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

Heart failure is associated with an increase in plasma nitrate and nitrite (NOx). To date there is still some controversy regarding the causes of nitrate accumulation during the development of heart failure. The goal of this study was to analyze the underlying mechanisms that cause accumulation of plasma nitrates during the development of heart failure in dogs. Dogs were chronically instrumented for measurement of hemodynamics and renal function. Hearts were paced initially at 210 bpm for 3 weeks and then at 240 until the development of heart failure. Hemodynamics, renal function, renal blood flow, arterial blood gases, hemoglobin, plasma and urine NOx levels, and creatinine levels were measured weekly. Heart failure was assessed by hemodynamic alterations, physical signs such as lethargy, ascites, cachexia, and postmortem evidence of cardiac hypertrophy. LVSP (from 127 +/- 3 to 106 +/- 3 mmHg), LV dP/dt (from 2658 +/- 173 to 1439 +/- 217 mmHg/s), MAP (from 101 +/- 1.9 to 83 +/- 1.8 mmHg) fell, whereas LVEDP tripled (from 6.4 +/- 0.9 to 20 +/- 2.6 mmHg), and heart rate rose (from 101 +/- 4.2 to 117 +/- 6.3 bpm), all changes P < 0.05. RBF (from 146 +/- 10 to 96 +/- 9.9 ml/min), urine output (V) (from 0.26 +/- 0.02 to 0.16 +/- 0.02 ml/min), GFR (from 63 +/- 1.8 to 49 +/- 2 ml/min), and Na excretion (from 45 +/- 4.5 to 14 +/- 4.6 microEq/min) all decreased (P < 0.05), whereas RVR increased (from 0.68 +/- 0.05 to 0.94 +/- 0.1 mmHg/ml/min). These changes took place during a rise in plasma NOx (from 3.7 +/- 0.5 to 16+/-3.3 microM), a decrease in urine NOx (from 33 +/- 9.9 to 8.1 +/- 4.9 microM), and a concurrent increase in NOx reabsorption (from 221 +/- 31 to 818 +/- 166 nmol/min). There was a direct correlation between the increase in plasma NOx levels and an increase in filtered load (r(2) = 0.97, P = 0.02), a negative correlation between NOx levels and NOx excretion (r(2) = 0.65 P < 0.09), and a direct correlation between plasma NOx levels and NOx reabsorption (r(2) = 0.97, P = 0.02). These results indicate that elevated plasma NOx during heart failure are most likely the result of an impairment of the renal function and not increased NOx production. Furthermore, without knowing changes in renal function the measurement of plasma NOx in and of itself is a meaningless index of NO formation.
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PMID:Plasma nitrate accumulation during the development of pacing-induced dilated cardiac myopathy in conscious dogs is due to renal impairment. 1117 32

The physiological role of the prostaglandin (PG) E2 receptor EP4 subtype was investigated by the generation of EP4-deficient mice by gene targeting. Loss of the EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and lethargic approximately 24 h after birth, and died within 72 h. Less than 5% of the EP4 (-/-) mice survived and grew normally more than a year. Marked congestion in the pulmonary capillaries were observed before death, suggesting that EP4 (-/-) neonates had left-sided heart failure. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors. In situ hybridization study showed that EP4 mRNA was strongly expressed in the ductus. The treatment of indomethacin, an inhibitor of PG synthesis, on wild-type fetus induced constriction of ductus arteriosus, while the ductus in EP4 (-/-) fetus was insensitive to indomethacin. These results suggest that neonatal death is at least partly due to patent ductus arteriosus, and that the EP4 receptor plays a role in the regulation of the patency of this vessel. They also indicate that the normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system.
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PMID:[A study for functions of prostaglandin E receptor EP4 subtype by analysing knockout mice]. 1120 Nov 61

