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PubMed1998

A single dose of milrinone facilitates separation from cardiopulmonary bypass in patients with pre-existing left ventricular dysfunction.

Milrinone is used during cardiac surgery to facilitate separation from cardiopulmonary bypass (CPB) and/or to treat myocardial dysfunction in the post-bypass period. We have demonstrated, in patients with preoperative depression of systolic function undergoing aorto-coronary artery bypass surgery, sustained improvement in cardiac function after a single loading dose of milrinone 50 micrograms kg-1, administered at the end of bypass, thus significantly decreasing the need for beta-agonist therapy.

Adult↗
PubMed2004

The pseudorestrictive pattern of transmitral Doppler flow pattern after conversion of atrial fibrillation to sinus rhythm: is atrial or ventricular dysfunction to blame?

Patients with paroxysmal atrial fibrillation (AF) who have recently converted from AF to sinus rhythm often exhibit a restrictive Doppler pattern in the transmitral flow (TMF) velocity. However, the mechanism of this phenomenon has not been well defined. We evaluated the temporal change of TMF pattern and hemodynamics after conversion of AF to in sinus rhythm in an animal model. Eight open-chest dogs underwent 3 hours of pacing-induced AF. TMF velocities and pressure data were acquired at baseline (sinus rhythm), immediately after conversion of AF, and every 10 minutes thereafter. Early diastolic TMF velocity was increased immediately after conversion and recovered to the baseline value in 20 minutes. Atrial systolic TMF velocity was reduced after AF and recovered to baseline value in 20 to 30 minutes. Early diastolic/atrial systolic TMF velocity was increased after conversion, and recovered to baseline value in 20 to 30 minutes. The mean left atrial (LA) pressure increased immediately, 10 and 20 minutes after the conversion of AF to sinus rhythm. The left ventricular end-diastolic pressure was increased and positive left ventricular dP/dt and tau were decreased immediately after AF, whereas they recovered within 10 minutes. In conclusion, a pseudorestrictive pattern of TMF after AF occurred as a result of transient LA mechanical functional impairment and increased LA pressure caused by LA stunning. Transient left ventricular diastolic dysfunction also effected the TMF velocity immediately after the conversion from AF to sinus rhythm, although it recovered faster than LA mechanical dysfunction.

Animals↗
PubMed1997

Reasons for underuse of angiotensin-converting enzyme inhibitors in patients with heart failure and left ventricular dysfunction.

We reviewed the records of 242 patients admitted over 1 year with heart failure and an ejection fraction < or = 45% to assess the use of angiotensin-converting enzyme inhibitors. Most patients were treated with angiotensin-converting enzyme inhibitors. However, an important minority (8%) had no apparent reason for the lack of this treatment, highlighting the need for strategies to increase the use of these beneficial agents.

Aged↗
PubMed2003

Partial inferior vena cava snaring to control ischemic left ventricular dysfunction.

PURPOSE: To describe the hemodynamic and intraoperative transesophageal echocardiographic evaluation of cardiac systolic and diastolic function in a patient undergoing off-pump coronary artery bypass graft (OP-CABG) surgery who developed pulmonary artery hypertension controlled by inferior vena cava (IVC) snaring. CLINICAL FEATURES: A 63-yr-old man was referred to our hospital for elective OP-CABG surgery. His preoperative ventriculopathy revealed a decreased systolic function (ejection fraction of 35%), and a mild mitral regurgitation. Intraoperatively, after application of the stabilizer and clamping of the diagonal artery, he developed a marked increase in pulmonary artery pressure (PAP) with a decrease in systemic arterial pressure, non responsive to iv norepinephrine and nitroglycerin. Transesophageal echocardiographic evaluation revealed a marked decrease in systolic function and presence of a restrictive diastolic filling pattern. Partial IVC snaring decreased the venous return and PAP decreased cardiac chamber dimensions, improved systolic function and improved diastolic filling pattern. CONCLUSION: Partial IVC snaring was used successfully to treat a hemodynamically unstable patient with sudden increase in PAP caused by ischemic left ventricular failure during OP-CABG.

