Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Felodipine is a dihydropyridine calcium antagonist which lowers total peripheral resistance and blood pressure in doses which have no effect on cardiac conduction and contractility. It increases the urinary excretion of sodium and water due to decreased renal tubular reabsorption from the glomerular ultrafiltrate. This is observed at low doses which do not affect blood pressure, renal blood flow (RBF) or glomerular filtration rate (GFR). Felodipine decreases total renal vascular resistance and causes a transient increase in RBF in patients with normal RBF. In patients with low pretreatment values, RBF is increased during chronic treatment. Felodipine does not affect normal GFR. Thus filtration fraction may decrease. In patients with severe hypertension and reduced GFR, felodipine treatment results in good blood pressure control and increased GFR. In animal models of progressive renal disease due to hyperfiltration, felodipine has no negative effect on GFR, glomerulosclerosis or survival although proteinuria may increase. In salt-sensitive rats given high salt diet, resulting in hypertension, hypoperfused kidneys and progressive renal damage, felodipine treatment results in reduced blood pressure, increased RBF and GFR, and reduced proteinuria and glomerulosclerosis. In patients with previously refractory hypertension and progressive impairment of renal function, felodipine treatment results in good blood pressure control and a reduced rate of progression. In animals, felodipine limits the extent of renal damage after ischemia and reperfusion.
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PMID:Renal effects of felodipine--a review. 161 69

This manuscript reviews the experimental evidence for a functional antagonism of Ca-antagonists against alpha-adrenoceptor-mediated increases in coronary vasomotor tone. In studies on anesthetized dogs, intravenous nifedipine effectively prevented the alpha 1-adrenoceptor-mediated increase in epicardial coronary resistance, as well as the increase in end-diastolic resistance mediated by both alpha 1- and alpha 2-adrenoceptors during cardiac sympathetic nerve stimulation. Both intracoronary and intravenous administration of nifedipine also prevented the alpha 2-adrenoceptor-mediated increase in coronary resistance distal to severe stenoses, as well as the resulting ischemic dysfunction and net lactate production during cardiac sympathetic nerve stimulation. Felodipine was equally effective as nifedipine in preventing an alpha 2-adrenoceptor-mediated increase in coronary resistance and the resulting contractile dysfunction distal to severe coronary stenoses. alpha 1- and alpha 2-Adrenergic coronary constriction also contribute to the severity of myocardial ischemia in conscious dogs during treadmill exercise. Again, nifedipine improved regional myocardial blood flow and attenuated regional contractile dysfunction during exercise-induced ischemia in conscious dogs with a chronic coronary stenosis. This beneficial effect of nifedipine was attributed to a recruitment of coronary dilator reserve and not to a reduction in heart rate or afterload. In conclusion, there is solid experimental evidence for a functional antagonism of Ca-antagonists against alpha-adrenergic coronary constriction and its contribution to myocardial ischemia.
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PMID:Prevention of alpha-adrenergic coronary constriction by calcium-antagonists. 196 99

