Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case.
 ...
PMID:Mitochondrial tRNA(Ile) mutation in fatal cardiomyopathy. 163 86

Experimental hyperthyroidism induced in rats by daily injections of 3,3',5,5'-tetraiode-L-thyroxine (0.5 mg/kg i.p.) for 14 days resulted in a significant increase in heart weight and heart weight/body weight ratio. Hemodynamic and morphological studies were performed in one group. Thyroxine-treated rats showed a characteristic cardiovascular hyperdynamic state, such as tachycardia and augmented rate of contraction, but no evidence of heart failure such as elevated end-diastolic pressures. The cardiac cells in hyperthyroid rats had a significantly larger diameter and more mitochondria than did those of the control rats. In another group the activities of cardiac enzymes involved in energy utilization and liberation were measured biochemically and compared with those of normal controls. Hyperthyroidism resulted in increased specific activity of cytochrome C oxidase and actomyosin ATPase in the myocardium. The specific activity of long-chain acyl-CoA synthetase, carnitine palmityl-transferase, carnitine acetyltransferase, malate dehydrogenase and citrate synthase showed a moderate to marked increment, whereas the specific activity of lactate dehydrogenase and pyruvate kinase remained at the control values. These results suggest that in hyperthyroid rat hearts the functions of both energy liberation and utilization systems are enhanced to meet the added workload. Moreover, the increased activity of the enzymes participating in fatty acid metabolism suggest that in thyroxine-induced hypertrophic and hyperdynamic rat hearts, fatty acids contribute more to the energy supply than do carbohydrates.
 ...
PMID:Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat myocardium. 315 81

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.
 ...
PMID:Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. 887 78

In patients with congestive heart failure, skeletal muscle is characterized by a smaller proportion of slow-twitch oxidative fibers and reduced oxidative enzyme activity. However, whether these changes result from disuse or occur as a direct consequence of heart failure is unresolved. To address this issue, 18 rats with heart failure 8 weeks after left coronary artery ligation and 13 sham-operated control rats underwent quantification of locomotor activity by a photocell activation technique, measurements of hemodynamics and infarct size, histochemical and morphological analyses of the soleus and plantaris muscles, and Northern analyses of muscle contractile protein and oxidative enzyme mRNA expression. Although the rats with heart failure had elevated left ventricular end-diastolic pressures (24.1 +/- 2.6 mm Hg) and a mean infarct size of 35.1 +/- 4.1%, activity levels were similar to those found in the sham-operated rats (3849 +/- 304 versus 3526 +/- 130 counts per hour). With heart failure, there was a significant reduction of type I fibers in the soleus muscle and type IIa fibers in the plantaris muscle, with corresponding increases in intermediate staining of type IIab fibers in both muscles. This was associated with a 17% decrease in citrate synthase activity in both the soleus and plantaris muscles (26.2 +/- 1.6 versus 30.7 +/- 3.4 and 29.1 +/- 2.4 versus 35.7 +/- 3.4 mumol/L per minute per gram, respectively [P < .05]). In the soleus muscle, mRNA for both beta-myosin heavy chains and cytochrome C oxidase III (normalized to 18S RNA) was reduced (0.27 +/- 0.02 versus 0.65 +/- 0.02 and 0.23 +/- 0.04 versus 0.64 +/- 0.02 U), whereas the messages for IIx and IIb myosin heavy chains were increased. A similar decrease in messages for cytochrome oxidase and the primary myosin isoform was observed in the plantaris muscle. Both soleus beta-myosin heavy chain and cytochrome C oxidase expression show significant inverse relationships to left ventricular end-diastolic pressure and infarct size. In contrast, there was no relationship between either beta-myosin heavy chain or cytochrome C oxidase expression and locomotor activity. These results indicate that in rats heart failure produces changes in skeletal muscle gene expression at the pretranslational level that cannot be explained by inactivity.
 ...
PMID:Heart failure in rats causes changes in skeletal muscle morphology and gene expression that are not explained by reduced activity. 892 60

Regular exercise is regarded as a mainstay of physical fitness and endurance; it remains to be determined, however, whether patients with severe impairment of left ventricular performance derive profit from this treatment to the same extent as patients with normal myocardial contractility. Irrespective of the underlying cause profound changes are initiated by heart failure with respect to neurohumoral factors, ultrastructure of skeletal muscle, and peripheral vascular resistance. Initially these changes are set in motion by the inability of the heart to provide sufficient flow to the peripheral organs; eventually, however, they attain a role of their own and contribute to the disease independently. Intolerance of physical exercise, in particular, is not so much the result of pulmonary congestion and low cardiac output. Reduction of oxidative capacity of skeletal muscle, excessive peripheral vascular resistance, and impairment of vasodilatation in response to metabolic needs seem to contribute more to this incapacitating symptom. Until recently, physical exercise was regarded as harmful in patients with severe impairment of left ventricular performance; in order to prevent further deterioration patients were frequently treated by bedrest. Controlled trials, however, have shown that regular physical exercise in these patients may favourably influence the course of this disease, or even reverse some harmful changes. The following results were obtained in a group of 12 patients with depressed left ventricular ejection fraction (LV-EF 25 +/- 10%) participating in an ambulatory training program: 1) Left ventricular end-diastolic dimension was significantly reduced from 70 +/- 5 mm to 66 +/- 3 mm (p < 0.05). 2) There was significant improvement of skeletal muscle perfusion and oxygen uptake during submaximal and maximal exercise resulting in delayed onset of anaerobic metabolism and increased exercise capacity. 3) Intrinsic change of skeletal muscle ultrastructure were in part corrected; mitochondrial volume density increased significantly. There was a close correlation between changes in maximal oxygen uptake and changes of cytochrome-C-oxidase positive mitochondrial volume density. 4) Cardiac output and left ventricular ejection fraction in response to exercise, however, remained unchanged, indicating that no significant central effects were achieved by regular exercise.
 ...
PMID:[Physical training of patients with high grade compromise of heart pumping function]. 906 74