Ateleia glazioviana is an important poisonous plant from southern Brazil. Heavy losses in cattle from this region occur each year due to ingestion of the plant. The epidemiological, clinical, gross and histopathological features of A. glazioviana poisoning in cattle are described here from a 5-year field survey in southern Brazil. A. glazioviana poisoning in cattle induces 3 clinical presentations: abortions, disease characterized by lethargy, and cardiac failure. The latter is associated with marked necrosis and fibrosis of the myocardium and can cause sudden death or congestive heart failure.
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PMID:Field observations of Ateleia glazioviana poisoning in cattle in Southern Brazil. 1120 77

Young mice tolerate myocardial loss after coronary artery ligation (CAL) without congestive heart failure (CHF) signs or mortality. We predicted a CHF phenotype after CAL in aged mice. Left coronary artery ligation produced permanent myocardial infarcts (MI). Mortality was higher in male 14-mo-old C57BL/6N mice (Older mice) than in 2-mo-old mice (Young mice) (16 of 25 Older mice died vs. 0 of 10 Young mice, P < 0.02). After 8 wk, rales, weight loss, and lethargy preceded deaths. Captopril (50 mg x kg(-1) x day(-1)) increased Older mouse survival (6 of 22 died, P < 0.02). Captopril improved systolic function (peak aortic blood velocity) from 76 +/- 6% of baseline in untreated Older mice to 93 +/- 8% (P < 0.036). At 24 h, MI comprised 28 +/- 4% of the left ventricle in Young mice, surprisingly larger than that in Older mice (18 +/- 2%, P < 0.011). Endocardial area underlying the infarct scar was significantly larger in Older mice than in Young mice. Captopril did not reduce expansion but markedly reduced septal hypertrophy. Aging reduces compensatory ability in mice despite smaller acute infarcts. Less effective myocardial repair, greater infarct expansion, and septal hypertrophy are seen with aging. Aging is a more relevant murine model of post-MI heart failure in patients.
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PMID:Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure. 1178 10

