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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Felodipine is a new calcium antagonist that was developed aiming particularly at reduction in vascular resistance-without any decrease in heart pump function. Studies in animals have demonstrated that felodipine given intravenously induces an acute fall in total peripheral resistance and blood pressure (BP), associated with acute reflex tachycardia and an increase in cardiac output (CO). During chronic treatment, the reflex tachycardia is abolished, while resistance and BP remain reduced. Acute vasodilatation has been demonstrated in the heart, kidneys, intestines, and skeletal muscles. Increased blood flow has also been demonstrated in the coronary arteries. Acute studies in humans with essential hypertension have demonstrated similar effects to what has been observed in the spontaneously hypertensive rat (SHR): a marked fall in total peripheral resistance and BP-associated with reflex tachycardia and increased CO. There is also an increase in coronary renal, and forearm blood flow. Catheterization studies have indicated that felodipine also dilates large coronary arteries. During chronic treatment in 16 males with initial diastolic BP of 100-120 mm Hg, felodipine reduced total peripheral resistance approximately 15% at rest and during exercise without significant changes in cardiac index (CI), heart rate (HR), and stroke volume (SV). As in animals, no reflex tachycardia is seen during chronic treatment. It is concluded that felodipine reduces BP in hypertensive animals and humans because of the marked effect on total peripheral resistance. CO is not reduced either at rest or during exercise. During chronic treatment, reflex tachycardia is abolished.
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PMID:Hemodynamic effects of felodipine in hypertension: a review. 169 23

Sixteen men with previously untreated diastolic blood pressure of 100-120 mm Hg were studied hemodynamically at rest supine and sitting and during a 100 W bicycle exercise. Blood pressure (BP) was recorded intra-arterially, and cardiac output (CO) by the dye-dilution method. After initial study, patients were treated with tiapamil in increasing doses (300-600 mg b.i.d., with a mean daily dose of 980 mg). The patients were restudied and then changed to felodipine (5-10 mg b.i.d., with a mean daily dose of 15 mg). Casual (cuff) BP at rest sitting was as follows: end placebo, 166/105 mm Hg; 1 year of tiapamil, 148/92 mm Hg; 1 year of felodipine, 139/86 mm Hg. Pretreatment hemodynamic results at rest sitting were as follows: BP, 169/105 mm Hg; MAP, 129 mm Hg; cardiac index (CI), 2.43 L/min/m2; total peripheral resistance index (TPRI), 4,305 dyn s/cm-5/m2. Both drugs reduced systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressure significantly in all situations. BP reduction seemed to be more pronounced on felodipine than on tiapamil. Felodipine reduced MAP by 15% at rest supine, 14% at rest sitting, and 11% during exercise. The BP reduction was entirely due to reduction in TPRI (15, 16, and 13%, respectively). CI as well as stroke index (SI) and heart rate (HR) were unchanged. Tiapamil did not reduce TPRI significantly and the fall in BP was due to a combination fall in TPRI and CI.
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PMID:Chronic hemodynamic effects of tiapamil and felodipine in essential hypertension at rest and during exercise. 169 26

Felodipine, a potent dihydropyridine calcium antagonist with a pronounced vascular selectivity, was given intravenously (0.006-0.025 mumol kg-1) to anaesthetized, open-chest dogs with denervated hearts. The result was a dose-dependent decrease in mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and left ventricular end-diastolic pressure remained relatively unchanged. Cardiac tension work (TTI) and oxygen consumption (MVO2) were reduced, probably due to the decrease in afterload. The relative reduction of the coronary vascular resistance (CVR) was greater than that of TPR. The hypotensive effect of verapamil (0.05-0.20 mumol kg-1) was small and MAP decreased mainly via a decrease in HR and SV. Higher doses of verapamil which induced vasodilatation could not be given without the development of complete atrio-ventricular dissociation. Hydralazine (11-45 mumol kg-1) decreased TPR and CVR in parallel but the decrease in MAP was partly counteracted by a powerful increase in HR, SV and cardiac inotropy which was associated with elevated catecholamine levels in plasma. When MAP and HR were maintained constant by means of aortic balloon inflation and atrial pacing, felodipine markedly increased coronary blood flow and coronary sinus oxygen saturation while SV, TTI, inotropy and MVO2 remained relatively unchanged. It is concluded that felodipine markedly dilates peripheral resistance vessels, and in particular those in the coronary vascular bed, without any cardiodepressant effects.
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PMID:Acute haemodynamic effects of felodipine, verapamil and hydralazine in the anaesthetized dog. 186 91

