84 research outputs found
Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion.
No full textOBJECTIVE:
In animal models, formation of oxidants during postischemic reperfusion may exert deleterious effects ("oxidative stress"). Cardioplegic arrest/reperfusion during cardiac surgery might similarly induce oxidative stress. However, the phenomenon has not been precisely characterized in patients, and therefore the role of antioxidant therapy at cardiac surgery is a matter of debate. Thus, we wanted to ascertain whether the relationship between oxidant formation and development of myocardial injury also translates to the situation of patients subjected to cardioplegic arrest.
METHODS:
In 24 patients undergoing coronary artery bypass, trans-cardiac blood samples and myocardial biopsies were taken before cardioplegic arrest and again following reperfusion.
RESULTS:
Cardiac glutathione release (marker of oxidant production) was negligible at baseline (0.02+/-0.04 micromol/L), but it increased 15 min into reperfusion (1.10+/-0.40 micromol/L; p<0.05); concomitantly, myocardial concentration of the antioxidant ubiquinol decreased from 144.5+/-52.0 to 97.6+/-82.0 nmol/g (p<0.05). Although these changes document cardiac exposure to oxidants, they were not accompanied by evidence of injury. Neither coronary sinus blood nor cardiac biopsies showed increased lipid peroxide concentrations. Furthermore, electron microscopy showed no major ultrastructural alterations. Finally, full recovery of left ventricular systolic and diastolic function was observed.
CONCLUSIONS:
Careful investigation reveals that while oxidant production does occur during cardiac surgery in patients with chronic ischemic heart disease, cardiac oxidative stress may not progress through membrane damage and irreversible injury
Clinical use of transoesophageal atrial stimulation in terminating ventricular tachycardia
No full textThis study was performed to evaluate whether transoesophageal atrial pacing could also stop ventricular tachycardias with low rates and no haemodynamic impairment. Prior to resorting to ventricular endocardial pacing, seven male patients, aged between 15 and 73 years, were treated by transoesophageal atrial pacing for 10 spontaneous episodes of sustained ventricular tachycardia at rates between 105 and 160 beats per minute, without haemodynamic impairment. When atrial pacing did not allow ventricular capture, atropine sulphate was administered. Transoesophageal atrial pacing led to ventricular capture in seven episodes, which made overdriving possible, and blocked six episodes of ventricular tachycardia. In no case did transoesophageal atrial pacing lead to an acceleration of ventricular tachycardia or to degeneration into ventricular fibrillation. Transoesophageal atrial pacing can block low-rate sustained ventricular tachycardias (≤ 150 beats per minute). For low-rate sustained ventricular tachycardias without haemodynamic impairment, transoesophageal atrial pacing can thus be used as the method of choice thanks to its good ratio of risk to efficiency. © 1990
[The early hemodynamic and hormonal changes in patients with left ventricular dysfunction].
No full textThe aim of this study was to highlight a different hormonal and hemodynamic pattern in patients with mild cardiomyopathy. For this purpose, we studied subjects with mild heart failure (CHF; NYHA class I and II; post-ischemic and idiopathic) who underwent an isotonic saline load (SL) (0.22 ml/kg/min of 0.9% NaCl for 120 min). A second group of age- and sex-matched normal subjects (C) was studied as a control. Basal hormonal and hemodynamic values of the 2 groups differed only in atrial natriuretic factor (ANF), left ventricular end-diastolic diameter and ejection fraction (EF). There were, on the contrary, no differences in basal plasma renin activity (PRA) and plasma aldosterone (PA) values. After SL, in C, percent changes in EF, cardiac output and ANF values were significantly higher than in CHF while total peripheral resistances increased only in CHF but not in C. In both groups there were decrements of PRA and PA, but these responses were significantly higher in C than in CHF. In conclusion, our results show that hormonal, renal and hemodynamic responses to salt/volume load are compromised in the early asymptomatic phase of heart failure. These abnormalities may predict the progressive deterioration of cardiac function, and may indicate appropriate therapeutic interventions since the early phases of the disease
A short burst of oxygen radicals at reflow induces sustained release of oxidized glutathione from postischemic hearts.
