Increased Left Ventricular Stiffness Research Articles

Diastolic Dysfunction and Collagen Structure in Canine Pacing-Induced Heart Failure

Heart failure is characterized not only by systolic, but also by diastolic dysfunction. The present study tested whether or not diastolic dysfunction is associated with changes in tissue properties and collagen network structure. Heart failure was induced in seven chronically instrumented, conscious dogs by rapid left ventricular pacing (250 min−1). After 2–5 [mean: 4±1 (s.d.)] weeks pacing, heart failure was apparent from clinical symptoms (ascites, cachexia, edema, exercise intolerance) and hemodynamic parameters (significant increases of heart rate and left ventricular end-diastolic pressure and decreases of left ventricular maximal pressure, dP/dtmaxand systolic wall thickening). The left ventricle was dilated, as indicated by a decrease of end-diastolic wall thickness (6.3±2.0v7.2±2.1 mmP<0.05; sonomicrometry). The left ventricular end-diastolic pressure—strain relation (strain: relative change of end-diastolic wall thickness) was obtained during alterations of loading conditions by inferior caval vein and descending thoracic aortic occlusion. The slope of this relation increased from 85±20 to 428±188 in heart failure, indicating an increase of left ventricular stiffness. Collagen was stained with picrosirius red and analyzed using polarized light microscopy. In heart failure, the collagen volume fraction remained unchanged (1.9±1.2v2.3±1.3%; N.S.), while the nonuniformity of collagen orientation, as reflected by its standard deviation, was increased (11.1±1.8v6.1±0.4 oP<0.05). The nonuniformity of collagen fiber orientation correlated with left ventricular stiffness [r=0.75].

Myocardial edema: Comparison of effects on filling volume and stiffness of the left ventricle in rats and pigs

This study compared the adverse effects of crystalloid-induced myocardial edema on left ventricular (LV) compliance in small and large hearts. Plegisol (289 mOsm/L) was perfused into the coronary arteries of pigs (n = 8) and 1:1 dilute Plegisol (145 mOsm/L) into the coronary arteries of rats (n = 6). Pressure-volume relations, heart weight, and water content were then determined. The pressure-volume relations were compared using an LV volume at a pressure of 10 mm Hg. Edema in rats was associated with significant (p < 0.05) increases in heart weight (1.1 +/- 0.0 g versus 1.4 +/- 0.1 g [average +/- standard error of the mean]) and water content (76.8% +/- 0.4% versus 81.3% +/- 0.8%), but an increase in LV stiffness (7.91 +/- 0.52 versus 9.27 +/- 1.42) and a decrease in the LV volume at 10 mm Hg (0.25 +/- 0.02 mL versus 0.14 +/- 0.05 mL) were not statistically significant. Edema in pigs was associated with statistically significant (p < 0.05) increases in LV stiffness beta (0.050 +/- 0.004 versus 0.072 +/- 0.008), heart weight (207 +/- 8 g versus 274 +/- 9 g), and water content (79.8% +/- 0.6% versus 85.3% +/- 0.6%) and a significant decrease in the LV volume at 10 mm Hg (88.4 +/- 5.8 mL versus 60.4 +/- 6.8 mL). Myocardial edema is associated with an increase in water content and LV stiffness and a decrease in the LV volume at 10 mm Hg in both species. In rats, however, the water content is smaller in the control state and a more hypotonic perfusate is needed to induce a given degree of edema.

Assessment of mitral A-wave transit time to cardiac outflow tract and isovolumic relaxation time of left ventricle in the appropriate and small-for-gestational-age human fetus

Mitral A-wave transit time (Ta; ms) from the mitral valve to the left ventricular outflow tract and left ventricular isovolumic relaxation time (IRT) were studied by pulsed Doppler ultrasound in 17 appropriate-for-gestational-age fetuses (AGA, 30–39 wk) and 12 small-for-gestational-age fetuses (SGA, 30–36 wk). Ta was measured from the peak of the A-wave to the peak of the reflected A-wave (Ar) from the left ventricular wall. IRT was determined from the interval between the aortic valve closure artefact and the onset of transmitral flow. The mean Ta in the SGA fetus (42 ± 7 [1 SD] ms) was significantly shorter ( p < 0.03) than in the AGA fetus (47 ± 11 [1 SD] ms), whereas this was not so for IRT (51 ± 8 [1 SD] ms vs. 60 ± 15 [1 SD] ms). In the SGA fetus, a positive correlation ( r = +0.82, p < 0.01) was established between Ta (ms) and gestational age. No such correlation existed for the AGA fetus. It is speculated that, in the SGA fetus, the shorter Ta may reflect an increase in left ventricular stiffness.

