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Care and management of the patient with right heart failure secondary to diastolic dysfunction: an advanced practice perspective and case review.

Until recently, most clinical trials associated with heart failure have studied systolic dysfunction. With the escalating geriatric population and dramatic increases in costs related to cardiovascular management regimens, more attention is being given to understanding diastolic failure induced by uncontrolled hypertension and cardiomyopathies. Researchers have demonstrated that the compensatory mechanisms associated with left ventricular diastolic dysfunction lead to elevated right heart pressures and eventually to right heart failure. When congestive heart failure is diagnosed, studies should be accomplished to differentiate between ventricular systolic or ventricular diastolic origins of the disease process, both to understand the origins of the heart failure and to guide clinical management. Therapy regimens and treatment goals must be directed toward controlling both systolic and diastolic pressures in order to achieve optimum outcomes.

Cardiovascular Agents↗

ANP but not BNP reflects early left diastolic dysfunction in type 1 diabetics with myocardial dysinnervation.

OBJECTIVE: We investigated whether plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) reflect impaired diastolic relaxation or its improvement after ACE inhibition. METHODS: 7 long-term Type 1 diabetic patients with normal systolic but impaired diastolic function and with sympathetic myocardial dysinnervation and 10 controls were included. Exercise tolerance and maximal O 2 uptake were evaluated by bicycle exercise prior to the study. ANP, BNP and norepinephrine/epinephrine (NE/E) were determined at baseline and at 80 % .VO2 max workload and after recovery, before and following 12 weeks of treatment with fosinopril (10 mg/d). RESULTS: Isovolumetric relaxation time (IVRT) and A/E wave ratio were increased by 26.7 +/- 11.5 % and 54.4 +/- 26.1 % in diabetic patients as compared to controls, respectively (p < 0.02). After 12 weeks of fosinopril treatment, no differences in IVRT or A/E wave ratio were detectable between groups. ANP was enhanced in Type 1 diabetes as compared to controls (baseline: 9.2 +/- 3.0 vs. 4.5 +/- 1.1; exercise: 22.4 +/- 7.7 vs. 7.9 +/- 1.2; recovery: 20.3. +/- 4.6 vs. 9.5 +/- 2.0 fmol/ml, p < 0.02). Fosinopril treatment abolished any differences between groups. BNP plasma levels did not differ between groups and no exercise dependent changes were observed. NE- and E-increase was greater at 80 % .VO2 max work load in Type 1 diabetes than in controls (p < 0.05). Again, fosinopril abolished differences between groups. CONCLUSION: In Type 1 diabetes, impaired diastolic function is associated with elevated ANP and catecholamine plasma levels that are normalized after ACE inhibition. Thus, ANP but not BNP appears to be a sensitive biochemical marker for early diastolic dysfunction in Type 1 diabetes.

Adult↗

An infant with hypereosinophilic syndrome and heart failure markedly responded to prednisolone: serial changes of left ventricular wall thickening and left ventricular diastolic dysfunction observed by echocardiography.

We encountered an infant with congestive heart failure due to idiopathic hypereosinophilic syndrome. The patient showed marked thickening of the left ventricular wall and left ventricular diastolic dysfunction, both of which, shortly after prednisolone therapy, markedly improved together with improvement of the congestive heart failure and hypereosinophilia. Observation of pulmonary venous flow patterns detected by pulsed Doppler echocardiography may be useful for evaluation of left ventricular diastolic function.

Echocardiography, Doppler, Pulsed↗

Prognosis in heart failure: is systolic or diastolic dysfunction more important?

The clinical syndrome of congestive heart failure can result from inadequate myocardial contraction (systolic myocardial failure), from pseudo-heart failure due to circulatory overload, or from failure of the ventricles to fill at low pressure (diastolic myocardial failure). The presence of systolic or diastolic heart failure is most precisely defined by an examination of left ventricular pressure-volume relations. Diastolic failure commonly coexists with systolic dysfunction. However, in many patients, diastolic dysfunction may exist alone or as the predominant physiologic disturbance. This is especially true in such common disease states as systemic hypertension and ischemic heart disease. Like systolic heart failure, diastolic failure results in significant morbidity and mortality. Diastolic heart failure may correlate better with prognosis for symptoms and survival than traditional indices of systolic function. The presence of predominantly diastolic dysfunction in large numbers of patients with the diagnosis of congestive heart failure has important therapeutic implications.

