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

Subjects with plasma cholesterol levels greater than 240 mg/dl (6.21 mmol/liter) and those with greater than 200 mg/dl (5.18 mmol/liter) who have coronary artery disease, or those with 2 risk factors for ischemic heart disease who do not respond to a hypocholesterolemic diet should all be treated. Lovastatin, which is an inhibitor of hydroxymethygluteryl coenzyme A reductase, is a new agent for treating hypercholesterolemia and is administered in a dose of 20 to 80 mg/day. A study was conducted in which only 10 mg of lovastatin was given to 28 subjects with plasma cholesterol of 200 to 240 mg/dl (5.18 to 6.21 mmol/liter). Cholesterol plasma levels decreased in 19% and low-density lipoprotein cholesterol decreased by 24% from baseline levels after 20 weeks of treatment. All 28 patients decreased their cholesterol values to less than 200 mg% (5.18 mmol/liter), and only 1 had a low-density lipoprotein level greater than 130 mg% (3.36 mmol/liter) at termination of the study. Achievement of desirable values of cholesterol with 10 mg of lovastatin was accompanied by less adverse effects and with significant financial saving. The calculated saving for lovastatin consumers in the USA could be an amount of $60,000,000. Thus, it is recommended that this drug be manufactured in 10 mg tablets.
 ...
PMID:Cholesterol-lowering effects of a 10 mg daily dose of lovastatin in patients with initial total cholesterol levels 200 to 240 mg/dl (5.18 to 6.21 mmol/liter). 195 Oct 68

Hypercholesterolemia was induced in New Zealand white rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 2 wk. Half of the cholesterol-fed rabbits were given lovastatin, a potent inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis, and the other half were given its vehicle (i.e., DMSO). At the end of 2 wk, the rabbits underwent experimental myocardial ischemia or a sham ischemia procedure. Ischemic animals fed the cholesterol-enriched diet for 2 wk experienced much greater cardiac damage than ischemic rabbits fed the control diet, despite the absence of any atherosclerosis. Lovastatin was shown to protect the ischemic rabbit myocardium by three different indices of ischemic damage: (a) maintenance of creatine kinase (CK) activity in the ischemic myocardium; (b) reduced loss of free amino-nitrogen containing compounds from the ischemic myocardium; and (c) blunting the rise of plasma CK activity. These effects were not due to differences in myocardial oxygen demand between the groups. Arteries isolated from animals fed the cholesterol-enriched diet developed defects in endothelium-dependent relaxation in both large vessels as well as coronary resistance vessels. Acute hypercholesterolemia increases the severity of myocardial ischemia while at the same time impairing endothelium-dependent relaxation. These deleterious changes can be significantly attenuated by treatment with lovastatin.
 ...
PMID:Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment. 291 50

Ischemic myocardium was produced by occluding the left circumflex coronary artery in anesthetized dogs. Autolyzed myocardium was produced by incubating transmural samples of canine left ventricle at 37 degrees C. Tissue pH was recorded continuously in each model using a microcombination pH electrode impaled into the midmyocardium. The activities of the five mitochondrial inner membrane enzyme complexes of electron transport and coupled oxidative phosphorylation were assayed as a function of time of ischemia or autolysis. While the activities of complex II (succinate-CoQ reductase) and IV (cytochrome c oxidase) were completely stable, that of complex I (NADH-CoQ reductase) decreased markedly, but largely only after 20 min of ischemia or autolysis. At 20 min and beyond, the decrease in the activity of complex I paralleled closely the decrease in whole mitochondrial oxygen uptake with NAD-linked substrates in both models. The activity of complex III (CoQH2-c reductase) decreased at a more gradual rate during ischemia or autolysis, and its rate of decrease paralleled that of succinate-supported oxygen uptake. The activity of complex V (oligomycin-sensitive ATPase) decreased most rapidly (by 40% in only 5 min of autolysis) but nearly leveled off beyond 20 min in the two models. A strikingly similar pattern of differential enzyme lability was observed in isolated control mitochondria incubated at lowered pH values. The results demonstrate 1) differential enzyme lability within the mitochondrial inner membrane, 2) a connection between severity of acidosis and the degree of enzyme activity loss, and 3) the usefulness of simple tissue autolysis as an analogue of in situ myocardial ischemia.
 ...
PMID:Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia and autolysis. 630 12

Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are potent cholesterol reducing agents that have been successfully used for the treatment of heterozygous familial hypercholesterolaemia (FH). A recent investigation revealed that several constitutional and genetic factors significantly determined the response of plasma lipids and lipoproteins to the HMG CoA reductase inhibitor fluvastatin. Gender has been identified through multivariate analysis as a major determinant of the plasma high density lipoprotein (HDL) cholesterol response. The current analysis was undertaken to determine possible gender-related fluvastatin dose-response differences. The analysis revealed that for HDL cholesterol, gender-related differences reach statistical significance only at the highest fluvastatin dose of 40 mg/day (females 22.9%, males 12.9%, p < 0.01). In parallel, the change in low density lipoprotein (LDL) cholesterol: HDL cholesterol ratio, an indicator of ischaemic heart disease risk, was also found to be affected by gender (females -38.4%, males -32.2%, p < 0.01). For LDL cholesterol, no consistent gender-related differences were found. In conclusion, the response of plasma lipid levels to fluvastatin in heterozygote FH patients is significantly affected by gender, with females achieving a more marked overall response, as indicated by higher HDL cholesterol levels and a lower LDL cholesterol: HDL cholesterol ratio.
 ...
PMID:Gender-related response to fluvastatin in patients with heterozygous familial hypercholesterolaemia. 751 34

Patients with ischemic heart disease are often affected by a mixed hyperlipoproteinemia, where a hypercholesterolemia of various severity is accompanied by slight or moderate hypertriglyceridemia (type IIb dyslipidemia). Current epidemiologic evidence suggests that hypertriglyceridemia has not to be disregarded, particularly in certain subgroups of patients. We evaluated the effect of the association of simvastatin 10 mg/day [an hydroxymethyl-glutaryl-CoA (HMG-CoA) reductase inhibitor] and omega-3 polyunsaturated fatty acids (n3-PUFA) in comparison with simvastatin 10 mg/day alone. The subjects undergoing the study were affected by coronary artery disease and showed hypercholesterolemia (LDL-cholesterol > 160 mg/dl) and moderate hypertriglyceridemia (serum triglycerides 200-400 mg/dl) after 2 months of moderate dietary therapy for hyperlipidemia (Step 1 of the National Cholesterol Education Program [NCEP]). Thirty-nine patients were randomized to have 1 of 2 scheduled treatments. At the same time the patients underwent severe dietary therapy for hyperlipidemia (Step 2 of the NCEP). After 3 months of treatment, total-cholesterol, LDL-cholesterol, and triglycerides were significantly lower than basal values in both groups (p < 0.05). Total-cholesterol, LDL-cholesterol, and triglycerides were lower in the group treated with n3-PUFA and simvastatin compared to simvastatin alone. However, only for triglycerides was the difference significant (-39.99% in patients treated with n3-PUFA and simvastatin versus -25.65% in patients treated with simvastatin alone, particularly in the first group of 35.85%; p < 0.05). With regard to HDL-cholesterol, the differences between the basal values and the 2 groups of treatments were non significant. Remarkable side effects were not observed in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Efficacy and tolerability of simvastatin and omega-3 fatty acid combination in patients with coronary disease, hypercholesterolemia and hypertriglyceridemia]. 820 11

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.
 ...
PMID:[Endothelial regulation of coronary circulation: current status]. 906 75

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.
 ...
PMID:Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. 930 31