Coronary Artery Bypass↗
PubMed2002

Heart failure and ventricular dysfunction in patients with single or systemic right ventricles.

BACKGROUND: Previous studies suggested a high incidence of congestive heart failure in patients with single and/or systemic right ventricles. The corresponding risk in an adult population is unknown. METHODS AND RESULTS: A cohort of 188 consecutive adult patients with single or systemic right ventricles was prospectively assessed with gated radionuclide angiography (n=135) or 2D echocardiography (n=188) and followed up clinically. Clinical assessment showed 82.4% of the patients were in New York Heart Association class I or II, 13.3% were in class III, and 4.3% were in class IV. Heart failure occurred in 22.2% of patients with transposition of the great arteries and a Mustard procedure, 32.3% of patients with congenitally corrected transposition of the great arteries, and 40% of Fontan-palliated patients. Symptomatic patients had significantly lower anaerobic thresholds (10.3 +/- 2.8 versus 13.2 +/- 4.8 mL center dot kg(-1) center dot min(-1), P=0.006) and peak (center dot)VO(2) (15.2 +/- 4.8 versus 20.3 +/- 6.8 mL center dot kg(-1) center dot min(-1), P<0.00029). Systemic ventricular ejection fraction in symptomatic versus asymptomatic patients at rest was 34.8 +/- 15.7% versus 46.7 +/- 13.4% (P=0.00001). Mortality was 47.1% among symptomatic patients and 5% among asymptomatic patients at 15.7 years of postoperative follow-up. Seven of 12 patients with potentially correctable surgical lesions died or persisted in heart failure despite surgery. Best predictors for mortality were New York Heart Association class, systemic ejection fraction, and age at operation. CONCLUSIONS: Patients with single or systemic right ventricles have significant risk for heart failure accompanied by high mortality. This study suggests the importance of identifying this group of patients who are at risk for heart failure and considering strategies to preserve ventricular function.

Adolescent↗
PubMed2002

Vasopeptidase inhibition in a canine model of exercise-induced left ventricular dysfunction.

1. The present study compared the acute efficacies of vasopeptidase inhibition with omapatrilat, nitroglycerin and angiotensin-converting enzyme (ACE) inhibition in exercise-induced myocardial dysfunction. Omapatrilat, a vasopeptidase inhibitor, inhibits both neutral endopeptidase and ACE. Whereas vasopeptidase inhibitors have demonstrated clinical efficacy in hypertension and heart failure, their effects in myocardial ischaemia remain unclear. 2. Omapatrilat (0.3 mg/kg) was compared with vehicle (saline), an ACE inhibitor (fosinoprilat; 0.44 mg/kg) and nitroglycerin (8.0 microg/kg per min), in an established canine model of exercise-induced myocardial dysfunction induced by progressive closure of an ameroid constrictor placed about the proximal circumflex coronary artery. Maximal treadmill exercise tests, terminated when heart rate failed to increase with increasing workload or failure to continue exercise, were performed in chronically instrumented dogs. 3. During exercise, omapatrilat and nitroglycerin similarly increased ischaemic wall thickening (P< or = 0.0001, ANOVA, 12 d.f.), whereas fosinoprilat and vehicle were without effect. Ischaemic zone ST changes were decreased with nitroglycerin (P = 0.0006, ANOVA, 12 d.f.) and tended to decrease with omapatrilat (P = 0.07, ANOVA, 12 d.f.). Peak exercise capacity was increased with nitroglycerin (9.7 +/- 1.1 vs 11.2 +/- 1.0 kcal, control vs 4 h, respectively; n = 6) and omapatrilat (9.7 +/- 0.8 vs 11.4 +/- 0.6 kcal, control vs 4 h, respectively; n = 6) and was unchanged with ACE inhibition (9.0 +/- 1.2 vs 9.5 +/- 1.1 kcal, control vs 4 h, respectively; n = 7). Omapatrilat differentially increased double product during exercise (P = 0.001, ANOVA, 12 d.f.) compared with other treatments. 4. During exercise-induced myocardial dysfunction, acute ACE inhibition did not attenuate ischaemic changes and failed to improve exercise capacity. Increased exercise capacity with omapatrilat was accompanied by a differential increase in double product, consistent with increased oxygen supply and demand. Improvements in ischaemic function were comparable between omapatrilat and nitroglycerin, suggesting that omapatrilat may represent a novel therapy in demand-induced ischaemia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Pharmacologic treatment of heart failure due to ventricular dysfunction by myocardial stunning: potential role of levosimendan.

