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PubMedDate not supplied

The role of automatic endocardial edge detection in the evaluation of left ventricular diastolic function in children.

Forty-nine normal children underwent echocardiography to study the role of automatic border detection (ABD) in diastolic evaluation by (1) determining the relationship of diastolic ABD indexes to heart rate and traditional diastolic indexes and (2) establishing inter-observer variability. ABD diastolic indexes were less associated with heart rate than were M-mode and Doppler diastolic indexes. ABD left ventricular peak filling rate correlated with Doppler mitral E wave peak velocity. Interobserver variability for ABD indexes ranged from 4% to 24%. We then compared the ability of ABD left ventricular filling rate to M-mode and Doppler indexes to detect diastolic dysfunction in a test group of 20 children with diastolic disease. ABD left ventricular peak filling rate had the highest sensitivity of all indexes (90%). Thus ABD left ventricular peak filling rate is an accurate index of diastolic function that is readily usable by almost all clinical laboratories.

Adolescent↗
PubMed2006

Acute effects of VVI pacing on ventricular diastolic performance in elderly patients with normal left ventricular systolic function.

Elderly patients may have left ventricular (LV) diastolic dysfunction, which is associated with worse outcome. To assess LV diastolic function we sought relationships between echocardiographic tissue Doppler imaging (TDI) and color M-Mode (CMM) techniques and B-type natriuretic peptide (BNP) responses following short-term VVI pacing in dual-chamber pacemaker recipients with normal LV ejection fraction. In 58 clinically stable elderly patients baseline TDI and CMM data, and BNP [median (IQR)] levels during atrioventricular rhythm were obtained and compared with echocardiographic data during VVI pacing and BNP responses following a 30-min VVI pacing period. Overall, VVI pacing worsened LV diastolic function and increased the E/Ea mean (P<0.05). Baseline BNP levels [58 (23-138) pg/ml] increased approximately 26% following VVI pacing. Short-term VVI pacing in elderly patients may deteriorate LV function and provoke BNP increases.

Acute Disease↗
PubMed1990

Silent myocardial ischemia in patients with coronary artery disease. Possible links with diastolic left ventricular dysfunction.

Silent myocardial ischemia is now recognized as a common manifestation within the clinical spectrum of coronary artery disease and has important physiological, hemodynamic, and prognostic implications. Asymptomatic ST segment shifts during ambulatory 24-hour electrocardiographic monitoring and exercise treadmill testing are far more frequent than symptomatic ST shifts and are associated with abnormal myocardial perfusion as assessed by radionuclide scintigraphy. Seemingly healthy asymptomatic patients and patients with stable coronary artery disease, unstable angina, or recent myocardial infarction are all at higher risk of subsequent cardiovascular morbidity if there is evidence of silent ischemia. Hemodynamic studies have clearly documented the adverse effects of ischemia on left ventricular systolic function. Furthermore, diastolic relaxation and filling appear to be altered by both symptomatic and asymptomatic ischemia during atrial pacing and dynamic exercise independent of changes in systolic function. The majority of patients with coronary artery disease have abnormal diastolic parameters at rest, regardless of anginal symptoms, which are partially reversible after coronary revascularization procedures such as angioplasty and bypass surgery. Regional diastolic dysfunction from scar or ischemia can lead to asynchronous myocardial relaxation and thus affect global diastolic function, depending on the extent and severity of the regional abnormalities. Diastolic function seems more susceptible to ischemia than systolic function and can take longer to recover.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMedDate not supplied

A clinical algorithm to differentiate heart failure with a normal ejection fraction by pathophysiologic mechanism.

The incidence and prevalence of heart failure are increasing as the population ages. Epidemiologic studies demonstrate that more than half of heart failure patients have a normal ejection fraction. The pathophysiology of this disorder is not completely understood. It is primarily attributed to left ventricular diastolic dysfunction (a leftward- and upward-shifted end-diastolic pressure-volume relation), where left ventricular diastolic chamber size is normal or reduced despite greater-than-normal filling pressures, resulting in reduced stroke volume and cardiac output. Using classic measures derived from pressure-volume analysis, we delineate other possible combinations of the end-systolic and end-diastolic pressure-volume relation, and hence possible pathophysiologic mechanisms that could underlie the syndrome of heart failure with normal ejection fraction. We propose an algorithm for identifying the primary pathophysiologic mechanism of heart failure in the setting of a normal ejection fraction using three simple factors: blood pressure, electrocardiographic/echocardiographic evidence of left ventricular hypertrophy, and left ventricular size. The application of this algorithm may aid in guiding management and targeting much-needed therapies for this population.

