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

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional responses of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glutathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probably due to the production of free radical species associated with the development of inflammation.
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PMID:Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat. 756 73

We investigated systematically the structure of the myocardium obtained from patients with dilated cardiomyopathy undergoing transplantation because of intractable heart failure. Hearts were explanted at the time of surgery from 12 patients (10 men and 2 women, aged 31-57 years, ejection fraction < 20%) and numerous samples were taken for light and electron microscopy. Biopsies from the left ventricle of 8 patients during operations for atrial septal defect served as control tissue. The most obvious qualitative findings were focal hypertrophy and atrophy of myocytes, enlargement and bizarre shape of nuclei, lack of contractile material and occurrence of numerous small mitochondria. On a quantitative level, the nuclear density was reduced (18%, p < 0.05) but the nuclear profile area was significantly increased (85%, p < 0.001). Thus the nucleus/cytoplasm relationship was altered. The volume density of the contractile filaments was decreased (25%, p < 0.001), but the mitochondrial volume density was unchanged. There was an increase in cell width (39%, p < 0.01) and of the connective tissue content (= fibrosis) (112%, p < 0.001). It is suggested that the nuclear abnormalities may be the primary event in the pathogenesis of dilated cardiomyopathy. These may then lead to a reduced transcriptional rate which most probably is the cause of the lack of myofilaments and other degenerative changes. The deterioration of the structural quality of the hypertrophied myocytes results finally in atrophy and fibrosis and may be the structural correlate of functional disturbances in dilated cardiomyopathy.
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PMID:Altered nucleus/cytoplasm relationship and degenerative structural changes in human dilated cardiomyopathy. 791 49

We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30 degrees C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca2+]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/- dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF group at rates above 2.4 Hz but did not decline in the WKY group. Peak [Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates. Peak systolic pressure did not fall significantly in the WKY group at any heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and pressure alternans were present in 8 of 13 SHR-F hearts at the highest stimulation rate, findings that were absent in both the WKY and SHR-NF hearts. We conclude the following: (1) Under baseline conditions, depressed contractile function of failing myocardium cannot be explained by decreased peak [Ca2+]i, (2) relative increases in [Ca2+]i and inotropy with increasing [Ca2+]o are proportional among groups; and (3) although peak systolic [Ca2+]i and inotropy are maintained with increasing stimulation rate in the WKY and SHR-NF groups, peak systolic [Ca2+]i and pressure decrease in parallel in the SHR-F heart with increasing stimulation rate, suggesting that impaired calcium cycling may contribute to compromised pump function in the SHR-F heart.
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PMID:Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat. 808 41

Hypertrophy and heart failure were induced by placing a mildly constrictive band around the ascending aorta in young guinea pigs. Based on heart weight, left ventricular wall thickness, hemodynamic data, and other clinical signs, these animals were found to have physiological hypertrophy at 10 wk and congestive heart failure (CHF) at 20 wk. Hearts from these two groups of animals were examined for superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase activities as well as lipid peroxidation and glutathione [reduced glutathione (GSH)/oxidized glutathione (GSSG)] levels. There was an age-dependent increase in SOD activity and GSH content in sham controls. SOD activity was 28% higher in the 10-wk-hypertrophy group and 46% lower in the CHF group than in respective sham controls. GSHPx activity increased significantly in the hypertrophied hearts, whereas in the failing hearts, the activity was not different from the 20-wk controls but was significantly lower than in the hypertrophied hearts. Catalase activity did not change at either stage. GSH content in the hypertrophied hearts was significantly higher compared with sham controls. In the CHF group, GSH content was significantly lower and GSSG content was significantly higher than in sham controls. Lipid peroxidation, as indicated by malondialdehyde content, was significantly decreased in the hypertrophy group but increased toward control levels in the failure group. It is proposed that a relative deficit in myocardial antioxidant capacity as well as in the redox state may play a role in the pathogenesis of cardiac failure.
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PMID:Antioxidant changes in hypertrophied and failing guinea pig hearts. 818 5

Left ventricular isovolumic stress development and metabolic parameters were studied in 18-24-month-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rat controls using the isolated, isovolumic (balloon in left ventricle) buffer-perfused rat heart preparation. After WKY rats and all SHRs were compared, SHRs were divided into two groups: those animals with (SHR-F) and without (SHR-NF) evidence of heart failure. Hearts were perfused at 100 mm Hg using a constant pressure system at a temperature of 37 degrees C. In the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak midwall stress was greatest in the WKY group and, again, lowest in the SHR-F group. Oxygen consumption was lowest in the SHR-F group. When the oxygen cost of stress development was estimated by normalizing myocardial oxygen consumption by peak developed midwall stress, values were lowest in the WKY, greater in the SHR-NF, and greatest in the SHR-F group. Lactate production did not occur in the baseline state in any of the groups. Functional and metabolic responses to graded hypoxia, induced by changing the gas mixture of the perfusate from 95% to 50%, 25%, and 0% oxygen at perfusion pressures of 100 and 130 mm Hg, were studied. Increasing perfusion pressure generally resulted in small increases in peak systolic pressure and myocardial oxygen consumption but did not substantially reverse the contractile or metabolic deficit present in the SHR-F group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen cost of stress development in hypertrophied and failing hearts from the spontaneously hypertensive rat. 841 24

