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

The hemodynamic responses to bolus injection of endothelin I (ET) at 5, 15, and 50 micrograms were examined in conscious sheep (n = 5) before and after infusion of nisoldipine at 25 micrograms/kg/h. Endothelin produced dose-dependent increases in mean arterial pressure (MAP + 87 +/- 6 mm Hg at 50 micrograms) and calculated total peripheral resistance (CTPR + 54 +/- 15 mm Hg/L/min at 50 micrograms) and decreases in heart rate (HR - 34 +/- 6 beats/min at 50 micrograms) and cardiac output (CO - 2.6 +/- 0.3 L/min at 50 micrograms) but no change in stroke volume (SV). Nisoldipine attenuated (P less than .05) the endothelin-induced changes in MAP (+26 +/- 3 mm Hg at 5 micrograms) and CTPR (+13.0 +/- 2.1 mm Hg/L/min at 50 micrograms), but not the fall in heart rate or cardiac output. These data are compatible with the hypothesis that vasoconstrictor effects of ET in sheep are in part dependent on influx of calcium through L-type channels.
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PMID:Effects of calcium channel blockade on the hemodynamic responses to endothelin infusion in conscious sheep. 193 Aug 55

To study the haemodynamic and neurohumoral effects of nisoldipine (2 X 10 mg) vs captopril (3 X 25 mg), 24 patients with heart failure (New York Heart Association class II and III) due to coronary artery disease were treated in a randomized double-blind trial over 3 months. Both drugs were well tolerated. Clinical status was similarly improved in both groups, nisoldipine exerted an additional antiischaemic effect. Nisoldipine lowered the mean arterial pressure and capillary wedge pressure acutely and also after long-term treatment. The increase in cardiac index and stroke volume index, however, which was pronounced after acute administration, was no longer present after 3 months of therapy at rest and was abolished during exercise. Norepinephrine plasma concentration increased after the first dose, plasma renin activity did not change, and aldosterone plasma concentration showed a small insignificant decrease. Urine concentrations of norepinephrine and vasopressin were slightly elevated after the 3-month therapy. After captopril, mean arterial pressure and pulmonary capillary wedge pressure decreased acutely and at follow up. Cardiac index and stroke volume index increased significantly only during exercise at follow-up. Plasma renin activity was significantly elevated and aldosterone plasma concentration only slightly lowered. In contrast to what was seen with nisoldipine, plasma norepinephrine concentration and urine catecholamine and vasopressin concentrations remained unchanged. In conclusion, the pronounced haemodynamic effects seen after the first dose of nisoldipine are mostly abolished after long-term treatment, probably due to neurohumoral counterregulation. The haemodynamic response to captopril is complete only after long-term treatment, without evidence of activation of the neurohumoral systems.
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PMID:Acute and long-term haemodynamic and neurohumoral response to nisoldipine vs captopril in patients with heart failure: a randomized double-blind study. 168 8

We studied the acute effects of the calcium antagonist nisoldipine in 10 conscious pigs with chronic heart failure. Left ventricular dysfunction was induced by permanent ligation of the left circumflex coronary artery. Two to three weeks after myocardial infarction the effects of four consecutive 10 min intravenous infusions of nisoldipine (0.05; 0.1; 0.25 and 0.5 micrograms kg-1 min-1) or its solvent on systemic haemodynamics were evaluated. In addition, we used the radioactive microsphere technique to study the distribution of cardiac output after each dose of nisoldipine. Nisoldipine significantly (P less than 0.05) increased heart rate (from 144 +/- 9 to 161 +/- 8 beats min-1), cardiac output (from 2.1 +/- 0.1 to 2.9 +/- 0.2 l min-1), stroke volume (from 14 +/- 1 to 18 +/- 1 ml) and left ventricular dP/dtmax (from 2600 +/- 100 to 3500 +/- 250 mmHg s-1), but had no effect on arterial blood pressure. Left ventricular end-diastolic pressure (from 19 +/- 2 to 16 +/- 1 mmHg) and systemic vascular resistance (from 52 +/- 3 to 37 +/- 3 mmHg min l-1) decreased after nisoldipine. The nisoldipine-induced increase in cardiac output did not affect blood flow to the kidneys, brain, liver or skin, but perfusion of the stomach (84%), adrenals (84%) and normal myocardium (from 200 +/- 25 to 321 +/- 38 ml min-1 100 g-1) as well as infarcted myocardium (from 41 +/- 8 to 61 +/- 19 ml min-1 100 g-1) increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nisoldipine improves blood flow to skeletal muscles in conscious pigs with chronic heart failure. 235 Nov 64

