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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

Congestive Heart Failure (CHF) is a major health problem with a high mortality rate. Its ultimate therapy, heart transplantation, is limited by the shortage of donor hearts. Since decades researchers have been working to solve this problem by developing Mechanical Circulatory Support Systems (MCSS) that can replace or assist the failing heart. Short-term and intermediate-term ventricular assist devices are used nowadays frequently to bridge patients with severe heart failure to recovery. Long-term ventricular assist devices (VADs) and Total Artificial Hearts (TAHs) are used increasingly as a bridge to heart transplantations or as permanent circulatory support in patients with end-stage heart failure that are contraindicated for heart transplantation. The early TAHs and VADs were mainly driven from an external pneumatic drive unit. The latest generation TAHs and long-term assist devices are electrically powered, ultracompact, totally implantable, and have small wearable drive/control consoles, allowing patients to return to their daily activities. The article categorizes and reviews the development of MCSS, highlights the medical indications and contraindications of pump implantation, advantages and disadvantages of the various systems, and results of animal and clinical studies.
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PMID:Mechanical circulatory support systems--a review. 1120 71

Hypertrophic cardiomyopathy (HC) is associated with an increased risk of sudden cardiac death or death from heart failure. Little is known of the pathologic substrate for risk of premature death in this disease. We therefore set out to correlate the pathologic findings with the mode of death and risk profile in 75 patients with HC. Hearts with HC were obtained after death or transplantation. The clinical details were correlated with the macroscopic findings and the percent fibrosis, disarray, and small-vessel disease across 19 sections of each heart. Thirty-nine patients died suddenly, 28 had end-stage heart failure, and 8 died of other causes. Myocyte disarray correlated positively with evidence of ischemia (r = 0.5, p <0.0001), and was greater in patients who died before age 21 years (mean disarray 33% vs 18%, p <0.0001) and in those with an abnormal vascular response to exercise (mean disarray and 30% vs 19%, p = 0.04). Myocardial fibrosis was greater in patients who died in heart failure (mean percent fibrosis was 2.8% versus 0.9%, p = 0.003), and in patients with nonsustained ventricular tachycardia or a high risk fractionation study (4.9% vs 2.7%, p = 0.04, and 6.84% vs 2.8%, p = 0.03, respectively). In conclusion, young patients who die with HC have greater disarray than their older counterparts. In contrast, myocardial fibrosis is the substrate for premature deaths from heart failure and is associated with an increased risk of a primary ventricular arrhythmia.
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PMID:Relation between myocyte disarray and outcome in hypertrophic cardiomyopathy. 1147 7

Abnormalities of T-type calcium channel function reported to occur in the transition phase to heart failure in the hamster cardiomyopathy may contribute to progression of the disease. We tested the hypothesis that chronic exposure to mibefradil, a selective T-type calcium channel blocker, improves the deleterious cardiac remodeling observed in this condition. In the present study, 40 normal (N) and 40 UM-X7.1 cardiomyopathic hamsters (CMH), aged 180 days, were treated daily by gavage for 21 days with mibefradil (30 mg/Kg). Eight to 10 animals from each group were sacrificed at the end of the treatment period while the remainder were followed for an additional 30 days without treatment (washout period). Hearts were harvested, fixed with 10%-buffered paraformaldehyde and then cut in half down the middle. Several slices were dehydrated, embedded in paraffin and stained with Masson Trichrome. Wall thickness and dilatation index of the left ventricle were estimated by planimetry. Myocardial capillary density was also computed. The greater heart weight/body weight ratio seen in untreated CMH (7.7 +/- 0.4 vs 5.5 +/- 0.2 in N, p < 0.05) was improved with mibefradil. The dilatation index averaged 0.504 +/- 0.04 in N was increased in untreated CMH (0.566 +/- 0.03) and ameliorated in mibefradil-treated CMH. The 1-month washout period led to further deterioration of the dilatation index in untreated and mibefradil-treated CMH. Capillary density averaged 10,000 +/- 781 per mm2 in hearts from untreated N hamsters and 8,830 +/- 795 per mm2 in untreated CMH (p = NS). Chronic exposure to mibefradil resulted in a significant reduction of capillary density in both N and CMH hearts. Following the 1-month washout period, the change in myocardial capillary density associated with mibefradil was no longer detectable. In conclusion, chronic exposure to mibefradil, a T- and L-type calcium channel blocker, exerts opposite effects during the transition phase to heart failure in CMH, improving the deleterious left ventricular remodeling in UM-X7.1 hamsters and reducting myocardial capillary density independently of the disease process.
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PMID:Effects of mibefradil, a T- and L-type calcium channel blocker, on cardiac remodeling in the UM-X7.1 cardiomyopathic hamster. 1150 62