Diastole↗

Course of left ventricular diastolic dysfunction in end-stage renal disease on long-term continuous ambulatory peritoneal dialysis.

To determine factors contributing to abnormal left ventricular (LV) diastolic filling in patients on long-term continuous ambulatory peritoneal dialysis (CAPD), 11 (age: 55 +/- 13 years; CAPD duration: 33 +/- 32 months) out of 42 originally studied CAPD patients were followed over 35 months with echocardiography and pulsed Doppler echocardiography. LV dimensions and systolic function remained normal. Doppler parameters indicated diastolic LV dysfunction in 9/11 patients in the initial study. Despite a significant increase in LV mass (234 +/- 54 vs. 299 +/- 65 g; p < 0.05) and a decrease in LV volume/mass ratios (0.78 +/- 0.18 vs. 0.54 +/- 0.12 ml/g; p < 0.001), no change was observed in any of the diastolic LV filling parameters such as peak early and atrial filling velocities and their ratios, atrial filling fractions and peak filling rate normalized for mitral stroke volume. Individual changes of E/A-max were inversely correlated with systolic blood pressure (p < 0.01), alterations of normalized peak filling rate were inversely correlated with serum creatinine (p < 0.01). No influence on individual changes of LV diastolic filling parameters was observed for LV volume, muscle mass, volume/mass ratios, ejection fractions, patient age, dialysis duration, and hemoglobin concentration. These findings suggest that arterial hypertension and the quality of blood purification play a central role in the development of LV diastolic dysfunction in patients on CAPD, while LV muscle mass and LV volume/mass relations have no relevant influence on changes of LV diastolic function in these patients.

Adult↗

[Effect of captopril on left ventricular diastolic dysfunction in young insulin dependent diabetic patients with microalbuminuria].

BACKGROUND: Diabetic cardiomyopathy (DMC) is a complication of diabetes mellitus (DM)that is more frequently observed in those patients with microalbuminuria. Left ventricular diastolic dysfunction (LVDD) in patients with diabetes, in absence of another etiology that justifies it, is an early marker of DMC. We carried out a prospective study on young diabetic type 1 patients with microalbuminuria, aimed at knowing the effect of captopril on LVDD. PATIENTS AND METHOD: We included 30 patients (18 males and 12 females) diagnosed with type 1 DM,aged 40 years old, who had been recently found to have microalbuminuria and thus they were candidates to receive captopril. We excluded patients having factors different from DM that could modify the diastolic function. All patients underwent a complete biochemical and echocardiographic study before starting the treatment with captopril and six months later. A diagnosis of LVDD was made when at least one of the following parameters was present in the echocardiographic study: isovolumetric relaxing time (IRT) >100 ms, deceleration time (DT) > 220 ms or early filling rate peak/late filling rate peak ratio (E/A) < 1. According to the results of the second echocardiogram, patients were classified in two groups: improved group (when there was at least a 10% improvement of initial LVDD altered parameters) and non-improved group. A control group of 28 type 1 diabetic patients without microalbuminuria who were not given captopril was included (group C). RESULTS: The initial echocardiographic study yielded 11 patients having a normal diastolic function (group FDN) and 19 patients having LVDD (group FDA). After 6 moths of captopril treatment, an improvement of the ratio E/A was observed in the group FDN: from 1.58 (0.36)in the beginning to 1,68 (0.29) six moths later (p < 0.05),and in the group FDA: from 1.09 (0.24) to 1.24 (0.28) (p <0.05). In the group FDA, an improvement of IRT was found: from 110 (16) ms to 99.9 (9.6) ms (p < 0.01). Moreover, in the group FDA, LVDD improved after sixth months in 15 (78.9%) patients but not in 4 (21,6%). This LVDD improvement was associated with a decrease of the diastolic blood pressure (DBP) and the systolic blood pressure (SBP) at the end of the study. A logistic regression analysis showed an independent association between the reduction of the mean SBP and the improvement of LVDD. CONCLUSION: Our results suggest that captopril can improve LVDD in young patients with type 1 diabetes and microalbuminuria, possibly due to a decrease of blood pressure.

