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 cumulative evidence acquired over 20 years suggests that beta-blockers improve functional capacity, ventricular function, and decrease mortality in patients with heart failure either due to dilated cardiomyopathy or ischaemic heart disease. This effect is independent of the beneficial effects of digoxin, diuretics and particularly ACE inhibitors and has resulted in re-evaluation of requirements for transplantation in patients with advanced cardiac failure. Ninety percent of patients appear to respond to beta-blockers but no clinical or biochemical parameters can identify a favourable response. The beneficial effects occur slowly but last for years. Further ongoing trials will provide more information but beta-blockade therapy should be considered in addition to other therapy in the management of heart failure.
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PMID:Beta-blocker therapy in heart failure: myths or realities. 895 85

ACE inhibitors have been proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. In an attempt to investigate this effect in a model of syngeneic liver transplantation in the rat, we compared a control group with an ACE inhibitor treatment group, in which enalapril was given i.v. before and during reperfusion. By means of in vivo microscopy, sinusoidal perfusion rate, permanent leukocyte sticking in sinusoids and postsinusoidal venules, and leukocyte rolling in postsinusoidal venules were assessed. Liver function was evaluated by measuring bile output. The sinusoidal perfusion rate was significantly improved by enalapril treatment. Leukocyte sticking in both sinusoids and postsinusoidal venules was found to be remarkably reduced in enalapril-treated animals; the fraction of rolling leukocytes remained unchanged. Bile output was increased in enalapril-treated animals. These results demonstrated, in a model of rat liver transplantation, that ACE inhibition by enalapril is effective in reducing hepatic ischemia/reperfusion damage as assessed by the leukocyte-endothelium interaction using in vivo microscopy and postreperfusion bile production.
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PMID:Impact of enalapril on microvascular perfusion and leukocyte adherence in a model of rat liver transplantation assessed by in vivo microscopy. 895

ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nephropathy. The effect of the ACE inhibitors is mainly due to the inhibition of the angiotensin converting-enzyme, but they also potentiate the effect of bradykinine. Sargent et al. have indicated, that SH-containing ACE-inhibitors show an effect on KATP-channel open probability in vascular smooth muscle. In our experiments, we used isolated bovine coronary arteries and guinea pig aortas, which were cut transversally and brought into Normal-Tyrode-solution. The vessels were precontracted with phenylephrine or U 46619, and after that a cumulative dose of the SH-containing ACE-inhibitors Captopril or Zofenopril was added to obtain a relaxation curve. In a second series we blocked the KATP-channels with glibenclamide to see if the relaxation could be attenuated. In bovine coronary arteries the relaxing effect of Captopril could not be attenuated by glibenclamide, a specific blocker of KATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effect of Zofenopril was also not effected by glibenclamide. The concentrations of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal effect could be seen at a concentration of 10(-5) mol/l. Experiments with the non SH-containing ACE-inhibitor Enalapril did also not show any statistically significant difference between the 2 groups of series. We conclude, that, in contrast to Sargent's conclusions, there is little or no effect on KATP-channels due to the presence of SH-groups.
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PMID:[ACE inhibitors with SH groups have no effect of ATP-dependent K channels--a dissertation]. 896 87

Recently we have shown that ACE inhibitors and platelet activating factor antagonists inhibit iron-dependent lipid peroxidation in murine ventricular membranes and possess beneficial effects on ischemia and ischemia reperfusion-induced myocardial injury, which has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study we investigated the effects of beta-adrenoceptor blockers and calcium antagonists on iron-dependent lipid peroxidation (LPO) in murine ventricular membranes and compared them with the lazaroid U-74500A, a potent antioxidant. Fe(2+)-vitamin C induced LPO in a concentration- and time-dependent manner, measured as thiobarbituric acid reactive substances (TBARS) formation. Pretreatment of ventricular membranes with gallopamil, verapamil, propranolol and metaprolol at concentrations of 5 microM and higher inhibited Fe(2+)-vitamin C-induced LPO in a concentration-dependent manner with IC50 values of 192.8-208.3 microM; however, they were less potent than U-74500A (IC50 6.8 microM). In contrast, atenolol, timolol, diltiazem and nifedipine inhibited LPO at very high concentrations with IC50 values of 864.5-971.5 microM. Inhibition of LPO may not be due to the drugs' classical pharmacological actions, but rather to their characteristic chemical structures or physicochemical interactions with biological membranes. In view of the pathological importance of LPO in cardiac ischemic injury, inhibition of LPO by gallopamil, verapamil, propranolol and metaprolol may provide additional cardioprotective activity and thus reinforces their beneficial effects in the treatment of ischemic heart disease.
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PMID:Comparative antioxidant effects of beta-adrenoceptor blockers, calcium antagonists and U-74500A against iron-dependent lipid peroxidation in murine ventricular microsomal membranes. 901 Aug 29