No full textOxygen radical generation induced by postischemic reperfusion can overwhelm endogenous radical scavenging systems, resulting in ‘‘oxidative stress.’’ Release of oxidized glutathione (GSSG) upon reflow has been taken as evidence for the occurrence of oxidative stress in postischemic hearts. However, demonstration that GSSG release is due to oxygen radicals and not to other consequences of ischemia/reperfusion is lacking. To address this issue, isolated rabbit hearts underwent 30 min of global ischemia at 37C. At reflow, control hearts were perfused with standard buffer for 45 min (n 8) ; treated hearts received the oxygen radical scavenger superoxide dismutase (hSOD) for 15 min, followed by 30 min of standard perfusion (n 8) . During reperfusion control hearts showed a prominent release of GSSG, which peaked 5 min after reflow. Interestingly, GSSG release was still significantly elevated 45 min into reperfusion, at a time when oxygen radical generation has long ceased. In contrast, in hSOD treated hearts GSSG release was negligible. Prevention of oxidative stress was also associated with significantly greater recovery of function. Thus, GSSG release occurs in postischemic hearts as a direct consequence of oxygen radical generation, and it may outlast the initial oxidant load
Transition from asymptomatic left ventricular dysfunction to congestive heart failure
No full textOne of the main goals of modern management and care of heart failure is to prevent the disease to progress toward congestion and death. The achievement of such an objective may, in fact, guarantee a sufficient quality of life and reduce the exposure of patients to the most common life-threatening complications associated with the congestive stage of the disease. Early identification of left ventricular dysfunction as well as a better knowledge of the mechanisms that favor the progression to more advanced stages of heart failure are fundamental requirements for the proper treatment of asymptomatic heart failure and for preventing the transition to symptomatic and more severe heart failure. The authors reviewed the literature on this topic, with emphasis on a series of studies they performed, to characterize the pathophysiologic profile of mild heart failure and the mechanisms that are possibly involved in the progression to congestive heart failure. © 1995 Churchill Livingstone Inc
Impairment of atrial natriuretic factor response to acute saline load in hypertensives with family history of cardiovascular accidents.
No full textAngiotensin converting enzyme inhibition restores cardiac and hormonal responses to volume overload in patients with dilated cardiomyopathy and mild heart failure.
No full textBACKGROUND: Angiotensin converting enzyme (ACE) inhibition exerts a favorable effect on the response to exercise in heart failure. This study was planned to define the influence of ACE inhibition on the adaptation to volume overload.
METHODS AND RESULTS: We studied the hemodynamic, hormonal, and renal responses to acute volume expansion (sodium chloride, 0.9%, 0.25 ml.kg-1.min-1 for 2 hours) in patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (New York Heart Association class I or II, ejection fraction < or = 50%). The patients were studied without any pretreatment (n = 14) or after 1 week of treatment with the oral ACE inhibitor quinapril at a dosage of 10 mg/day (n = 11). Seven patients were studied during constant intravenous infusion with nitroglycerin (0.1 micrograms.kg-1.min-1). The study groups had similar hemodynamic and clinical characteristics and hormonal profile at baseline evaluation. In the untreated patients, volume expansion did not increase left ventricular end-diastolic volume measured by echocardiography and was associated with a reduction in ejection fraction (p < 0.05) and with a paradoxical increase in forearm vascular resistance (p < 0.05) estimated by plethysmography. In addition, plasma atrial natriuretic factor did not change, and plasma norepinephrine was increased by saline loading. In contrast, in the patients treated with quinapril, volume expansion induced an increase of both left ventricular volumes (p < 0.001) without changing ejection fraction and reduced forearm vascular resistance (p < 0.05). In addition, in this group, plasma atrial natriuretic factor levels increased (p < 0.05) and plasma norepinephrine did not change during volume overload. During nitroglycerin infusion, volume expansion was associated with peripheral vasodilatation, increases of left ventricular volumes, and no change in ejection fraction. In this group, however, plasma atrial natriuretic factor levels did not change in response to volume overload.
CONCLUSIONS: We conclude that pretreatment with the ACE inhibitor quinapril significantly improves compromised responses to acute isotonic volume overload in patients with dilated cardiomyopathy and mild heart failure. The favorable influence of ACE inhibition on cardiovascular and hormonal responses to volume expansion seems to be related to the cardiac unloading produced by this treatmen
Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles.
