Left Ventricular Diastolic Stiffness Research Articles

Aortic Elastic Properties Are Related to Left Ventricular Diastolic Function in Patients with Type 1 Diabetes Mellitus

Objective: The aim of the study was to evaluate left ventricular diastolic function and its relation to aortic wall stiffness in patients with type 1 diabetes mellitus without coronary artery disease or hypertension. Patients: Sixty-six patients with type 1 diabetes mellitus were examined by echocardiography and divided into two groups according to the diastolic filling pattern determined by mitral annulus tissue Doppler velocities. Group A patients (n = 21) presented diastolic dysfunction with a peak early diastolic mitral annular velocity (Em)/peak late diastolic mitral annular velocity (Am) ratio <1 whereas in group B patients (n = 45) the Em/Am ratio was >1. Coronary artery disease was excluded based on normal thallium scintigraphy. Aortic stiffness index was calculated from aortic diameters measured by echocardiography, using accepted criteria. Results: Aortic stiffness index differed significantly among the two groups. Significant correlations were found between parameters of left ventricular diastolic function (Em/Am, isovolumic relaxation time, deceleration time) and aortic stiffness index. Multiple stepwise linear regression analysis revealed aortic stiffness index (β = –0.39, p = 0.001) and isovolumic relaxation time (β = –0.46, p < 0.001) as the main predictors of Em/Am ratio. Conclusions: Aortic stiffness is increased in type 1 diabetic patients with left ventricular diastolic dysfunction. This impairment in aortic elastic properties seems to be related to parameters of diastolic function.

Revisiting methods for assessing and comparing left ventricular diastolic stiffness: impact of relaxation, external forces, hypertrophy, and comparators

Understanding diastolic function mandates feasible and accurate methods to construct and compare the diastolic pressure (P)-volume (V) relationship (PVR). This study compared the relaxation-corrected single beat (RC-SB) to the multiple-beat (MB) (vena cava occlusion) method for constructing the diastolic PVR in 26 young normal or old hypertensive dogs before and after increases in afterload (phenylephrine) or acute volume expansion in the presence (n = 14) or absence (n = 12) of the pericardium. The PVR data were fit to P = alphae(beta x V). Derived stiffness indexes compared included the stiffness coefficient (beta), curve-fitting constant (alpha), and the end-diastolic volume (EDV) at 10, 20, or 30 mmHg [EDV(x) = ln(P(x)/alpha)/beta] to account for covariance in alpha and beta. In pericardium-intact young normal and old hypertensive dogs studied over varying afterloads, the MB and RC-SB PVR appeared identical. The beta (r = 0.62) and alpha (r = 0.69) derived from the RC-SB vs. MB PVR showed moderate correlation but poor agreement. In contrast, the EDV(10-30) derived from RC-SB vs. MB PVR showed excellent correlation (r = 0.97) and agreement. The uncorrected SB method underestimated stiffness. As expected, after acute volume expansion, the RC-SB PVR was shifted upward from the MB PVR (decreased EDV(10-30); P < 0.05) in the pericardium-intact but not pericardium-absent dogs. The RC-SB method can substitute for the MB technique in construction of PVR in the absence of acute volume expansion. The concordance between these two methods was poorly reflected by comparing the derived alpha and beta but apparent when using EDV(10-30), which provides information regarding the position of the PVR in a single number.

Revisiting Methods for Assessing and Comparing Left Ventricular Diastolic Stiffness

