Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of diltiazem, a calcium antagonist drug, we compared with those of placebo on exercise performance during a series of symptom-limited upright exercise tests. Ten patients with chronic stable angina were studied over a period of 7 weeks. The drug was administered in a random double-blind fashion and was evaluated at increasing dose levels of 120, 180 and 240 mg/day. Diltiazem was effective in increasing the total duration of exercise (p < 0.001) and the time the first onset of angina (p < 0.02) and to the first appearance of 1 mm of S-T depression (p < 0.02). These effects were most marked at the highest dose level of diltiazem. The heart rate was reduced at rest (p < 0.05) and during submaximal exercise (p < 0.001). There was a reduction in diastolic blood pressure during submaximal exercise (p < 0.04) but no change in systolic pressure. Pressure-rate product was significantly reduced at submaximal (p < 0.001) but not maximal exercise. The reduction in pressure-rate product is postulated as the mechanism by which diltiazem enhances duration of exercise. There was no reduction in electrocardiographic evidence of myocardial ischemia at peak exercise by either clinical observation or computer analysis of spatial electrocardiographic variables Five of the six patients who continued to take the drug maintained or improved their exercise performance on follow-up study 8 to 10 months later.
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PMID:Improved exercise performance in persons with stable angina pectoris receiving diltiazem. 745 15

We investigated whether analysis of heart rate (HR) variability may be used to predict the efficacy of drug treatment of myocardial ischemia. In a double-blind, crossover study, 28 patients with stable angina pectoris, proven coronary artery disease, and myocardial ischemia during Holter monitoring received metoprolol controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a placebo run-in phase and after each treatment period, 72-hour Holter recordings were obtained for HR variability and ST-segment analysis. At baseline, the total duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24 hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol significantly reduced the total duration of ischemia by -8.7 minutes (95% CI -14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients with a low SD of normal-to-normal intervals at baseline (SDNN), using the median value of 50 ms as a cut-off value. In contrast, significant treatment effects were not observed in patients with a high SDNN at baseline. Similar results were obtained using baseline total power or low-frequency power, but not when using baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9 minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to metoprolol, efficacy of diltiazem was not related to baseline HR variability. In conclusion, patients with reduced HR variability at baseline responded to treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris. 757 50

In a randomized, double-blind, cross-over, multicenter study with a placebo run-in phase, the efficacy and safety of two oral formulations of diltiazem, standard three or four times daily (t.i.d. or q.i.d.) and controlled release twice daily (b.i.d.), were compared in 49 patients with stable angina pectoris. ST-segment depression at maximum exercise 12 h after tablet intake was less frequently observed with diltiazem controlled release than with standard diltiazem (34 of 49, 69% vs. 43 of 49, 88%, p = 0.007). In patients with ST-segment depression after both treatments (n = 33), the average time to 1-mm ST-segment depression was 55.4 +/- 19.9 s longer with diltiazem controlled release than with standard diltiazem [476 +/- 195 vs. 422 +/- 163 s, p = 0.009; 95% confidence interval (CI) 14.8-96 s]. Reduction in mean number of anginal attacks and nitroglycerin (NTG) intake was not significantly different between treatment with standard diltiazem and diltiazem controlled release. The incidence of side effects was low and not different between the two treatments. Both formulations are equally effective in reducing the number of anginal attacks and are well tolerated. Diltiazem controlled release is more effective than standard diltiazem in preventing myocardial ischemia 12 h after tablet intake. Thus, diltiazem controlled release allows twice-daily intake frequency and may therefore be preferable to standard diltiazem in treatment of stable angina pectoris.
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PMID:Comparison of diltiazem standard formulation and diltiazem controlled release in patients with stable angina pectoris: a randomized, double-blind, cross-over, multicenter study. 768 99

Diltiazem is a calcium channel blocker whose effects on left ventricular function (LVF) are controversial. We studied 12 patients with ischemic heart disease (IHD) before starting and 15 and 30 days after having initiated Diltiazem 60 mg t.i.d. LVF was accessed by means of the normalized indexes of the calibrated apexcardiogram: nS for systolic LVF evaluation and nA for diastolic LVF evaluation. Recent works have shown that these indexes have a good correlation with invasive parameters of LVF. We verified that nS did not change and nA decreased significantly (p < 0.05) after Diltiazem. We preliminary concluded that Diltiazem has no deleterious effect on LV systolic function and improves LV diastolic function, by decreasing nA, a parameter which correlates well with LV end diastolic pressure.
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PMID:Diltiazem effects on left ventricular function preliminary results of 12 patients evaluated by calibrated apexcardiogram. 777 Nov 72

Diltiazem is a widely used calcium channel blocker, and has been found to be effective in the treatment of hypertension, stable, variant and unstable angina, as well as oesophageal spasm. Calcium channel antagonists have been shown to diminish the contractility of gut smooth muscle, but have not as yet been reported to cause clinically significant inhibition of gut motility when used alone. We report a case of reversible functional intestinal obstruction, immediately following diltiazem treatment in a patient with ischaemic heart disease.
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PMID:Paralytic ileus as a result of diltiazem treatment. 820 68