Aged↗
PubMed2006

Cardiac involvement in adults with m.3243A>G MELAS gene mutation.

Cardiac data in adults with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS syndrome) or asymptomatic gene carriers with the mitochondrial deoxyribonucleic acid adenine-to-guanine point mutation at nucleotide pair 3243 are scarce. Twelve subjects (mean age 35 +/- 13 years), 8 with MELAS syndrome (patients) and 4 asymptomatic gene carriers (carriers), were enrolled in the study. Each subject underwent electrocardiography, exercise testing, Holter monitoring, echocardiography, and genetic and biochemical analysis for respiratory chain enzyme activity (complex I rest activity) in skeletal muscle. On electrocardiography and Holter monitoring, none of the subjects had evidence of preexcitation, cardiac arrhythmias, or conduction abnormalities. Patients had significantly lower (42 +/- 17% from normal vs 103 +/- 14%, p <0.02) exercise tolerance. All but 1 of the patients and none of the gene carriers had ragged red fibers on muscle biopsy. The mean percentage of gene mutation in skeletal muscle tended to be higher in patients (53 +/- 19%, range 19% to 73%) compared with carriers (33 +/- 20%, range 15% to 62%). Mean complex I rest activity in patients (36 +/- 18%, range 10% to 58%) was significantly (p <0.01) lower compared with carriers (120 +/- 60%, range 72% to 205%). Left ventricular (LV) abnormalities were confined to patients with MELAS syndrome. Two patients had LV hypertrophy, 5 had LV systolic abnormalities, and 5 had LV diastolic dysfunction. Apart from 1 patient with an isolated LV diastolic abnormality, all patients with LV abnormalities had ragged red fibers. Patients with abnormal systolic LV function had a trend toward a higher percentage of mutated skeletal muscle (59.7 +/- 10.7% vs 35.8 +/- 21.3%, p <0.10) and significantly lower complex I rest activity (26.7 +/- 14.0% vs 97.8% +/- 57.9, p <0.01). In conclusion, none of the MELAS gene carriers had cardiac abnormalities, whereas most patients with the MELAS phenotype, particularly those with ragged red fibers, had LV involvement.

Adolescent↗
PubMed2006

Age-related changes in left ventricular twist assessed by two-dimensional speckle-tracking imaging.

The aim of this study was to determine the normal value of left ventricular (LV) twist, and to examine the effects of aging on LV twist by newly developed 2-dimensional ultrasound speckle-tracking imaging. We acquired basal and apical LV short-axis second harmonic images in 118 healthy volunteers. Using commercially available 2-dimensional strain software, time-domain speckle tracking was performed, and mean value of LV rotation obtained at each plane. LV twist was defined as apical rotation relative to the base. Adequate data were obtained in 113 volunteers. During systole, the LV performs a wringing motion with a counterclockwise rotation at the apex and a clockwise rotation at the base. The mean value of peak twist was 7.7 +/- 3.5 degrees. Immediately after end systole, rapid untwisting develops. Different LV twist profiles are noted according to age. Peak LV twist was significantly higher, and the rate of LV untwisting significantly reduced and delayed, with advancing age. LV twist can be measured noninvasively by 2-dimensional ultrasound speckle-tracking imaging. The observed reduced and delayed diastolic untwisting with aging may contribute toward the tendency of diastolic dysfunction. This novel method allows the detailed study of diastolic function in various cardiovascular diseases.

Adult↗
PubMed2000

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats.

OBJECTIVE: There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. MATERIALS AND METHODS: Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. RESULTS: The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. CONCLUSION: These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

Animals↗
PubMed2001

Baroreflex sensitivity and oxidative stress in adriamycin-induced heart failure.