Background: Controversies over the pathophysiology of heart failure with preserved EF have renewed interest in characterization and comparison of LV diastolic stiffness, best assessed using the LV end-diastolic (ED) pressure (P)-volume (V) relationship obtained from multiple beats (MB) during rapid preload reduction. As the MB method is difficult, the diastolic P-V over a single beat with P corrected for effect of ongoing relaxation (RCSB) has been used in human studies but not validated against MB method. Further, the LV stiffness coefficient β in the relation EDP = αeβ∗EDV has been used to compare stiffness, but β covaries with α. This covariance is accounted for by comparing derived EDV at similar EDP, calculated from α, β and EDP of 10, 20 or 30 mmHg (EDV10-30). Objective: Determine if the RCSB method of assessing diastolic stiffness (as quantified by β or EDV10-30) shows good correlation and agreement with the MB method. Methods: P, V were invasively measured and the RCSB followed by MB methods performed in 26 young normal or elderly hypertensive dogs before and during phenylephrine (to vary afterload) or acute volume expansion. In the RCSB method, diastolic P was corrected by subtracting the P due to relaxation, monoexponentially extrapolated from isovolumic relaxation. Correlation was assessed by linear regression. Agreement was expressed as the mean ± SD of the paired difference between MB and RCSB values for β or EDV10-30, expressed as percentages of their mean values; p is for paired t-test. Results: Over widely varying afterloads (LV systolic P 95 to 236 mmHg), EDV10-30 derived from RCSB and MB methods showed excellent correlation (r = 0.98, p < 0.0001) and agreement (0.6 ± 5%, p = 0.6). Correlation (r = 0.62, p = 0.002) and agreement (4.2 ± 45%, p = 0.7) between β from SB and MB was poorer. Use of a limited number of P and V points for the RCSB method (at minimum LV P, pre-atrial contraction, and ED) resulted in less agreement between the methods in assessing EDV10-30 (4.4 ± 9%, p = 0.0003) or β (21 ± 40%, p = 0.025). Neither β (12.5 ± 55%, p = 0.5) nor EDV10-30 (10 ± 10%, p < 0.0001) derived from RCSB agreed with MB after marked volume expansion in presence of pericardium. Conclusion: Clinical studies seeking to compare diastolic stiffness between groups can use the clinically more feasible RCSB to substitute for the complex MB technique under a wide range of afterload. Accuracy will be influenced by the number of P and V points used and by presence of acute volume overload. Comparison of stiffness between groups will be enhanced by methods which account for the covariance between α and β.

Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats

During ischemic heart diseases and when heart failure progresses depletion of myocardial energy stores occurs. D-Ribose (R) has been shown to improve cardiac function and energy status after ischemia. Folic acid (FA) is an essential cofactor in the formation of adenine nucleotides. Therefore, we assessed whether chronic R-FA administration during the development of hypertrophy resulted in an improved cardiac function and energy status. In Wistar rats (n = 40) compensatory right ventricular (RV) hypertrophy was induced by monocrotaline (30 mg/kg; MCT), whereas saline served as control. Both groups received a daily oral dose of either 150 mg.kg(-1).day(-1) dextrose (placebo) or R-FA (150 and 40 mg.kg(-1).day(-1), respectively). In Langendorff-perfused hearts, RV and left ventricular (LV) pressure development and collagen content as well as total RV adenine nucleotides (TAN), creatine content, and RV and LV collagen content were determined. In the control group R-FA had no effect. In the MCT-placebo group, TAN and creatine content were reduced, RV and LV diastolic pressure-volume relations were steeper, RV systolic pressures were elevated, RV and LV collagen content was increased, and RV-LV diastolic interaction was altered compared with controls. In the MCT-R-FA group, TAN, RV and LV diastolic stiffness, RV and LV collagen content, and RV-LV diastolic interaction were normalized to the values in the control group while creatine content remained depressed and RV systolic function remained elevated. In conclusion, the depression of energy status in compensated hypertrophic myocardium observed was partly prevented by chronic R-FA administration and accompanied by a preservation of diastolic function and collagen deposition.