The treatment of heart failure continues to pose a real challenge for clinicians. This condition is sometimes reversible and therapy should therefore pursue this outcome. In the context of coronary ischemic syndromes, myocardial stunning can cause heart failure and even cardiogenic shock, with important prognostic repercussions. Myocardial stunning is mainly due to calcium overload in the cytosol of myocardial cells, the loss of myofilaments and their reduced sensitivity to calcium. Enhanced immune activation with inflammatory phenomena also plays an important role in the pathophysiology of cardiac dysfunction. Increasing evidence has shown that the myocardial ATP-dependent potassium channel (K(ATP)) plays an important role in many myocardial cell functions and that it is involved in ischemia-reperfusion injury and myocardial stunning. K(ATP) is thus considered a therapeutic target in this setting. Currently used inotropic drugs improve contractility by increasing intracellular concentrations of free calcium, but they increase myocardial consumption of energy and even produce arrhythmia; therefore, in this clinical context, they do not seem to be 'pathophysiologically correct' drugs. Levosimendan, a new calcium-sensitizing agent, increases contractility by enhancing the sensitivity of myofilaments to calcium by binding to the C cardiac troponin in cardiac muscle in a calcium-dependent way. Levosimendan also exerts a coronary and systemic vasodilatory effect through its K(ATP) channel-opening properties and may exert other cardioprotective actions through this mechanism. Levosimendan produces positive hemodynamic effects without increasing myocardial oxygen demand or causing arrhythmias. Intravenous levosimendan is generally well tolerated and has been approved by several European countries, and recently recommended in European Society of Cardiology guidelines, as inotropic therapy for the short-term treatment of acute severe decompensated heart failure in adults. Randomized, double-blind trials have shown that levosimendan is not only more clinically and hemodynamically effective but also that it significantly reduces morbidity and mortality when compared with dobutamine or placebo. Clinical trials addressing the use and efficacy of intravenous levosimendan in acute heart failure in patients with systolic dysfunction or cardiogenic shock due to myocardial stunning are scarce. Beneficial effects on myocardial contractility in patients with myocardial stunning have only been shown in small clinical trials. A positive experience with levosimendan in a small series of patients with cardiogenic shock complicating ST-elevation myocardial infarction suggests that the use of this drug in cardiogenic shock should be further evaluated.

Adenosine Triphosphate↗
PubMed2004

Current concepts for the neurohormonal management of left ventricular dysfunction after myocardial infarction.

The importance of addressing neurohormonal activation in patients after a myocardial infarction is now well-appreciated. Inhibition of the renin-angiotensin-aldosterone axis and the sympathetic nervous system can result in improved cardiac function and survival. As we learn more about other systems, we should be able to realize further benefits. In particular, the roles of endothelin, matrix metalloproteinases, and cytokines in remodeling are being investigated, with the potential to result in better outcomes for patients.

Adrenergic beta-Antagonists↗
PubMed2006

Tea catechins improve left ventricular dysfunction, suppress myocardial inflammation and fibrosis, and alter cytokine expression in rat autoimmune myocarditis.