Left ventricular assist devices (LVAD) may improve cardiac function. The pathogenesis of this phenomenon, called 'reverse remodelling', is not completely elucidated. To examine the hypothesis that LVAD support eliminates tissue stress by reducing local hypoxia, the distribution of heme oxygenase-1 (HO-1), a stress protein inducible by hypoxia, was examined in vivo and in vitro. The immunoreactivity for HO-1 was semi-quantitatively analysed in left ventricular tissue of 23 patients (14 dilated cardiomyopathy (DCM), six ischaemic heart disease (IHD), three myocarditis/congenital heart disease) with end-stage heart failure before and after LVAD support, while two unused donor hearts served as controls. Control hearts stained almost negative for HO-1, while failing hearts showed immunoreactivity mainly in cardiomyocytes, but also in endothelial cells, some smooth muscle cells and fibroblasts. Hearts with IHD showed significantly higher HO-1 immunoreactivity than hearts with DCM or myocarditis/congenital heart disease. After LVAD support, the HO-1 content decreased significantly in the DCM and IHD group and was significantly higher in the subendocardium than in the subepicardium. In vitro, under hypoxic conditions, neonatal rat cardiomyocytes showed an increase of HO-1 protein content up to sixfold above the normal level, which returned to normal values after normoxic cultivation. Mechanical support reduces the HO-1 content of the failing heart and HO-1 is inducible in vitro under hypoxia and is reversible under normoxia. This supports the concept that restoration of cardiac normoxia by mechanical unloading, particularly in the subendocardium, may be in part responsible for the phenomenon of 'reverse remodelling'.
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PMID:Reduction of hypoxia-inducible heme oxygenase-1 in the myocardium after left ventricular mechanical support. 1201 48

We tested the hypotheses that myocardial infarction in mice would lead to progressively worsening heart failure 12-18 weeks later and that exercise testing would provide a suitable means to evaluate left ventricular function sequentially. C57BL/6 mice (n = 69) underwent left coronary artery ligation (n = 50) or thoracotomy without ligation (n = 19). Sixteen animals (32%) died within 24 h of coronary ligation. Twenty additional animals (40%) died between days 3 and 14, and these mice showed infarct sizes of > 50% of the left ventricle. Fourteen animals (28%) that survived two weeks underwent echocardiography and treadmill testing 12 and 18 weeks after infarction, with no further mortality. Mice were then killed, morphometric assessment made, infarct size evaluated, and myocardial norepinephrine content and expression of BNP and ANF measured. Mice with infarcts >30% of the left ventricle (n = 6; 12% of original cohort) had left ventricular dilation (p < 0.0001) and hypertrophy (p < 0.001), impaired left ventricular systolic function (p < 0.0001) and reduced exercise duration (p = 0.03) and total work (p = 0.03) 12-18 weeks after infarction. Mice with infarcts <30% of the left ventricle (n = 8; 16% of original cohort) had no significant functional changes or left ventricular remodeling. Hearts from mice with infarcts > 30 % had reduced myocardial norepinephrine levels (MI <30%: 177+/-54 pg/mg, n = 6; MI >30%: 66+/-14 pg/mg wet weight, n = 4; p = 0.005) and increased mRNA content of BNP (p < 0.03) and ANF (p = 0.023). Coronary artery occlusion in mice provides a relevant model of clinical heart failure that is progressive and can be assessed by sequential exercise testing, providing a means to study the development of heart failure and its treatment.
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PMID:Progressive heart failure after myocardial infarction in mice. 1206 90

Temporary or persistent heart failure is one of the major complications after myocardial infarction (MI). In order to elucidate the pathogenesis of MI, we studied the spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in cardiomyocytes in a rat model of ligation of the left anterior descending branch of the coronary artery. The lethality in this model was 18%. Hearts were dissected at 0, 3, 6, 12, 24, 48 h, and 1, 2, 4, 6 weeks after the operation. The cardiac level of 8-OHdG was evaluated biochemically as well as by immunohistochemistry with monoclonal antibody N45.1. Three to 6h after ligation, the 8-OHdG levels were increased in the cardiomyocytes of MI (six-fold) and peri-MI (four-fold) areas. After 24 h, the myocardium in the MI area was necrotized, and thereafter the 8-OHdG level decreased. 8-OHdG levels in the myocardium of peri-MI areas returned once to a normal level, but were significantly increased at 2-4 weeks along with the appearance of apoptotic cardiomyocytes in this area. The heart after MI has been generally considered as clinically stable after four weeks. However, cardiomyocytes near the infarcted area were oxidatively stressed even after four weeks when the affected lesion was extensive. The present data support the use of supplementary antioxidant therapies to save functional myocardium after MI. (213 words)
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PMID:Spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine levels in cardiomyocytes after myocardial infarction in rats. 1242 Jul 43

Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it also has effects on contractility. The interaction of endothelin-1 and the Frank-Starling response is unknown. The present study aimed to characterize the role of endothelin-1 in the regulation of the Frank-Starling response, one of the major mechanisms regulating cardiac contractile force, in both normal and hypertrophied hearts. Nontransgenic rat hearts and hypertrophic hearts of hypertensive double transgenic rats harboring human angiotensinogen and renin genes were studied in a Langendorff isolated heart setup with a liquid-filled balloon inside the left ventricle used to measure contractile parameters. The rats were studied at compensated phase, before showing any signs of heart failure. Compensated hypertrophy in double transgenic rat hearts resulted in improved contractility at a given level of preload when compared with nontransgenic rat hearts. Hearts of both rat lines showed preserved Frank-Starling responses, that is, increased contractile function in response to increased end-diastolic pressure. The mixed endothelin A/B receptor antagonist bosentan attenuated the Frank-Starling response by 53% (P<0.01) in the double transgenic hearts but not in nontransgenic hearts. The diastolic parameters remained unaffected. The left ventricles of the double transgenic rat hearts showed an 82% higher level of endothelin type A receptor mRNA and a 25% higher level of immunoreactive endothelin-1 compared with nontransgenic rat hearts. The type 1 angiotensin II receptor antagonist CV-11974 had no significant effect on contractile function in response to load in either strain. These results show that endogenous endothelin-1 contributes to the Frank-Starling response in hypertrophied rat hearts by affecting systolic performance.
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PMID:Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts. 1251 36

Poor metabolic control resulting from insulin withdrawal in chronic type 1 diabetic rats results in ischemic heart failure. In the present study, we determined whether heart failure occurs in acute type 1 diabetic rats following insulin withdrawal and if prior exercise training can prevent this dysfunction. Four-week-old diabetic prone BB Wor rats were either sedentary or moderately exercised by daily treadmill running. Training was discontinued at the onset of diabetes. Isolated working rat heart function was then assessed in the following groups: diabetic resistant, uncontrolled sedentary diabetic (USD), controlled sedentary diabetic (CSD), uncontrolled trained diabetic (UTD), and controlled trained diabetic (CTD) rats. To induce an uncontrolled state, insulin treatment was withheld for 24 hours. During increased metabolic demand and reperfusion following ischemia, heart rate, contractility, and cardiac output were depressed in hearts from USD animals. Treatment with insulin prevented the depressions in cardiac performance from occurring. Hearts from UTD rats perfused under these conditions showed comparable cardiac function to that seen in the controlled state. This occurred despite poor metabolic control, reflected by elevated levels of plasma glucose and free fatty acids. Our results indicate that metabolic deteriorations in acute diabetes result in ischemic heart failure. However, this cardiac dysfunction can be prevented with exercise training.
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PMID:Prevention of ischemic heart failure by exercise in spontaneously diabetic BB Wor rats subjected to insulin withdrawal. 1280 Jan 8

Myocardial contractile dysfunction accompanies both systemic and cardiac insults. Septic shock and burn trauma can lead to reversible contractile deficits, whereas ischemia and direct inflammation of the heart can precipitate transient or permanent impairments in contractility. Many of the insults that trigger contractile dysfunction also activate the innate immune system. Activation of the innate immune response to infection is coordinated by the conserved Toll/interleukin-1 (IL-1) signal transduction pathway. Interestingly, components of this pathway are also expressed in normal and failing hearts, although their function is unknown. The hypotheses that Toll/IL-1 signaling occurs in the heart and that intact pathway function is required for contractile dysfunction after different insults were tested. Results from these experiments demonstrate that lipopolysaccharides (LPS) activate Toll/IL-1 signaling and IL-1 receptor-associated kinase-1 (IRAK1), a critical pathway intermediate in the heart, indicating that the function of this pathway is not limited to immune system tissues. Moreover, hearts lacking IRAK1 exhibit impaired LPS-triggered downstream signal transduction. Hearts from IRAK1-deficient mice also resist acute LPS-induced contractile dysfunction. Finally, IRAK1 inactivation enhances survival of transgenic mice that develop severe myocarditis and lethal heart failure. Thus the Toll/IL-1 pathway is active in myocardial tissue and interference with pathway function, through IRAK1 inactivation, may represent a novel strategy to protect against cardiac contractile dysfunction.
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PMID:IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction. 1286 May 65


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