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)

Ventricular action potentials and longitudinal conduction times over short distances of epicardium were recorded in isolated rabbit hearts. Global ischemia produced a progressive decrease of resting membrane potential, depression of action potentials, and conduction slowing to approximately 50% of control values over 8 to 10 min. Verapamil (2 X 10(-6) M) markedly attenuated ischemia-induced conduction slowing in association with less depression of maximum upstroke velocity (Vmax) and slightly less change in resting membrane potential. In contrast, Bay K 8644 (10(-7) M), a calcium-channel agonist, exacerbated ischemia-induced conduction slowing and depression of Vmax but did not significantly affect resting membrane potential. Regression analysis of Vmax vs resting membrane potential and the square of conduction velocity vs Vmax demonstrated that verapamil and Bay K 8644 shifted these relationships in opposite directions. The results indicate that the calcium-channel activation state can modulate slowing of conduction during early ischemia. This is most likely due to alterations in calcium influx before and/or during ischemia. There appear to be three possible components to this effect: (1) a small alteration in the magnitude of ischemia-induced depolarization, (2) alterations of membrane responsiveness at depolarized values of resting membrane potential, and (3) alterations in "nonactive" components of conduction during ischemia, such as changes in excitability or cell-to-cell coupling.
 ...
PMID:Modulation of conduction slowing in ischemic rabbit myocardium by calcium-channel activation and blockade. 245 5

The effects of calcium channel antagonists and an agonist on susceptibility to ventricular fibrillation were investigated using chronically instrumented dogs with a healed anterior wall myocardial infarction. Three to 4 weeks after the infarction, a 2-min coronary occlusion was initiated during the last minute of exercise and continued for 1 min after cessation of exercise. Twenty-two dogs developed ventricular fibrillation (susceptible) whereas the remaining 14 animals did not (resistant) during this exercise plus ischemia test. The exercise plus ischemia test was repeated in the susceptible dogs after the following treatments: verapamil (n = 17, 250 micrograms/kg), nifedipine (n = 9, 10 and 100 micrograms/kg) and magnesium sulfate (n = 9, 100 mg/kg). Verapamil prevented ventricular fibrillation in all dogs whereas the high dose of nifedipine protected eight of nine animals; the low dose of nifedipine protected one of nine animals and magnesium sulfate protected seven of nine dogs. Finally, the calcium channel agonist Bay K8644 (n = 9, 30 micrograms/kg) was given to resistant animals. All resistant dogs developed ventricular fibrillation when the exercise plus ischemia test was repeated after Bay K8644. These data suggest that calcium entry may play a critical role in the development of arrhythmias during ischemia, with increased calcium entry provoking arrhythmias and calcium entry blockade preventing the lethal events.
 ...
PMID:Effect of calcium channel antagonists on susceptibility to sudden cardiac death: protection from ventricular fibrillation. 246 81

Ro 40-5967 is a structurally novel calcium antagonist that binds to the verapamil binding site but has very weak negative inotropic effects compared to verapamil. The goals of the present study were to assess the effects of Ro 40-5967 on myocardial function during ischemia, and to compare them to those of verapamil. For this purpose, in anesthetized dogs where the circumflex coronary artery was cannulated and perfused at controlled pressure, myocardial function was measured using piezo electric crystals implanted into the endocardium. Myocardial distribution of coronary blood flow was assessed using radioactive microspheres. Ischemia was produced by lowering perfusion pressure from 100 to 15 mm Hg in steps. During ischemia, Ro 40-5967 partially prevented the decrease of segmental shortening (p less than 0.01) and increased coronary flow, especially in the endocardium (p less than 0.01). In contrast, verapamil did not improve myocardial function during ischemia. The protective effect of Ro 40-5967 could be partially explained by the decrease of arterial pressure and heart rate induced by Ro 40-5967. However, Ro 40-5967 injected directly inside the coronary artery did not induce systemic effects, but still had protective effects (p less than 0.05). Verapamil injected intracoronary produced severe cardiac depression. We conclude that in the present model during ischemia Ro 40-5967 has no negative inotropic effects, and in contrast to verapamil can improve the myocardial function.
 ...
PMID:Effects of Ro 40-5967, a novel calcium antagonist, on myocardial function during ischemia induced by lowering coronary perfusion pressure in dogs: comparison with verapamil. 248 Nov 85