BACKGROUND: Myocarditis is a clinically serious disease. Tea catechins have been shown to reduce inflammation; however the effects of catechins on the development of myocarditis have not been well studied. AIMS: To clarify the role of catechins, using an experimental autoimmune myocarditis (EAM) model. METHODS AND RESULTS: Lewis rats were immunized with porcine cardiac myosin to establish EAM. Tea catechins were administered orally from day 0 to day 21 (Group A, n=12), from day 14 to day 21 (Group B, n=8), or saline (Group C, n=9) daily. Rats were killed on day 21. Echocardiograms indicated that Group A showed significantly improved cardiac function compared to Group C. Pathologically, non-treated EAM hearts showed severe myocardial cell infiltration and fibrosis; however Group A showed significantly less area. Immunohistochemistry revealed enhanced expression of NF-kappaB and ICAM-1 in non-treated EAM hearts, which was suppressed by catechin administration in Group A. mRNA levels of TNF-alpha were decreased and Th2 cytokines were markedly enhanced in Group A compared with the control group. Late catechin administration (Group B) showed limited effects on EAM. CONCLUSION: The catechins suppressed ventricular remodelling in EAM; thus catechin treatment might be a promising option for the prevention of EAM myocarditis.

Animals↗
PubMed2006

Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction.

BACKGROUND: Results on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and beta-blocker therapy. METHODS AND RESULTS: Nineteen patients with IDCM (age 58 +/- 8 years, ejection fraction 33 +/- 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate and [(11)C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of beta-blockade was estimated with a beta-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 +/- 2 versus 57 +/- 12 mm Hg.L.g(-1), P < .0001) and reduced myocardial FFA uptake (5.5 +/- 2.0 versus 6.4 +/- 1.2 mumol.100 g(-1).min(-1), P < .05), but the FFA beta-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = -0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA beta-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on beta-1 selective beta-blockers, beta-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective beta-blocker. CONCLUSIONS: Myocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure.

Adrenergic beta-Antagonists↗
PubMed2004

Effect of perindopril on platelet nitric oxide resistance in patients with chronic heart failure secondary to ischemic left ventricular dysfunction.

In 15 patients with chronic heart failure of ischemic origin who were not previously treated with angiotensin-converting enzyme inhibitors, platelets exhibited hyperaggregability and impaired responsiveness to the antiaggregatory and cyclic guanosine monophosphate-stimulatory effects of nitric oxide donor sodium nitroprusside compared with normal subjects; this was paralleled by increased blood levels of superoxide radicals. Treatment with perindopril for 4 days significantly improved platelet responses to sodium nitroprusside; there was also a trend toward a decrease in superoxide radical levels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Usefulness of indium-111 antimyosin scintigraphy in confirming myocardial injury in patients with anthracycline-associated left ventricular dysfunction.