The effects of the calcium antagonist nisoldipine on contractions stimulated by phenylephrine and B-HT 920 (agonists of alpha 1- and alpha 2-adrenoceptors) in isolated aortic rings from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto rats (WKY) were investigated in vitro. Phenylephrine and B-HT 920 produced concentration-dependent contractions of vessels from both groups of animals. The absolute force of the contractions was less in the aortae from hypertensive rats after all doses of both agonists. Nisoldipine inhibited the B-HT 920-induced contraction much more in vessels from SHRSP than in those from normotensive WKY rats (IC50 = 1.5 X 10(-10) versus 7 X 10(-9) g/ml). The phenylephrine contractions were inhibited in SHRSP aortae by higher concentrations (IC50 = 8.5 X 10(-8) g/ml) of nisoldipine; in WKY, nisoldipine only produced a slight inhibition of phenylephrine-induced contractions. The inhibitory concentrations of nisoldipine on BHT-920-induced contractions are similar to those for the inhibition of the calcium or depolarization-induced contractions in other experiments. The alpha 2-agonist-induced contractions of rat aorta are dependent on transmembrane calcium supply. The higher efficacy of nisoldipine in aortae from SHRSP suggests an increased transmembrane availability of calcium ions in hypertension.
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PMID:Interference of the calcium antagonist nisoldipine with the abnormal response of vessels from hypertensive rats to alpha-adrenergic stimulation. 241 97

Nisoldipine, a calcium entry blocker, was given to 10 patients with congestive heart failure. During a 2 month follow-up period, 7 of the 10 patients were readmitted with pulmonary edema; daily furosemide doses were increased (128 +/- 87 to 192 +/- 135 mg/day, p less than 0.01), and plasma creatinine increased (1.5 +/- 0.5 to 1.8 +/- 0.6 mg/dl, p less than 0.05) (all values mean +/- SD). Despite this unfavorable clinical course, nisoldipine caused some beneficial chronic (1 month) hemodynamic effects. It decreased systemic vascular resistance (from 1,781 +/- 229 to 1,306 +/- 345 dynes X s X cm-5, p less than 0.01), decreased mean arterial pressure (from 88 +/- 0 to 74 +/- 4 mm Hg, p less than 0.001) and increased stroke volume index (from 27 +/- 6 to 33 +/- 9 ml/min per m2, p less than 0.02). Heart rate, pulmonary capillary wedge pressure and stroke work index did not change. However, nisoldipine's chronic renal and neurohumoral effects were not as favorable. These were assessed during a 5 hour water load (15 ml/kg body weight of 5% dextrose in water) and compared with the effects of a water load before therapy. Nisoldipine did not change creatinine clearance or sodium excretion, but decreased water excretion (from 58 +/- 35 to 46 +/- 40% of water load in 5 hours). Over this 5 hour study, mean plasma vasopressin was also higher with nisoldipine (1.9 +/- 2.3 versus 2.7 +/- 3.2 pg/ml, p less than 0.05), but mean plasma aldosterone was lower (67 +/- 31 to 47 +/- 27 mg/dl, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic renal and neurohumoral effects of the calcium entry blocker nisoldipine in patients with congestive heart failure. 288 Aug 84

