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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case is described of an infant who suffered from progressive, severe dystrophy, hemolytic and megaloblastic anemia, hematuria, proteinuria and slight uremia. He died at 4 months of age following two acute episodes of heart failure. Abnormally increased excretion of methylmalonate and homocystine was detected by our screening program for metabolic disorders. Amino acid analyses showed that the plasma and urine levels of methionine were very low whereas those of cystathionine were raised. Vitamin B12 deficiency, malabsorption or abnormal cobalamin transport were excluded by a normal serum total cobalamin and normal transcobalamins. These findings suggested a congenital error of cobalamin metabolism. Treatment with vitamin B12 resulted in a biochemical though not a clinical response. Postmortem examination revealed severe vascular lesions with changes in the kidney characteristic of thrombotic microangiopathy supporting a diagnosis of hemolytic-uremic syndrome. It is assumed that the elevated plasma homocysteine induced the vascular lesions by causing detachment of endothelium.
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PMID:Congenital defect in intracellular cobalamin metabolism resulting in homocysteinuria and methylmalonic aciduria. I. Case report and histopathology. 52 29

We report a 65-year-old man with amyloidotic polyneuropathy, who first suffered from heart failure at the age of 57, 3 years before the onset of neurological symptoms. He had no obvious family history. We analysed the transthyretin gene of the patient and 6 asymptomatic family members using polymerase chain reaction (PCR). The single amino acid substitution of a methionine for valine at position 30, which is a common mutation of Japanese type I FAP patients, was found from the patient and his sister of 47 years. Though Type I FAP patients often have cardiac conduction block, they rarely have signs of heart failure until the end stage of the disease. This is the first report of Type I FAP with severe myocardial involvement, in which TTR mutation at position 30 was confirmed. The result revealed the clinical variation of Type I FAP.
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PMID:[A sporadic case of late onset familial amyloidotic polyneuropathy preceded by cardiac involvement]. 826 6

We report a new type of fatal mitochondrial disorder caused by selective deficiency of mitochondrial ATP synthase (ATPase). A hypotrophic newborn from a consanguineous marriage presented severe lactic acidosis, cardiomegaly and hepatomegaly and died from heart failure after 2 days. The activity of oligomycin-sensitive ATPase was only 31-34% of the control, both in muscle and heart, but the activities of cytochrome c oxidase, citrate synthase and pyruvate dehydrogenase were normal. Electrophoretic and western blot analysis revealed selective reduction of ATPase complex but normal levels of the respiratory chain complexes I, III and IV. The same selective deficiency of ATPase was found in cultured skin fibroblasts which showed similar decreases in ATPase content, ATPase hydrolytic activity and level of substrate-dependent ATP synthesis (20-25, 18 and 29-33% of the control, respectively). Pulse-chase labelling of patient fibroblasts revealed low incorporation of [(35)S]methionine into assembled ATPase complexes, but increased incorporation into immunoprecipitated ATPase subunit beta, which had a very short half-life. In contrast, no difference was found in the size and subunit composition of the assembled and newly produced ATPase complex. Transmitochondrial cybrids prepared from enucleated fibroblasts of the patient and rho degrees cells derived from 143B. TK(-)human osteosarcoma cells fully restored the ATPase activity, ATP synthesis and ATPase content, when compared with control cybrids. Likewise, the pattern of [(35)S]methionine labelling of ATPase was found to be normal in patient cybrids. We conclude that the generalized deficiency of mitochondrial ATPase described is of nuclear origin and is caused by altered biosynthesis of the enzyme.
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PMID:A novel deficiency of mitochondrial ATPase of nuclear origin. 1048 64

We examined the effects of MET-88 on haemodynamics and cardiac hypertrophy in rats with an aortocaval shunt (A-V shunt). On the day of surgery, an A-V shunt was produced by using an 18-gauge needle in Wistar rats as described by Garcia and Diebold. MET-88 and captopril were orally administered to rats 1 week after surgery, and the administration was continued for 3 weeks. Four weeks after the surgery, A-V shunt-operated rats had biventricular hypertrophy and higher right atrial pressure (RAP) and left ventricular end-diastolic pressure (LVEDP) than sham-operated rats. Compared with untreated A-V shunt rats, those treated with MET-88 showed significant attenuation of the development of left ventricular (LV) hypertrophy and of the increased LVEDP. Captopril-treated A-V shunt rats also failed to show increases in LV weight and LVEDP. In in vitro studies, MET-88 had no effect on renin and angiotensin-converting enzyme (ACE) activities in the plasma of normal rats. These results suggest that MET-88 improved LV hypertrophy and LV dysfunction in rats with an A-V shunt. Furthermore, the data indicate that the beneficial effects of MET-88 may be attributed to some pathway, not involving the renin-angiotensin system, such as myocardial energy metabolism, venous return, etc. We conclude that MET-88 may be a novel agent for the therapy of chronic heart failure.
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PMID:Beneficial effects of MET-88 on left ventricular dysfunction and hypertrophy with volume overload in rats. 1052 Jul 23