An acute coronary occlusion causes severe low-flow ischemia in the occluded region. Calcium antagonists have the potential to reduce the rate of ischemic injury by decreasing myocardial oxygen demand, as well as by other mechanisms, especially when given prior to the onset of ischemia. However, their clinical use may be limited by their negative inotropic effects. The purpose of this study was to assess the effects of felodipine as a potentially protective agent against myocardial ischemia and reperfusion injury, independent of any negative inotropic actions, when given after the onset of low-flow ischemia. Isolated isovolumic (balloon-in-LV), blood-perfused rabbit hearts, paced at a constant heart rate, were subjected to 90 minutes of low-flow ischemia at a coronary perfusion pressure of 10 mmHg, which reduced coronary blood flow to 22-24% of baseline. After 15 minutes of low-flow ischemia, hearts received 2 x 10(-6) M felodipine (n = 7) or no drug (controls, n = 8). Felodipine was given until 15 minutes of reperfusion. During low-flow ischemia both groups of hearts had identical coronary blood flow, heart rate, left ventricular (LV) developed pressure, lactate production, and O2 consumption. However, felodipine markedly protected against ischemic diastolic dysfunction. At the end of low-flow ischemia, LV end-diastolic pressure (LVEDP) had increased from 10 +/- 1 to 28 +/- 5 mmHg in the felodipine group, while in the controls LVEDP increased to 48 +/- 8 mmHg (p < 0.05). During 30 minutes of reperfusion, felodipine had a beneficial effect upon coronary blood flow (initial postischemic hyperemia 245 +/- 38% of baseline in the felodipine group vs. 124 +/- 18% in the controls; p < 0.01) Felodipine markedly improved the recovery of contractile function [LV developed pressure recovered from a baseline of 104 +/- 4 to 75 +/- 6 mmHg (72%) in the felodipine group vs. 34 +/- 10 mmHg (32%) in the control group; p < 0.01], as well as diastolic function (LVEDP = 25 +/- 4 mmHg in the felodipine group vs. 61 +/- 10 mmHg in the controls; p < 0.05), and ATP levels (8.5 +/- 1.4 mumoles/g d.w. in the felodipine group vs. 3.9 +/- 1.4 mumoles/g d.w. in the control group, p < 0.05). Felodipine, given after the onset of low-flow ischemia, protects the myocardium during both ischemia and reperfusion by mechanisms other than reducing myocardial oxygen demand.
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PMID:Beneficial effects of felodipine on myocardial and coronary function during low-flow ischemia and reperfusion. 884 9

To assess whether the administration of felodipine protects the myocardium in a dose-dependent manner against ischemia and reperfusion, isolated rabbit hearts were infused with three different concentrations of felodipine: 10(-10), 10(-9), and 10(-8) M. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for CPK activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity; and ATP production and calcium content and tissue concentration of ATP, creatine phosphate (CP), and calcium were determined. The occurrence of oxidative stress during ischemia and reperfusion was also monitored in terms of tissue content and release of reduced (GSH) and oxidized (GSSG) glutathione. Treatment with felodipine at 10(-10) and 10(-9) M had no effect on the hearts when perfused under aerobic conditions, whilst the higher dose reduced developed pressure from 57.7 +/- 2.6 to 30.0 +/- 2.6 mmHg (p < 0.01). On reperfusion treated hearts recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. Recovery of developed pressure was 100% at 10(-8) M, 55% at 10(-9) M, and 46% at 10(-10) M. The reperfusion-induced tissue and mitochondrial calcium overload, release of CPK and noradrenaline, and oxidative stress were also significantly reduced. The effects of felodipine were dose dependent. Felodipine inhibited the initial rate of ATP-driven calcium uptake but failed to affect the initial rate of mitochondrial calcium transport. It is concluded that felodipine infusion provides dose-dependent protection of the heart against ischemia and reperfusion. Because this protection also occurred at 10(-9) M and 10(-10) M in the absence of a negative inotropic effect during normoxia and of a coronary dilatory effect during ischaemia, it cannot be attributed to an energy-sparing effect or to improvement in oxygen delivery. From our data we can envisage two other major mechanisms-(1) membrane protection and (2) reduction in oxygen toxicity. The ATP-sparing effect occurring at 10(-8) M is likely to be responsible for the further protection.
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PMID:Effects of felodipine on the ischemic heart: insight into the mechanism of cytoprotection. 892 56