Adult↗

Association of reduced carbon monoxide diffusing capacity with moderate or severe left ventricular diastolic dysfunction in obese persons.

STUDY OBJECTIVES: To determine the association of reduced diffusing capacity of the lung for carbon monoxide (D(LCO)) with moderate or severe left ventricular diastolic dysfunction (LVDD) in obese persons. DESIGN: We investigated the association of D(LCO) with LVDD in 105 patients with a mean +/- SD body mass index of 49 +/- 5 kg/m2. An abnormal D(LCO) was < 80%. LVDD was investigated by Doppler and by tissue Doppler echocardiography. The Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether the D(LCO) was normal or abnormal. SETTING: A university hospital. PATIENTS: The 105 patients included 19 men and 86 women (mean age, 45 +/- 9 years). RESULTS: An abnormal D(LCO) was present in 62 of 105 patients (59%). Moderate or severe LVDD was present in 35 of 105 patients (33%). Moderate or severe LVDD was present in 25 of 62 patients (40%) with an abnormal D(LCO) and in 10 of 43 patients (23%) with a normal D(LCO) (p < 0.05). CONCLUSION: Obese patients with a decreased D(LCO) have an increased prevalence of moderate or severe LVDD.

Adult↗

Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure.

Fifteen elderly patients with normal left ventricular (LV) systolic function and New York Heart Association functional class II-III were studied. The effect of verapamil on LV diastolic function was assessed by congestive heart failure (CHF) score, treadmill exercise test, and Doppler echocardiography at baseline, and after each three-month treatment period (placebo or verapamil 120 mg once daily), separated by a one-week washout period before crossover. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. Verapamil treatment significantly improved CHF score at 3 months (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/- 0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05) and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF, three months treatment with verapamil can improve CHF, increase exercise tolerance and improve LV diastolic function.

Aged↗

Diastolic dysfunction is associated with anaemia in patients with Type II diabetes.

Anaemia is common in patients with diabetes and associated with an increased risk of diabetic complications. Although the role of anaemia in heart failure is established, we hypothesize that anaemia also contributes to an increased risk of cardiac dysfunction in patients with Type II diabetes. In the present study, 228 consecutive adults with diabetes were investigated using transthoracic echocardiography. Echocardiographic parameters were correlated with the Hb (haemoglobin) level and adjusted for other risk factors for cardiac dysfunction using multivariate analysis. More than one in five patients (23%) had anaemia, which was an independent risk factor for cardiac dysfunction on echocardiography. Over one-third of all patients with evidence of abnormal cardiac function (diastolic and/or systolic dysfunction) on echocardiography had anaemia compared with <5% of patients with normal echocardiographic findings. Most patients with anaemia had cardiac dysfunction (94%), with the major abnormality being diastolic dysfunction associated with an increased left ventricular mass and impaired relaxation indices. A continuous association between diastolic function and Hb was also observed in patients without anaemia. In patients with a history of cardiovascular disease, systolic dysfunction was twice as common in patients with anaemia. Anaemia was also correlated with plasma markers of cardiac risk, including BNP (brain natriuretic peptide), CRP (C-reactive protein) and AVP (arginine vasopressin). Notably, the predictive utility of these markers was eliminated after adjusting for Hb. Consequently, the inexpensive measurement of Hb may be a useful tool to identify diabetic patients at increased risk of cardiac dysfunction.

Aged↗

Concealed left ventricular hypertrophy and diastolic dysfunction in hypertrophic cardiomyopathy in the presence of acute left ventricular volume overload. A case report.

We report a patient in whom hypertrophic cardiomyopathy, with both left ventricular hypertrophy and diastolic dysfunction, was masked by acute severe aortic regurgitation and marked left ventricular dilation. Upon admission, 1) two-dimensional echocardiogram of the left ventricle revealed a dynamic and flail vegetation on the aortic right coronary cusp and marked left ventricular dilation, 2) a massive aortic regurgitant signal was recorded by color Doppler flow imaging, and 3) transmitral flow velocity by pulsed Doppler echocardiogram revealed a pseudonormalization. However, symmetric hypertrophy of the left ventricular wall, a decrease in early diastolic wave and a compensatory increase in atrial systolic wave of the transmitral flow velocity appeared after successful aortic valve replacement.