Calcium antagonists such as verapamil/diltiazem predominantly delay av-nodal conduction. Thus, the most important clinical indications for their application are the av-nodal-reentrant-tachycardia as well as the slowing of rapid ventricular response in intraatrial tachyarrhythmias. To reestablish sinus rhythm in atrial fibrillation, verapamil should be combined with chinidin. Usually, ventricular arrhythmias cannot be suppressed by calcium antagonists, but they may be indicated in exercise-induced ventricular arrhythmias and tachycardias arising from the right ventricular outflow tract. Verapamil/diltiazem are effective in ischemia-induced tachyarrhythmias, especially ventricular fibrillation, because of the reduction of ischemia-related conduction delay in the ischemic zone. The effectiveness of calcium antagonists in the secondary prevention of myocardial infarction can not yet be definitively defined.
 ...
PMID:[Anti-arrhythmia effects of calcium antagonists]. 269 64

This study was performed to determine if the changes in cellular coupling induced by simulated ischemia were rate-dependent and if they contributed to the rate-dependent conduction slowing that occurs in this setting. We also sought to determine if the known ability of verapamil to prevent ischemia-induced conduction changes might be related to the preservation of cellular coupling. We studied the effects of increasing stimulation frequency from 0.5 to 2.0 Hz on the simultaneous changes in the maximum rate of rise (Vmax) of the action potential upstroke, conduction velocity, and internal longitudinal resistance (ri) determined by the voltage ratio method in superfused guinea pig papillary muscles under conditions of simulated ischemia (SI). When stimulation frequency was 0.5 Hz, 30 minutes of SI caused a 16.5% decrease in Vmax, a 16% increase in ri, and a 12.9% decrease in conduction velocity. When stimulation frequency was increased to 2.0 Hz, 30 minutes of SI caused a 30% decrease in Vmax, a 72.9% increase in ri, and a 21.4% decrease in conduction velocity. Thus, the changes were rate-dependent. Verapamil (1 X 10(-6) M) did not influence the changes in these parameters during SI at 0.5 Hz nor the decrease in Vmax during SI at 2.0 Hz, but it did prevent the rate-dependent increase in ri. Verapamil also prevented the rate-dependent decrease in conduction velocity induced by SI. Our results suggest that during simulated ischemia the rate-dependent component of the increase in Ri contributes to the rate-dependence of the conduction slowing.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of rate-dependent cellular uncoupling on conduction change during simulated ischemia in guinea pig papillary muscles: effect of verapamil. 273 41

Inability to maintain cellular calcium homeostasis is a critical factor in the pathogenesis of cellular ischemic injury and may mediate oxygen radical release in the reperfusion period. We assessed the effect of the selective calcium channel blocker verapamil on the performance of rat hyperemic island skin flaps. Pretreatment with verapamil markedly improved survival of skin flaps after 6 hours of venous cross-clamping compared with animals receiving placebo only (99% vs 53.3%; p less than 0.01). Verapamil also prevented the formation of lipid peroxidation products and the depletion of the endogenous antioxidant glutathione, suggesting that the beneficial effect of verapamil is the result of protection against oxygen radical injury. After 12 hours of venous cross-clamping, verapamil did not improve survival of skin flaps despite protection against lipid peroxidation. Oxygen radical release is therefore a crucial event in the pathogenesis of skin flap necrosis after short-term ischemia but is of less significance in long-term ischemia.
 ...
PMID:Verapamil improves survival of rat hyperemic island skin flaps. 279 37

The authors made a comparative analysis of structural and functional changes of the myocardium of 21 dogs after a 30 minute limitation of the blood circulation in the circumflex branch of the left coronary artery with subsequent 30-minute reperfusion during intravenous administration of verapamil in the period and before the beginning of limitation of the coronary circulation. Verapamil produced an essential cardioprotective effect during its preventive use. The effect was less pronounced when the agent was administered after the development of ischemia.
 ...
PMID:[Morphofunctional analysis of the efficacy of verapamil in experimental ischemia]. 280 May 8

