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

We have investigated whether Ca2+ antagonists of the dihydropyridine type (nifedipine, nisoldipine, and nitrendipine) attenuate or abolish the ischemia-reperfusion-induced depletion of the cardiac stores of norepinephrine (NE). The experiments were performed using isolated, Langendorff-perfused rat hearts. Ischemia (global) was induced for 15 or 60 min at 37 degrees C and was followed by normothermic reperfusion. Left ventricular NE content was assayed by high-performance liquid chromatography with electrochemical detection. The continued presence of nifedipine (0.03 microM), nisoldipine (0.03 microM), or nitrendipine (0.03 microM) before and after the ischemic episode abolished the loss of NE caused by 15 min but not 60 min of ischemia and reperfusion. Nifedipine, 0.03 microM, but not diltiazem, 0.24-1.22 microM, or verapamil, 0.22-1.09 microM, attenuated (p less than 0.05) NE depletion when added only on reperfusion.
 ...
PMID:Inhibitory effect of calcium antagonists on the depletion of cardiac norepinephrine during postischemic reperfusion. 241 Jun 93

The effects of nifedipine against ischemia- and reperfusion-induced arrhythmias were investigated using anesthetized rats with transient coronary artery occlusion. Nifedipine (5 micrograms/kg i.v.) administered 10 min prior to occlusion significantly decreased the incidence of arrhythmias occurring during 20-min coronary occlusion. The incidence and duration of reperfusion-induced ventricular fibrillation and subsequent mortality following 5-min coronary occlusion were also significantly reduced by this intervention. However, administration of nifedipine 1 min prior to reperfusion afforded no protection against reperfusion arrhythmias. To investigate whether nifedipine possesses a true antiarrhythmic action or merely extends the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances, reperfusion was initiated after 3, 5, 7, 10, 20, and 30 min of ischemia. Nifedipine reduced the incidence of reperfusion-induced ventricular fibrillation after all ischemic intervals, with no change in the time of peak vulnerability to reperfusion arrhythmias. Measurements of coronary flow with 153Gadolinium microspheres indicated that flow within ischemic tissue relative to that in normal tissue was significantly increased by nifedipine. Thus, administration of nifedipine prior to occlusion affords a protective effect against ischemia- and reperfusion-induced arrhythmias, and this action is not due to extension of the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances.
 ...
PMID:Ischemia- and reperfusion-induced arrhythmias: beneficial actions of nifedipine. 243 54

In order to further elucidate the mechanisms involved in therapeutic effects of prostacyclin and Iloprost in peripheral ischemic disease, the actions on microvascular tone, capillary density, and increases in venular permeability induced by inflammatory mediators and by ischemia were investigated in the cheek pouch of anaesthetized Syrian hamsters using intravital videomicroscopy and--for quantification of vascular permeability--venular leakage of fluorescein-labelled dextran (FITC-D; Mw 70,000). Iloprost at the nonhypotensive, platelet aggregation-inhibiting dose of 0.5 microgram/kg/min i.v. significantly increased the diameters of arterioles and venules and the density of perfused capillaries and antagonized vasoconstriction and decrease of perfused capillary density as induced by Leukotriene D4 (LTD4; 10(-7) M). Iloprost significantly antagonized venular leakage of FITC-D induced by histamine (10(-5) M), serotonin (10(-5) M), bradykinin (10(-6) M) and reperfusion after 30 min ischemia. Topical application of Iloprost (10(-8) M), intraarterial infusion of Prostaglandin E1 (PGE1; 2.0 micrograms/kg/min), and topical Forskolin (10(-5) M) also attenuated histamine-induced venular FITC-D leakage, while topical PGE1 (10(-7) M) and i.v. infusion of Nifedipine (30 micrograms/kg + 10 micrograms/kg/min) were not effective. It is concluded, that microvascular effects of Iloprost by improvement of tissue perfusion and functional antagonism of mediator-induced tissue edema and vasospasm could contribute to therapeutic effectiveness in ischemic diseases.
 ...
PMID:Action of the stable prostacyclin analogue iloprost on microvascular tone and -permeability in the hamster cheek pouch. 244 31