Nisoldipine, a new dihydropyridine calcium antagonist, was examined for its dose-related haemodynamic effects using exercise-induced changes in aortic blood flow as measured by Doppler ultrasound. Following a two-week placebo run-in, 24 patients with stable angina pectoris were assigned double-blind to one of three groups receiving doses ranging from 2.5-20 mg/day over 8 weeks, given once or twice daily. Doppler studies identified the low dose group as responding less well at the placebo phase compared to the other two groups. There was an overall improvement in percentage change of peak velocity and stroke distance with exercise at all doses, with a dose of 5 mg/day giving optimal benefit in both variables (P less than 0.05) and no additional benefit being seen on twice-daily dosage. Six patients reporting increased chest pain exhibited a significantly worse rise in peak velocity and a fall in stroke distance to exercise (P less than 0.05) whilst on active drug compared to those who responded favourably. Doppler ultrasound can be of benefit in the haemodynamic assessment of new drugs, the recognition of non-responders and the optimization of therapeutic regimes.
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PMID:Use of exercise Doppler for non-invasive haemodynamic optimization of dose and identification of poor responders to an oral anti-anginal agent. A double-blind dose-finding study of nisoldipine. 307 61

Nisoldipine (BAY k 5552) like nifedipine, is a dihidropyridine compound with strong calcium blocking activity. The purpose of this study was to measure and compare the absolute hemodynamic effects of these two drugs before and at 30 min, 60 min and 120 min after oral intake in 20 ischemic heart disease patients with radionuclide gated cardiac scintigraphy. No significant change was seen in end diastolic volume index with either of the drugs. With nifedipine the stroke volume index (SVI) increased significantly from the basal value at 30 min (P = 0.004) and 60 min (P = 0.034) yet not significantly at 120 min. The same trend was seen in left ventricular ejection fraction (LVEF) with significant increases at 30 min (P = 0.02) and 60 min (P = 0.025) yet not at 120 min. The cardiac index increased significantly at 30 min (P = 0.001), 60 min (P = 0.002) and 120 min (P = 0.025) but the latter value was significantly lower than the 30 min value indicating the maximal effect had already passed. With nisoldipine the SVI increased significantly at 60 min (P = 0.004) and 120 min (P = 0.001) but not at 30 min. These changes were again reflected by a significant increase in LVEF at 60 min (P = 0.021) and 120 min (P = 0.002) without significant increase at 30 min. The increase in CI was highly significant at 60 min (P = 0.003) and 120 min (P = 0.001) without significant change at 30 min. Nisoldipine proved to be a potent calcium antagonist with slower onset and longer duration of action than nifedipine.
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PMID:A comparison of the acute hemodynamic effects of nifedipine and nisoldipine in patients with ischemic reduced left ventricular function. 330 60

The newer dihydropyridine calcium antagonists are structurally related to nifedipine, but may provide greater vascular selectivity and wider clinical utility. Five new dihydropyridines-nisoldipine, nicardipine, nimodipine, felodipine and nitrendipine-are reviewed with regard to their preclinical pharmacology, haemodynamic effects and clinical indications. Nisoldipine is a potent arterial vasodilator with minimal electrophysiological and negative inotropic effects. Although data are still preliminary, the drug has shown some efficacy in both exertional angina and essential hypertension. The dosing interval is not yet clearly established, but may be twice daily. Utility in congestive heart failure awaits confirmation, but preliminary studies are promising. Nicardipine is an especially potent peripheral, cerebral and coronary arterial vasodilator that causes 10-fold less myocardial depression in animals than nifedipine, and may provide important cardioprotective effects during ischaemia. Human haemodynamic studies have confirmed nicardipine's lack of negative inotropism, its ability to reduce coronary and peripheral vascular resistance, and its lack of effect on cardiac conduction. Several controlled trials have documented its efficacy in exertional angina, vasospastic angina, and essential hypertension. Nicardipine's potential as an antiatherosclerotic agent is currently under investigation. Nimodipine is undergoing a unique clinical development programme aimed at cerebrovascular disorders. In almost all species, nimodipine selectively increases cerebral blood flow and reverses cerebral artery spasm without altering cerebral oxidative metabolism or systemic blood pressure. In humans, a large, double-blind, placebo-controlled trial in subarachnoid haemorrhage showed that nimodipine significantly reduced the severity of neurological deficits associated with delayed cerebral vasospasm. Several uncontrolled trials with larger numbers of patients support these results. Nimodipine has also proved useful in reducing cerebral artery spasm during intracranial surgery, and in the prophylactic treatment of migraine headaches. A preliminary study of nimodipine in acute stroke showed promising results in limiting neurological disability. Felodipine is a very potent systemic arterial vasodilator with negligible myocardial depressant activity. It is also a renal artery vasodilator. Unlike the other new dihydropyridines, felodipine prolongs the A-H interval on electrophysiological testing, but only to about 50% of that observed with verapamil. Felodipine is undergoing clinical trials in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:'Second generation' dihydropyridine calcium antagonists. Greater vascular selectivity and some unique applications. 331 91