The present study was initiated to determine whether pretreatment of gerbils with calcium channel blockers, flunarizine and verapamil would prevent injury to cerebral ATPases following secondary ischemia consisting of 60-min bilateral clamping of the carotids followed by 40 min of reperfusion. The sequence of ischemia produced a deficit in Na+,K+-ATPase activity without influencing Ca++,Mg++- or Mn++-sensitive ATPases. Pretreatment with flunarizine significantly prevented the damage to Na+,K+-ATPase while the effect of verapamil was marginal. Verapamil, along with dimethylsulfoxide (DMSO), reduced the mortality rate of gerbils subjected to the paradigm of ischemia. When added directly to the cerebral fractions in vitro the two calcium channel blockers inhibited Na+,K+-ATPase alone. Flunarizine was more potent in vitro than verapamil.
 ...
PMID:Protective action of calcium channel blockers on Na+,K+-ATPase in gerbil cerebral cortex following ischemia. 283 93

Atropine, calcium, calcium-channel blockers, beta-adrenergic-receptor blockers, oxygen, morphine, vasodilators, and potent diuretics are frequently used in advanced cardiac life support (ACLS). Since the last AHA conference on ACLS standards, little controversy has arisen regarding the use of oxygen, morphine, vasodilators, or potent diuretics. In 1979, a full vagolytic dose of atropine was recommended for use early in the course of asystolic or bradycardiac arrest. Since then reports suggest that this higher dose of atropine may be of some limited value in treating this highly resistant form of arrest. The routine use of calcium for asystole, bradycardiac arrest, and electromechanical dissociation has come under intense scrutiny. Studies have failed to demonstrate improved survival and have found potentially deleterious levels of serum calcium when calcium was administered according to AHA standards. It is also possible that postanoxic cerebral injury is exacerbated by the use of calcium. No controversy exists, however, concerning the use of calcium for the moribund patient with possible hypocalcemia or with an excess of calcium-channel blockers. The use of calcium-channel blockers has been advocated to prevent or retard the intracellular accumulation of calcium, which may cause irreversible postanoxic tissue damage. Calcium-channel blockers may also be useful in preventing or decreasing cerebral and coronary arteriospasm. These drugs have antianginal properties that may decrease ischemia. The antiarrhythmic effect of verapamil is particularly useful in the treatment of uncomplicated paroxysmal supraventricular tachycardia. Verapamil and diltiazem slow conduction through the atrioventricular node and may be used to slow the ventricular response in atrial fibrillation and flutter.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiovascular pharmacology. III: Atropine, calcium, calcium blockers, and beta-blockers. 287 54

It remains unknown whether the actions of verapamil to depress and nifedipine to enhance contractile function of ischemic myocardium influence the degree of myocardial ischemic injury. Thus, we measured intramyocardial pH using fiberoptic pH probes in 43 anesthetized open-chest dogs pretreated for 30 min with verapamil, or nifedipine in doses that decreased aortic pressure 10 to 15 mm Hg before ligation of the left anterior descending coronary artery for 15 min. Drugs were continued during the 15-min ischemic period until the animals were euthanized without reperfusion: verapamil, 10-20 micrograms/kg/min and nifedipine, 2 to 4 micrograms/kg/min i.v. Verapamil-treated dogs showed higher pH of ischemic subendocardium after 15 min ischemia (6.75 +/- 0.07) than did the nifedipine (6.48 +/- 0.04) or placebo (6.43 +/- 0.05) groups, even if the animals were paced (6.71 +/- 0.11) to prevent the negative chronotropic effect of verapamil (P less than 0.01). Neither verapamil nor nifedipine changed collateral myocardial blood flow from 0.10 +/- 0.02 in the subendocardium and 0.17 +/- 0.03 ml/min/g in the subepicardium. Left ventricular function estimated by left ventricular dp/dt was depressed 15% by verapamil and enhanced 26% by nifedipine. Thus, verapamil, but not nifedipine, relieves acidosis of ischemic myocardium after acute coronary occlusion in doses that sustain a 10 to 15 mm Hg decrease in aortic pressure. Nifedipine, in doses that produced the same 10 to 15 mm Hg decrease in mean aortic pressure, did not increase intramyocardial pH, as it enhanced contractile function, estimated by left ventricular dp/dt.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Contrasting effects of verapamil and nifedipine on pH of ischemic myocardium in the dog. 291 74


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