Arginine8-vasopressin (AVP) causes hindlimb paralysis, loss of nociceptive responsiveness and increased arterial pressure after spinal subarachnoid injection in rats. In these experiments, the effects of paralytic intrathecal doses of AVP on rat brain and spinal cord blood flow, vascular resistance and cardiac output were measured using radiolabeled microspheres. Ten minutes after injection, AVP (10-100 pmol) elevated mean arterial pressures significantly, increased vascular resistances in thoracic and lumbosacral spinal cord and reduced blood flow to the lumbosacral spinal cord without altering cardiac output, total peripheral resistance and blood flow to brain and other spinal cord regions. Lumbosacral blood flows remained significantly reduced 30 min after injection of 100 pmol of AVP, and recovered to pretreatment base-line levels by 60 min postinjection. Lactic acid concentrations were elevated significantly in spinal cerebrospinal fluid samples removed 5 to 15 min after AVP injection (100 pmol). The selective AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arg8-vasopressin, which previously blocked the effects of AVP on hindlimb motor and nociceptive function, in these experiments also blocked the AVP-induced increases in arterial pressure and reductions in lumbosacral perfusion. Intravenous infusion of the vasodilators papaverine and nifedipine failed to block AVP-induced hindlimb paralysis. Nifedipine, however, did accelerate subsequent recovery of hindlimb motor function, although it did not alter the lumbosacral blood flow reductions measured at 10 and 30 min after AVP injection. These findings indicate that AVP has significant vascular effects in the rat spinal cord that are associated with ischemia and neurological dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Arginine8-vasopressin reduces spinal cord blood flow after spinal subarachnoid injection in rats. 252 87

The Nifedipine-Total Ischemia Awareness Program was designed to evaluate the prevalence, prognostic implications and effect of therapy on painful and painless myocardial ischemic episodes in a nationwide study of patients with angina pectoris. Three hundred forty-eight patients with at least 2 anginal attacks/week while taking antianginal medications were enrolled at 53 participating centers between September 1, 1986 and March 31, 1988; 312 of the 348 patients formed the study group, while 36 patients formed the control group. At least 1 episode of ST-segment depression during two 48-hour periods of Holter monitoring was present in 136 of the 312 patients in the study group. In these 136 patients, there was a total of 372 episodes of ST-segment depression, of which only 69 (18%) were painful; 85% of the 136 patients had either painless episodes only or both painless and painful episodes. Despite apparently adequate antianginal therapy, 48 patients had greater than or equal to 3 episodes of ST-segment depression/48 hours of ambulatory electrocardiographic monitoring, and 38 patients greater than 60 minutes of ST-segment depression. After nifedipine was administered, there was a 23% reduction in the mean number of episodes of ST-segment depression (2.7 +/- 0.3 to 2.1 +/- 0.2, p less than 0.01). The most pronounced effects were found in the 48 patients with greater than or equal to 3 episodes of ST-segment depression and the 38 patients with greater than or equal to 60 minutes of total ischemic time.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The Nifedipine-Total Ischemia Awareness Program: a national survey of painful and painless myocardial ischemia including results of antiischemic therapy. 256 24

The effects of intracoronary nifedipine on myocardial blood flow (flow probe or microspheres) and regional function (ultrasonic crystals in subendocardium) were examined both in the normal myocardium and in myocardium made ischemic by a partial coronary occlusion in the open-chest anesthetized dog. In a first group of experiments (n = 7), without ischemia, nifedipine infused into the left anterior descending coronary artery (LAD) during a 1-min period (doses 0.75-8 nmol/kg body weight) decreased coronary vascular resistance with a maximal effect at 4 nmol/kg. Systolic segment shortening was decreased from 10.7 to 7.4% (p less than 0.05) by 6 nmol/kg, whereas lower doses had no effect. In a second experimental group (n = 7), a partial LAD occlusion was applied to decrease subendocardial segment shortening by about 50%. Nifedipine (2 nmol/kg) injected into the partially occluded LAD induced a marked segmental bulging during early systole and systolic segment shortening was eliminated (from 4.2 to -3.1%, p less than 0.02) in the LAD-dependent myocardium. Concomitant with the decreased regional function, nifedipine caused a transmural redistribution of myocardial blood flow in the ischemic area, the endocardial/epicardial blood flow ratio increasing from 0.49 to 0.61 (p less than 0.02). It is concluded that ischemia potentiates the direct depressant effect of nifedipine on myocardial regional function.
 ...
PMID:Effects of intracoronary nifedipine on blood flow and segment shortening in normal and ischemic myocardium: potentiation by ischemia of the negative inotropic effect. 258 Jan 33