The objective of this study was to test the hypothesis that treatment with the calcium antagonist felodipine in normal clinical dosages may have a myocardio-protective effect in the event of ischemia followed by reperfusion. Comparing the cardioprotective effects of felodipine and an agent of another class allowed the influence of blood pressure reduction per se to be evaluated. Twenty open-chest pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery (LAD) followed by 240 minutes of reperfusion. Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7) was administered intravenously starting at 180 minutes before the LAD occlusion in a dose that was intended to reduce the mean arterial blood pressure (MAP) by 30%. Six pigs (vehicle group) serving as controls received a mixture of polyethylene glycol (PEG) and 5% glucose, the vehicles for felodipine and SNP, intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the preinfusion levels, respectively. Infarct size as a percentage of the area at risk was 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the vehicle groups, respectively. Felodipine, given in a dose resulting in plasma levels corresponding to the therapeutic range in patients on antihypertensive treatment, reduced infarct size following myocardial ischemia/reperfusion. Afterload reduction induced by nitroprusside did not influence infarct size. Thus, felodipine exerted a myocardioprotective effect unrelated to the mechanism of afterload reduction in clinically relevant antihypertensive dosages.
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PMID:Myocardioprotective effects of felodipine in an antihypertensive dosage: an experimental study in pigs. 960 31

Felodipine is a Calcium blocker and nitroglycerin, a nitrate vasodilating agent, were compared. Two parameters were studied in vitro on bovine aortic media. Calcium uptake and vascular tone. The Calcium uptake measurement was performed by incubating in Krebs solution small slices of the preparation in the presence of 45Ca. Studies on vascular tone were performed on deendothelialized bovine aortic rings suspended in Krebs solution. Felodipine (1nM-100microM) decreases Ca2+ uptake and relaxes the preparation while nitroglycerin's 1nM-100microM) action is also inhibiting but very weak. When the preparation is stimulated by alpha 1-adrenergic against phenylephrine 1microM, then nitroglycerin 100microM has a much stronger inhibiting effect on Call uptake and vascular tone than felodipine 100microM. These results are reversed when the preparation is stimulated by KC165.4mM. Then felodipine 100nM exerts a strong inhibiting effect on Ca2+ uptake and vascular tone while nitroglycerin's 100nM inhibiting action is very weak. It is well known that in cases of endothelium disfunction the adrenergic stimulation provokes vasoconstriction and ischemia. This ischemia induces a second phase of vasoconstriction that is due to a depolarization provoked by the increased levels of extracellular K+. Felodipine is able to antagonize the consequences of such a depolarization. Thus, felodipine may be useful as an additional agent to nitroglycerin's treatment and that is the clinical message of our findings.
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PMID:Comparison of felodipine and nitroglycerin actions on vasomotion physiology. 1279 61

The results of 24-hour blood pressure monitoring (BPM) help to divide patients into therapeutic groups according to the leading hemodynamic mechanism offorming essential arterial hypertension (EAH). In patients with a mean day heart rate of > or =73 bpm antihypertensive therapy should begin with beta1-adrenoblockers when not contraindicated. In patients with a mean day heart rate of < or =73 bpm antihypertensive therapy may be started with preparations of other pharmaceutical groups. In this study, Plendil or Concor was administered as a chronotherapy; later their combination was used, and diuretics or ACE inhibitors were added when necessary. At any stage of the study, starting from the second week of therapy, if blood pressure (BP) was normal and there were ischemic episodes according to matched 24-hour BPM and ECG, Cardiket and, when not contraindicated, Aspirin, were added. The offered algorithm of choice of therapy made it possible to achieve a good antihypertensive effect in 84% of patients and a satisfactory effect in 7% of patients, which was accompanied by a tendency towards the shortening of total ischemia duration and lowering the frequency of myocardial hypokinesia. The effect of the therapy was poor only in 9% of patients, 2% of whom one left the study due to adverse reactions before BP was normalized. BP was normalized on the 8th week of treatment in 75% of patients. It is appropriate to include matched 24-hour BPM and ECG in the follow-up of patients with EAH and coronary artery disease upon discharge under the conditions of routine physical load. According to 24-hour BPM, mean day heart rate and total length of ischemia grow during this period due to an increase in physical and emotional load, which requires correction of the therapy.
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PMID:[Treatment of patients with essential hypertension using bifunctional 24-hour blood pressure and ECG monitoring]. 1720 Dec 72