Although calcium channel blockers may preserve function in ischemic myocardium, they may also produce myocardial depression and dysfunction in the presence of decreased coronary flow. This study was designed to examine the issue of possible protection afforded by diltiazem against ischemia-induced myocardial dysfunction during propofol anesthesia. In eight anesthetized and ventilated dogs, regional myocardial (ultrasonic crystals in both left anterior descending [LAD] and left circumflex [LC] perfusion areas) and global ventricular function were evaluated during progressively severe degrees of myocardial ischemia (LAD constriction) before and after intravenous diltiazem (150 micrograms/kg). As coronary flow decreased, heart rate increased, and arterial and coronary perfusion pressures, left ventricular dP/dt, and cardiac output decreased. Systemic vascular resistance was unaffected. Diltiazem without coronary constriction increased heart rate, and decreased diastolic arterial pressures, left ventricular (LV) end-diastolic, coronary perfusion pressures, LV dP/dt max, LAD coronary blood flow, stroke volume, and cardiac output. At all levels of coronary constriction following diltiazem, there were decreases in systolic and diastolic arterial pressures, stroke volume, cardiac output, LV dP/dt, and coronary perfusion pressure. Heart rate increased at critical coronary constriction, and then remained constant relative to the prediltiazem state. The regional muscle effects of the reductions in coronary flow in the LAD perfusion territory included decreased systolic shortening and increased postsystolic shortening before and after diltiazem. Diltiazem did not alter the magnitude of the alterations in systolic or postsystolic shortening brought about by coronary constriction. No changes occurred in the LC area.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diltiazem and regional left ventricular function during graded coronary constriction and propofol anesthesia in the dog. 830 61

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
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PMID:Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts. 832 Oct 5

Diabetes mellitus and cardiovascular disorders are both common disorders, and it could be anticipated that they coexist in many patients. Diltiazem (DZ) is widely used alone or in combination with propranolol (PROP) for the treatment of hypertension and ischemic heart disease. These drugs could interfere with carbohydrate metabolism and impair glucose tolerance. The purpose of this study was to investigate the effect of oral administration of DZ, PROP (100 and 25 mg kg-1, respectively) and their combination on fasting serum glucose and insulin levels in normal and diabetic Wistar rats. Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (60 mg kg-1). In normal animals, serum glucose was significantly increased after DZ, PROP and DZ/PROP treatment compared to the initial values. In diabetic rats, serum glucose was significantly increased after PROP and DZ/PROP treatments, while it was slightly increased after diltiazem treatment compared to the initial values. In normal animals, plasma cAMP is significantly decreased in all treatment groups compared to the control value, while in the plasma of diabetic rats, cAMP was significantly decreased after PROP and DZ/PROP treatments when compared to the control value. Serum potassium of normal rats decreased after the diltiazem and DZ/PROP treatments, and they tend to increase slightly after PROP treatment. Serum potassium of diabetic rats was increased significantly after PROP and DZ/PROP treatments compared to the initial values. Body weight is decreased significantly in all treatment groups in normal rats while this significant decrease was observed only after DZ/PROP treatment in diabetic rats. This investigation suggests that diltiazem alone has no worsening effects on the glycemic control in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of diltiazem and/or propranolol on rat blood glucose levels in normal and diabetic animals. 838 58

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

Effects of CD-832 on isoproterenol (ISO)-induced myocardial ischemia were studied in dogs with partial coronary stenosis of the left circumflex coronary artery and findings were compared with those for nifedipine or diltiazem. In the presence of coronary artery stenosis, 3-min periods of intracoronary ISO infusion (10 ng/kg/min) increased heart rate and maximal rate of left ventricular pressure rise, which resulted in a decrease in percentage segmental shortening and ST-segment elevation of the epicardial electrocardiogram. After the control ISO infusion with stenosis was performed, equihypotensive doses of CD-832 (3 and 10 micrograms/kg/min, n = 7), nifedipine (1 and 3 micrograms/kg/min, n = 9) or diltiazem (10 and 30 micrograms/kg/min, n = 7) were infused 5 min before and during the second and third ISO infusion. Both CD-832 and diltiazem, but not nifedipine, significantly reduced the increase in heart rate induced by ISO infusion. In contrast to nifedipine, CD-832 (10 micrograms/kg/min) prevented the decrease in percentage segmental shortening from 32 +/- 12% to 115 +/- 26% of the control value (P < .01) and ST-segment elevation from 5.6 +/- 1.0 mV to 1.6 +/- 1.3 mV (P < .01) at 3 min after ISO infusion with stenosis. Diltiazem (30 micrograms/kg/min) also prevented the decrease in percentage segmental shortening from 34 +/- 14% to 63 +/- 18% of the control value (P < .05) and ST-segment elevation from 4.7 +/- 0.7 mV to 2.1 +/- 0.7 mV (P < .01) at 3 min after ISO infusion with stenosis. These data show that CD-832 improves myocardial ischemia during ISO infusion with stenosis and suggest that the negative chronotropic property of CD-832 plays a major role in the beneficial effects of CD-832.
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PMID:Effects of a new calcium antagonist, CD-832, on isoproterenol-induced myocardial ischemia in dogs with partial coronary stenosis. 881 82


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