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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The postischemic acute renal failure is one of the most important and frequent complications after surgery for renal artery and thoracoabdominal aortic diseases. In a canine model we studied the possible beneficial effects of Prostaglandin E1 (PGE1), Diltiazem and Superoxiddismutase (SOD) on postischemic renal function. 46 dogs were exposed to 3 hours ischemia. In 35 dogs PGE1 (n = 10), Diltiazem (n = 10), Superoxiddismutase (n = 10) or both PGE1 and SOD (n = 5) were given intravenously. 11 dogs treated with normal saline served as controls. Glomerular filtration rate, renal plasma flow, plasma creatinine, blood urea nitrogen, urine volume, free water clearance and renovascular resistance were calculated before and after renal ischemia. Radionuclide studies were performed on the third postoperative day. Two weeks later clearance measurements were repeated and kidneys were removed for histology. PGE1, Diltiazem and SOD significantly attenuated the post-ischemic fall in glomerular filtration rate and renal concentrating ability as well as the postischemic changes of tubular epithelium on histology.
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PMID:[The role of pharmacologic kidney protection in preventing post-ischemic renal failure in animal experiment]. 837 23

The alteration of calcium homeostasis is of outstanding importance for the cytotoxic reactions that place after ischemia, for this reason calcium channel blockers have been used with the purpose to protect the lung during transplantation. This work analyses the effect of Diltiazem at two different doses (10 mg/l and 50 mg/l) on Wistar rat alveolar type II cells, incubated for 8 hours at 37 degrees C and at 4 degrees in an electrolytic solution. Total protein content and the rate of protein synthesis derived from 35S Methionine uptake were used to evaluate cells viability. The data showed that Diltiazem did not improve cellular viability after warm and cold metabolic ischemia either using 10 mg/l or 50 mg/l, while at 4 degrees C a significantly cytotoxic effect (p < 0.05) was observed. At this temperature toxicity was independent on the dose used.
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PMID:The influence of high and low doses of diltiazem on isolated alveolar type II cells during normothermic and hypothermic ischemia: cytoprotection or cytotoxicity? 859 20

Calcium channel antagonists can reduce calcium overload induced by myocardial ischemia and thereby protect against malignant arrhythmias. However, these drugs may also adversely affect cardiac contractile function. Mibefradil is a new calcium antagonist that can inhibit cardiac calcium current without reducing myocardial force development. The effects of mibefradil on the inducibility of arrhythmias both before and during ischemia were therefore evaluated in animals with healed infarctions. First, a 2-min coronary occlusion was made during the last minute of exercise (n = 48): 25 animals had ventricular fibrillation (susceptible), whereas 23 did not (resistant). On a subsequent day, programmed electrical stimulation (PES, 8 paced beats followed by two extrastimuli) induced ventricular tachycardia in 19 of 25 susceptible animals but in none of the resistant animals (chi square = 24.6, P < .001). Verapamil (n = 14), diltiazem (n = 13) and mibefradil (n = 14) elicited significant dose-dependent decreases in refractory period and in the Q-Tc interval (except mibefradil) yet failed to prevent PES-induced arrhythmias. Diltiazem and verapamil also increased P-R interval and reduced the maximum rate of change of left ventricular pressure, whereas mibefradil did not. However, all three drugs abolished arrhythmias induced by PES during ischemia. In contrast, lidocaine suppressed PES-induced arrhythmias but failed to prevent ischemically induced arrhythmias. Thus mibefradil can prevent ischemically induced ventricular fibrillation without adverse actions on either A-V nodal conduction or contractile function. These data further suggest that calcium entry may play a critical role in the initiation of ventricular fibrillation during ischemia, whereas other factors must be responsible for the extrasystoles induced by PES.
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PMID:The effects of mibefradil, a novel calcium channel antagonist on ventricular arrhythmias induced by myocardial ischemia and programmed electrical stimulation. 866 18

In the 10 years since our previous review of this topic, the acute coronary syndromes (Q wave myocardial infarction [QMI], non-Q wave MI [NQMI], and unstable angina) have been more clearly categorized. Many of the differences delineated between QMI and NQMI still hold: a less extensive infarction and a lower in-hospital mortality, but a larger degree of jeopardized myocardium leading to a higher incidence of reinfarction and recurrent angina. The pathophysiology of NQMI appears to be similar to that of unstable angina except for the greater incidence and extent of thrombus formation and coronary artery occlusion with NQMI. Prognostic studies have shown that ST depression and anterior infarct location are associated with a greater risk for posthospital clinical events than the findings of ST elevation and other infarct locations. Symptom-limited stress testing using electrocardiogram and thallium-201 imaging are now recommended before discharge or in the early postdischarge period, with coronary arteriography recommended for evidence of residual ischemia. Aspirin and low dose heparin should be administered on admission after NQMI to decrease further thrombus formation, and aspirin continued in the posthospital period. Diltiazem administration is recommended in NQMI without evidence of pulmonary congestion to prevent recurrent nonfatal acute myocardial infarction. Percutaneous transluminal coronary angioplasty and surgical revascularization should be reserved for patients with NQMI with residual ischemia.
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PMID:The non-Q wave myocardial infarction revisited: 10 years later. 912 24