The efficacy of pre-, intra-, and postoperative prevention of hemodynamic disorders by creatinine phosphate, cytochrome C, and glutamic acid was evaluated in 61 coronary patients with decreased myocardial contractility. All these agents exerted a positive inotropic effect in coronary patients with ejection fraction below 0.4, increasing the stroke volume and left-ventricular ejection fraction without modifying heart rate. Glutamic acid is not recommended for preoperative treatment, because it increases oxygen consumption by the myocardium above the reserve potential of the coronary bed. Cytochrome C is the most effective drug for preoperative treatment. Intraoperative preischemic protection of the myocardium by cytochrome C in coronary patients during high risk operations prevents the development of unfavorable hemodynamic complications during induction and maintenance of anesthesia before artificial circulation, provides favorable recovery of cardiac activity, decreases the incidence of severe arrhythmias, promotes a rapid and full-value recovery of myocardial contractile function after ischemia, and decreases the incidence of acute heart failure.
 ...
PMID:[Prevention of disorders of myocardial contractile function in patients with ischemic heart disease during aortocoronary shunting]. 1145 65

Erectile dysfunction (ED) in men is amenable to correction with Viagra in a majority of patients. The accumulated experience of prescribing Viagra across the broad continuum of men suffering from ED is sufficient for a meaningful assessment of the safety of Viagra in clinical practice. The use of Viagra necessitates caution in cardiac failure and when used within six months of acute myocardial infarction and stroke. It is inadvisable in patients with unstable angina pectoris. The co-administration of Viagra with organic nitrates, for example, glyceryl trinitrate or isosorbide dinitrate, is unsafe. The relative contraindications to Viagra in cardiovascular disease are uncontrolled hypertension and impaired cardiac reserve. With respect to interactions with other drugs, the potential influence on the metabolism of Viagra by medications that affect the cytochrome-P-450 system does not translate into clinical effects. The vasodilatory properties of sildenafil citrate are largely responsible for unwanted effects. The most common side effects are headache, flushing (due to vasodilation), and dyspepsia (due to relaxation of the smooth muscle of the gastroesophageal sphincter with reflux). In the recommended single-dose range (25-100 mg), the use of Viagra for erectile dysfunction, in the absence of contraindications, is extremely safe provided the drug is taken under proper conditions.
 ...
PMID:The clinical safety of viagra. 1207 89

We report the cases of 2 previously healthy young patients with acute carbon monoxide intoxication who deteriorated to cardiogenic shock in the face of apparent metabolic and neurologic recovery. Prolonged exposure to sublethal levels of carbon monoxide (>24 hours, carboxyhemoglobin level of 20.4% and 22.6%) and massive binding of the toxin to myocardial myoglobin and mitochondrial cytochrome chain enzymes might explain their protracted cardiac failure. The good response to inotropic agents and the findings of repeated echocardiographic studies support the probable diagnosis of myocardial stunning. Complete cardiac recovery was observed in both patients.
 ...
PMID:Cardiogenic shock complicating acute carbon monoxide poisoning despite neurologic and metabolic recovery. 1223 99

Two cases of interstitial pneumonia with cardiac failure developing in patients treated with the new antidepressant venlafaxine are presented. A strong relationship between the development of the patients' illness and the initiation of venlafaxine treatment was identified. The cytochrome P (CYP) 450 system is involved in the metabolism of venlafaxine, suggesting that alterations in the drug metabolic clearance might be, at least in part, responsible for the development of drug-induced damage in these cases. This might occur either as a consequence of a genetic factor or concomitant drug therapy with an inhibitor of the related CYP system. After identifying the causative agent in the first case, withdrawal of the antidepressant together with corticosteroid treatment led to a favorable outcome. In the other case, the multiorgan failure became fatal. These cases highlight a hitherto undescribed association of an adverse lung reaction and heart failure due to venlafaxine.
 ...
PMID:Drug-induced pneumonitis and heart failure simultaneously associated with venlafaxine. 1266 37

An 89-year-old man with severe hypertension (190/82 mm Hg) and chronic heart failure (New York Heart Association class II) despite treatment with benidipine, doxazosin mesylate (INN, doxazosin), and furosemide was given oral candesartan cilexetil (4 mg/d), an angiotensin II type 1 receptor blocker metabolized via cytochrome p450 (CYP) 2C9. Two days later, he started to have severe dizziness and returned to the hospital on the fourth day without taking any of his medications. The blood pressure 30 hours after the last dose of candesartan was 126/64 mm Hg. Polymorphism analysis revealed the heterozygous poor metabolizer genotype CYP2C9*1/*3. The area under the concentration-time curve and the mean residence time of candesartan were both increased 2.5-fold, and the oral clearance of candesartan was 48% lower than that of the average elderly Japanese patient with hypertension. These results suggest that the CYP2C9*1/*3 genotype could be associated with decreased clearance and increased plasma concentration of candesartan, potentially enhancing its hypotensive effect.
 ...
PMID:Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype. 1458 91


1 2 3 4 5 Next >>