressure but increased coronary blood flow, heart rate, and myocardial oxygen consumption. With bicycle exercise performed to evoke myocardial ischemia, nicardipine prolonged exercise duration, time to of 1 mm ST segment depression, and increased cardiac work to onset of angina in most patients. These changes in cardiac performance were not associated with alteration in the product of systolic pressure and heart rate or with increased left ventricular end-diastolic pressure. During increased heart rate induced by atrial pacing to cause ischemia, the heart rate threshold for myocardial ischemia was not changed by nicardipine. This occurred despite decreased myocardial oxygen consumption, unchanged coronary blood flow, and otherwise similar hemodynamic changes as those observed during exercise. However, left ventricular end-diastolic pressure remained lower and stroke volume increased more after nicardipine with pacing stress when compared with observations before nicardipine with the same heart rate stress. These findings support beneficial antiischemic actions of nicardipine with possible prevention of ischemia-related left ventricular dysfunction.
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PMID:Acute antianginal hemodynamic effects of nicardipine in coronary artery disease. 230 Dec 44

Calcium channel blockers such as nicardipine improve outcome after global cerebral ischemia and may attenuate ischemic neuronal injury by preventing calcium influx and binding to calmodulin. We followed the temporal and regional sequence of neuronal calcium-calmodulin binding in normal rats (n = 6), untreated ischemic rats (n = 15), and ischemic rats treated with 0.05 mg/kg/hr s.c. nicardipine (n = 13). After 30 minutes of four-vessel occlusion, 40-microns brain sections were incubated in an anti-calmodulin antibody specific for calmodulin not bound to calcium and brain protein. Light-microscopic sections were examined immediately after ischemia and after 2 and 24 hours of reperfusion. Extensive staining of unbound calmodulin was seen in all hippocampal regions and in the cortex in normal rats. In untreated ischemic control rats, staining was lost, indicating calcium-calmodulin binding immediately after ischemia in all regions. However, after 24 hours, staining returned to normal in the cortex and dentate, and minimal staining returned in CA1 and CA3. Nicardipine-treated animals had significantly less calcium-calmodulin binding in CA1 and in the dentate after 2 hours of reperfusion. This study demonstrates that in clinically relevant doses nicardipine has a limited effect on calcium-calmodulin binding in selectively vulnerable regions after severe ischemia.
Stroke 1990 Jun
PMID:Calcium-calmodulin binding in ischemic rat neurons after calcium channel blocker therapy. 234 99

Renal effects of CV-4093, a newly developed dihydropyridine calcium channel blocker, were examined using anesthetized stroke-prone spontaneously hypertensive rats, and the findings were compared with those of nicardipine. An intravenous injection of CV-4093 (2 micrograms/kg) produced long-lasting hypotension with a slow-onset accompanied by moderate renal vasodilation. There were no appreciable alterations in glomerular filtration rate (GFR) and urine formation, except that urine flow (UF) increased significantly during the first 10 min after injection. When CV-4093 was administered at 10 micrograms/kg, the hypotensive action was markedly augmented. Eighty minutes after the injection, a decrease in mean arterial pressure of about 45 mmHg was observed. Simultaneously, renal blood flow increased significantly from the control value of 5.76 +/- 0.46 ml/g.min to 6.94 +/- 0.28 ml/g.min. Renal vascular resistance decreased immediately after the injection, and the response lasted for over 3 hr, thereby indicating the marked and sustained renal vasodilating effect of CV-4093. GFR was constant throughout the experiment, but UF and urinary excretion of sodium were increased significantly. Fractional excretion of sodium was also elevated, thereby suggesting an inhibitory action of CV-4093 on renal tubular reabsorption of sodium. Nicardipine at a dose of 10 micrograms/kg, a dose producing an effective hypotensive action, caused no significant increases in RBF and urine formation. The renal vasodilating and diuretic actions of CV-4093 may provide a beneficial effect in the treatment of hypertension.
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PMID:Effects of CV-4093, a new dihydropyridine calcium channel blocker, on renal hemodynamics and function in stroke-prone spontaneously hypertensive rats (SHRSP). 259 83

1. A novel formulation of nicardipine (50% standard (short acting), 50% sustained release) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled study, using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. Nicardipine 60 mg twice daily for 28 days produced a highly significant reduction in sitting blood pressure compared with placebo both pre dose (mean difference 17/8 mm Hg) and 2 h post dose (mean difference 34/26 mm Hg). 3. Home recordings confirmed the hypotensive effect and also revealed a consistent 'peak' effect between 2-4 h after dosing (mean difference 32/22) mm Hg). 4. Doppler aortovelography at 2 h post-dose showed a significant increase in in stroke and minute distance (linear analogues of stroke volume and cardiac output respectively) compared with placebo. The increase in stroke distance was linearly related to change in plasma concentration of nicardipine. 5. Of the 14 patients enrolled in the study, nine experienced troublesome adverse effects on nicardipine (headaches, facial flushing, palpitations, ankle oedema) and two of these were unable to complete the study as a result. 6. This formulation of nicardipine, in the fixed dosage used in this study, is characterized by an effective antihypertensive action but also by an unacceptable adverse effect profile, presumably due to an excess of its 'short acting' component.
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PMID:Evaluation of a long acting formulation of nicardipine in hypertension by clinic and home recorded blood pressures and Doppler aortovelography. 275 80


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