In the presence of severe rejection, cardiac allograft perfusion has been shown to be impaired. Since a functionally reversible vasoconstrictor component has been identified in this condition and rejection does not reverse if ischemia does not, we hypothesized that diltiazem may be beneficial in this condition. Experiments were performed on dogs with heterotopic heart transplants and chronic instrumentation for the assessment of allograft perfusion. Two groups of cardiac allograft recipients were studied: untreated recipients and recipients treated with the calcium antagonist diltiazem (180 mg twice daily, orally). Allograft blood flow was monitored daily along with plasma diltiazem levels. The lymphoproliferative response to mitogens was studied at selected intervals until terminal rejection. Contractile function of the graft was assessed daily by palpation. Without immunosuppression, terminal rejection was observed within 7 days. Rejection was confirmed by histology; cellular infiltration and myocyte necrosis were present in all cardiac allografts but to a significantly lesser degree in diltiazem-treated recipients. The mean blood flow of heterotopically implanted hearts was in the range of 35-50 ml/min, which decreased steadily in untreated recipients. In contrast, significant improvement of allograft perfusion was observed in diltiazem-treated recipients at days 4-6 after transplantation. Diltiazem also significantly attenuated mitogen-induced lymphocyte proliferation at peak sensitivity (2 days after transplantation). Diltiazem plasma concentrations were in the therapeutic range (30-60 ng/ml) before and after cardiac transplantation. Results of the present study demonstrate beneficial effects of diltiazem in the course of severe cardiac rejection. Such findings support its use during rejection when maintenance of graft blood flow and myocyte protection may be important for myocardial function and viability.
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PMID:Cardioprotective effects of diltiazem during acute rejection on heterotopic heart transplants. 916 40

Class I antiarrhythmic drugs do not decrease, but increase, the risk of ventricular fibrillation in the ischemic myocardium. On the contrary, vulnerability to fibrillation related to ischemia appears to be substantially reduced by calcium antagonists. We assessed whether the calcium antagonist diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusion) could prevent the profibrillatory effect or even partially restore the antifibrillatory effect of a class I antiarrhythmic drug, flecainide (1 mg/kg bolus plus 0.04 mg/kg/min infusion) in the ischemic myocardium of anesthetized, open-chest pigs. Ischemia was obtained by completely occluding the left anterior descending coronary artery near its origin. Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with diastolic impulses of 100 msec duration delivered at a rate of 180 beats/minute. Diltiazem did not oppose the rise in EFT induced by flecainide in the absence of ischemia (6.8 +/- 1.2 to 9.9 +/- 0.9 mA, p<0.001). It limited the fall in EFT observed under the dual influence of ischemia and flecainide (4.2 +/- 0.9 vs 1.3 +/- 0.6 mA, p<0.001). By reducing calcium entry into myocardial fibers, diltiazem delayed ischemic depolarization, as evidenced by reduced shortening of the monophasic action potential duration from 215 +/- 7 to 200 +/- 4 msec, instead of 178 +/- 6 (p<0.001), and reduced lengthening of intraventricular conduction time from 33 +/- 5 to 43 +/- 4 msec, instead of 53 +/- 4 (p<0.01). Therefore, diltiazem is likely to prevent the loss and even the reversal of the antifibrillatory properties of flecainide due to myocardial ischemia in dosages that do not adversely affect myocardial contractility or atrioventricular conduction to a large extent.
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PMID:Prevention by calcium antagonists of profibrillatory effects of class I antiarrhythmic drugs in acute myocardial ischemia: study in pig heart in situ. 925 May 51

During myocardial ischemia, the extracellular potassium concentration increases in a triphasic pattern, an initial early increase, a constant phase, and a late increasing phase. The aim of this study was to determine whether diltiazem inhibits the late increasing phase by maintaining glycolytic adenosine triphosphate (ATP) synthesis in ischemic myocardium. The extracellular potassium concentration and pH were measured simultaneously with ion-sensitive electrodes during 30 min of global ischemia in isolated guinea-pig hearts. In the control hearts, the late increasing phase occurred 13 min after the onset of ischemia when the change in extracellular pH had reached a plateau. There was a sharp increase in the myocardial lactate level in the control hearts, which was maintained for approximately 8 min after the onset of ischemia. Iodoacetate (1 mM) led to a ATP depletion and rapid accumulation in extracellular potassium shortly after the onset of ischemia without a decrease in extracellular pH. The preischemic treatment with diltiazem (3 microM) reduced cardiac function both before ischemia and during the early period of ischemia. Diltiazem almost completely abolished the late increasing phase with a continuous decrease in extracellular pH throughout the ischemic period. The myocardial lactate level in the diltiazem-treated group increased sharply between 2 and 15 min after the onset of ischemia. The myocardial ATP level was preserved throughout the ischemic period. This study shows that diltiazem inhibits the late increasing phase in extracellular potassium by maintaining glycolytic ATP synthesis during ischemia.
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PMID:Diltiazem inhibits the late increase in extracellular potassium by maintaining glycolytic ATP synthesis during myocardial ischemia. 933