The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is prevented by cyclooxygenase inhibition with indomethacin. In the clinical setting of ischemia/reperfusion however, the cyclooxygenase inhibitor aspirin is widely used to prevent platelet aggregation. The present study therefore investigated whether aspirin in dosages sufficient to inhibit platelet aggregation interferes with the attenuation of myocardial stunning by ramiprilat. Fifteen dogs received either 1 mg/(kg.day) (group I, n = 7) or 10 mg/(kg.day) (group II, n = 8) aspirin orally for 1 week. Both dosages of aspirin inhibited ADP-induced platelet aggregation. The dogs were then anesthetized thoracotomized and subjected to 15 min LCx-occlusion and 4 h reperfusion. Before LCx-occlusion, groups I and II received ramiprilat (20 micrograms/kg, i.v.). Systemic hemodynamics, posterior myocardial blood flow (PMBF, colored microspheres) and wall thickening (PWT, sonomicrometry) of these groups were measured and data compared to placebo-controls (group III, n = 11) and dogs receiving only ramiprilat before LCx-occlusion (group IV, n = 11). Four dogs received 10 mg/(kg.day) aspirin without ramiprilat (group V). Mean aortic pressure was kept constant by an intra-aortic balloon, and heart rate did not change. PMBF was not different between the five groups. Under control conditions and during myocardial ischemia PWT was also not different. At 4 h reperfusion PWT was still depressed in group III (-5 +/- 20% of control) and group V (-23 +/- 6%) whereas PWT recovered to the same extent in groups I (46 +/- 23%), II (50 +/- 15%) and IV (58 +/- 18%) (all P < 0.05 v groups III and V). The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is not prevented by aspirin in dosages which are nevertheless sufficient to inhibit platelet aggregation.
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PMID:Aspirin does not prevent the attenuation of myocardial stunning by the ACE inhibitor ramiprilat. 901 43

The endothelium plays a crucial role in the regulation of coronary artery vasomotor tone by conducting stimuli from the blood into changes of vascular smooth muscle tone. Disturbance of this endothelial function might inadequately reduce myocardial oxygen supply, and, therefore, contribute to myocardial ischemia. Different risk factors for coronary artery disease are accompanied by a reduced bioactivity of vasorelaxing nitric oxide (NO), produced by the endothelium. In hypercholesterolemia, oxidized LDL and vascular wall macrophages induce an oxidative stress with increased production of superoxide anions, capable to inactivate NO. Therefore, NO-mediated vasorelaxation is blunted in epicardial arteries as well as in the microcirculation. In case of sympathetic stimulation, e.g. by physical exercise or cold exposure, the direct vasoconstrictor action of catecholamines on the vascular smooth muscle cells might dominate due to reduced bioactivity of NO. Especially, in the presence of coronary stenoses, myocardial ischemia might be aggravated. Although "exogenous" NO, derived from nitrates, also relaxes coronary vessels, these drugs are not able to simulate the physiological, demand-adjusted endothelial production of "endogenous" NO. In contrast, following a 6 months therapy with HMG-CoA-reductase inhibitors, impairment of endothelium-dependent vasorelaxation could be improved. In addition, ACE-inhibitors have been shown to ameliorate endothelium-mediated coronary vasodilator function. However, whether improved endothelium-dependent vasodilator function due to ACE-inhibitor or HMG-CoA-reductase inhibitor therapy relate to the improved coronary mortality observed with these drugs, remains to be determined.
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PMID:[Endothelial regulation of coronary circulation: current status]. 906 75