Relative systolic dysfunction in female spontaneously hypertensive rat myocardium

Hypertension and exercise independently induce left ventricular (LV) remodeling and alter LV function. The purpose of this study was to determine systolic and diastolic LV pressure-volume relationships (LV-PV) in spontaneously hypertensive rats (SHR) with and without LV hypertrophy, and to determine whether 6 mo of exercise training modified the LV-PV in SHR. Four-month-old female SHR (n = 20), were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (approximately 60% peak O2 consumption, 5 days/wk, 6 mo), while age-matched female Wistar-Kyoto rats (WKY; n = 13) served as normotensive controls. The LV-PV was determined using a Langendorff isolated heart preparation at 4 (no hypertrophy: WKY, n = 5; SHR, n = 5) and 10 mo of age (hypertrophy: WKY, n = 8; SHR-SED, n = 8; SHR-TRD, n = 7). At 4 mo, the LV-PV in SHR was similar to that observed in WKY controls. However, at 10 mo of age, a rightward shift in the LV-PV occurred in SHR. Exercise training did not alter the extent of the shift in the LV-PV relative to SHR-SED. Relative systolic function, i.e., relative systolic elastance, was approximately 50% lower in SHR than WKY at 10 mo of age (P < 0.05). Doppler-derived LV filling parameters [early wave (E), atrial wave (A), and the E/A ratio] were similar between groups. LV capacitance was increased in SHR at 10 mo (P < 0.05), whereas LV diastolic chamber stiffness was similar between groups at 10 mo. Hypertrophic remodeling at 10 mo of age in female SHR is manifest with relative systolic decompensation and normal LV diastolic function. Exercise training did not alter the LV-PV in SHR.

The role of oxidative stress in the development of myocardial diastolic dysfunction with diabetes mellitus

It is already known that myocardial diastolic dysfunction develops already at early stages of I type diabetes mellitus. Current investigations represent the importance of oxidative stress in the development of complications of diabetes mellitus. The purpose of our work was to show the role of oxidative stress in progress of disturbances of myocardial relaxation function in rats with streptozotocin-induced diabetes and to explore possible mechanisms of heart protection. The essential increase of left ventricular diastolic stiffness (considered as ΔEDP/ΔV) is represented with Langendorff isolated heart of rats that had experimental diabetes.

Myocardial diastolic dysfunction at experimental diabetes mellitus—the role of nitric oxide

The clinical investigations shows that myocardial diastolic dysfunction develops already at early stages of I type diabetes mellitus. The purpose of our work was to reveal disturbances of myocardial relaxation function in rats with streptozotocin-induced diabetes and to investigate possible mechanisms of such infringements development. On Langendorff isolated heart, the essential increase of left ventricular diastolic stiffness (considered as ΔEDP/ΔV) was shown at experimental diabetes. At dosed left ventricular stretching with balloon, the sharp growth of EDP meanings in diabetic hearts was observed at significantly smaller value of balloon volume gain, than in control hearts.

Effects of Preemptive Enoximone on Left Ventricular Diastolic Function After Valve Replacement for Aortic Stenosis

Left ventricular (LV) hypertrophy is associated with increased diastolic chamber stiffness early after aortic valve replacement for valve stenosis. Enoximone, a phosphodiesterase III inhibitor, has been shown to improve myocardial contractility and relaxation when administered as a single dose after cardiac surgery. The present study investigated, by analysis of transmitral flow velocity patterns and end-diastolic pressure-area relations, whether enoximone administered before aortic valve surgery has an effect on LV diastolic properties. Prospective, randomized study. Referral center for cardiothoracic surgery at a university hospital. Thirty-four patients undergoing aortic valve replacement for aortic stenosis. Patients in the enoximone group (n = 17) received a bolus dose of 0.35 mg/kg (0.15 mg/kg before aortic cross-clamping and 0.2 mg/kg added to the cardioplegic solution). Individual pressure-area relations (pulmonary capillary wedge pressure v left ventricular end-diastolic area) were obtained by using volume loading by leg elevation before and after surgery with closed chest. The pressure-area relation on the pressure-area plot was shifted to the left after surgery, indicating decreased LV diastolic distensibility in the enoximone and control groups and providing evidence of decreased LV diastolic function. Indices of LV diastolic chamber stiffness, LV operating stiffness (K(LV)) derived from the deceleration time of early ventricular filling, and the constant of chamber stiffness (beta) derived from pressure-area relations were not different after enoximone treatment. Systolic LV function was unaltered after cardiac surgery in both groups. Analysis of changes in transmitral flow patterns identified an increased atrial filling fraction in enoximone-treated patients, suggesting increased atrial systolic function. The unaltered systolic pulmonary venous flow velocity compared with the decrease in the control group after volume loading further supports preservation of left atrial reservoir function with enoximone in the absence of evidence for decreased LV stiffness. Preemptive enoximone did not change LV diastolic function based on diastolic filling patterns or LV stiffness indices (K(LV) and beta) derived from Doppler early filling deceleration time and pressure-area relations. Doppler data suggested improvement of left atrial systolic function and preservation of left atrial reservoir function with enoximone.

