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PubMed2002

Analysis of left atrial volume change rate during left ventricular diastolic phase with M-mode echocardiography for differentiation between normal and pseudonormal mitral inflow.

Pseudonormalization of mitral inflow is a diagnostic problem in clinical practice. An excellent correlation exists between the change in the left atrial (LA) angiographic area and posterior aortic wall motion. Therefore, we sought to define the role of LA wall motion, indicating LA volume change rate, in patients with normal and pseudonormal mitral inflow. We performed echocardiography after cardiac catheterization in 62 patients with a velocity ratio of early-to-late mitral inflow (E/A ratio) >1. Study patients were classified into 2 groups according to the response of mitral inflow to phase II of the Valsalva maneuver: patients with E/A >1 after the Valsalva maneuver (n = 31, control group), and patients with <1 after the Valsalva maneuver (n = 31, pseudonormal group). The slopes (slope E and A) of early diastolic and late diastolic motion of the LA wall were derived from M-mode analysis together with the time constant of left ventricular (LV) isovolumic relaxation from cardiac catheterization. The values of slope E (41 plus minus 11 vs 61 plus minus 12 mm/s, p <0.001) and slope E/A (0.69 plus minus 0.13 vs 1.32 plus minus 0.35, p <0.001) were significantly lower in the pseudonormal group and were inversely correlated with the time constant of LV isovolumic relaxation (r = 0.64, p <0.001 and r = 0.73, p <0.001, respectively). Using slope E/A <1 as an indicator of relaxation abnormality, the sensitivity, specificity, positive predictive value, and negative predictive value for the detection of pseudonormalization were 94%, 100%, 100%, and 94%, respectively. The slope of LA wall motion, indicating LA volume change rate, during the LV diastolic phase is useful for evaluating pseudonormal LV diastolic dysfunction in the selected patient population.

Adult↗
PubMed1999

Left ventricular diastolic function in congenital myotonic dystrophy.

OBJECTIVE: Examination of left ventricular function and conduction abnormalities in myotonic dystrophy. DESIGN: Twelve patients (median age, 13.7 years) with myotonic dystrophy had detailed electrocardiography and echocardiography performed. Echocardiographic parameters were compared with body surface area (BSA) matched median normal values. RESULTS: Fractional shortening was slightly reduced (by 28-29%) in three patients and three patients had mild mitral valve prolapse. Diastolic function was abnormal; isovolumic relaxation time (IVRT) and duration of early filling were prolonged compared with control values (median IVRT, 74 v 61 ms). Peak E velocity was increased (median, 0.82 v 0.78 m/s) but atrial phase filling was normal. Heart rate was reduced (median, 68 v 81 beats/min). Conduction abnormalities were common but showed no clear relations with diastolic abnormalities. CONCLUSIONS: Young patients with myotonic dystrophy have myocardial diastolic dysfunction as well as abnormal electrophysiology. The prognostic implications of such abnormalities require further study.

Adolescent↗
PubMed1999

Subunit expression of the cardiac L-type calcium channel is differentially regulated in diastolic heart failure of the cardiac allograft.