To investigate current drug therapy for elderly hypertensive patients, we performed a case-card study at Sapporo Medical University and its branch hospitals. The case-card was designed to show prescriptions given for hypertension, complications, and blood pressure. In the 2897 valid cases, calcium antagonists were prescribed in 76.3%, followed by beta-blockers (31.4%), angiotensin-converting enzyme inhibitors (ACE-I) (25.1%) and natriuretic diuretics (18.1%). When the patients were divided into an elderly group (> or = 65 y.o., n = 1475), beta-blockers and ACE-I were found to be more frequently used in the non-elderly group, and diuretics were more frequently prescribed in the elderly group. Calcium antagonists were the most frequently used drugs, irrespective of age. As monotherapy drugs, calcium antagonists were chosen most frequently in both groups. Diuretics were the second most frequently used drug in the elderly group, but beta-blockers occupied that position in the younger group and these patients as a whole. In the elderly group, the manner of prescription was analyzed according to major complications. In patients with ischemic heart disease, beta-blockers and diuretics were used more frequently than in patients without that condition. Diuretics were prescribed more frequently in patients with renal dysfunction. Calcium antagonists and ACE-I were used more frequently in the patients with diabetes mellitus. The same differences were found in the non-elderly patients with those complications. However, among patients with stroke, calcium antagonists were more frequently used in the elderly group and ACE-I were performed in the younger patients. In conclusion, calcium antagonists were used very often regardless of age, and the other drugs were used according to age-dependent differences in pathophysiologic mechanism.
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PMID:[Treatment of elderly patients with hypertension--complications and current drug therapy]. 907 2

Vascular tolerance develops rapidly in isolated vascular strips exposed to millimolar concentrations of nitroglycerin. Several mechanisms, including depletion of sulfhydryl groups, reduced biotransformation of nitrates to NO or nitrosothiols, oxygen free radical injury, and downregulation of a membrane-bound enzyme or a nitrate receptor, have been proposed, but the exact mechanism responsible for in-vitro tolerance remains unknown. In-vivo tolerance of the beneficial effects of nitrates on hemodynamics, myocardial ischemia, and exercise performance develops rapidly. It has been suggested, but remains to be proven, that development of venous tolerance and not arterial tolerance is responsible for the attenuation of nitrate effects during long-term nitrate therapy. Several mechanisms, including neurohormonal activation, depletion of sulfhdryl groups, and the shift of fluid from the extravascular to intravascular compartment have been implicated. However, the use of agents to counteract these mechanisms (ACE inhibitors, sulfhydryl donors, diuretics) has produced conflicting results. Thus, at present the mechanism responsible for in vivo tolerance to nitrates remains unknown. Both in vitro and in vivo vascular tolerance to nitrates can be prevented or minimized by providing nitrate-free or low-nitrate intervals. However, during nitrate-free periods, rebound phenomena (rest angina in patients with ischemic heart disease or a deterioration in exercise performance prior to the renewal of the morning dose in patients with stable angina) remain a clinical concern. When treating patients with stable angina pectoris, it must be recognized that none of the nitrate preparations or formulations can provide round-the-clock antianginal or antiischemic prophylaxis. In these patients, beneficial antianginal and antiischemic effects of nitrates for 10-14 hours during the daytime can be maintained by using formulations and dosing regimens that avoid or minimize the development of tolerance (standard formulation of isosorbide-5-mononitrate, 20 mg in the morning and 7 hours later; slow-release formulation of isosorbide-5-mononitrate, 120-240 mg once a day; or nitroglycerin patch delivering 0.6 nitroglycerin per hour for 10-12 hours each day). Only the patch on and off treatment is associated with nitrate rebound. Although intermittent nitrate therapy is not associated with the development of tolerance, this strategy cannot be recommended for treating unstable angina because rebound angina during nitrate-free periods complicates clinical decision making. In the acute phase of unstable angina, continuous treatment with intravenous nitroglycerin is recommended because it permits rapid up- or down-titration. Tolerance towards antianginal and antiischemic effects does develop in a substantial number of patients with 24 hours, but this can be overridden by dose escalation and restoration of the therapeutic effectiveness of nitroglycerin. Tolerance towards the beneficial effects of nitrates on hemodynamics and on exercise performance also develops rapidly during continuous or long-term nitrate therapy, and for these reasons nitrates are not used as first-line therapy to treat chronic heart failure. In combination with hydralazine, high-dose isosorbide dinitrate (30-40 mg four times a day) improves survival, but this combination therapy is inferior to ACE inhibitors.
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PMID:Nitrate tolerance, rebound, and their clinical relevance in stable angina pectoris, unstable angina, and heart failure. 911 Jan 17