We assessed the effect of felodipine on left ventricular (LV) performance in 10 healthy, conscious, chronically instrumented dogs, using load-independent measures derived from variably loaded pressure-volume relations. With all reflexes intact, felodipine (25 nmol/kg, intravenously) caused significant decreases in LV end-systolic pressure (132 +/- 13 vs. 109 +/- 14 mm Hg, P less than .05) and effective arterial elastance (11.1 +/- 1.6 vs. 8.7 +/- 1.1 mm Hg/ml, P less than .01), while the heart rate increased (109 +/- 15 vs. 118 +/- 16 min-1, P less than .05). There were no significant changes in LV end-systolic volume, stroke volume or the maximum time derivative of LV pressure. The plasma felodipine concentration was 16.1 +/- 1.4 nmol/l (mean +/- time S.D.). Three relations that provide load-insensitive measures of LV performance were determined from variably loaded pressure-volume loops produced by transient caval occlusions. Felodipine increased the slopes of the LV end-systolic pressure-volume relation (8.1 +/- 0.9 vs. 10.3 +/- 1.3 mm Hg/ml, mean +/- S.D., P less than .05), the maximal time-derivative of LV pressure-end-diastolic volume relation (103 +/- 28 vs. 127 +/- 34 mm Hg/sec ml, P less than .05) and the stroke work-end diastolic volume relation (82 +/- 4 vs. 93 +/- 6 mm Hg, P less than .05). All three relations were shifted toward the left after felodipine. Similar increases in slopes and leftward shifts with felodipine, indicating enhanced contractile effect, were also present after autonomic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of felodipine on left ventricular performance in conscious dogs: assessment by left ventricular pressure-volume analysis. 201 84

The pharmacodynamics of felodipine were analyzed in patients with congestive heart failure in a randomized, double-blind, placebo-controlled study. Felodipine at a dose of 1 mg (n = 11) or placebo (n = 12) was given intravenously during a 60-min period. Hemodynamic measurements and plasma samples were obtained every 15 min during a 2-hour period. An increase in heart rate (HR, +8%, p less than 0.01) and cardiac output (CO, +36%, p less than 0.001), and a decrease in mean arterial pressure (MAP, -24%, p less than 0.001) and systemic vascular resistance (SVR, -46%, p less than 0.001), were found. Pulmonary artery, right atrial, wedge pressure, and stroke-work index did not change. Linear regression analysis showed a significant correlation between felodipine plasma levels and changes in HR (r = 0.71, p less than 0.05), MAP (r = 0.94, p less than 0.01), CO (r = 0.73, p less than 0.05), and SVR (r = 0.88, p less than 0.01). A strong hyperbolic correlation was demonstrated between individual plasma levels and changes in MAP (r = 0.97, p less than 0.001). Hysteresis analysis showed that plasma levels are directly related to the concentration at the receptor site. A clockwise hysteresis was found in HR, CO, and SVR, but not in MAP. It is concluded that changes in flow and resistance are based on a physiological adjustment, a baroreflex-mediated response to vasodilation induced by felodipine, resulting in MAPs that remain closely related to felodipine plasma levels over a wide range.
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PMID:Plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure. 247 24