BACKGROUND: Left ventricular diastolic dysfunction is a major cause of cardiac allograft failure. Multimeric L-type calcium channels (alpha1-, alpha2/delta-, and beta-subunits) are essential for excitation/contraction coupling in the heart. Their gene expression was studied in allografts that developed diastolic heart failure. METHODS AND RESULTS: mRNA levels of calcium channel subunits were measured by competitive reverse transcriptase-polymerase chain reaction in microbiopsy samples from the interventricular septum. Size and tissue variabilities between biopsy samples were assessed by determination of cardiac calsequestrin mRNA levels. In the cardiac allografts studied, mRNA levels in microbiopsy samples were considered to represent left ventricular gene expression, because septal and left ventricular gene expression in Northern blots was equivalent, and left ventricles contracted homogeneously. Biopsy samples (n=72) were taken from allografts with normal left ventricular end-diastolic pressure (LVEDP; 8 to 13 mm Hg; n=30), moderately elevated LVEDP (14 to 18 mm Hg; n=26), and elevated LVEDP (19 to 28 mm Hg; n=16). Increased LVEDP was related to slowed diastolic relaxation determined by the time constant tau (r2=0.86), whereas systolic performance (dP/dt; ejection fraction) was preserved. With increasing LVEDP, mRNA levels of the pore-forming alpha1c-subunit (n=15) and of the regulatory alpha2/delta-subunit (n=17) remained unchanged but decreased exponentially (r2=-0.83) for the regulatory beta-subunit (n=40). Compared with cardiac allografts with normal LVEDP (n=15), beta-subunit mRNA level was reduced by 75% at elevated LVEDP (n=9; P=0.012). In an explanted, diastolically failing cardiac allograft, beta-subunit expression was reduced correspondingly by 72% and 76% on the mRNA level in septal and left ventricular myocardium and by 80% on the protein level. CONCLUSIONS: The downregulated expression of the calcium channel beta-subunit might contribute to altered calcium handling in diastolically failing cardiac allografts.

Adult↗
PubMed2001

Annulus paradoxus: transmitral flow velocity to mitral annular velocity ratio is inversely proportional to pulmonary capillary wedge pressure in patients with constrictive pericarditis.

BACKGROUND: The early diastolic velocity of the mitral annulus (E') is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E' has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E' is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E' and PCWP in patients with CP. METHODS AND RESULTS: We studied 10 patients (8 men; mean age, 64+/-7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E'. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E' were 91+/-15 cm/s and 11+/-4 cm/s, respectively. Mean PCWP was 25+/-6 mm Hg. E' was positively correlated with PCWP (r=0.69, P=0.027). There was a significant inverse correlation between E/E' and PCWP (r=-0.74, P=0.014). Despite high left ventricular filling pressures, E/E' (mean, 9+/-4) was <15 in all but 1 patient. CONCLUSIONS: Paradoxical to the positive correlation between E/E' and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.

Aged↗
PubMed1985

Left ventricular diastolic performance at rest in patients with angina and normal systolic function--assessment by equilibrium radionuclide angiography.

The aim of the study was to correlate diastolic function, as evaluated by peak filling rate (PFR) and relative time (TPFR), with the severity of ischemic heart disease, as evaluated by exercise electrocardiography. Accordingly, 83 ischemic patients with effort angina, but normal ejection function at rest and normal left ventricular size, were studied by equilibrium radionuclide angiocardiography within two weeks from the exercise ECG. Diastolic dysfunction, as determined from PFR and, to a lesser extent, from TPFR, is common in patients with ischemic heart disease and normal systolic function. The prevalence and severity of such dysfunction is related more to the severity of the ischemia, as evaluated by the exercise ECG, than to the presence of an old myocardial infarction. Such findings are consistent with the hypothesis that PFR reflects mainly the early diastolic active uncoupling process.

Adult↗
PubMed2006

Cardiac damage secondary to occupational exposure to tin vapor.