From a pathophysiologic point of view heart failure can be divided into systolic and diastolic dysfunction. Systolic dysfunction is characterized by a decreased ejection fraction and increased chamber volume which can be typically found in young people with congestive cardiomyopathy. Diastolic dysfunction is associated with an enhanced filling pressure but with a normal systolic pump function. This disorder can be typically found in elderly patients with myocardial hypertrophy. Treatment of congestive heart failure includes. 1.) reduction of central blood volume (preload reduction) 2.) decrease of peripheral resistance afterload reduction) 3.) regression of myocardial hypertrophy (improving myocardial stiffness) 4.) maintenance of atrial contraction (atrial kick) 5.) decrease of heart rate (prolongation of diastolic filling time and increase in contractility) 6.) improvement of LV relaxation (positive lusitropic effect) and 7.) prevention of myocardial ischemia (improvement in contractility and relaxation). The primary goal of medical therapy is symptomatic improvement. Reduction in morbidity and mortality is only a secondary consideration. To achieve this goal ACE-inhibitors and in certain cases betablockers (cave: neg. inotropic action) are suited best. Additionally, digitalis-especially in the presence of atrial fibrillation- and vasodilators can be used to further improve quality of life. In the case of severe heart failure with or without atrial fibrillation oral anticoagulation is indicated to prevent systemic embolication. Diuretics are often used for symptomatic improvement but have no effect on long-term survival. Aldosterone antagonists (e.g, spironolactone) have a beneficial effect on LV remodeling and probably also on mortality. The role of endothelin antagonists and atriopeptidase inhibitors in the treatment of heart failure are not yet clear.
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PMID:[Diuretics in the treatment of heart failure: current pathophysiological aspects]. 919 52

Beta blockers have been used as first-line drugs in the treatment of numerous cardiovascular disorders such as hypertension and ischemic heart disease, as well as for certain non-cardiovascular diseases for more than 30 years. However, the administration of these safe and effective drugs declined during the 1980s, whereas the use of others such as calcium antagonists and ACE inhibitors increased for these indications, frequently without convincing evidence of any clinical advantages of these agents in hard end points. During the past two or three years there has been a renaissance of beta adrenoceptor antagonists, most probably due to increasing awareness that beta blockers have been shown to reduce morbidity and mortality when compared with other therapeutic agents or placebo in numerous diseases. Furthermore, congestive heart failure has changed from being a contraindication to an indication, and suspected side effects were not confirmed on further investigation. Last but not least the reasonable costs of beta blocking drugs may have become a more important consideration than before. The trend back to beta blockers may also be due to the fact that physicians attach more importance to effects on the hard end points, namely a decrease in morbidity and mortality, than to surrogate end points. According to the present state of the art, beta blockers should be recognized as the drugs of choice, particularly in the treatment of arterial hypertension and coronary artery disease (especially after myocardial infarction), unless contraindications are present or unacceptable side effects occur. Congestive heart failure, peripheral arterial disease (PAD) and diabetes mellitus are no longer considered absolute contraindications.
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PMID:[Beta blockers--1997 update]. 920 1


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