Recently, there has been some controversy concerning calcium antagonists, suggesting the need for further debate on this heterogeneous class of drugs. Three chemical families, dihydropyridines (DHP), phenylalkylamines (verapamil) and benzothiazepines (diltiazem) bind to the type L receptors of the calcium channels with different binding, modulation and tissue selectivity characteristics. DHP are selective for type L receptors and block the extracellular portion of the channel leading to vigorous vasodilatation and little or no cardiodepressive effect. Diltiazem and verapamil also interfere with type T channel receptors. These drugs have a cardiodepressive and a bradycardia effect. Verapamil blocks the intracellular portion of the calcium channel at the site where part of the catecholamine effect occurs, leading to less reflex sympathetic activation than with other calcium antagonists (namely DHP). Deleterious sympathetic stimulation is proportional to the intensity and degree of rapid onset of arterial vasodilatation and is attenuated with slow-release formulations. Calcium antagonists in general have an anti-angina effect but high-dose short-acting DHP can cause excessive vasodilatator leading to subsequent ischemia. In chronic stable angina, slow-release verapamil has been shown to have a preventive clinical effect comparable to that of beta blockers. Slow-release nifedipine is effective and safe but must be associated with betablockers. In unstable angina, only those calcium antagonists with a bradycardia effect appear to have an effect similar to beta blockers. Beta blockers are nevertheless to be preferred in these patients (excepting Prinzmetal angina) until results of convincing clinical studies are available. After the initial phase of myocardial infarction, again only calcium antagonists with a bradycardia effect have been shown to have a beneficial effect, in patients without cardiac failure: diltiazem in infarction without Q-wave and verapamil in all infarctions, in case of residual ischemia to reduce the risk of recurrence.
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PMID:[Calcium antagonists in ischemic heart disease]. 941 Oct 6

To examine whether amiloride protects against ischemia-induced or reperfusion-induced damage to the heart, mechanical and metabolic studies were performed in the isolated, working rat heart. Ischemia decreased both mechanical function and the tissue levels of high-energy phosphates and increased the tissue levels of free fatty acids (FFAs). Reperfusion restored the levels of high-energy phosphates but further increased FFA accumulation. For this reason, accumulation of FFAs was used as an indicator of both ischemia-induced and reperfusion-induced damage. Drugs were added to the perfusion solution 5 min before ischemia until the end of ischemia (pre) or until 10 min after reperfusion (pre + post). Diltiazem (1 or 5 mumol/L pre) decreased the mechanical function of the non-ischemic heart and attenuated both ischemia-induced and reperfusion-induced accumulation of FFAs. Amiloride (50 mumol/L pre) did not affect the mechanical function of the non-ischemic heart or attenuate ischemia-induced or reperfusion-induced FFA accumulation effectively. However, amiloride (50 mumol/L pre + post) did markedly attenuate the reperfusion-induced accumulation of FFAs. In conclusion, diltiazem attenuates both ischemia-induced and reperfusion-induced myocardial damage, probably through its energy-sparing effect as a result of a decrease in mechanical function before ischemia. In contrast, amiloride attenuates only the reperfusion-induced myocardial damage through mechanisms other than the energy-sparing effect.
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PMID:Protective effect of amiloride against reperfusion damage as evidenced by inhibition of accumulation of free fatty acids in working rat hearts. 941 67

The effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) on major ion transporters were studied in canine cardiac sarcolemmal and sarcoplasmic reticular vesicles. KB-R7943 inhibited the Na+/Ca2+ exchange more potently than the Na+/H+ exchange, the Na+/K(+)-ATPase and the Ca2(+)-ATPase. The effects of KB-R7943 on ischemia/reperfusion-induced injury were studied in isolated rat perfused hearts in comparison with those of diltiazem and lidocaine. In normal hearts, diltiazem (10 microM) and lidocaine (100 microM) markedly reduced contractile function, but KB-R7943 (1, 10 microM) had no such effect. In the hearts subjected to 25-min ischemia and 30-min reperfusion, KB-R7943 concentration-dependently and significantly improved post-ischemic recovery of left ventricular developed pressure, left ventricular dP/dtmax and left ventricular end-diastolic pressure by pre-ischemic treatment (5 min) or post-ischemic treatment (10 min). Diltiazem and lidocaine showed similar improvement of recovery by pre-ischemic treatment, but they had no effect by post-ischemic treatment. Furthermore, the effect of KB-R7943 on arrhythmia was studied in anesthetized rats subjected to 5-min cardiac ischmeia and 10-min reperfusion. KB-R7943 (1, 10 mg/kg, i.v.) dose-dependently reduced the incidence and the duration of ventricular fibrillation. These results indicate that KB-R7943, a selective Na+/Ca2+ exchange inhibitor, has beneficial effects against myocardial ischemia/reperfusion injury and suggest that activation of the Na+/Ca2+ exchange mainly occurs immediately after reperfusion in the pathophysiological process of myocardial ischemia/reperfusion injury.
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PMID:[Effects of KB-R7943, a novel Na+/Ca2+ exchange inhibitor, on myocardial ischemia/reperfusion injury]. 955 49


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