Effects of Quinapril on Left Atrial Structural Remodeling and Arterial Stiffness

Left atrial (LA) enlargement, left ventricular (LV) diastolic dysfunction, and increased arterial stiffness are all associated with adverse cardiovascular outcomes. The rate, magnitude, and concordance of modifiability of these risk markers have not been well characterized. Twenty-one patients (mean age 69 +/- 8 years; 52% women) with isolated diastolic dysfunction and indexed LA volumes > or =32 ml/m(2) were randomly assigned to receive either quinapril at a target dose of 60 mg/day or matching placebo for 12 months. Echocardiographic maximum LA volume and LV diastolic function and arterial stiffness by the augmentation index were measured at baseline and 6 and 12 months. Analysis was based on intention to treat. Baseline characteristics were comparable between the treatment (n = 9) and placebo (n = 12) groups. The mean reduction in LA volume of 4.2 +/- 7.8 ml/m(2) in the quinapril group was significant (p = 0.01) compared with the increase in LA volume in the placebo group (5.5 +/- 8.1 ml/m(2)). This represents a relative improvement of 9.7 ml/m(2). Change in LV filling pressure in terms of E/e' and diastolic function grade did not reach significance. A reduction in the augmentation index was associated with a decrease in indexed LA volume (odds ratio 11, p = 0.046), independent of changes in systolic blood pressure. In conclusion, LA structural remodeling appeared reversible with quinapril, which occurred in parallel with an improvement in arterial stiffness but independent of blood pressure changes.

Correlations between the Left Ventricular Diastolic Function and Aortic Stiffness in Healthy Aged Subjects

Background and Objectives:Arterial stiffness and wave reflections increase with advancing age, and the systolic and pulse pressures are elevated. These changes in aortic stiffness and pulse wave velocity with aging may change the cardiac function. The diastolic function of the left ventricle declines with aging even in normal healthy subjects too. This investigation was designed to assess the correlations between the left ventricular diastolic function and arterial stiffness with using echocardiography including doppler tissue imaging (DTI) and an applanation tonometer. Subjects and Methods:The subjects were 100 healthy volunteers who had normal left ventricular systolic function and no major cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes, obesity and smoking. The left ventricular diastolic function was assessed with the mitral inflow indexes and DTI, and the pulmonary venous return was measured by echocardiography. The central aorta blood pressure, the augmentation index (AIx) and the pulse wave velocity (PWV) were evaluated by using an applanation tonometer (SphygmoCoR system). Results:With advancing age, the left mitral E/A ratio decreased (r=-.738, p<0.05) and the DTI early/late diastolic velocity (E’/A’) ratio decreased (r=-.759, p<0.05), which showed a significant change of the left ventricular diastolic function. The Aix (r=.406, p<0.05) and PWV (r=.614, p<0.05) increased with aging. The PWV correlated significantly with the E/A ratio (r=-.593, p<0.05) and the E’/A’ ratio (r=-.559, p<0.05). Conclusion:This study showed that increases of the large conduit vessel stiffness with aging are associated with a decline of the left ventricular diastolic function in healthy subjects. (Korean Circulation J 2006;36:393-399)