Tin is commonly used as a coating on copper kitchen appliances, and "tinsmithing" as a trade is common in many non-Western countries, where cooking utensils are re-tinned when the cooking surface wears thin. Tinsmiths, or "tinkers," are commonly exposed to the following fumes during their work: stannic [tin(IV)] oxide, ammonium chloride, and hydrochloric acid. In this study we assessed workers from tinsmith workshops of our province for signs, symptoms, and laboratory evidence of cardiac end-organ damage. Between June 2002 and March 2003, researchers went to the main tinsmith workshop area of our province to interview tinsmiths in their workplaces and to gather addresses of their "traveling tinker" colleagues, who work with portable equipment. All workers were interviewed and underwent a complete physical examination, blood testing for lipid parameters, and echocardiography. Twenty-six tin workers (mean age 49+/- 10 y) and 25 control patients (convenience sample of hospital employees) were included in the study. Tobacco use, incidence of hypertension, and serum lipid parameters were not significantly different between the two groups (p < .05). The differences in myocardial performance index, systolic function, and mitral flow A velocity were also nonsignificant. However, the mitral inflow E velocity in the tinsmiths was significantly less than in controls (0.71+/- 0.1 vs. 0.95+/- 0.1 m/s, p < .001). The mitral deceleration time was also much longer in the tinsmith group (216+/- 71 ms vs. 143+/- 14 ms, p < .001). Eleven of the tinkers (23%) were found to have aortic valve sclerosis (severe in one, moderate in another, mild in the other nine), but aortic valve sclerosis was found in none of the control subjects. One tinsmith was found to have three-vessel coronary disease on angiogram. Another tinker with "myocarditis" in the past, and slow flow on angiography, had normalization of his cardiac tests after refraining from tin exposure for 6 mo. Thus, occupational exposure to heavy tin fumes is associated with left ventricle diastolic dysfunction and sclerosis of the aortic valve. Tin workers should minimize their exposure to tin fumes, and physicians should monitor tinsmiths closely for signs of heart disease.

Adult↗
PubMed1998

Effect of improved myocardial protection on edema and diastolic properties of the rat left ventricle during acute allograft rejection.

BACKGROUND: Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture. METHODS: Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals. RESULTS: On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5. CONCLUSIONS: Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.

Adenosine↗
PubMed2004

Relation of impaired left ventricular filling to systolic midwall mechanics in hypertensive patients with normal left ventricular systolic chamber function: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study.

BACKGROUND: Patients with hypertensive left ventricular (LV) hypertrophy commonly have diastolic dysfunction with preserved LV ejection fraction. LV systolic midwall shortening (MWS) may be impaired in hypertensive patients with normal LV ejection fraction. However, it is unclear whether impaired LV filling is related to depressed systolic midwall mechanics. METHODS: Echocardiographic measures of LV diastolic filling and systolic performance were compared in 632 unmedicated patients with stage II or III hypertension and LV hypertrophy determined by electrocardiogram, with LV ejection fraction >55% and <2+ mitral regurgitation. RESULTS: Stress-corrected LV MWS, an index of myocardial contractility, was lower in patients with abnormal as opposed to normal LV filling patterns (98% +/- 12% vs 102% +/- 10%, P <.001) and in patients with prolonged as opposed to normal isovolumic relaxation time (IVRT) (98% +/- 13% vs 101% +/- 12%, P =.014). Stress-corrected MWS was <85% of predicted levels in more patients with abnormal LV filling patterns (11.8% vs 6.3%) or with long IVRT (> or =105 msec) (34% vs 21%, both P <.05). In regression analyses, lower stress-corrected MWS and higher LV mass were independent correlates of longer IVRT, while lower stress-corrected MWS was the only independent correlate of prolonged mitral valve deceleration time (P =.017). Higher LV mass had strong, statistically independent relationships to longer IVRT (by 0.3 g/msec) and decreased stress-corrected MWS (by 0.5 g/%; both P <.0001), independent of body size and age. CONCLUSION: In patients with moderate hypertension and target organ damage who have normal LV ejection fraction, impaired early diastolic LV relaxation (abnormal E/A ratio, prolonged IVRT and deceleration time) is associated with impaired LV systolic midwall mechanics independent of higher LV mass.

Aged↗
PubMed1999

Cell death in acromegalic cardiomyopathy.