Although hypothermia and cardioplegic cardiac arrest provide effective protection during cardiac surgery, ischemia of long duration, poor preoperative myocardial function, and ventricular hypertrophy may lead to heterogeneous delivery of cardioplegic solutions, incomplete protection, and impaired postischemic recovery. Calcium antagonists are potent cardioprotective agents, but their efficacy in the presence of cold cardioplegia is still controversial, especially in heart failure, since it is often believed that failing hearts are more sensitive to their negative inotropic and chronotropic actions. However, recent data have demonstrated that the benzothiazepine-like calcium antagonists diltiazem and clentiazem, in selected dose ranges, elicit significant cardioprotection independently of intrinsic cardiodepression, thus lending support to their use in cardioprotective maneuvers involving the failing heart. We therefore evaluated the cardioprotective interaction of diltiazem, clentiazem, and cold cardioplegia in both normal and failing ischemic hearts. Hearts were excised from 200- to 225-day-old cardiomyopathic hamsters (CMHs) of the UM-X7.1 line and age-matched normal healthy controls. Ex vivo perfusion was performed at a constant pressure (140 cmH2O; 1 cmH2O = 98.1 Pa) according to the method of Langendorff. Heart rate, left ventricular developed pressure (LVDP), and coronary flow were monitored throughout the study. Global ischemia was produced for 90 min by shutting down the perfusate flow, followed by reperfusion for 30 min. Normal and failing CMH hearts were either untreated (control) or perfused at the onset of global ischemia with one of the following combinations: cold cardioplegia alone (St. Thomas' Hospital cardioplegic solution, 4 degrees C, infused for 2 min), cold cardioplegia + 10 nM diltiazem, or cold cardioplegia + 10 nM clentiazem. The cardiac and coronary dilator properties of 10 nM diltiazem and 10 nM clentiazem alone were investigated in separate groups of isolated preparations. Failing CMH hearts had lower basal LVDP (42 +/- 2 vs. 77 +/- 2 mmHg (1 mmHg = 133.3 Pa) for normal hearts, p < 0.05), while coronary flow was only slightly reduced (5.6 +/- 0.2 vs. 6.2 +/- 0.2 mL/min for normal hearts). Following 90 min global ischemia, coronary flow was increased in both groups, but the peak hyperemic response declined only in failing CMH hearts (+50 +/- 17 vs. +82 +/- 17% in normal hearts). In normal hearts, LVDP virtually recovered within 5 min of reperfusion but steadily decreased thereafter (-37 +/- 4% at 30 min). In contrast, in failing CMH hearts, LVDP significantly decreased early during reperfusion but improved over time (-19 +/- 7% at 30 min). In normal hearts, the addition of diltiazem or clentiazem to cold cardioplegic solutions resulted in improved postischemic contractile function for the duration of reperfusion (85 +/- 4% vs. only 71 +/- 6% for cardioplegia, p < 0.05). The post-ischemic increase in coronary flow was similar in all groups. In failing CMH hearts, the addition of diltiazem or clentiazem afforded no significant contractile benefit at reperfusion. In nonischemic normal hearts, infusion of diltiazem or clentiazem (10 nM) alone increased coronary flow (+6 +/- 1% for diltiazem and +24 +/- 3% for clentiazem) without significant negative inotropic or chronotropic effects. In nonischemic failing CMH hearts, infusion of diltiazem or clentiazem did not elicit cardiodepression. In contrast their coronary dilator actions reverted to vasoconstriction (diltiazem) or were significantly attenuated (clentiazem). From these experiments we can conclude that, compared with the normal heart, the failing CMH heart adapted differently to global ischemia.
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PMID:Resistance of the failing dystrophic hamster heart to the cardioprotective effects of diltiazem and clentiazem: evidence of coronary vascular dysfunctions. 856 77

Hearts fail because myocardial power fails. Assist, support, or replacement devices fail, at least in part, because their blood-contacting surfaces fail. Mechanical repowering of a failing heart might circumvent these difficulties by preserving a largely healthy endocardium while correcting the basic deficit, power. Any serious consideration of doing this though must confront some difficult requirements. Effective indefinite support must be coupled with preservation or restoration of valve competence, coronary flow, rapid low-impedance refilling and independent left and right pressures; the avoidance of wall coaptation; hardware that fits in the available space; and unless muscle powered, adaptability to a deliverable form of power. Despite earlier intense interest in acute mechanical devices and later empiric study of muscle wraps, little systematic methodical work has been done on elucidating and meeting these practical requirements. Concerted efforts toward developing research tools and techniques for their study and then finding mechanisms to meet them could well yield one or more effective modalities that circumvent a major obstacle to the indefinite mechanical treatment of heart failure.
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PMID:Long-term ventricular wall actuation: can and should it be systematically explored? 864 33