Mineralocorticoid Receptor Antagonism Ameliorates Left Ventricular Diastolic Dysfunction and Myocardial Fibrosis in Mildly Symptomatic Patients With Idiopathic Dilated Cardiomyopathy

Mineralocorticoid receptor antagonism reduces mortality associated with heart failure by mechanisms that remain unclear. The effects of the mineralocorticoid receptor antagonist spironolactone on left ventricular (LV) function and chamber stiffness associated with myocardial fibrosis were investigated in mildly symptomatic patients with idiopathic dilated cardiomyopathy (DCM). Twenty-five DCM patients with a New York Heart Association functional class of I or II were examined before and after treatment with spironolactone for 12 months. LV pressures and volumes were measured simultaneously, and LV endomyocardial biopsy specimens were obtained. Serum concentrations of the carboxyl-terminal propeptide (PIP) and carboxyl-terminal telopeptide (CITP) of collagen type I were measured. The patients were divided into 2 groups on the basis of the serum PIP/CITP ratio (< or =35, group A, n=12; >35, group B, n=13), an index of myocardial collagen accumulation. LV diastolic chamber stiffness, the collagen volume fraction, and abundance of collagen type I and III mRNAs in biopsy tissue were greater and the LV early diastolic strain rate (tissue Doppler echocardiography) was smaller in group B than in group A at baseline. These differences and the difference in PIP/CITP were greatly reduced after treatment of patients in group B with spironolactone, with treatment having no effect on these parameters in group A. The collagen volume fraction was significantly correlated with PIP/CITP, LV early diastolic strain rate, and LV diastolic chamber stiffness for all patients before and after treatment with spironolactone. Spironolactone ameliorated LV diastolic dysfunction and reduced chamber stiffness in association with regression of myocardial fibrosis in mildly symptomatic patients with DCM. These effects appeared limited, however, to patients with increased myocardial collagen accumulation.

Sprint training improves postischemic, left ventricular diastolic performance

We examined the effects of sprint training on left ventricular diastolic stiffness during normoxia and after ischemia-reperfusion (I/R). Thirty-seven, male Sprague-Dawley rats, weighing 150-175 g at the initiation of the experiment, were randomly assigned to a sedentary, control group (n = 20) or to a high-intensity, sprint-trained group (n = 17). Animals were trained 5 days/wk on a motor-driven treadmill for 6 wk. High-intensity sprint training consisted of running five 1-min sprints at 75 m/min, 15% grade, interspersed with 1-min active recovery runs at a speed of 20 m/min, 15% grade. Langendorff-derived isolated heart performance was measured before and after 20 min of no-flow ischemia followed by 30 min of reperfusion. Isolated myocytes were harvested from a subset of postischemic hearts. Sprint training reduced Langendorff-derived LV chamber stiffness (P < 0.05) and induced a rightward shift in the LV pressure-volume relationship during both normoxic perfusion and after I/R. LV developed pressure after I/R was also better preserved in hearts obtained from sprint-trained animals (P < 0.05), a result that is in part related to a lower postischemic LV chamber stiffness in sprint-trained hearts. The putative impact of sprint training on postischemic LV chamber stiffness was masked by glycolytic inhibition with iodoacetate, suggesting that glycolysis was involved in the better postischemic recovery observed in sprint-trained hearts. There was a tendency for enhanced postischemic cardiomyocyte shortening in sprint-trained cardiomyocytes compared with control. The rate of myocyte relaxation, i.e., time for 50% relaxation of the Ca(2+) transient amplitude, was similar between groups. These data suggest that additional mechanisms unrelated to Ca(2+) were involved in sprint-induced protection from ischemia-reperfusion-induced LV diastolic dysfunction.

Ventricular Structure and Function in Aged Dogs With Renal Hypertension

Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF. Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (tau=53+/-6 ms) compared with OC (tau=35+/-3 ms; P<0.05) and YC (tau=33+/-6 ms; P<0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116+/-30%) compared with OC (69+/-8%; P<0.05) and YC (35+/-5%; P<0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs. Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.