Oxazepam is one of a number of benzodiazepines used therapeutically as a sedative-hypnotic and antianxiety agent. Toxicology and carcinogenesis studies were performed by administering oxazepam (greater than 99% pure) in feed to male and female Swiss-Webster and B6C3F1 mice for 14 weeks, 57 weeks (Swiss-Webster), or 2 years (B6C3F1). Neurobehavioral assessments were performed during the studies. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells, and peripheral blood samples were analyzed for frequency of micronucleated normochromatic erythrocytes. Supplemental studies were performed to compare the metabolism and toxicokinetics of oxazepam in the two mouse strains, to evaluate the effect on liver cell replication rates, to perform clinical pathology assessments, and to examine the mutation spectrum and frequency of activated H-ras oncogenes in liver neoplasms from the 2-year study with B6C3F1 mice. 14-WEEK STUDY IN SWISS-WEBSTER MICE: Groups of 10 male and 10 female Swiss-Webster mice received oxazepam in feed at concentrations of 0, 625, 1,250, 5,000, 10,000 ppm for 14 weeks. One 625 ppm male and one 10,000 female were killed moribund before the end of the study, and the condition of the female mouse was attributed to oxazepam exposure. Mean body weight gains of exposed groups were similar to those of the controls. Exposed mice displayed chemical-related sedation and lethargy during the first study week, but appeared normal thereafter. In the neurobehavioral studies, reductions in grip strength were evident in both male and female mice at week 2 and persisted in males through week 11. An antianxiety effect was detected in exposed mice in measures of motor activity, startle response, and reactions to thermal stimulus. At necropsy, absolute and relative liver weights were increased in an exposure-related manner and were approximately two-fold greater in 10,000 ppm mice than in controls. Centrilobular hepatocellular hypertrophy was present only in exposed mice, and the severity increased with dose. 14-WEEK STUDY IN B6C3F1 MICE: Groups of 10 male and 10 female B6C3F1 mice received oxazepam in feed at concentrations of 0, Groups of 10 male and 10 female Swiss-Webster mice 625, 1,250, 2,500, 5,000, or 10,000 ppm for 14 weeks. received oxazepam in feed at concentrations of 0, There were no deaths that were clearly related to 625,1,250, 2,500, 5,000, or 10,000 ppm for 14 weeks. oxazepam exposure. Mean body weight gains of One 625 ppm male and one 10,000 ppm female were exposed groups were similar to those of the controls. Exposed mice displayed chemical-related sedation and lethargy during only the first study week. In neurobehavioral studies, reductions in grip strength were evident in males at week 2 but were no longer observed at week 12. An antianxiety effect was noted in exposed mice in measures of motor activity, startle response, and reactions to a thermal stimulus (females). At necropsy, absolute and relative liver weights were increased in an exposure-related manner and were approximately two-fold greater in 10,000 ppm mice than in controls. Centrilobular hepatocellular hypertrophy was present only in exposed mice, and the severity increased with dose. CHRONIC STUDIES: Groups of 60 male and 60 female Swiss-Webster and B6C3F1 mice received oxazepam in feed at concentrations of 0, 2,500, or 5,000 ppm. Additional groups of 60 male and 60 female B6C3F1 mice received 125 ppm in feed to allow for study of a group with projected serum concentrations of oxazepam similar to those achieved in humans taking a therapeutic dose. Ten male and 10 female B6C3F1 mice per group were evaluated at 15 months. Average daily oxazepam consumption varied throughout the studies, and the overall daily average ranged from 10 to 29 mg/kg body weight for the 125 ppm groups, 234 to 512 mg/kg for the 2,500 ppm groups, and 444 to 1,085 mg/kg for the 5,000 ppm groups. Serum oxazepam concentrations determined at 57 weeks in Swiss-Webster mice and at the 15-month interim evaluation of B6C3F1 mice 1 mice were approximately 1 ug/mL in the 125 ppm groups, 4 to 7 &mu;g/mL in the 2,500 ppm groups, and 7 to 10 &mu;g/mL in the 5,000 ppm groups. Neurobehavioral assessments during the chronic studies of each strain of mice were confounded by the poor survival and deteriorating condition of mice with hepatic neoplasia. However, within the limitations of the studies, there were no notable changes in the types of behaviors observed compared to those observed in the 14-week studies, nor was there an enhancement in the degree to which they were exhibited. 