Exophthalmos and clinical signs of heart failure occurred sporadically in 3- to 12-month-old cotton rats (Sigmodon hispidus) in a colony originally derived from three male and four female littermates. Macroscopic lesions in severely affected animals included subcutaneous edema, hydrothorax, right ventricular dilatation, unilateral or bilateral atrial thrombosis, and exophthalmos. Hearts from 17 cotton rats that were found dead or were euthanatized because of exophthalmos or dyspnea and 33 control cotton rats were examined microscopically. Myocardial lesions were present in 46 of 46 cotton rats > or = 1 month of age and consisted of multifocal cardiac myocyte necrosis, mineralization, and mononuclear inflammatory cell infiltration. Cotton rats > 5 months of age also had foci of interstitial fibrosis and myocyte atrophy. Twelve of 24 (50%) necropsied cotton rats had chronic pulmonary congestion, and livers from eight of 24 (33%) had chronic periacinar congestion and atrophy. Thrombi were present in one or both cardiac atria in nine of 50 (18%) hearts, and in at least one orbital venous sinus in 14 of 24 (58%) necropsied cotton rats and in 12 of 14 (86%) with exophthalmos. Exophthalmos in this colony of cotton rats appears to have resulted predominantly from orbital venous sinus thrombosis caused by stasis of venous blood secondary to right heart failure associated with a heritable cardiomyopathy.
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PMID:Spontaneous cardiomyopathy and exophthalmos in cotton rats (Sigmodon hispidus). 881 34

Myocardial mechanics and energetics were investigated in an animal model of moderate chronic heart failure (CHF) created by repeated coronary microembolizations in six dogs. The final fractional area change was 34 +/- 4%. Hearts of these animals were isolated and cross-perfused, and balloons were placed in the left ventricle (LV). Chamber contractile state was markedly depressed in embolized hearts as assessed by the slope (Ees 2.74 +/- 0.49 vs. 4.00 +/- 1.18 mmHg/ml, P < 0.01) and volume axis intercept (V: 8.7 +/- 5.9 vs. 1.0 +/- 3.2 ml, P < 0.01) of end-systolic pressure-volume relation compared with a group of six normal dogs. The end-diastolic pressure-volume relation of embolized hearts was shifted to the right, indicating a dilation of the LV. However, systolic and diastolic stress strain relationships were similar in the two groups, suggesting that the average myocardial properties of the embolized hearts are similar to those of normal hearts. The relationship between oxygen consumption and pressure-volume area in embolized hearts had smaller intercept (2.98 +/- 0.44 vs 3.92 +/- 0.39 x 10(-2) ml O2.beat-1.100 g LV-1, P < 0.01) compared with the control group, with no change in the slope. These results contrast with previous findings in pacing CHF and serve as an important characterization of ventricular properties in this model of CHF from different etiology.
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PMID:Characterizing ventricular mechanics and energetics following repeated coronary microembolization. 903 37

Exercise training improves functional class in patients with chronic heart failure (CHF) via effects on the periphery with no previously documented effect on intrinsic left ventricular (LV) properties. However, because methods used to evaluate in vivo LV function are limited, it is possible that some effects of exercise training on the failing heart have thus far eluded detection. Twelve dogs were instrumented for cardiac pacing and hemodynamic recordings. Hearts were paced rapidly for 4 wk. Six of the dogs received daily treadmill exercise (CHF(EX), 4.4 km/h, 2 h/day) concurrent with rapid pacing, while the other dogs remained sedentary (CHFs). Hemodynamic measurements taken in vivo at the end of 4 wk revealed relative preservation of maximum rate of pressure rise (2,540 +/- 440 vs. 1,720 +/- 300 mmHg/s, P < 0.05) and LV end-diastolic pressure (9 +/- 5 vs. 19 +/- 4 mmHg, P < 0.05) in CHF(EX) compared with CHFs. The hearts were then isolated and cross perfused for in vitro measurement of isovolumic pressure-volume relations; these results were compared with those of six normal dogs (N). Systolic function was similarly depressed in both groups of pacing animals [end-systolic elastance (Ees) values of 1.66 +/- 0.47 in CHFs, 1.77 +/- 0.38 in CHF(EX), and 3.05 +/- 0.81 mmHg/ml in N, with no changes in volume axis interceptors of the end-systolic pressure-volume relationship]. The diastolic myocardial stiffness constant, k, was elevated in CHFs and was normalized by exercise training (32 +/- 3 in CHFs, 21 +/- 3 in CHF(EX), 20 +/- 4 in N). Thus daily exercise training preserved in vivo hemodynamics during 4 wk of rapid cardiac pacing and was accompanied by a significant change in diastolic myocardial stiffness in vitro. These findings suggest that changes in heart function may contribute to the overall beneficial hemodynamic effects of exercise training in CHF by a significant effect on diastolic properties.
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PMID:Impact of exercise training on ventricular properties in a canine model of congestive heart failure. 908 15


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