In myocardial necrosis produced by isoproterenol (beta-adrenergic agonist) marked increase in creatine phosphokinase, phospholipase and significant decrease in cardiac glycogen and phospholipid levels were observed. The enhanced levels of lipid peroxides, xanthine oxidase activity and lowering of superoxide dismutase may lead to excessive formation of free radicals resulting in cardiac cell damage. Nifedipine--a calcium antagonist, Propranolol--a beta-blocker and guggulsterone a lipid lowering agent showed marked reversal of these metabolic changes related to ischemia induced by isoproterenol.
 ...
PMID:Reversal of changes of lipid peroxide, xanthine oxidase and superoxide dismutase by cardio-protective drugs in isoproterenol induced myocardial necrosis in rats. 263 88

The characteristics of ischemic episodes in exercise test and daily activities were observed in a silent myocardial ischemia (SMI) group and an anginal group (23 patients each). 15 patients in the SMI group were treated with nifedipine. In exercise test, the time of onset of ischemia was earlier and the ischemic threshold was lower in SMI group. During daily activities, the frequency of SMI was high. The heart rate just before onset of SMI was lower than the mean heart rate in 24-hour Holter monitoring. The highest frequency of SMI was found between 5 AM and 12 noon. Postinfarction patients had a higher frequency and a longer duration of SMI than noninfarction patients. The frequency and duration of SMI decreased in the 15 patients treated with nifedipine in SMI group. It is concluded that silent ischemic episodes were frequent and occurred easily. They might be associated with poor prognosis in CAD patients. Nifedipine was effective in reducing the frequency and duration of SMI in our patients.
 ...
PMID:[Clinical characteristics of silent myocardial ischemia and the effect of nifedipine treatment]. 263 87

A placebo-controlled, double-blind, crossover study was conducted to determine the effects of nifedipine (60 to 90 mg per day) monotherapy and propranolol (240 mg per day) monotherapy on symptoms, angina threshold, and cardiac function in patients with chronic stable angina. Following a two-week placebo period, patients were randomly assigned to receive either nifedipine or propranolol for a five-week treatment period, after which they crossed over to the alternative regimen. All 21 patients were men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. New York Heart Association functional class improved in patients taking either nifedipine or propranolol, and nitroglycerin consumption decreased with both treatments compared with placebo. Nifedipine significantly delayed the onset of chest pain and 1 mm of ST-segment depression during bicycle exercise; increases with propranolol were smaller and not statistically significant. Nine patients had a preferential clinical response to nifedipine compared with six patients to propranolol; this was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvement in radionuclide ejection fraction at identical work loads. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14 percent (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output. Thus, nifedipine is more effective on several measurements than propranolol when administered as single drug therapy in stable angina and has the advantage of preserving cardiac output during exercise.
 ...
PMID:Chronic stable angina monotherapy. Nifedipine versus propranolol. 264 28

In the guinea pig heart-lung preparation, the protective effects of nifedipine and R 58735 on cardiovascular alterations following mild (35 min) and severe (60 min) ischemia and reperfusion (30 min) were studied. Nifedipine and R 58735 were equi-protective against the effects of mild ischemia with respect to functional (LVP, dp/dt, and cardiac output) and biochemical (ATP, CrP, and adenylate charge) parameters. A clear difference, however, was observed between nifedipine and R 58735 upon severe ischemia, where R 58735 produced a significantly greater protection of functional, but not of biochemical parameters. Since no significant differences between the two compounds were found with respect to the concentrations of high energy phosphates after 35 and 60 min of ischemia before reperfusion, an energy sparing effect is not likely to be responsible for the difference between nifedipine and R 58735 in severe ischemia. An additional protective effect of R 58735 upon reperfusion in severe ischemia experiments may explain the difference between the two compounds.
 ...
PMID:Protective activity of nifedipine and R 58735 upon damage caused by global ischemia in the guinea pig heart-lung preparation. 281 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>