Adriamycin cardiotoxicity is associated with oxidative stress in the presence of globally depressed cardiac function. It is unknown if there is a similar profile with early diastolic changes and how it relates to baroreflex control of circulation. In this study, we evaluated baroreflex control of circulation in adriamycin-treated Wistar rats compared with controls, using invasive blood pressure recording processed by a data acquisition system (CODAS, 1 KHz). Baroreflex sensitivity was evaluated by modulating blood pressure with phenylephrine and sodium nitroprusside. Oxidative stress was quantified by chemiluminescence and by glutathione peroxidase enzyme activity. Diastolic dysfunction was characterized by increased left ventricle end-diastolic pressure in adriamycin-treated rats compared with controls with preserved ascending aortic flow. Baroreflex sensitivity in response to blood pressure elevation and reduction were similar in adriamycin (-2+/-0.27 and -3.19+/-0.56 bpm/mm Hg) and control rats (-1.35+/-0.15 and -2.52+/-0.39 bpm/mm Hg). Chemiluminescence was higher (20450+/-1286 versus 16517+/-1020 counts per second/mg protein) and glutathione peroxidase activity was lower (45.6+/-4.3 versus 76.4+/-6.9 micromol. min(-1). mg(-1) protein) in adriamycin rats compared with controls. Inverse correlations were observed between glutathione peroxidase activity and left ventricle end-diastolic pressure (r=-0.72, P=0.02), between baroreflex sensitivity to phenylephrine and left ventricle end-diastolic pressure (r=-0.77, P=0.004), and between chemiluminescence and baroreflex sensitivity to sodium nitroprusside (r=-0.75, P=0.02), whereas a positive correlation was observed between baroreflex sensitivity to sodium nitroprusside and glutathione peroxidase activity (r=0.7, P=0.04). Thus, adriamycin led to increased left ventricle end-diastolic pressure without changes in baroreflex sensitivity, and associated increased oxidative stress appeared to be related to reduction of reflex control of circulation.

Analysis of Variance↗
PubMed2000

[Cardiac amyloidosis].

In our experience, QS pattern of poor R wave progression and atrio-ventricular block of varying degrees on electrocardiogram, cardiomegaly with pleural effusion on chest X-ray film, left ventricular wall thickening, pericardial effusion and findings suggesting left ventricular diastolic dysfunction on echocardiogram and increased right ventricular end-diastolic pressure in cardiac catheterization were frequently observed in patients with cardiac amyloidosis. Though none of these findings are specific, we should suspect cardiac amyloidosis as a possibility when some of these signs are observed in patients with chronic cardiac failure of unknown etiology. Left ventricular mass obtained from echocardiography could be useful predictive parameter of prognosis in patients with cardiac amyloidosis.

Amyloidosis↗
PubMed2002

Early cardiovascular involvement in patients with systemic sclerosis (SSc).

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin, and by distinctive forms of internal organ involvement. Symptoms usually occur relatively late and are nonspecific, thus often unrecognized. The purpose of our study was to evaluate cardiac function in patients with SSc by means of non-invasive methods in order to detect early dysfunction of the cardiovascular system. MATERIAL/METHODS: A group of 22 patients with SSc was compared with a group of 22 healthy volunteers. Standard EKG, 24-hour Holter monitoring (HM), and echocardiography were performed in all subjects. RESULTS: In patients with SSc, HM revealed a tendency to tachycardia. Conduction disturbances were observed in 3 patients. In 6 patients significant ventricular arrhythmia was found. Silent ischemia episodes were detected in 6 patients. In HRV analysis, significantly lower values were detected in patients with SSc than in controls. LPs were present in one patient with SSc, and none in the control group. The mean values for QT interval did not exceed the range of normal values. No signs of systolic cardiac dysfunction were detected, while in 6 patients left ventricle diastolic dysfunction was recognized. Valvular lesions were observed in 8 patients, but only in 2 patients were they hemodynamically important. CONCLUSIONS: 24-hour Holter monitoring and echocardiography enable the early detection of cardiovascular dysfunction in patients with systemic sclerosis presenting without apparent cardiac impairment symptoms.

Adolescent↗
PubMed2000

Increased left ventricular mass is not associated with impaired left ventricular diastolic filling in normal individuals.