57-Week Study in Swiss-Webster Mice: Survival, Body Weights, Feed and Compound Consumption, and Clinical Findings: At 57 weeks, survival of exposed mice was significantly lower than that of controls (males: O ppm, 45/60; 2,500 ppm, 19/60; 5,000 ppm, 10/60; females: 47/60, 28/59, 17/59), causing the study to be terminated. Mean body weights of exposed males were similar to controls until week 17; afterwards, mean body weights of exposed male groups were lower than those of controls. Final mean body weights of exposed males were 9% lower than that of the controls. The mean body weight of 2,500 ppm females was greater than that of the controls throughout the study. Females receiving 5,000 ppm had a mean body weight greater than that of the controls early in the study; after week 29, the mean body weight of this group was similar to that of the controls. Feed consumption by exposed males and females was slightly lower than that by the controls, and females in all groups, including controls, consumed slightly more feed than males throughout the study. Dietary levels of 2,500 and 5,000 ppm oxazepam resulted in average daily compound consumption levels of 270 and 570 mg/kg for males and 320 and 670 mg/kg for females. Hypoactivity and sedation were observed in exposed mice during the first week of the study. There were no other clinical findings associated with oxazepam exposure. Pathology Findings: Systemic amyloidosis was the principal cause of death in mice dying before the study was terminated. The lower survival of mice receiving oxazepam was attributed to an increase in the extent and severity of amyloid deposits in many organs, including the heart and kidney. Atrial thrombosis and pulmonary lesions consistent with chronic heart failure occurred at higher incidences and with greater severity in exposed mice. The incidence of hepatocellular adenomas (males: 1/60, 35/60, 50/60; females: 0/60, 22/59, 47/59) and carcinomas (males: 0/60, 5/60,19/60; females: 1/60, 1/59, 11/59) were increased in exposed mice. The incidences of eosinophilic foci were also increased in exposed mice (males: 0/60, 22/60, 22/60; females: 0/60, 20/59, 14/59), and there was evidence of increased centrilobular hepatocyte hypertrophy (males: 12/60, 46/60, 47/60; females: 3/60, 51/59, 53/59). 2-Year Study in B6C3F1 Mice: Survival, Body Weights, Feed and Compound Consumption, and Clinical Findings: Survival of mice receiving 2,500 and 5,000 ppm was significantly lower than that of controls (males: O ppm, 45/50; 125 ppm, 44/50; 2,500 ppm, 15/50; 5,000 ppm, 0/50; females: 39/50, 41/50, 2/50, 0/50). Mean body weight gains of exposed male and female mice were similar to controls until about week 15 when weight gains for mice exposed to 2,500 or 5,000 ppm slowed in relation to controls, resulting in weight gains approximately 30&percnt; to 40&percnt; lower than those of the controls throughout the remainder of the study. Mean body weight gain of male mice exposed to 125 ppm was similar to that of the controls, while that of female mice receiving 125 ppm was 10&percnt; to 15&percnt; lower than that of the controls after about week 45. Feed consumption by exposed males and females was similar to that by controls. Dietary levels of 125, 2,500, and 5,000 ppm resulted in average daily oxazepam consumption levels of 12, 310, and 690 mg/kg body weight for males and 15, 350, and 780 mg/kg for females. In the 5,000 ppm groups, lethargy and sedation were observed in a few mice during the first week of study. Pathology Findings: The early deaths of many of the B6C3F1 mice exposed to oxazepam were attributed to a marked increase in the incidences of hepatoblastoma (males: 0/49, 2/50, 21/50, 13/50; females: 0/50, 1/50, 8/50, 8/50), hepatocellular adenoma (males: 17/49,18/50, 34/50, 32/50; females: 25/50, 35/50, 35/50, 36/50), and hepatocellular carcinoma (males: 9/49, 5/50, 45/50, 50/50; females: 9/50, 5/50, 49/50, 44/50). Moderate hypertrophy of centrilobular hepatocytes occurred in mice receiving 2,500 and 5,000 ppm (males: 0/49, 2/50, 26/50, 43/50; females: 0/50, 2/50,11/50, 29/50). An increase in the incidence of follicular cell hyperplasia of the thyroid gland