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not from normotensive Wistar-Kyoto rats (WKY), exhibit oscillatory contractions in response to norepinephrine. Previous studies indicate that the mechanism for these oscillations involves altered membrane calcium and/or potassium handling, and that this vascular change is a genetic defect associated with hypertension in SHRSP. The purpose of this experiment was to determine whether treatment of SHRSP with the calcium entry blocker felodipine would alter oscillatory activity. Adult SHRSP and WKY rats were treated orally with felodipine for 8 weeks. Felodipine treatment produced a significant decrease in blood pressure in SHRSP (control SHRSP: 240 +/- 7 mmHg, n = 6; felodipine-treated SHRSP: 164 +/- 8 mmHg, n = 5, P less than 0.05; tail-cuff method). Helically-cut tail artery strips from all rats were mounted in tissue baths for isometric force recording and exposed to norepinephrine (6 x 10(-9) to 6 x 10(-6) mol/l) for 20 min at each concentration. Oscillatory activity was defined as the sum of the magnitudes of all phasic contractions occurring during the final 10 min of norepinephrine incubation. Oscillatory activity was markedly reduced in tail arteries from felodipine-treated SHRSP when compared with control SHRSP. Felodipine also inhibited oscillatory activity when added directly to the tissue bath. It seems, therefore, that felodipine may lower blood pressure in SHRSP, at least in part, by correcting the genetic defect responsible for oscillatory activity.
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PMID:Effect of felodipine on blood pressure and vascular reactivity in stroke-prone spontaneously hypertensive rats. 270 10

The hemodynamic effects of increasing dosages of felodipine, a new calcium antagonist with selective vasodilator properties, were studied in 13 patients with chronic cardiac failure. A Swan-Ganz thermodilution catheter was positioned in the pulmonary artery and hemodynamic parameters were monitored from 9 am to 6 pm for five days. On the first and the fifth day patients received placebo (P) and on the second, third, and fourth day patients received felodipine 5, 10, and 20 mg, respectively. Symptom-limited exercise tests with a bicycle ergometer were performed on both days of P and on the fourth day. A marked reduction of systemic vascular resistance (SVR) and a significant increase of cardiac index without increments of heart rate (HR) were observed after felodipine at rest. A dose response effect could be demonstrated. During exercise a significant increment of cardiac index and decrease of pulmonary wedge pressure was observed after felodipine. Felodipine showed a potent vasodilator action on systemic circulation with significant changes on both stroke volume and filling pressures at rest and during exercise without side effects.
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PMID:Hemodynamic effects of felodipine in congestive heart failure. 315 19

1. The efficacy of felodipine a new calcium channel blocker with selective vasodilator activity in the management of severe low output cardiac failure, secondary to coronary heart disease, was determined in 10 patients. 2. Haemodynamic measurements were made at rest and during dynamic exercise and left ventricular function was assessed by radionuclide ventriculography. 3. Significant increases in cardiac index, stroke volume index and ejection fraction were found particularly during exercise, both acutely and following 4 weeks administration of felodipine therapy. 4. Felodipine could well have a significant role in the long term management of the patient with chronic cardiac failure.
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PMID:Sustained haemodynamic effects of felodipine in patients with chronic cardiac failure. 320 40

Adult spontaneously hypertensive stroke-prone rats (SHRSP) and age- and sex-matched Wistar-Kyoto rats (WKY) were treated with the calcium-channel antagonist felodipine for 2-4 weeks (1 mg/g in rat chow powder). Control rats of both strains were fed untreated chow. At the end of the treatment period we measured blood pressure, net potassium efflux and intralymphocytic calcium concentration. In the untreated rats the values for these parameters were significantly higher in SHRSP than in WKY. Felodipine treatment caused a reduction in the SHRSP values to WKY levels. We conclude that the high blood pressure of SHRSP results from an increase in membrane permeability to calcium. The resultant increase in intralymphocytic calcium concentration causes an increase in net potassium efflux via calcium-activated potassium channels. By reducing the membrane permeability to calcium with felodipine, these parameters were returned to normal or near-normal levels.
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PMID:Effects of felodipine on blood pressure and lymphocyte membrane characteristics in spontaneously hypertensive stroke-prone rats. 324 Dec 7

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.
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PMID:Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress. 331 56


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