Increased Calcium Influx Mediates Increased Cardiac Stiffness in Hyperthyroid Rats

Cardiac remodeling (hypertrophy and fibrosis) and an increased left ventricular diastolic stiffness characterize models of hypertension such as the SHR and DOCA-salt hypertensive rats. By contrast, hyperthyroidism induces hypertrophy and hypertension, yet collagen expression and deposition is unchanged or decreased, whereas diastolic stiffness is increased. We determined the possible role of increased calcium influx in the development of increased diastolic stiffness in hyperthyroidism by administering verapamil (15 mg/[kg x d] orally) to rats given triiodothyronine (T3) (0.5 mg/[kg x d] subcutaneously for 14 d). Administration of T3 significantly increased body temperature (control: 36.7 +/- 0.2 degrees C; T3: 39.6 +/- 0.2 degrees C), left ventricular wet weight (control: 2.09 +/- 0.02 mg/kg; T3 3.07 +/- 0.07 mg/kg), systolic blood pressure (control: 128 +/- 5 mmHg; T3: 156 +/- 4 mmHg), and left ventricular diastolic stiffness (control: 20.6 +/- 2.0; T3: 28.8 +/- 1.4). Collagen content of the left ventricle was unchanged. Contractile response to noradrenaline in thoracic aortic rings was reduced. Relaxation in response to acetylcholine (ACh) was also reduced in T3-treated rats, whereas sodium nitroprusside response was unchanged. Verapamil treatment of hyperthyroid rats completely prevented the increased diastolic stiffness and systolic blood pressure while attenuating the increased body temperature and left ventricular weight; collagen content remained unchanged. ACh response in thoracic aortic rings was restored by verapamil. Thus, in hyperthyroid rats, an increased calcium influx is a potential mediator of the increased diastolic stiffness independent of changes in collagen.

Effect of spironolactone on chamber stiffness and diastolic function associated with regression of myocardial fibrosis in dilated cardiomyopathy

We investigated whether spironolactone-induced regression of myocardial fibrosis is associated with improvement of left ventricular (LV) diastolic function in dilated cardiomyopathy (DCM). Methods and Results: Tissue Doppler echocardiography, LV catheterization and biopsies were performed in 10 DCM patients before and after 12 months of treatment with spironolactone. The biochemical index of coupling between the synthesis (PIP) and degradation (CITP) of collagen type-I revealed the presence of 2 subgroups: 5 with PIP/CITP < 40 (GroupA) and 5 with PIP/CITP > 40 (GroupB). After the treatment, collagen volume fraction (CVF), LV chamber stiffness, and diastolic strain-rate were significantly improved in GroupB accompanied with a reduction of PIP/CITP, but not in GroupA (Table). CVF correlated with PIP/CITP (r = 0.70). Conclusions: Spironolactone improves LV diastolic function and chamber stiffness accompanied with regression of fibrosis in patients with higher PIP/CITP. [Display omitted]

Imaging and Diagnostic Testing: Diastolic dysfunction after coronary artery bypass grafting: a frequent finding of clinical significance not influenced by intravenous calcium