Myocardial ischemia can cause myocardial infarction and as a consequence, heart failure. 3-(2,2,2-trimethylhydrazinium) propionate (MET-88) inhibits gamma-butyrobetaine hydroxylase and has cardioprotective effects on the ischemic heart. We now examined the effects of MET-88 in rats with congestive heart failure following myocardial infarction. Congestive heart failure was produced by left coronary artery ligation in rats. MET-88 at 100 mg/kg/day was orally administered from the 2nd day after surgery. We performed a survival study for 181 days, and measured ventricular remodeling, cardiac function, and myocardial high-energy phosphate levels after treatment for 20 days. MET-88 prolonged survival with a median 50% survival of 103 days compared to 79 days for the heart-failure control rats. The expansion of the left ventricular cavity (ventricular remodeling) in heart-failure rats was prevented by treatment with MET-88, and the effect of MET-88 was similar to that of captopril at 20 mg/kg. MET-88 attenuated the rise in right atrial pressure in heart-failure rats and augmented cardiac functional adaptability against an increased load. Also, MET-88 improved the myocardial energy state in heart-failure rats. The present results indicate that MET-88 improves the pathosis in rats with heart failure induced by myocardial infarction.
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PMID:Beneficial effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor in rats with heart failure following myocardial infarction. 1081 52

It was previously reported that inhibition of carnitine synthesis by 3-(2,2,2-trimethyl-hydrazinium) propionate (MET-88) restores left ventricular (LV) systolic and diastolic function in rats with myocardial infarction (MI). Preservation of the calcium uptake function of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) is one of the possible mechanisms by which MET-88 alleviates hemodynamic dysfunction. To test this hypothesis, the effects of MET-88 on protein content of SERCA2 were evaluated using the same rat model of heart failure. Myocardial protein content of hexokinase, which is one of the key enzymes of glucose utilization, was also measured. Either MET-88 (MET-88 group) or a placebo (MI group) was administered for 20 days to rats with MI induced by coronary artery ligation. The control group underwent sham surgery (no ligation) and received placebo. In LV myocardial homogenates, the myocardial SERCA2 protein content was 32% lower (p<0.05) in the MI group than in the control group. However, in the MET-88 group myocardial SERCA2 content was the same as in the control group. Hexokinase I protein content was 29 % lower (p<0.05) in the MI group compared with the control. In contrast, hexokinase II protein content did not differ significantly among the three groups. Consequently, inhibition of carnitine synthesis ameliorates depression of SERCA2 and hexokinase I protein content which may reduce tissue damage caused by MI.
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PMID:Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasmic reticulum Ca2+-ATPase and hexokinase type I in rat hearts with myocardial infarction. 1109 60

Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.
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PMID:Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. 1173 95