Aortic Valve↗

Prolonged mechanical systole and increased arterial wave reflections in diastolic dysfunction.

OBJECTIVE: To evaluate whether left ventricular ejection time indexed for heart rate (left ventricular ejection time index (LVETI)) and arterial wave reflections (augmented pressure (AP)) are increased in patients with diastolic dysfunction (DD). DESIGN: Prospective observational study. SETTING: University teaching hospital providing primary and tertiary care. SUBJECTS: 235 consecutive patients undergoing left heart catheterisation were categorised as having definite DD, possible DD or no DD (controls) on the basis of their left ventricular end diastolic pressures and N-terminal brain natriuretic peptide concentrations. MAIN OUTCOME MEASURES: LVETI and AP were prospectively assessed non-invasively by radial applanation tonometry. In addition, all patients underwent comprehensive echocardiography, including tissue Doppler imaging of mitral annulus velocity in early diastole (E'). RESULTS: LVETI was longer in patients with definite DD than in patients with possible DD and in controls (433.6 (SD 17.2), 425.9 (17.9) and 414.3 (13.6) ms, respectively, p < 0.000001). Arterial wave reflections were higher in definite DD than in possible DD and control groups (AP was 19.4 (SD 8.9), 15.2 (8.0) and 10.7 (6.8) mm Hg, respectively, p < 0.000001). In receiver operating characteristic curve analysis, LVETI detected DD as well as echocardiography (E:E'). Area under the curve for LVETI to differentiate patients with definite DD from normal controls was 0.81 (95% CI 0.72 to 0.89, p < 0.0001). In multivariable logistic regression analysis, LVETI added significant independent power to clinical and echocardiographic variables for prediction of DD. CONCLUSIONS: Mechanical systole is prolonged and arterial wave reflections are increased in most patients with DD. Rapid non-invasive assessment of these parameters may aid in confirming or excluding DD.

Aged↗

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction.

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.

Adult↗

Adaptation of passive rat left ventricle in diastolic dysfunction.

This article deals with providing a theoretical explanation for quantitative changes in the geometry, the opening angle and the deformation parameters of the rat ventricular wall during adaptation of the passive left ventricle in diastolic dysfunction. A large deformation theory is applied to analyse transmural stress and strain distribution in the left ventricular wall considering it to be made of homogeneous, incompressible, transversely isotropic, non-linear elastic material. The basic assumptions made for computing stress distributions are that the average circumferential stress and strain for the adaptive ventricle is equal to the average circumferential stress and strain in the normotensive ventricle, respectively. All the relevant parameters, such as opening angle, twist per unit length, axial extension, internal and external radii and others, in the stress-free, unloaded and loaded states of normotensive, hypertensive and adaptive left ventricle are determined. The circumferential stress and strain distribution through the ventricular wall are also computed. Our analysis predicts that during adaptation, wall thickness and wall mass of the ventricle increase. These results are consistent with experimental findings and are the indications of initiation of congestive heart failure.

Adaptation, Physiological↗

Left ventricular diastolic dysfunction is accompanied by increased aortic stiffness in the early stages of essential hypertension: a TDI approach.