BackgroundDiastolic dysfunction is common immediately after coronary artery bypass surgery (CABG). The duration of this phenomenon is unknown. Intravenous calcium is frequently administered during separation from cardiopulmonary bypass (CPB). We sought to determine whether intravenous calcium influences perioperative diastolic function and whether diastolic dysfunction persists into the postoperative period. Methods and resultsPatients undergoing first-time elective CABG (n = 29) were randomly assigned to receive intravenous calcium chloride (n = 13) or placebo (n = 16) during separation from CPB. Diastolic function was assessed by the pressure-area relation with transesophageal echocardiography and pulmonary capillary wedge pressure (PCWP) measured simultaneously. Left ventricular end-diastolic area (LVEDA) and Doppler indexes were measured at comparable PCWP (within 2 mm Hg) at baseline, after separation from CPB, after sternal closure, and 3 hours after surgery. After CABG, both groups had a significant decrease in LVEDA and mitral E-wave deceleration time that persisted at 3 hours. Because there were no significant differences between the calcium and control groups at any time point, the data for the entire study cohort was analyzed. The LVEDA decreased (stiffness increased) progressively from 16.9 ± 3.4 cm2 at baseline to 15.8 ± 2.9 cm2 after CPB, 14.9 ± 2.5 cm2 after sternal closure, and 14.3 ± 3.1 cm2 at 3 hours after surgery (P < .0001). The mitral E-wave deceleration time measured at the same time points was 168 ± 47 ms, 136 ± 25 ms, 137 ± 36 ms, and 111 ± 44 ms (P = .0001). ConclusionsAn increase in left ventricular diastolic chamber stiffness is nearly universal after CABG, and it persists for at least 3 hours after surgery. An intravenous bolus of calcium chloride given during separation from CPB has no measurable negative effect on diastolic function. In the setting of increased chamber stiffness, the PCWP alone does not adequately reflect the volume status and effective preload of the left ventricle.

Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats.

To assess whether the variable impact of quantitative changes in myocardial collagen on left ventricular (LV) diastolic myocardial stiffness (myocardial k) and remodelling (increased volume intercept of diastolic pressure-volume relations) in LV hypertrophy (LVH) is associated with alterations in myocardial collagen cross-linking. We evaluated myocardial collagen content (hydroxyproline concentrations [HPRO]) and the degree of myocardial collagen cross-linking (solubility to cyanogen bromide digestion) in 14-15- and 21-22-month-old spontaneously hypertensive rats (SHRs), and in aortic-banded rats with pressure overload hypertrophy (POH). In rats with POH and in SHRs irrespective of age, increases in myocardial [HPRO] were noted. However, hypertensive rats differed in the material and geometric properties of the myocardium, and in qualitative aspects of fibrosis. In 14-15-month-old SHRs myocardial k (determined from diastolic stress-strain relations) and insoluble (cross-linked) [HPRO] were increased, but no LV remodelling or increases in myocardial soluble (non-cross-linked) [HPRO] were noted. In rats with POH, LV remodelling and increases in soluble myocardial [HPRO] occurred, but no increase in k or insoluble myocardial [HPRO] were observed. In 21-22-month-old SHRs, increases in k, soluble and insoluble myocardial [HPRO], as well as LV remodelling occurred. Collagen cross-linking may determine the diverse relation that exists between increases in myocardial collagen concentrations and either myocardial stiffness or chamber remodelling in hypertension. These findings support the notion that fibrosis contributes to myocardial stiffness as well as LV dilatation in LVH, albeit an effect that is modulated by collagen quality.

Can left ventricular diastolic stiffness be measured noninvasively?

Background: A noninvasive estimation of left ventricular (LV) diastolic chamber stiffness (KLV) is still a challenge. Experimental data suggests that Klv can be obtained by using Doppler mitral flow deceleration time (DT) as the only variable: Klv = (70/[DT−20])2 mm Hg/mL. We assessed the accuracy of this noninvasive estimate of Klv by comparing it with invasive measurement of Klv in intact patients with a wide range of LV size and function under varying loading conditions. Methods: Twenty-five patients (age 54 ± 12 years) with ischemic heart disease (n = 19) or primary LV dysfunction (n = 6), with a wide range of DT (79-324 ms) and ejection fraction (8%-57%), underwent simultaneous assessment of LV pressure by micromanometer and volume by 2-dimensional (2D) echocardiogrpahy-guided Doppler mitral flow velocity (where volume = mitral flow velocity integral × annular area) calibrated to 2D echocardiography stroke volume. Invasive Klv [delta pressure (from minimum to end-diastolic)/delta volume (during the same time interval)] was obtained at baseline and in 23 patients after LV unloading by prostaglandin E1 (30-60 ng/kg/min) (n = 12), nitroglycerin (0.2 mg) (n = 9) or magnesium (1 g) (n = 2). Noninvasive Klv was estimated according to the above formula. Results: In this set of patients with normal mitral annular area (3.9 ± 1.1 cm2/m2), multivariate analysis showed that DT is inversely related to Klv (P <.001) but not to left atrial chamber stiffness, LV volume, relaxation time constant, mitral valve opening pressure, or area. The relation between noninvasively calculated and directly measured Klv was close to the line of identity under all conditions, (y = 0.93x + 0.05, r = 0.67, n = 48, P <.001), although with a wide standard error of the estimate (0.26 mm Hg/mL). Conclusion: We conclude that Klv can be calculated ± 0.5 mm Hg/mL from noninvasively measured DT in patients. (J Am Soc Echocardiogr 2002;15:935-43.)