No full textPlasma levels of erythropoietin (mU/ml) were measured in patients with congestive heart failure (CHF) (n = 108) and in a control group of normal subjects (n = 45). In normal subjects, plasma levels of erythropoietin were 1.9 +/- 0.2. In patients with CHF, plasma levels of erythropoietin increased progressively according to New York Heart Association (NYHA) class (I: 1.4 +/- 0.2, n = 28; II: 5.4 +/- 0.8, n = 27; III: 9.6 +/- 2, n = 32; IV: 34 +/- 8, n = 21; F = 57.7, p < 0.001) and were significantly higher in NYHA classes II, III, and IV than in normal subjects. Plasma erythropoietin significantly decreased (from 43 +/- 14 to 12 +/- 3 mU/ml, p < 0.01) in patients with severe CHF (n = 9) when enalapril (20 mg/day administered orally) was added to long-term treatment for 3 weeks. Finally, in a subgroup of patients with NYHA class IV CHF (n = 9) and high plasma erythropoietin levels (37 +/- 9 mU/ml), packed red blood cell volume, assessed by the iodine-125-albumin dilution method, was higher than that in normal subjects (n = 11) (2,616 +/- 235 vs 2,028 +/- 119 ml, p < 0.05). The present study demonstrates that plasma erythropoietin levels are elevated in a large cohort of patients with CHF of varying etiology, and that this increase is related to the progression of the disease. The increase in circulating erythropoietin is associated with augmented packed red blood cell volume in patients with severe CHF. These results suggest a participation of erythropoietin in the complex neurohormonal response that occurs in CHF
Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow.
No full textPrevious in vitro studies have shown that isolated mitochondria can generate oxygen radicals. However, whether a similar phenomenon can also occur in intact organs is unknown. In the present studwy,e tested the hypothesis that resumption of mitochondrial respiration upon reperfusion might be a mechanism of oxygen radical formation in postischemic hearts, and that treatment with inhibitorosf mitochondrial respiration might prevent this phenomenon. Three groups of Langendorff- perfused rabbit hearts were subjected to 30 min of global ischemia at 37 “C, followed by reflow. Throughout ischemia and early reperfusion the hearts received, respectively: (a) 6 mM KC1 (controls), (b) 6 mM sodium amobarbital (Amytal“, which blocks mitochondrial respiration at Site I, at the level of NADH dehydrogenase), and (c) 6 mM potassium cyanide (to block mitochondrial respiration distallya, t the level of cytochrome c oxidase). The hearts were thperonc essed to directly evaluatoex ygen radical generationb y electron paramagnetic resonances pectroscopy, or to measure oxygen radical-induced membrane lipid peroxidation by malonyl dialdehyde (MDA) content of subcellular fractions. Severity of ischemia, as assessed by “P-nuclear magnetic resonance measurements of cardiac ATP, phosphocreatine, and pH, was similar in all groups. Oxygen-centered free radical concentration averaged 3.84 f 0.64 PM in reperfused control hearts, and it was significantly reduced by Amytal treatment (1.98 2 0.26; p < 0.06), but not by KCN (2.68 f 0.96 PM; p = not significant (NS)), consistent with oxygen radicals being formed in them itochondrial respiratory chain at Site I. Membrane lipid peroxidation of reperfused hearts was also reduced by treatment with Amytal, but not with KCN. MDA content of the mitochondrial fraction averaged 0.76 f 0.06 nM/mg protein in controls, 0.72 f 0.06 in KCN-treated hearts, and0 .64groups). Similarly, MDA content of lysosomal membrane fraction was0 .64 f 0.09 nM/mg protein in controls, 0.79 C 0.16 in KCN-treated hearts, and 0.43 2 0.06 in Amytal-treated hearts ( p 0.06 versus both groups). Since the effects of Amytal are known to be reversible, in a second series of experiments we investigated whether transient mitochondrial inhibition during the initial1 0 min of reperfusion wasa lso associated with beneficial effects on subsequent recovery of cardiac function after wash-out of the drug. At the end of the experiment, recoveroyf left ventriculaer nddiastolic and of developed pressure was significantly greater in those hearts that had been treated with Amytal during ischemia and earlyre flow, as compared to untreated hearts. In conclusion, our data demonstrate that in intact hearts electron flow through the respiratory chain may be an important source of oxygen radicals, which may form at the sites of interactions between Fe-S clusters and ubiquinone, and that resumption of mitochondrial respiration upon reoxygenation might contribute to reperfusion injury
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