BACKGROUND: Prolonged untreated acromegaly leads to a nonspecific myopathy characterized by ventricular dysfunction and failure. However, the mechanisms responsible for the alterations of cardiac pump function remain to be defined. Because cell death is implicated in most cardiac disease processes, the possibility has been raised that myocyte apoptosis may occur in the acromegalic heart, contributing to the deterioration of ventricular hemodynamics. METHODS AND RESULTS: Ten acromegalic patients with diastolic dysfunction and 4 also with systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2-dimensional echocardiography, cardiac catheterization, and biventricular and coronary angiography before surgical removal of a growth hormone-secreting pituitary adenoma. Endomyocardial biopsies were obtained and analyzed quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis. Myocardial samples from papillary muscles of patients who underwent valve replacement for mitral stenosis were used for comparison. The presence of apoptosis in myocytes and interstitial cells was determined by confocal microscopy with the use of 2 histochemical methods, consisting of terminal deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation. Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis correlated with the extent of impairment in ejection fraction and the duration of the disease. A similar correlation was found with the magnitude of collagen accumulation, indicative of previous myocyte necrosis. Myocyte death was independent from the hormonal levels of growth hormone and insulin-like growth factor-1. Apoptosis of interstitial cells did not correlate with ejection fraction. CONCLUSIONS: Myocyte cell death, apoptotic and necrotic in nature, may be critical for the development of ventricular dysfunction and its progression to cardiac failure with acromegaly.

Acromegaly↗
PubMed2004

Relation of anemia to diastolic heart failure and the effect on outcome.

We evaluated the frequency and importance of anemia in 137 patients with heart failure and a normal ejection fraction (diastolic heart failure). We found that anemia is common in these patients and is associated with greater elevations in serum B-type natriuretic peptide, more severe diastolic dysfunction, and a worse prognosis.

Aged↗
PubMed2004

[Cardiac consequences of primary hyperaldosteronism].

The activation of the renin-angiotensin system is associated with vascular and cardiac hypertrophy. But there are few data on the renal and cardiac consequences of the hypersecretion of aldosterone. In the experimental setting, hyperaldosteronism leads to an excess of fibrous interstitial tissue and cardiac hypertrophy. In man, these consequences are those of hyperaldosteronism. The aim of this study was to assess the cardiac consequences of hyperaldosteronism in a series of 31 patients with a documented Conn adenoma, in comparison with a matched population of 31 patients with primary hypertension. For the same level of blood pressure, cardiac hypertrophy is more prominent in hyperaldosteronism and there is a positive correlation between the level of plasma aldosterone and left ventricular wall thickness. Left ventricular hypertrophy is of the concentric type. In addition, an increase in myocardial fibrosis (that can now be quantified by echocardiography) is observed, with a positive correlation between plasma aldosterone and reflected ultrasound which might correspond to increased myocardial collagen. These anatomic modifications of myocardial structure result in diastolic dysfunction. Overall, Conn adenoma is associated in accelerated disease, which is partly independent of the level of blood pressure.

Adenoma↗
PubMed2000

Left ventricular systolic and diastolic function and exercise testing in primary hyperparathyroidism-effects of parathyroidectomy.

BACKGROUND: Nontraditional manifestations of primary hyperparathyroidism (HPT) are controversial and may include morbidity, mortality, and risk factors for cardiovascular diseases. This study evaluates cardiovascular functions at rest and during exercise in HPT. METHOD: Thirty patients with HPT (mean serum calcium, 2.97 +/- 0.24 mmol/L) and 30 control people with normocalcemia, matched for age and sex, underwent symptom-limited exercise testing and echocardiography before and 13 months (mean) after having a parathyroidectomy. RESULTS: Despite similar maximal workload and blood pressures at rest in patients and healthy controls, HPT associated with higher systolic blood pressure during exercise (P =.03) and increased number of ventricular extrasystolic beats (P =.04). There was also an operatively reversible increase in ST-segment depression during exercise. Echocardiography showed an increased left ventricular (LV) isovolemic relaxation time (P =.02) and mitral deceleration time (P =.08), which indicate an LV diastolic dysfunction that could be partially reversed by operation. LV systolic function (ejection fraction and shortening fraction) tended to be elevated in HPT (P =.07 and.06, respectively) and diminished after parathyroidectomy. There was a trend toward higher LV mass, especially among the men with HPT (P =.06), which was unchanged postoperatively. CONCLUSIONS: HPT couples to reversible signs of myocardial ischemia and LV dysfunctions with a possible increased risk of life-threatening arrhythmia.