OBJECTIVE: To investigate the inter-relationship between aortic stiffness and left ventricular (LV) diastolic function in subjects with newly diagnosed uncomplicated essential hypertension. METHODS: We studied 106 consecutive newly diagnosed subjects (aged 51 years, 80 males) with stage I-II essential hypertension, and 50 normotensives matched for age, sex and body mass index. LV diastolic function was estimated by pulsed tissue Doppler imaging (TDI) echocardiography, averaging diastolic mitral annular velocity measurements (Emav, Amav, Emav/Amav ratio) from four separate sites (basal septal, lateral, anterior, and inferior LV wall). Moreover, aortic stiffness was evaluated by non-invasive carotid-femoral pulse wave velocity (c-f PWV) measurement. RESULTS: Hypertensives compared with normotensives exhibited greater LV mass index and Amav (110 versus 95 g/m and 10 versus 8.8 cm/s, respectively, P < 0.001 for both cases), and greater c-f PWV (8.47 versus 7.48 m/s, P < 0.03), as well as lower Emav and Emav/Amav values, (8.4 versus 10 cm/s and 0.82 versus 1.15, respectively, P < 0.001 for both cases). In the group of hypertensives, a univariate analysis revealed that c-f PWV was negatively associated with Emav (r = -0.305, P = 0.005), as well as with Emav/Amav ratio (r = -0.437, P < 0.001). Moreover, a multivariate analysis showed that the TDI-derived Emav/Amav ratio was significantly associated with age (P = 0.001), relative wall thickness (P = 0.006) and c-f PWV (P = 0.03), while the conventional Doppler-derived E/A ratio was significantly associated only with age (P = 0.001). CONCLUSIONS: TDI-detected LV diastolic dysfunction is accompanied by increased aortic stiffness in newly diagnosed essential hypertension, suggesting that there may be a common pathophysiological pathway linking these two entities.

Adult↗

Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes.

Diabetic cardiomyopathy is an ill-defined entity. This study was designed to explore the possible association between left ventricular diastolic dysfunction (LVDD) and cardiac autonomic neuropathy (CAN) independently from metabolic control. Three groups of 10 age-matched men each with well-controlled type 2 diabetes were studied: (1) subjects with normal diastolic function, (2) subjects with LVDD characterized by impaired LV relaxation, and (3) subjects with a more severe form of LVDD characterized by a pseudonormalized pattern of LV filling. No subject had evidence of clinical diabetic complications, coronary artery disease (CAD), hypertension, congestive heart failure, or thyroid or overt renal disease, and all had a negative maximal exercise test. LVDD was evaluated by Doppler echocardiographic and CAN was evaluated using spectral analysis of heart rate variability (HRV; time and frequency domains) from 24-hour Holter recordings. Findings showed that the high frequency power (HF: 0.15 to 0.4 Hz) tends to decrease with worsening diastolic function; 5.0 +/- 0.2 ms(2) (mean +/- SE) in group 1, 4.2 +/- 0.3 ms(2) in group 2, and 3.9 +/- 0.4 ms(2) (P =.03) in group 3, respectively, whereas the low frequency power (LF: 0.04 to 0.15 Hz) was similar between groups. In the time domain, the mean squared differences of the successive RR intervals (rMSDD) also showed the same pattern, ie, 31.0 +/- 2.8 ms, 23.8 +/- 1.6 ms, and 21.5 +/- 2.9 ms in groups 1, 2, and 3, respectively (P =.03). The E/A ratio correlated significantly with indices of parasympathetic modulation (HF; r = 0.448, P =.013; rMSDD: r = 0.457, P =.011; pNN50: r = 0.425, P =.019). LVDD and CAN are associated in patients with otherwise uncomplicated well-controlled type 2 diabetes. The parameters defining these 2 abnormalities may serve to better define diabetic cardiomyopathy as a distinct entity and could eventually become useful prognostic indicators as it has been shown in nondiabetic populations.

Autonomic Nervous System Diseases↗

Regression of left ventricular hypertrophy in experimental renovascular hypertension: diastolic dysfunction depends more on myocardial collagen than it does on myocardial mass.