occurred in all exposed groups of mice (males: 4/49, 22/50, 49/50, 47/50; females: 16/50, 34/50, 49/50, 44/50), and thyroid gland follicular cell adenoma was increased in exposed females (0/50, 4/50, 5/50, 6/50). Testicular atrophy occurred in the 2,500 and 5,000 ppm groups (1/50, 0/50, 25/50, 38/50), and the incidence of epididymal Iymphocyte infiltration was increased in all exposed groups (2/50,14/50, 33/50, 21/50). The frequency of hepatocellular neoplasms with an activated H-ras oncogene in the B6C3F1 mice and the mutation spectrum of the H-ras gene were determined. The mutation spectrum of the H-ras genes in the relatively few neoplasms from exposed mice that did have an activated H-ras did not differ from the spectrum of mutations observed in neoplasms from controls, but the proportion of neoplasms with an activated H-ras gene decreased with increasing oxazepam dose. While 11 of 19 (58&percnt;) neoplasms from control mice had an activated H-ras gene, only 1 of 40 neoplasms from mice receiving 2,500 or 5,000 ppm oxazepam exhibited a similar molecular lesion. Thirteen of 37 (35&percnt;) neoplasms from mice in the 125 ppm group had an activated H-ras oncogene, suggesting that, although the incidence of all liver neoplasms was not statistically increased compared to controls, there was an increase in a similar subset of neoplasms (lacking an activated H-ras) that occurred with increased incidence at higher doses. SUPPLEMENTAL STUDIES: Because exposure to oxazepam caused increased incidences of liver neoplasms, supplemental short-term studies were performed. Oxazepam given in feed to male B6C3F1 mice at 25, 125, 2,500, or 5,000 ppm for up to 13 weeks was found to cause a dose-related increase in nuclear labeling index in studies measuring the incorporation of bromodeoxyuridine into replicating liver cells. This increase was statistically significant at all but the 25 ppm exposure level and was limited to mice evaluated at 15 days. Cell replication rates in most groups evaluated at 30 days and after were similar to control rates. There was minimal evidence suggestive of hepatocyte necrosis either by light microscopy or in clinical chemistry measures. There was, however, evidence of cholestasis, likely due to physical obstruction of bile canaliculi by swollen hepatocytes. The metabolic fate and toxicokinetics of oxazepam were evaluated in each strain of mice and were compared to published data from human studies. Both mice and humans form glucuronides of oxazepam and form 3- and 4-hydroxy and methoxy derivatives of the phenyl group. Oxidative metabolism of the phenyl group appears to be more prevalent in mice than is reported for humans. Elimination half-lives of parent compound do not differ between Swiss-Webster and B6C3F1 mice and are similar to values reported for humans. GENETIC TOXICOLOGY: Oxazepam was not mutagenic in any of several strains of Salmonella typhimurium, nor did it induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. These in vitro tests were performed with and without S9 metabolic activation. Results from an in vivo mouse peripheral blood micronucleus test performed on the B6C3F1 mice used in the 14-week study were also negative. CONCLUSIONS: Under the conditions of these feed studies, there was clear evidence of carcinogenic activity of oxazepam in male and female Swiss-Webster mice based on increased incidences of hepatocellular adenoma and carcinoma. There was clear evidence of carcinogenic activity of oxazepam in male and female B6C3F1 mice based on increased incidences of hepatoblastoma and hepatocellular adenoma and carcinoma. Increased incidences of hyperplasia of thyroid gland follicular cells in male and female B6C3F1 mice and of follicular cell adenomas in female B6C3F1 mice were also related to oxazepam exposure. Administration of oxazepam to Swiss-Webster mice resulted in centrilobular hepatocellular hypertrophy and increased incidences and severity of systemic amyloidosis. Administration of oxazepam to B6C3F1 mice also resulted in centrilobular hepatocellular hypertrophy. Synonyms: 7-Chloro-1,3-dihydro-3-hydroxy-5-phenyl-2 H - 1,4-benzodiazepin-2-one Trade Names: Tazepam, Wy-3498, Serax
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PMID:NTP Toxicology and Carcinogenesis Studies of Oxazepam (CAS No. 604-75-1) in Swiss-Webster and B6C3F1 Mice (Feed Studies). 1259 20