Adult↗
PubMed1995

The effects of nitrous oxide on left ventricular systolic and diastolic performance before and after cardiopulmonary bypass: evaluation by computer-assisted two-dimensional and Doppler echocardiography in patients undergoing coronary artery surgery.

We investigated the effects of nitrous oxide (N2O) on central hemodynamics and left ventricular systolic and diastolic function in 25 patients undergoing coronary artery bypass surgery. All patients were receiving beta-blockers and had good left ventricular function. Global and regional systolic left ventricular performance and diastolic function were determined by computer-assisted analysis of transesophageal echocardiographic (TEE) images, and mitral Doppler flow profiles, respectively. The patients were anesthetized with fentanyl and ventilated with oxygen in air. Hemodynamic and TEE measurements were obtained before and after the introduction of N2O in oxygen (60%/40%), before and after cardiopulmonary bypass (CPB). N2O reduced mean arterial pressure, heart rate, stroke volume, and cardiac output both before and after CPB. Left ventricular global area ejection fraction (GAEF) was not changed by the introduction of N2O, either before or after CPB. N2O induced a significant change in regional wall motion after, but not before CPB, as assessed by the relationship between segmental area ejection fraction (SAEF) and GAEF. Analysis of the mitral flow profile indicated an increase in early diastolic relaxation in the pre-CPB period after introduction of N2O, that was absent in the post-CPB period. We conclude that N2O induces regional wall motion abnormalities and possibly diastolic dysfunction post-CPB.

Blood Pressure↗
PubMed1987

Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure.

Intracellular Ca2+ release and reuptake are essential for contraction and relaxation of normal heart muscle. Intracellular Ca2+ transients were recorded with aequorin during isometric contraction of myocardium from patients with end-stage heart failure. In contrast to controls, contractions and Ca2+ transients of muscles from failing hearts were markedly prolonged, and the Ca2+ transients exhibited 2 distinct components. Muscles from failing hearts showed a diminished capacity to restore low resting Ca2+ levels during diastole. These experiments provide the first direct evidence from actively contracting human myocardium that intracellular Ca2+ handling is abnormal and may cause systolic and diastolic dysfunction in heart failure.

Adolescent↗
PubMed1996

Diastolic plateau wave of pulmonary artery pressure in severe congestive heart failure.

We describe 3 cases of severe congestive heart failure. The patients exhibited a marked decrease in transmitral flow velocity during atrial contraction and an abnormal diastolic plateau wave of pulmonary artery pressure (PAP). The first patient was a 60-year-old man with acute myocardial infarction and acute renal failure in whom pulmonary capillary wedge pressure (PCWP) was raised to 20 mmHg. Pulsed Doppler echocardiography revealed a marked decrease in transmitral flow velocity during atrial contraction, and the PAP waveform showed a mid to late diastolic plateau wave. Treatment for congestive heart failure reduced PCWP to 10 mmHg and the PAP waveform returned to normal. Doppler examination revealed the normal transmitral flow velocity pattern. The second patient was a 37-year-old woman with subarachnoid hemorrhage and the third patient a 74-year-old man with acute myocardial infarction. In these patients, the PAP waveform also showed a diastolic plateau wave, which was abolished by treatment. We believe that the diastolic plateau wave of PAP indicates left ventricular diastolic dysfunction and marked elevation of left ventricular filling pressure.

Adult↗
PubMed1997

Preconditioning the globally ischaemic, isolated rat heart: the impact of the preconditioning model on post-ischaemic systolic and diastolic function.