BACKGROUND: Hypertensive left ventricular (LV) hypertrophy has been associated with diastolic dysfunction. However, the underlying physiological relationship between LV size and diastolic function remains to be clarified. The aim of this study was to evaluate the relationship between several measures of diastolic filling and LV mass in a population sample. METHODS: We used M-mode and Doppler echocardiography to compare left ventricular mass index (LVMI) and wall thickness with five measures of ventricular diastolic filling (ratio of the peak early mitral inflow velocity to the peak atrial mitral inflow velocity, deceleration time of early mitral inflow, isovolumetric relaxation time, ratio of the peak pulmonary venous systolic to diastolic flow and difference between the durations of the pulmonary venous and mitral inflow atrial waves) in 159 healthy volunteers. RESULTS: LVMI was significantly (P< 0.0001) greater in men (81.3 g/m2, interquartile range: 67-94) than women (59.7 g/m2, interquartile range: 49-74), but no gender differences were observed in diastolic filling. Higher age, blood pressure and heart rate showed significant correlation with diminished diastolic filling. However, no measure of diastolic filling correlated with LVMI or wall thickness in either univariate or multiple regression analyses that adjusted for relevant covariates. CONCLUSIONS: LVMI does not explain physiological differences in diastolic filling. The significant decline in diastolic filling with age reflects changes in the quality rather than the quantity of myocardial tissue.

Adult↗
PubMed1991

The 'athletic heart syndrome'. A critical review.

Cardiological findings in athletes are often similar to those observed in clinical cases. Electrocardiographic and cardiac imaging abnormalities as well as physical findings may be the same in both of these groups. Bradycardia and rhythm disturbances are the most common abnormalities in athletes. Most athletes with abnormal electrocardiograms are asymptomatic and numerous investigators have failed to detect heart disease in association with such electrocardiograms. In contrast to cardiac dysfunction observed in clinical cases, enhanced or normal ventricular systolic and diastolic function have been reported in athletes. In endurance athletes, this is associated with very high values for maximal aerobic power (VO2max). Absolute and body size-normalised cardiac dimensions in most athletes do not approach values from chronic disease states, and may not exceed echocardiographic normal limits. In addition, pathological and physiological enlargement appear to be biochemically and functionally different. Myosin ATPase enzyme expression and calcium metabolism are different in rats with pathologically or physiologically induced enlargement. The reported biochemical differences underlie systolic and diastolic dysfunction in pathological enlargement. Conversely, trained rodents and humans have demonstrated enhanced systolic and diastolic function. It is important to note that cardiac enlargement observed in athletes is the result of normal adaptation to physical conditioning and/or hereditary influences. Conversely, pathological changes result from disease processes which can lead in turn to reduced function, morbidity and mortality. Since the mid 1970s echocardiography has been used to compare cardiac dimensions in male endurance- and resistance-trained athletes. A sport-specific profile of eccentric and concentric enlargement has been documented in endurance and resistance athletes, respectively. Subsequent studies of athletes have examined factors such as age, sex and degree of competitive success to determine their contribution to these sport-specific cardiac profiles. Unique athletic subgroups have also been analysed and have included ballet dancers, rowers, basketball players and triathletes. However, there is a paucity of data on cardiac dimensions in female athletes. Finally, physical conditioning studies have also examined echocardiographic dimensions before and after endurance and resistance training. Significant enlargement of internal dimensions, wall thickness or left ventricular mass have been reported but such increases are relatively small and by no means universal. Several conflicting explanations for enlarged cardiac dimensions appear in the literature. Chronic volume and pressure haemodynamic overloading during physical conditioning has been proposed to explain eccentric and concentric cardiac enlargement in endurance- and resistance-trained athletes respectively. However, twin studies suggest that hereditary factors may be important determinants of cardiac dimensions and/or the degree of cardiac adaptability to physical conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Mass Index↗
PubMed1990

Influence of glucose and insulin on the exaggerated diastolic and systolic dysfunction of hypertrophied rat hearts during hypoxia.