A 4-year-old German Shepherd was evaluated for progressive depression, lethargy, anorexia, and dyspnea. Despite treatment with diuretics and antibiotics, the dog died. Based on clinical, radiographic, and pathologic findings, the diagnosis was heart failure resulting from aortic valvular endocarditis.
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PMID:Aortic valvular endocarditis in a dog. 1536 43

A male fennec fox (Fennecus zerda) kit was examined for lethargy, inappetence, and weight loss. Clinical findings included respiratory distress, a gallop rhythm, and retinochoroiditis. Radiography indicated pleural effusion and cardiomegaly. Echocardiographic findings included left ventricular dilatation, low left ventricular ejection fraction, and atrioventricular valvular regurgitation. Necropsy findings were compatible with a diagnosis of congestive heart failure caused by myocarditis. Histopathology showed a disseminated infection with Toxoplasma gondii causing myocarditis, skeletal polymyositis, gastrointestinal myositis, and panuveitis. Toxoplasma-induced myocarditis should be included in the differential diagnosis of heart failure and retinochoroiditis in the fennec fox.
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PMID:Heart failure caused by toxoplasmosis in a fennec fox (Fennecus zerda). 1553 72

Pericardial effusion is a potentially life-threatening problem leading to a rise in the intrapericardial pressure resulting in varying degrees of hemodynamic compromise. Cardiac tamponade occurs when the intrapericardial pressure equals or exceeds right ventricular diastolic filling pressures leading to a decreased cardiac output. In dogs, the most common causes of pericardial effusion that require pericardiocentesis are cardiac neoplasia and idiopathic pericardial effusion (IPE). The incidence of cardiac neoplasia in dogs is low, and it is rare in cats. In dogs, hemangiosarcoma and chemodectoma are the two most common types of cardiac neoplasia. In cats, lymphosarcoma is the most common form of cardiac neoplasia, but they are more likely to develop pericardial effusion secondary to congestive heart failure or feline infectious peritonitis. Common histories include lethargy, dyspnea, anorexia, collapse, and abdominal distension. Pericardiocentesis is used to stabilize animals with life-threatening cardiac tamponade, relieve the pressure leading to right-sided heart failure, and obtain fluid samples for diagnostic evaluation. The fluid should be quantified and characterized. Serious complications associated with pericardiocentesis are rare. Complications include cardiac puncture, arrhythmias, and laceration of a tumor or coronary artery resulting in intrapericardial hemorrhage or sudden death.
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PMID:Therapeutic pericardiocentesis in the dog and cat. 1618 Mar 97

Rosiglitazone is a peroxisome proliferator active receptor. gamma agonist, which increases insulin sensitivity in adipose tissue, muscle, and liver. Rosiglitazone is a member of the thiazolidinedione group, and because of its significantly positive effect on glycemic control, it is especially preferred in type 2 diabetic patients with a high cardiovascular disease risk. This drug, because of its decreasing effect on insulin resistance, is used alone or combined with type 2 diabetic drugs. A 73-year-old female patient was admitted to the emergency department with dyspnea, pink frothing phlegm, cyanosis, and tiredness. She was lethargic, uncooperative, and had no orientation. In arterial blood gases, hypoxemia and hypercapnia were found. She was taken to the general intensive care unit, and oxygen was applied via mask. The patient had a history of 10 years of diabetes mellitus, hypertension, and atherosclerotic cardiac disease, and she was using rosiglitazone for the past 6 weeks. Her chest x-ray was taken, and acute pulmonary edema was diagnosed. In her last echocardiography, which was performed 1 year before, no signs indicating cardiac failure and pleural effusion could be found. Therefore, it was concluded that pulmonary edema occurred as a complication of rosiglitazone use. After stabilizing the patient's vital signs, blood glucose levels, and lactate levels, medical treatment of diabetes mellitus was rearranged, and she was discharged on the seventh day after her admittance. In a patient with diabetes mellitus who has been admitted to the intensive care unit because of acute pulmonary edema, for differential diagnosis, use of rosiglitazone should be kept in mind during the determination of treatment. Therefore, the authors aim to discuss the effect of rosiglitazone on creating acute pulmonary edema with a case report presentation.
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PMID:Acute pulmonary edema due to rosiglitazone use in a patient with diabetes mellitus. 1669 44

CASE DESCRIPTION-A 12-week-old female English Springer Spaniel was evaluated for lethargy, vomiting, and pyrexia 1 week after treatment of patent ductus arteriosus (PDA) via coil occlusion. CLINICAL FINDINGS-Test results were consistent with septicemia, and the assumption was made that the PDA occlusion coils were infected. Radiography revealed partial migration of the coil mass into the pulmonary artery and signs of congestive heart failure. TREATMENT AND OUTCOME-After successful treatment of the septicemia and heart failure, surgical removal of the coils and resection of the PDA were undertaken. Although the coil that embolized to the pulmonary vasculature was left in place, the dog's clinical signs resolved. CLINICAL RELEVANCE-This case highlights the fact that as PDA coil occlusion devices become more widely used in dogs, practitioners must be prepared to treat implant infections aggressively, with both medical and surgical interventions if necessary.
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PMID:Septicemia in a young dog following treatment of patent ductus arteriosus via coil occlusion. 1678 81


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