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)

A study was performed to compare isosorbide dinitrate and nifedipine as adjunctive therapy in 14 patients with coronary artery disease and stable angina pectoris taking maximal beta-blocking drugs. Drug titration phases ensured maximal therapy of propranolol, isosorbide or nifedipine. The combination of nifedipine and propranolol was more effective than the combination of isosorbide and propranolol in reducing angina and increasing exercise capacity (323 vs 416 seconds, p less than 0.005) during exercise treadmill testing. Nifedipine produced a greater reduction in systolic blood pressure at submaximal exercise than isosorbide. Global and regional ejection fraction at rest and exercise was assessed with radionuclide ventriculography. The substitution of nifedipine for isosorbide depressed the global ejection fraction at rest (0.61 to 0.56 p less than 0.05) and produced a slight improvement in exercise ejection fraction (0.47 to 0.51, difference not significant). The decrease in ejection fraction from rest to exercise was 0.14 to 0.04 with nifedipine (p less than 0.005). The benefit of nifedipine compared with isosorbide occurred in regions with marked exercise-induced ischemia. In patients treated with maximal beta-blocking therapy, nifedipine is an effective alternative to isosorbide as a combination agent with propranolol. The salutary effects of nifedipine included afterload reduction with exercise and possible improvements in coronary blood supply.
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PMID:Comparison of nifedipine and isosorbide dinitrate when added to maximal propranolol therapy in stable angina pectoris. 361 86

Thromboxane B2 and 6-keto-PGF1 alpha (6KPGF1 alpha), the major stable metabolites of thromboxane and prostacyclin, are present in the CNS, where they appear to be mainly produced within and/or acting upon the vascular district. Their concentrations are of few pg/mg protein in rat brain cortex of animals sacrificed by microwave (MW) radiation, procedure which inactivates tissue enzymes and allows the determination of endogenous "basal" levels of eicosanoids. Levels of 6KPGF1 alpha and especially those of TxB2 increase several fold over the basal values in brain cortex of animals sacrificed by decapitation followed by a few minute interval before analysis (post-decapitation ischemia, PDI). Pretreatment of animals with the vasoactive drug papaverine, resulted in elevation of brain basal levels of 6KPGF1 alpha and with the carbochromene derivative AD6 in reduction of basal levels of TxB2, whereas the calcium antagonist nifedipine and dipyridamole did not modify basal levels of the two eicosanoids. Treatments with papaverine and AD6 reduced the accumulation of TxB2 and enhanced that of 6KPGF1 alpha occurring after PDI, to different extents, both resulting, however, in reduction of the TxB2/6KPGF1 alpha ratio. Nifedipine instead, decreased the release of both eicosanoids and resulted in elevation of the TxB2/6KPGF1 alpha ratio, whereas dipyridamole had no effect. In conclusion, the evaluation of the overall effects of drug treatments on the TxB2/6KPGF1 alpha ratio in cerebral tissue, provided useful informations on the pharmacological modulation of vascular eicosanoids in this district.
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PMID:Differential effects of various vasoactive drugs on basal and stimulated levels of TXB2 and 6-keto-PGF1 alpha in rat brain. 383 85

Abnormal left ventricular (LV) diastolic performance is a characteristic feature of hypertrophic cardiomyopathy (HC) and an important contributor to the development of symptoms. Impaired diastolic filling of the hypertrophied left ventricle results from both diminished distensibility and prolonged or incomplete relaxation. LV distensibility is not only influenced by fixed anatomic abnormalities (such as fibrosis or hypertrophy) that determine the passive elastic properties of the left ventricle, but also is modulated by the dynamics of myocardial relaxation: prolonged or incomplete LV relaxation may restrict the rate and extent of LV filling and result in altered pressure-volume relations throughout diastole. Several studies indicate that impaired LV relaxation and filling in HC may be modified favorably by verapamil or nifedipine administered on a short-term basis in the catheterization laboratory, associated with improved diastolic pressure-volume relations. Verapamil also improves LV filling during oral therapy. Improved indexes of LV filling correlate with symptomatic improvement, both short-term and long-term: Approximately 80% of patients having a persistent increase in peak LV filling rate have persistent improvement in objective exercise tolerance compared with preverapamil values. Altered LV relaxation and filling are also often observed in patients with coronary artery disease (CAD) after myocardial infarction or during acute ischemia. Moreover, impaired filling occurs under resting conditions in many patients who have normal systolic function and no evidence of previous infarction. Nifedipine improves indexes of LV relaxation and distensibility during pacing-induced ischemia and verapamil improves indexes of LV filling at rest and during exercise-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of calcium-channel blocking agents on left ventricular diastolic function in hypertrophic cardiomyopathy and in coronary artery disease. 388 11