We studied the acute effects of nisoldipine, a new second-generation calcium channel-blocking drug, on cardiac hemodynamics and left ventricular (LV) contractility in 10 patients with grade 2 to 4 cardiac failure. Pressures were measured from an arterial line and a flow-guided catheter in the pulmonary artery, cardiac output by thermodilution, and LV ejection fraction simultaneously by radionuclide ventriculography. Ventricular loading conditions were altered by sublingual nitroglycerin to facilitate construction of LV end-systolic pressure (radial stress)-volume and stress-shortening curves. Nisoldipine, given by continuous intravenous infusion (0.12 micrograms/kg/min), reduced mean arterial pressure (p = 0.001), systemic vascular resistance (p less than 0.05), and the double product, a measurement of myocardial oxygen demand (p less than 0.01). Cardiac index, stroke index, and LV ejection fraction increased in 8 of the 10 patients. LV contractility was initially greatly reduced and was unchanged or slightly decreased during the administration of nisoldipine. Emax, the slope of the end-systolic pressure-volume curve, was unaltered in half of the patients and decreased in the others (NS), whereas the end-systolic stress-shortening curve did not change. In summary, nisoldipine has a potentially useful acute hemodynamic profile in patients with cardiac failure; it increases forward blood flow in most patients, decreases the determinants of myocardial oxygen demand, and produces little measurable changes in the inotropic state of the left ventricle.
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PMID:Effect of the second-generation calcium channel blocker nisoldipine on left ventricular contractility in cardiac failure. 337 41

1. The effects of oral nisoldipine on the perfusion and wall function of a myocardial segment distal to a fixed coronary artery stenosis were studied in 2 groups of conscious pigs with different degrees of stenosis. In group 1 (n = 8) systolic wall thickening (SWT) of the post-stenotic segment was more than 15% (27 +/- 4%); in group 2 (n = 7) SWT was less than 10% (7 +/- 1%). 2. The systemic haemodynamic profiles at baseline and during nisoldipine were similar in both groups. Dose-titrations of nisoldipine (0.24 +/- 0.02 mg kg-1 and 0.47 +/- 0.04 mg kg-1) were performed to obtain increases in heart rate of 25% and 50%, respectively. These increases were accompanied by increases in cardiac output (up to 50%) and left ventricular (LV)dP/dt max (60%), while systemic vascular resistance (35%) and mean arterial blood pressure (10%) were reduced. Left ventricular systolic and end-diastolic blood pressure and stroke volume were not affected. 3. In both groups, nisoldipine caused increases in blood flow to the non-stenotic area which favoured the subepicardium more than the subendocardium. Blood flow to the post-stenotic area of group 1 was normal at baseline and was only slightly enhanced (preferentially to the subepicardium) by nisoldipine. In the post-stenotic area of group 2 transmural and subendocardial blood flow were lower at baseline compared to the control area. Nisoldipine did not affect subepicardial blood flow but reduced subendocardial blood flow. 4. In spite of the reflex-mediated positive chronotropic actions of nisoldipine, the acute poststenotic systolic wall thickening was not affected by nisoldipine in either group. 5. We conclude that, under the experimental conditions employed (concentric stenosis, no coronary collaterals and acute drug administration), nisoldipine does not have a useful effect on post-stenotic myocardial blood flow, particularly in animals with severe stenosis. In view of a possible resetting of the baroreceptors (subsiding of the tachycardia) with chronic treatment and the presence of eccentric stenosis in many patients, additional studies are warranted.
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PMID:Nisoldipine and perfusion of post-stenotic myocardium in conscious pigs with different degrees of concentric stenosis. 340 39


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