OBJECTIVE: To evaluate regression of experimental left ventricular hypertrophy (LVH) in terms of its effects both on myocardial collagen levels and on diastolic stiffness. METHODS: Two-kidney, one clip Goldblatt hypertensive rats were left untreated for 4 weeks (HT4W, n = 12) or 12 weeks (HT12W, n = 11) and compared with rats the treatment of which was started after 4 weeks of hypertension with 30 mg/kg per day losartan for 8 weeks (LOS, n = 12), or 50 mg/l enalapril for 8 weeks (ENA, n = 11). A group of sham-operated rats served as controls (SHAM, n = 9). RESULTS: The blood pressure of the rats increased significantly and LVH developed both after 4 and after 12 weeks of hypertension. Treatment with losartan or enalapril significantly decreased blood pressure and induced complete regression of LVH. Myocardial hydroxyproline concentrations increased in groups HT4W and HT12W (530 +/- 153 and 581 +/- 111 micrograms/g, respectively) relative to that in the SHAM group (421 +/- 22 micrograms/g). None of the treatments induced regression of increased myocardial collagen levels. The slopes of the end-diastolic stress-strain relationships in the isolated beating hearts were significantly higher in HT4W, HT12W and in both treated groups compared with those in the SHAM group, indicating increased diastolic myocardial stiffness. CONCLUSION: Losartan and enalapril treatments decreased blood pressure and induced complete regression of LVH in this model of renovascular hypertension. In contrast, none of the treatments induced regression of increased myocardial collagen levels or reduced the abnormal left ventricular diastolic stiffness. These data suggest that diastolic dysfunction depends more on increased myocardial collagen levels than it does on myocardial mass in this model of pathological LVH.

Animals↗

Left ventricular diastolic dysfunction limits use of maximum systolic elastance as an index of contractile function.

We tested the hypothesis that maximum systolic elastance (Emax) fails to detect a decline in left ventricular (LV) contractile function when diastolic dysfunction is present. Canine hearts were studied in an isolated blood-perfused heart apparatus (isovolumic LV); contractile dysfunction was produced by 60 or 90 minutes of global ischemia, followed by 90 minutes of reperfusion. Nine normal hearts underwent 60 minutes of ischemia, and five underwent 90 minutes of ischemia. After the ischemia-reperfusion sequence, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 14 hearts. In the group undergoing 60 minutes of ischemia, LV diastolic pressure did not increase, whereas Emax decreased from 5.2 +/- 2.5 to 2.9 +/- 1.4 mm Hg/ml (p less than 0.05). In the group undergoing 90 minutes of ischemia, diastolic pressure increased (from 10 +/- 2 to 37 +/- 20 mm Hg, p less than 0.05), and Emax did not change significantly (from 5.1 +/- 4.3 to 4.3 +/- 2.5 mm Hg/ml). A second series of experiments was performed in 13 hearts with pressure-overload hypertrophy (aortic-band model with echocardiography and catheterization studies before the ischemia-reperfusion protocol). Five had evidence for pump failure, whereas eight remained compensated. After 60 minutes of ischemia and 90 minutes of reperfusion, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 13 hearts. In the group with compensated LV hypertrophy, LV diastolic pressure did not change, whereas Emax decreased from 6.9 +/- 3.0 to 3.1 +/- 2.3 mm Hg/ml (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

[Effect of enalaprilat on postischemic systolic and diastolic dysfunction (stunned myocardium) on the isolated rabbit heart].

The aim was to determine: 1) whether Enalaprilat (0.08 mg/kg/min) administration: a) before ischemia or b) at the beginning of reperfusion improved the postischemic systolic and diastolic dysfunction ("stunned myocardium") and attenuated the "hyperfunction" phase at the beginning of reperfusion; and 2) whether creatine kinase (CPK), and lactate dehydrogenase (LDH) activities, and lactate release are involved in the protective effects of Enalaprilat. An isolated isovolumic rabbit heart preparation was used as experimental model and subjected to 15 minutes of ischemia followed by 30 minutes of reperfusion, without (group 1), and with Enalaprilat before the ischemia (group 2) and at the beginning of reperfusion (group 3). Left ventricular developed pressure, and end diastolic pressure (diastolic stiffness) were measured and the time constant of isovolumic relaxation (t, Tau) and the ratio between +dP/dtmax and -dP/dtmax were calculated. For the determinations of lactate release and CPK and LDH activities in the perfusate, samples were taken from the coronary effluent for spectrophotometrical measurements. In comparison to the stunned group (group 1) both Enalaprilat preischemia (group 2) and postischemia (group 3) exerted a significant protective effect on the postischemic recovery of contractile state and diastolic stiffness, and attenuated the "hypercontractile" phase in both groups. However Enalaprilat failed to improve myocardial relaxation. Lactate release was also attenuated, but the enzyme activities were not modified.

Angiotensin-Converting Enzyme Inhibitors↗