Myocardial hypertrophy can result in increased sensitivity toward the development of mechanical dysfunction during hypoxia. Alterations in glycolytic metabolism may contribute to this. We studied the response to 15 minutes of hypoxia in hypertrophied (deoxycorticosterone-salt hypertension model) and nonhypertrophied rat hearts and examined the influence of a high glucose (27.5 mM) and insulin (100 mU/ml) concentration. In response to hypoxia in the presence of a normal glucose concentration (5.5 mM), left ventricular end-diastolic pressure was higher in hypertrophied than in nonhypertrophied hearts (65 +/- 6 vs. 44 +/- 4 mm Hg; p less than 0.05). Perfusion with high glucose and insulin blunted the rise in left ventricular end-diastolic pressure in both hypertrophied and nonhypertrophied hearts and abolished the difference in diastolic dysfunction between groups during hypoxia (26 +/- 2 vs. 32 +/- 4 mm Hg, respectively; p = NS). At end hypoxia in the presence of a normal glucose concentration, developed pressure was more depressed in hypertrophied than in nonhypertrophied hearts (11 +/- 1 vs. 18 +/- 1% of baseline, respectively; p less than 0.05). Perfusion with high glucose and insulin resulted in improved function in both groups during hypoxia such that a greater impairment of developed pressure was no longer present in the hypertrophied versus nonhypertrophied hearts (21 +/- 1 vs. 24 +/- 2% of baseline, respectively; p = NS). At the end of hypoxic perfusion in the presence of a normal glucose concentration, hypertrophied hearts were producing 38% less lactate than nonhypertrophied hearts. Perfusion with high glucose and insulin increased lactate production in both groups and equalized lactate production between groups. Thus, the greater deterioration in hemodynamic function in hypertrophied hearts compared with nonhypertrophied hearts during hypoxia is associated with lower lactate production. Both the exaggerated hemodynamic dysfunction and deficient lactate production can be ameliorated by perfusion with a high glucose concentration and insulin.

Animals↗
PubMed1993

[Left ventricular function in patients with dilated cardiomyopathy].

Functional state of left ventricle was studied in 43 patients with dilated cardiomyopathy. All the patients showed pronouncedly reduced total ejection, stroke volume and cardiac index, increased final diastolic and final systolic volumes, decreased ejection rate indices. Analysis of regional contractility of left ventricle allowed to detect significant fall of ejection fraction in 96.3% of segments. Diastolic dysfunction was characterized by disorders of isovolumetric relaxation, changes in hemodynamical structure and contribution of atrial systole to ventricular filling, decrease of volumetric compliance of left ventricle. The data obtained give a reason to consider that appropriate therapy of dilated cardiomyopathy should be carried out with taking into account both systolic and diastolic left ventricle dysfunction.

Adult↗
PubMed1994

Loss of elastic recoil in postischemic myocardium induces rightward shift of the systolic pressure-volume relationship.

Ischemia-induced systolic dysfunction has been ascribed to changes in cellular excitation-contraction coupling and diastolic dysfunction because of disruption of the extracellular collagen matrix. Therefore, systolic and diastolic pressure-volume relationships and O2 consumption were determined before and after 5 min of global ischemia in isolated blood-perfused porcine hearts. The slope of the systolic pressure-volume relationship was 7.2 +/- 0.6 (SE) mmHg.ml-1.100 g-1 (n = 18) at baseline and did not change during reperfusion, but the systolic volume intercept shifted from 1.0 +/- 0.4 ml/100 g at baseline to 3.7 +/- 1.4, 4.1 +/- 1.1, and 4.2 +/- 0.9 ml/100 g at 15, 30, and 60 min of reperfusion, respectively (all P < 0.05). The diastolic volume intercept was 8.2 +/- 0.7 ml/100 g at baseline and remained unchanged during reperfusion. Therefore, the difference of the systolic-diastolic volume intercepts, an index of elastic recoil forces, was decreased to 57 +/- 8, 49 +/- 7, and 47 +/- 9% of baseline values (P < 0.05). The shift of the systolic pressure-volume relationship was accompanied by a transient decrease of contractile efficiency (slope of O2 consumption-pressure-volume-area relationship) at 15 min of reperfusion (from 43 +/- 6 to 27 +/- 7%). We hypothesize that the rightward shift of the systolic pressure-volume relationship was compatible with a decrease of elastic-restoring forces, probably induced by alterations in the extracellular collagen matrix and/or the cytoskeleton, and thereby our data imply that left ventricular dysfunction of postischemic myocardium does not result solely from disturbances in excitation-contraction coupling.