Glibenclamide improves postischemic recovery of myocardial contractile function in trained and sedentary rats

In this study, we sought to determine whether there was any evidence for the idea that cardiac ATP-sensitive K+ (K(ATP)) channels play a role in the training-induced increase in the resistance of the heart to ischemia-reperfusion (I/R) injury. To do so, the effects of training and an K(ATP) channel blocker, glibenclamide (Glib), on the recovery of left ventricular (LV) contractile function after 45 min of ischemia and 45 min of reperfusion were examined. Female Sprague-Dawley rats were sedentary (Sed; n = 18) or were trained (Tr; n = 17) for >20 wk by treadmill running, and the hearts from these animals used in a Langendorff-perfused isovolumic LV preparation to assess contractile function. A significant increase in the amount of 72-kDa class of heat shock protein was observed in hearts isolated from Tr rats. The I/R protocol elicited significant and substantial decrements in LV developed pressure (LVDP), minimum pressure (MP), rate of pressure development, and rate of pressure decline and elevations in myocardial Ca(2+) content in both Sed and Tr hearts. In addition, I/R elicited a significant increase in LV diastolic stiffness in Sed, but not Tr, hearts. When administered in the perfusate, Glib (1 microM) elicited a normalization of all indexes of LV contractile function and reductions in myocardial Ca(2+) content in both Sed and Tr hearts. Training increased the functional sensitivity of the heart to Glib because LVDP and MP values normalized more quickly with Glib treatment in the Tr than the Sed group. The increased sensitivity of Tr hearts to Glib is a novel finding that may implicate a role for cardiac K(ATP) channels in the training-induced protection of the heart from I/R injury.

Left ventricular diastolic filling response to stationary bicycle exercise during pregnancy and the postpartum period

Objective: The purpose of this study was to determine the effects of pregnancy and of maximal exercise on left ventricular diastolic filling response. Study Design: Transmitral pulsed Doppler echocardiography was obtained in 10 healthy women during each trimester of pregnancy and at 12 weeks after delivery. Doppler studies were performed at rest and at each exercise workload. The P-R interval, the early and atrial peak flow velocities, the mitral early deceleration time, and the isovolumetric relaxation time were analyzed. Data are expressed as the mean and standard deviation of the mean. Values obtained during the last trimester of pregnancy were used as the pregnant value; values at the 12 weeks after delivery were used as the nonpregnant value. Paired t -test, analysis of variance, and mixed models were used to determine significance with a probability value of <.05. Results: Pregnancy significantly increased the early and atrial peak flow velocities. Pregnancy decreased the P-R interval, the early deceleration time, and the isovolumetric relaxation time. Exercise significantly decreased these diastolic functions; but pregnancy, in any of the 3 trimesters, did not significantly affect this response. Conclusion: Pregnancy increased left ventricular diastolic camber stiffness at rest and shifted left ventricular diastolic filling during exercise from predominantly early to atrial filling. This finding suggests that there is an increase in left ventricular chamber stiffness during maximal upright bicycle exercise in pregnancy. (Am J Obstet Gynecol 2001;185:822-7.)