BACKGROUND: In patients with cardiac dysfunction due to anthracycline-induced myocyte damage, continuation of anthracyclines carries a high risk, and modification of chemotherapy is thus indicated. The condition, however, must be distinguished from other causes of cardiac dysfunction, e.g., the transient negative inotropic effect which may accompany and follow the intravenous administration of anthracyclines. In the present study the efficacy of 111In-antimyosin in confirming myocyte injury and its potential applicability in differentiating causes of cardiac dysfunction during anthracycline therapy are evaluated. PATIENTS AND METHODS: Twenty-seven patients with asymptomatic left ventricle ejection fraction (LVEF) decrease (median LVEF 47%, range 38%-50%) during chemotherapy with anthracyclines (dose range 100-700 mg/m2 doxorubicin or equivalent) were subsequently studied with 111In-antimyosin cardiac scintigraphy. The degree of myocardial uptake, an indicator of heart muscle cell injury, evaluated both visually and quantitatively by means of heart-to-lung ratios (HLR) obtained from 48-hour planar images, was analyzed in relation to the further clinical and LVEF course. The results were also compared with 111In-antimyosin data from 5 patients who had normal LVEF during chemotherapy and 5 patients who had received no anthracyclines. The distribution pattern of myocardial uptake was assessed by means of single photon emission computed tomography (SPECT). RESULTS: a) Fourteen patients presented with persistent LVEF decrease (median LVEF 42.5%, range 32%-47%) after discontinuation of anthracycline therapy. In 11 of these patients intense and diffuse, as shown by SPECT, cardiac uptake of 111In-antimyosin (HLR 1.87-2.45) was observed. In two patients with intense antimyosin cardiac uptake, spurious HLR values (1.23-1.55) were found which were caused by unexpected lung uptake and focal heart uptake, respectively. All patients with intense cardiac 111In-antimyosin uptake showed persistently decreased LVEF on follow-up (4-26 weeks) and 4 of them subsequently developed congestive heart failure. In another patient with no intense uptake (HLR 1.15) and persistent decrease in LVEF, metastatic cardiac involvement was found. b) In 13 patients with improvement or normalisation of the LVEF (median LVEF 53%, range 51%-63%), generally less intense or slight cardiac uptake (HLR range: 1.20-1.88) was seen; the HLR in these patients, who continued chemotherapy without complications, was consistently lower (p < 0.01) than in patients with persistently decreased LVEF, and comparable to values of patients who had normal LVEF. CONCLUSIONS: 111In-antimyosin scintigraphy can be useful to differentiate cardiac dysfunction caused by severe myocardial injury from temporary decreases in LVEF, without severe concomitant myocyte damage, which may occur during anthracycline therapy. Intense myocardial uptake of 111In-antimyosin can be used as an important confirmatory criterium for the clinical decision to discontinue anthracycline therapy.

Adult↗
PubMed2003

Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice.

Myoglobin-deficient mice are viable and have preserved cardiac function due to their ability to mount a complex compensatory response involving increased vascularization and the induction of the hypoxia gene program (hypoxia-inducible factor-1alpha, endothelial PAS, heat shock protein27, etc.). To further define and explore functional roles for myoglobin, we challenged age- and gender-matched wild-type and myoglobin-null mice to chronic hypoxia (10% oxygen for 1 day to 3 wk). We observed a 30% reduction in cardiac systolic function in the myoglobin mutant mice exposed to chronic hypoxia with no changes observed in the wild-type control hearts. The cardiac dysfunction observed in the hypoxic myoglobin-null mice was reversible with reexposure to normoxic conditions and could be prevented with treatment of an inhibitor of nitric oxide (NO) synthases. These results support the conclusion that hypoxia-induced cardiac dysfunction in myoglobin-null mice occurs via a NO-mediated mechanism. Utilizing enzymatic assays for NO synthases and immunohistochemical analyses, we observed a marked induction of inducible NO synthase in the hypoxic myoglobin mutant ventricle compared with the wild-type hypoxic control ventricle. These new data establish that myoglobin is an important cytoplasmic cardiac hemoprotein that functions in regulating NO homeostasis within cardiomyocytes.

Animals↗
PubMed1995

Effects of warfarin therapy on plasma fibrinogen, von Willebrand factor, and fibrin D-dimer in left ventricular dysfunction secondary to coronary artery disease with and without aneurysms.