In studies of preconditioning, a variety of models have been used. The aim of the present study was to find the optimal preconditioning model for preservation of cardiac function during reperfusion of globally ischaemic, Langendorff-perfused rat hearts. Cardiac function was assessed by the occurrence of severe reperfusion arrhythmias (ventricular fibrillation or asystolia), heart rate (HR), left ventricular systolic (LVSP), end diastolic (LVEDP), and developed pressures (LVDP = LVSP - LVEDP), as well as coronary flow (CF). Series 1 (n = 17) in each group: control perfusion for 20 min without preconditioning or 2 episodes of 2, 3, 4, or 5 min of ischaemia, each followed by 5 min reperfusion, before 25 min ischaemia and 60 min reperfusion. Preconditioning reduced the incidence of reperfusion arrhythmias, attenuated the reperfusion-induced increase of LVEDP, and increased CF, but did not influence LVSP, LVDP, or rate x pressure-product (RPP = LVSP x HR) during reperfusion. The greatest effect was found by 2 min ischaemia and 5 min reperfusion. In series 2 (n = 17 in each group) control perfusion for 7 or 28 min, or preconditioning with 1-4 episodes of 2 min ischaemia and 5 min reperfusion before 35 min ischaemia and 60 min reperfusion were compared. Reduction of severe reperfusion arrhythmias and LVEDP elevation, as well as improvement of CF, LVDP, and HR in preconditioned hearts were observed in series 2. Optimal cardioprotection was achieved by only one episode of preconditioning. In conclusion, preconditioning before global ischaemia improved cardiac function during reperfusion of isolated rat hearts. The most marked effects were reduction of severe reperfusion arrhythmias and attenuation of diastolic dysfunction. Although all preconditioning models employed were cardioprotective, 1 episode of 2 min ischaemia provided optimal protection.

Animals↗
PubMed1993

[Evaluation of left ventricular early diastolic function by first pass radionuclide angiocardiography after dipyridamole infusion in patients with coronary artery disease--comparison with exercise test].

To evaluate the left ventricular early diastolic function after dipyridamole infusion or during exercise, the first pass radionuclide angiocardiography (FPRA) by a multicrystal gamma camera (SIM-400) was performed in 32 patients with coronary artery disease (CAD) and 14 normal subjects. Dipyridamole was administered intravenously (0.56 mg/kg in 4 min). The first third filling fraction (FF 1/3) and the first third mean filling rate (MFR 1/3) were calculated from the time-activity curve. FF 1/3 decreased and MFR 1/3 increased in both normal subjects and patients with CAD during exercise. After dipyridamole infusion, FF 1/3 and MFR 1/3 unchanged in normal subjects, in contrast, FF 1/3 and MFR 1/3 decreased in patients with CAD. Thus, dipyridamole infusion FPRA is more sensitive method to detect early diastolic dysfunction in patients with CAD than FPRA during exercise.

Aged↗
PubMed2006

Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart.

Oxidative stress plays an important role in the structural and functional abnormalities of diabetic heart. Glutathione peroxidase (GSHPx) is a critical antioxidant enzyme that removes H(2)O(2) in both the cytosol and mitochondia. We hypothesized that the overexpression of GSHPx gene could attenuate left ventricular (LV) remodeling in diabetes mellitus (DM). We induced DM by injection of streptozotocin (160 mg/kg ip) in male GSHPx transgenic mice (TG+DM) and nontransgenic wildtype littermates (WT+DM). GSHPx activity was higher in the hearts of TG mice compared with WT mice, with no significant changes in other antioxidant enzymes. LV thiobarbituric acid-reactive substances measured in TG+DM at 8 wk were significantly lower than those in WT+DM (58 +/- 3 vs. 71 +/- 5 nmol/g, P < 0.05). Heart rate and aortic blood pressure were comparable between groups. Systolic function was preserved normal in WT+DM and TG+DM mice. In contrast, diastolic function was impaired in WT+DM and was improved in TG+DM as assessed by the deceleration time of peak velocity of transmitral diastolic flow and the time needed for relaxation of 50% maximal LV pressure to baseline value (tau; 13.5 +/- 1.2 vs. 8.9 +/- 0.7 ms, P < 0.01). The TG+DM values were comparable with those of WT+Control (tau; 7.8 +/- 0.2 ms). Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis, and apoptosis. Overexpression of GSHPx gene ameliorated LV remodeling and diastolic dysfunction in DM. Therapies designed to interfere with oxidative stress might be beneficial to prevent cardiac abnormalities in DM.

Animals↗