Calcium antagonists are now widely used in a variety of cardiocirculatory disorders, many of which are associated with varying levels of depressed myocardial function. Thus, the hemodynamic effects of calcium antagonists in patients with normal as well as depressed ventricular function are clinically relevant. None of the 3 agents verapamil, nifedipine or diltiazem exerts significant negative inotropic effects in patients with relatively normal myocardial function, although increases in left ventricular end-diastolic pressure may occur with verapamil and possibly diltiazem. In a setting in which ischemia, hypertension or arrhythmias contribute to cardiac failure, all 3 agents may ameliorate myocardial decompensation if they reverse the precipitating causes. In patients with depressed myocardial function, the effects of diltiazem are not known; verapamil may depress myocardial function, especially if the ventricular filling pressure is increased. Nifedipine generally has little depressant action in this setting and usually improves cardiac function, especially if the sympathetic reflexes are intact. However, hemodynamic deterioration after nifedipine administration has been reported. Thus, the available data do not support the use of calcium antagonists as afterload-reducing agents in heart failure and suggest caution in the use of these agents in patients with impaired ventricular performance.
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PMID:Use of calcium antagonists in ventricular dysfunction. 388 19

Carbon tetrachloride, chloroform, dimethylnitrosamine, thioacetamide or acetaminophen was each administered to rats in a single hepatotoxic dose. Nifedipine, verapamil or chlorpromazine was administered in association with the hepatotoxic agents to determine if calcium channel blocking agents would prevent an increase in liver cell calcium associated with hepatotoxicity and to determine if these agents would protect against the development of centrilobular necrosis. Following a latent period different for each toxic agent, a 4- to 18-fold increase in liver cell calcium content had occurred by 24 hr. The calcium increase and the centrilobular necrosis (mean histologic score) were correlated. A relatively high calcium to necrosis ratio was obtained with dimethylnitrosamine, thioacetamide and acetaminophen. A lesser calcium to necrosis ratio was obtained with chloroform and carbon tetrachloride, the two toxic agents that destroyed the intracellular calcium sequestration activity of the liver endoplasmic reticulum. Nifedipine or chlorpromazine, administered prior to and 7 hr after the toxic agent, completely prevented the centrilobular necrosis caused by thioacetamide, carbon tetrachloride and acetaminophen; almost completely prevented necrosis with dimethylnitrosamine; and provided partial protection against chloroform toxicity. Two doses of verapamil provided partial protection against necrosis when carbon tetrachloride was the toxic agent and provided almost complete protection with dimethylnitrosamine. A reduction in liver cell calcium was associated with the protective action of the three calcium channel blocking agents. These findings are compared with earlier studies of the protective effects of calcium channel blocking agents in cardiac ischemia.
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PMID:Effects of calcium channel blocking agents on calcium and centrilobular necrosis in the liver of rats treated with hepatotoxic agents. 394 99

This study was designed to compare the effects of the Ca2+ slow channel blocking agents verapamil (2 X 10(-6) M), diltiazem (7.5 X 10(-7) M), and buffer containing reduced Ca2+ content (0.95 mM) on myocardial ischemic injury. These treatments were equiactive, reducing cardiac function to 20% of the control value, and fully reversible in nonischemic, isolated, working rat hearts. Hearts which were reperfused (30 min) following 27 min of global ischemia recovered 17% of control cardiac function and had a markedly reduced ATP and creatine phosphate content and ATP/ADP ratio compared to nonischemic hearts. When verapamil, diltiazem, nifedipine, or low Ca2+ treatments were given before and during ischemia, equal improvement in cardiac function was observed upon reperfusion, and tissue ATP levels, creatine phosphate levels, and ATP/ADP ratio were significantly higher than in hearts which did not receive the treatments or which received the drug vehicle. Large increases in recovery of contractile function were observed with a partial preservation of ATP reserves. These treatments, which were equiactive in nonischemic hearts, provided equivalent preservation of cardiac function, ATP, and creatine phosphate in the reperfused ischemic hearts. When the ischemic period was increased to 33 min and the effective concentrations reduced to depress cardiac function to 40% of the control value (4.5 X 10(-7) M verapamil, 2.5 X 10(-6) M diltiazem, 3 X 10(-7) M Nifedipine, 1.25 mM Ca2+), equal improvement in cardiac function was again observed. Thus, major differences among these Ca2+ slow channel blockers or low Ca2+ treatment were not detected in this experimental system.
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PMID:Comparison of the protective effects of verapamil, diltiazem, nifedipine, and buffer containing low calcium upon global myocardial ischemic injury. 395 95