Cardiac impairment in patients is associated with intracardiac thrombus formation and thromboembolism. A high prothrombotic state may exist in such patients, and abnormalities in plasma markers of thrombogenesis may be indicative of such a state. The aim of this study was to determine the associations of left ventricular (LV) aneurysm formation and dysfunction with plasma fibrinogen, von Willebrand factor, and fibrin D-dimer, which are markers associated with thrombus formation (thrombogenesis) and to investigate the effects of warfarin given to patients with LV aneurysms on fibrinogen and D-dimer levels. A cross-sectional study of 112 patients with coronary artery disease was initially performed: 34 patients had normal LV function (group 1); 30 had LV dysfunction without aneurysm formation (group 2); 29 had LV aneurysms without anticoagulation (group 3a); and 19 patients had LV aneurysms with warfarin therapy (group 3b). Results were compared with 158 population controls from a random population sample. A longitudinal study of 10 patients given warfarin was also performed. In group 1, plasma fibrinogen (median difference 0.36 g/L; p = 0.0009) and von Willebrand factor (median difference 17 IU/dl; p = 0.04) were elevated, whereas plasma D-dimer levels (median difference 23.0 ng/ml; p = 0.001) were lower than those in population control subjects. There were no significant differences in plasma fibrinogen, von Willebrand factor, or D-dimer levels between groups 1 and 2. In group 3a, plasma fibrinogen was elevated when compared with group 1 (median difference 0.6 g/L; p = 0.0001), with a trend toward high von Willebrand factor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed2000

[Comparison of the effectiveness of crystalloid and warm blood cardioplegia in patients with significant left ventricular dysfunction].

UNLABELLED: In a group of 84 patients undergoing elective coronary artery bypass surgery and with the ejection fraction lower than 40% two types of myocardial protection were studied. Group I (41 cases) was given intermittent cold crystalloid cardioplegia and group II (43 patients) was given intermittent warm blood cardioplegia followed by normothermic reperfusion. Preoperative, intraoperative and postoperative data were retrospectively collected. There were no differences between the two groups except more rhythm disturbances in group I and higher incidence of neurological complications in group II. CONCLUSIONS: Warm blood cardioplegia is an effective, cheap and practical myocardial protection technique.

Adult↗
PubMed1995

CABG in advanced left ventricular dysfunction.

Concurrent, independent clinical series at Yale University and the University of Virginia demonstrate an important role for CABG in patients with advanced ischemic cardiomyopathy. It is found that CABG can be performed safely in these patients, both angina and congestive heart failure states improve, ejection fraction increases substantially, and good long-term longevity is achieved. Despite prior concerns, the internal mammary conduit can be used safely in these patients. It appears that CABG serves to protect viable noninfarcted muscle and to recruit hibernating ischemic muscle. CABG is suggested as an alternative to heart transplantation in this patient group.

Aged↗
PubMed2001

[Anticoagulation in primary prevention of thromboembolism in advanced left ventricular dysfunction].

BACKGROUND: Patients with heart failure have an increased risk for thromboembolic events. In clinical practice the physician is often confronted with the decision to establish a prophylactic anticoagulation. DATA: The incidence for clinical embolization is 1.5 to 3.5% per year. It seems that patients with a lower peak oxygen uptake and with a lower ejection fraction are at higher risk for embolic events. There is no evidence for a correlation of such events with the clinical classification (NYHA) or with the genesis of heart failure. Concerning a prophylactic anticoagulation, the results of the published studies and meta-analyses are inhomogenous with a benefit in some, no difference in others and a significant disadvantage for the patients with anticoagulation in a part of them compared to a non-treated control group. None of these data is established by a prospective, randomized, controlled study with the primary endpoint thromboembolic event in patients with or without anticoagulation. The incidence for a hemorrhage under anticoagulation is 0.6-5.3% per year for life-threatening and 0.04-0.64% for fatal bleeding. CONCLUSION: Because of similar incidences for thromboembolic events and for the bleeding complication of anticoagulation, there is no evidence for a general indication for anticoagulation of patients with heart failure, persistent sinus rhythm and lack of risk factors. In patients with high-grade heart failure (e.g. VO2max < 14 ml/min/kg body weight or left ventricular ejection fraction < 20-30%), who belong to a high-risk population, anticoagulation should be considered and may be acceptable in individual cases.

Anticoagulants↗
PubMed2006

Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury.

AIMS: Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. METHODS AND RESULTS: TDI-derived peak endocardial systolic velocity (V(ENDO)) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. V(ENDO) and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. CONCLUSION: In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.

Animals↗