Hyperlipidemia is recognized as one of the major risk factors for the development of coronary artery disease and progression of atherosclerotic lesions. Dietary therapy together with hypolipidemic drugs are central to the management of hyperlipidemia, which aims to prevent atherosclerotic plaque progression, induce regression, and so decrease the risk of acute coronary events in patients with pre-existing coronary or peripheral vascular disease. In patients at high risk of coronary artery disease but without evidence of atherosclerosis, treatment is designed to prevent the premature development of coronary artery disease, whereas in those with hypertriglyceridemia, treatment aims to prevent the development of hepatomegaly, splenomegaly, and pancreatitis. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most potent lipid-lowering agents currently available, and their use in the treatment of hyperlipidemia provides the focus for this review. Particular emphasis is given to cerivastatin, a new HMG-CoA reductase inhibitor that combines potent cholesterol-lowering properties with significant triglyceride-reducing effects. Recently completed primary and secondary intervention trials have shown that the significant reductions in low-density lipoprotein (LDL) cholesterol achieved with statins result in significant reductions in morbidity and mortality associated with coronary artery disease as well as reductions in the incidence of stroke and total mortality. Such benefits occur early in the course of statin therapy and have led to suggestions that these drugs may possess antiatherogenic effects over and above their capacity to lower atherogenic lipids and lipoproteins. Experimental studies have also shown statin-induced improvements in endothelial function, decreased platelet thrombus formation, improvements in fibrinolytic activity, and reductions in the frequency of transient myocardial ischemia.
 ...
PMID:Current and future treatment of hyperlipidemia: the role of statins. 973 40

Red cell redox-status and hemodynamic changes were studied in 60 old patients with ischemic heart disease. The treatment consisted of standard therapy (ST), ST + amino acid composition (glutaminic acid, glycine, cysteine) or preductal (15, 30 and 15 patients, respectively). Glutathione levels, activity of glutathione-transferase, reductase, peroxidase, catalase, Cu-, Zn-superoxide dismutase, red cell levels of malonic dialdehyde, hemodynamic parameters according to echo-CG and ECG monitoring were estimated before the treatment and 20 days after it. Endogenic antioxidant defense/hemodynamic parameters correlation coefficients were calculated. Close correlations were not found. However, ST + amino acid composition demonstrated the weakest correlations between the antioxidant defense and hemodynamics, while ST + preductal produced the greatest number of correlations. It is suggested that amino acids promote search for the antioxidant system's optimum while ST + preductal promotes closer correlations between red cell redox status and hemodynamic parameters.
 ...
PMID:[Parameters of hemodynamics and red cell redox-status in old patients with ischemic heart disease]. 1097 43

The choice of conduit is the most important factor influencing long-term patency of coronary artery bypass grafts (CABGs); arterial grafts are far superior to saphenous vein bypass grafts (SVGs) in this regard. Aspirin therapy should be started early in the perioperative period and continued indefinitely. Warfarin (Coumadin; Dupont, Wilmington, DE) and other platelet inhibitors offer no added value to aspirin, but may be used with benefit in aspirin-intolerant patients. Every effort should be made to reduce low-density lipoprotein cholesterol (LDL-C) to a value well below 100 mg/dL. In most instances, this will require the use of an 3-hydroxy-3-methyglutaryl coenzyme A (HMG CoA) reductase inhibitor. Avoidance of cigarette smoking is imperative. Achieving a normal blood pressure, ideal body weight, and a regular exercise program are helpful. Those patients who have important obstruction in a SVG or arterial graft and who are symptomatic, or who have important myocardial ischemia with orjwithout symptoms should be treated with a procedure to improve perfusion to the myocardium supplied by the occluded bypass graft. Successful percutaneous transluminal coronary angioplasty (PTCA) and stenting of the obstructed graft usually will lead to improved myocardial perfusion, although in other clinical circumstances repeat CABG surgery will be required. On occasion, reperfusion of the myocardium can be achieved by PTCA of the native coronary artery with or without stenting while the degenerated graft is abandoned. When planning therapy for myocardial ischemia, the higher rate of PTCA related restenosis and the increased risks from repeat CABG must be carefully considered.
 ...
PMID:Coronary Artery Bypass Graft Degenerative Disease. 1113 89


1 2 3 4 Next >>