The effect of intravenous nifedipine (5 micrograms/kg) on the recovery of myocardial function after occlusion of the left anterior descending coronary artery was studied in 18 closed chest dogs. Using computer-aided analysis of two-dimensional echocardiograms, systolic and diastolic function of ischemic segments in low papillary left ventricular cross sections were characterized, respectively, as holosystolic fractional area change and early diastolic velocity of luminal area change. The time required for systolic function to return to preocclusion values after a 1 minute untreated control occlusion (n = 12) was 5 to 10 minutes, and after a 2 minute occlusion (n = 6) it was 20 to 30 minutes. When nifedipine was administered during the occlusion, recovery after a 2 minute occlusion was accelerated slightly to 10 to 15 minutes. Recovery times of early diastolic function were substantially longer, and nifedipine effects were more pronounced. After a 1 or 2 minute control coronary occlusion, 60 to 75 minutes or 90 to 105 minutes were needed to return early diastolic function to normal levels. Nifedipine administered during a 1 or 2 minute coronary occlusion improved these recovery times to 10 to 15 minutes. When the dogs were treated with intravenous nifedipine before coronary occlusion, recovery after 1 or 2 minutes of acute ischemia was apparent as early as 2 minutes after reperfusion. Thus, intravenous nifedipine accelerates the recovery of myocardial function after brief periods of ischemia, and when administered before coronary occlusion, it assures very prompt recovery of function.
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PMID:Comparative echocardiographic study of recovery of diastolic versus systolic function after brief periods of coronary occlusion: differential effects of intravenous nifedipine administered before and during occlusion. 406 7

Nifedipine, a slow calcium-channel blocker, has been used to preserve myocardial function in the ischemic heart. To quantitatively evaluate the effectiveness of nifedipine as a cardioplegic agent during moderate hypothermia (28 degrees C), 15 pigs were evaluated on total and right heart bypass with measurement at normothermia and after 1 hour of hypothermic ischemia of stroke volume, coronary blood flow, myocardial oxygen consumption, and lactate extraction. Myocardial tissue gases (oxygen and carbon dioxide) were continuously monitored. Animals were divided into three groups: hypothermic ischemia, hypothermic ischemia with infusion of nifedipine carrier without nifedipine, and hypothermic ischemia with nifedipine and its carrier. A significant decrease in stroke volume was seen in all three groups; however, the depression was significantly greater following hypothermic ischemia than following cardioplegia with either nifedipine or its carrier. The mean recovery value of stroke volume was highest in the nifedipine group, but this difference between nifedipine and its carrier alone did not reach statistical significance. Coronary blood flow, myocardial oxygen consumption, lactate extraction, and tissue gases failed to substantiate a significant benefit when nifedipine was compared with its carrier alone. We conclude that under these hypothermic conditions, no proven statistically significant advantage was noted in the nifedipine group when compared with the nifedipine carrier group in swine. However, both nifedipine and the carrier were superior as a myocardial preservative when compared with hypothermic ischemic arrest alone.
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PMID:Quantitative evaluation of the myocardial preservative characteristics of nifedipine during hypothermic myocardial ischemia. 406 42

The effects of nicorandil and nifedipine on ischemia--reperfusion-induced myocardial infarct size following a 2-h occlusion and 30-min reperfusion period of the left anterior descending coronary artery (LAD) were compared in anesthetized dogs. Myocardial blood flow was measured using the radioactive microsphere technique, and infarct size was determined using triphenyl tetrazolium chloride histochemical stain. Vehicle, nicorandil (100-micrograms/kg bolus followed by 25 micrograms/kg/min), or nifedipine (10-micrograms/kg bolus followed by 1 microgram/kg/min) was administered intravenously 10 min after LAD occlusion and infused throughout the occlusion and reperfusion periods. Nicorandil and nifedipine reduced mean arterial blood pressure similarly (15 mm Hg) during infusion. However, neither drug altered collateral blood flow to the ischemic region during occlusion. In all three groups, left ventricular mass, area at risk mass, percentage of the left ventricle at risk, and retrograde flow during occlusion were similar. As compared with the control group, nicorandil reduced myocardial infarct size as determined by absolute mass, percentage of the area at risk infarcted, and percentage of the left ventricle infarcted. Nifedipine had no significant effect on infarct size. This beneficial effect of nicorandil was not related to an improvement in myocardial blood flow or a change in global hemodynamics.
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PMID:Effects of nicorandil and nifedipine on protection of ischemic myocardium. 620 83

Thirty dogs were studied acutely on cardiopulmonary bypass in four groups. Hearts in Groups 1C (standard cardioplegia, n = 5) and 2c (n = 10) were subjected to periods of global ischemia of 1 and 2 hours, respectively. Both groups received 300 cc boluses of hypothermic (4 degrees C), potassium-based cardioplegic solution infused via an 18 gauge needle proximal to the aortic cross-clamp, at every 30 minute interval of ischemia. Groups 1CN (standard cardioplegia plus nifedipine, n = 5) and 2CN (n = 10) were treated similarly, except that nifedipine (5 microgram/kg) was added to each 300 cc bolus of cardioplegic solution. The addition of nifedipine in Groups 1CN and 2CN resulted in statistically significant reduction in myocardial water content (p less than 0.005), mean left atrial pressure (MLAP) (p less than 0.05), and myocardial compliance (p less than 0.005) as compared to the control groups (1C and 2C). Recovery of left ventricular dp/dt in Experimental Group 2CN was also statistically better (p less than 0.025) than in Control Group 2C. Examination of myocardial biopsy tissue by electron microscopy was not conclusive. Nifedipine used in combination with hypothermic, potassium-based cardioplegia provided significant additional myocardial protection over cardioplegia alone.
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PMID:Improved myocardial protection with nifedipine and potassium-based cardioplegia. 626 12


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