Animals↗
PubMed2001

[Sinus node functions, sinoatrial conduction, atrial conductivity after incipient paroxysms of atrial fibrillation and flutter in patients with ischemic heart disease].

AIM: Prediction of the rate of recurrent paroxysms of atrial fibrillation (AF) and flutter (AFl) after the first arrhythmia episode; determination of relevant antiarrhythmic treatment. MATERIAL AND METHODS: 157 patients with ischemic heart disease (IHD) complicated by new episodes of AF and AFl entered the study. After the initial episode and 1-2 arrhythmia recurrences all the patients have undergone assessment of hemodynamics, atrial conduction of excitation, sinus node function using transesophageal pacing. The patients were divided into two groups: group 1 consisted of 42 patients having no recurrent paroxysms of AF or AFl for at least 6 months; 115 patients of group 2 had at least one episode of recurrent arrhythmia for 6 months after the first paroxysm. RESULTS: Patients of group 2 vs those of group 1 had a significantly longer first episode, more frequent occurrence of calcinosis of mitral and/or aortic valve, more serious systolic and diastolic dysfunctions and most frequent retrograde atrial excitation conduction after the first paroxysm. CONCLUSION: In detection of only disturbed intraatrial conduction in IHD patients after the first paroxysm of AF and AFl predicted are clinical recurrences of arrhythmia with the recurrence-free period more than 6 months. In retrograde atrial conduction of excitation combined with systolic and diastolic left ventricular dysfunction, sinus node dysfunction prognosis was made of more frequent episodes of AF and AFl.

Adult↗
PubMed2006

Immunomodulatory effects of poly(ADP-ribose) polymerase inhibition contribute to improved cardiac function and survival during acute cardiac rejection.

BACKGROUND: Recent studies have suggested that the peroxynitrite-poly(ADP-ribose) polymerase (PARP) pathway is activated during acute allograft rejection. Therefore, we investigated whether PARP inhibition improves transplant outcome and the extent to which immunologic factors contribute to the effects of PARP inhibition. METHODS: Isogeneic Lewis-to-Lewis and allogeneic Dark Agouti (DA)-to-Lewis rat cardiac transplants were studied under treatment with placebo, the PARP inhibitor INO-1001 (1 mg/kg/day), cyclosporine (2.5 or 5 mg/kg/day) or the combination of INO-1001 and low-dose cyclosporine. Functional, biochemical and histologic analyses were performed 3 and 5 days after transplantation in control and INO-1001-treated animals. In addition, stimulated T cells and endothelial cells were treated with INO-1001 to evaluate the potential immunosuppressive effects of PARP inhibition. RESULTS: PARP inhibition alone and in combination with cyclosporine significantly prolonged graft survival. Acute rejection led to a typical sequence of initial endothelial dysfunction and reduced contractile reserve followed by progressive systolic and diastolic dysfunction, which were reduced by PARP inhibition. PARP inhibition led to reduced antigen-specific and non-specific proliferation in stimulated T cells and dose-dependently inhibited intracellular adhesion molecule-1 (ICAM-1) up-regulation in stimulated endothelial cells. CONCLUSIONS: PARP inhibition was found to prolong graft survival and improve cardiac function during acute cardiac rejection. Direct immunosuppressive properties contribute at least partially to the beneficial effects of PARP inhibitors in graft rejection.

Animals↗
PubMed1996

Apical hypertrophic cardiomyopathy.

We report the case of a patient with recurrent admissions for congestive heart failure who was subsequently diagnosed with apical hypertrophic cardiomyopathy. The major physiologic characteristic of patients with apical hypertrophic cardiomyopathy is diastolic dysfunction due to abnormal stiffness of the left ventricle during diastole, with resultant impaired ventricular filling. In these patients, as in all patients with hypertrophic cardiomyopathy, the main pathology is inadequate relaxation of the ventricle; therefore, a regimen of diuretics and inotropic agents can actually worsen the clinical picture. We emphasize the need to consider hypertrophic cardiomyopathy in evaluating cases of congestive heart failure.

Aged↗