Cardiac insufficiency represents a major risk factor in patients about to undergo non-cardiac surgery. The post-operative mortality is linked to the severity of the pre-operative functional impairment: rising from 4% in NYHA class 1 to 67% in class IV. The operative risk is greater when the cardiac insufficiency is more disabling, the patient is older (> 70 years) and if there is a history of acute pulmonary oedema and a gallop bruit on auscultation. The use of metabolic equivalents (Duke Activity Status Index) is recommended: the functional capacity is defined as excellent if > 7 MET, moderate between 4 and 7, or poor if < 4. A non-invasive evaluation of left ventricular function is necessary in each patient with obvious congestive cardiac insufficiency or poor control under the American consensus, but it is rare that the patient has not already been seen by a cardiologist. The degree of per-operative haemodynamic constraint is linked to the surgical technique and is stratified according to the type of surgical intervention and whether or not it is performed as an emergency. An intervention duration > 5 hours is associated with an increased peri-operative risk of congestive cardiac insufficiency and non-cardiac death. Deaths from a cardiac cause are thus twice as frequent after intra-abdominal, non-cardiac thoracic or aortic surgery and the post-operative cardiac complications are six times more frequent. Numerous studies have attempted to document the impact of different anaesthetic techniques on the prognosis for the population at increased risk of post-operative cardiovascular complications. It is advisable to opt for peripheral nerve blocks. The cardiovascular morbidity and overall mortality do not differ between general anaesthetic, epidural anaesthetic or spinal nerve block. The ASA (American Society of Anesthesiologists) classification is widely used to determine the overall risk. The ASA class and the age are however too coarse as methods of evaluation for the individual risk and for giving judicious pre-operative advice. Multifactorial cardiac risk indexes such as that of Goldman allow overall evaluation (taking the patient and the intervention into account) of the peri-operative cardiovascular risk in non-cardiac surgery as a function of predictive clinical elements. Nine variables concerning the patient's history, the physical examination and several simple supplementary examinations are identified for which the relative weight is recorded under a points system. The average risk score for a given procedure is converted into an average risk for a given patient using a nomogram such as Detsky's. Surgical acts which do not impose major constraints on the cardiocirculatory apparatus (ophthalmic surgery for example) do not require supplementary examinations. The risk of post-operative cardiac complications is low in the absence of the 9 risk factors defined by Goldman, as is an ischaemic syndrome (angina on light physical activity, unstable angina, myocardial infarction). Certain risk factors (jugular congestion, gallop bruit, recent myocardial infarction, non-sinus rhythm, extrasystoles, aortic stenosis) obviously require appropriate treatment beforehand. The sometimes difficult process demands a dialogue between the cardiologist and the surgeon, the recognition of the risk of surgery in a given centre, and the opinion of the patient duly informed of the terms of the discussion about him.
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PMID:[Evaluation of the cardiac risks in non-cardiac surgery in patients with heart failure]. 1193 51

Data on the functional status of the cardiorespiratory system are required to identify patients at risk for postoperative complication in the presence of lung diseases. Very many factors influence the course of an operation and the postoperative period so there is no golden standard or the only parameter for predicting how the postoperative period runs. Patients with normal spirographic values (FEV1, more than 80%??) and without cardiovascular comorbidity are at a slight risk for postoperative complications. These patients do not need to be additionally examined. A less than one-month history of myocardial infarction, instable angina pectoris, decompensated heart failure, severe valvular disease are contraindications to planned surgery. The risk of cardiovascular events is high when the signs of myocardial ischemia occur with low exercise (less than 4 MET). Stress echocardiography, loading tests, and radioisotopic study are used as auxiliary techniques, FEV1, under 60%; ppo-FEV1, and ppo-DC, under 40%; VO2max, under 15 ml/kg/min are the values of a high risk for respiratory complications.
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PMID:[Functional studies in the prediction of postoperative complications in the presence of lung diseases]. 1452 92

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), which has been characterized as an "endogenous anti-atherosclerotic molecule". Synthesis of NO can be selectively inhibited by guanidino-substituted analogs of L-arginine, which act as competitive inhibitors at the active site of the enzyme. One such analog is asymmetric dimethylarginine (ADMA), a compound that has been found in human plasma and urine and exerts the activity of an endogenous inhibitor of NO synthase. In contrast to ADMA, its regioisomer symmetric dimethylarginine (SDMA) does not inhibit NO synthase. The methyl groups contained within the dimethylarginine molecules are derived from S-adenosylmethionine, an intermediate in the homocysteine/methionine pathway. There is experimental evidence that homocysteine may affect endothelium-dependent vascular function by increasing the formation of ADMA. Both ADMA and SDMA are eliminated from the body by renal excretion. In addition, the metabolism of ADMA, but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies suggest that ADMA inhibits vascular NO elaboration at concentrations found in pathophysiological conditions (i.e., 3-15 microM). ADMA likely acts as an autocrine regulator of endothelial NO synthase activity. When rabbits are placed on a diet enriched with 1% cholesterol, ADMA levels are increased within 4 weeks of dietary intervention as compared to control animals. Elevated plasma concentrations of ADMA are also present in hypercholesterolemic and hypertensive patients, in patients with chronic heart failure, and in other patient groups at high risk of developing cardiovascular disease. Elevation of ADMA induces dysfunction of the endothelium, which becomes clinically evident by impaired endothelium-dependent vasodilation, hyperaggregability of platelets, and enhanced monocyte adhesion. Recent prospective studies suggest that endothelial dysfunction indicates an increased risk of future cardiovascular events. In line with these observations, we and others found evidence that ADMA is a novel cardiovascular risk factor.
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PMID:Association of asymmetric dimethylarginine and endothelial dysfunction. 1465 27


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