Serial assessment of left ventricular chamber stiffness after acute myocardial infarction

Left ventricular (LV) systolic function after acute myocardial infarction (AMI) has been the subject of detailed studies during the last decade, but diastolic phenomena during and after AMI are less well understood. Recently, it has been shown that early filling deceleration time accurately predicted LV chamber stiffness in an experimental model. To assess changes of LV stiffness after AMI, we studied 116 consecutive patients with 2-dimensional and Doppler echocardiographic examinations 1, 2, 3, 7, 21, and 42 days after AMI. Coronary angiography was performed in 101 patients. For the entire study group, deceleration time decreased nonsignificantly on day 2 and subsequently increased on days 3 (p = 0.001) and 7 (p = 0.036), returning toward initial values afterward. Deceleration time was shorter in large (peak creatine kinase level > 1,000 U/L) versus small infarcts (p = 0.0008) and in patients with anterior versus inferior AMI (p = 0.02); there was no difference between patients with good and poor (⩽45%) ejection fraction. These data indicate that increased LV stiffness can be detected 24 to 48 hours after AMI, but returns to normal within several days. Chamber stiffness is higher in large and anterior infarcts, but appears to be independent of LV systolic function.

Left ventricular filling measured by Doppler echocar diography during dynamic exercise in patients with myocardial infarction

To assess left ventricular diastolic properties in response to dynamic exercise, mitral inflow velocity integrals were measured by pulsed-wave Doppler echocardiography in ten patients with myocardial infarction and in ten normal subjects, and simultaneous left ventricular pressure was obtained with micromanometry in the patients. Early filling velocity integrals were maintained in the patients during exercise. Late filling velocity integrals were not augmented during exercise in the patients, but were increased in the normal subjects. In the patients, there was an increase in mitral valve opening pressure, left ventricular end-diastolic pressure, and the time constant of left ventricular isovolumic pressure decay. The lowest diastolic pressure and the number of time constants that had elapsed before the lowest diastolic pressure remained unchanged. These results show that in patients with myocardial infarction, early filling is maintained by an increase in driving pressure during exercise, despite incomplete relaxation. Augmentation of late filling, seen in normal subjects, is impaired in patients with myocardial infarction, probably due to an increase in left ventricular stiffness.

Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dYsfunction and dilatation. Termination of SVT appears to improve symptoms of congestive heart failure. However, the structural events that occur during development and regression of SVT-induced cardiomyopathy are unknown. Accordingly, LV function (simultaneous echocardiogram-catheterization) and collagen content and distribution were measured in pigs (23-25 kg) assigned to three groups: 1) rapid atrial pacing (240 beats/min) for 3 wk (SVT, n = 10); 2) SVT for 3 wk, followed by deactivation of the pacemaker and a 4-wk recovery period (PST, n = 9); and 3) sham-operated controls (CON, n = 10). LV fractional shortening was 30 +/- 2% in CON, fell to 13 +/- 2% with SVT (P less than 0.05), and returned to CON values with PST (31 +/- 2%). SVT resulted in significantly increased LV end-diastolic dimension compared with CON (4.9 +/- 0.3 vs. 3.5 +/- 0.2 cm, P less than 0.05) and no change in LV wt/body wt (2.7 +/- 0.2 vs. 2.6 +/- 0.2 g/kg, P = 0.85). Termination of SVT (PST) resulted in development of hypertrophy, LV mass increased to 3.50 +/- 0.3 g/kg (P less than 0.05 vs. CON). With the use of pressure-dimension-thickness relations during diastole, the regional chamber stiffness constant (Kc) was computed. Kc was unchanged by SVT compared with CON (5.3 +/- 1.4 vs. 3.7 +/- 0.5, P greater than 0.35) but increased with PST (7.4 +/- 0.6, P less than 0.05). LV hydroxyproline content significantly fell with SVT compared with CON (2.24 +/- 0.58 vs. 2.68 +/- 0.45 mg/g dry wt, P less than 0.05, respectively) and significantly increased with PST (3.68 +/- 0.85 mg/g dry wt, P less than 0.05). With the use of transmission electron microscopy, collagen fibril diameter was reduced with SVT compared with CON (1.45 +/- 0.5 vs. 1.7 +/- 0.5 microns, P less than 0.05) and increased with PST (3.3 +/- 1.4 microns, P less than 0.05). Scanning electron microscopy revealed disruption of collagen struts between adjacent SVT myocytes and a thickened collagen weave with PST. Thus chronic SVT resulted in systolic and diastolic dysfunction and reduced collagen support of adjoining myocytes. Early recovery from SVT was associated with LV hypertrophy, increased collagen, and increased LV stiffness.

Effects of nifedipine on diastolic abnormalities in low-flow and pacing-induced ischemia in isolated rat hearts.

An animal experimental model which stimulates human effort angina, especially in terms of diastolic abnormalities, was developed using isovolumically beating perfused rat hearts. Using this model, we studied the effects of nifedipine, a Ca2+ channel blocker, on diastolic properties during pacing-induced ischemia. When the preload of the left ventricle was set at a low level, low-flow ischemia (coronary perfusion pressure of 40 mmHg) plus tachycardia (480 beats/min for 4 min) did not induce an increase in left ventricular end-diastolic pressure (LVEDP). However, with a high preload, low-flow ischemia plus pacing tachycardia induced an increase in LVEDP of 8.4 +/- 5.4 mmHg (p less than 0.01) and a prolongation of the time constant of ventricular pressure decline (6.8 +/- 4.6 msec, p less than 0.05) immediately after pacing tachycardia. Pretreatment with nifedipine (3 x 10(-8) M) prevented the rise in LVEDP induced by pacing tachycardia. Thus, in isolated perfused hearts, diastolic abnormalities similar to those seen in angina pectoris were obtained by low-flow ischemia plus pacing tachycardia. The response to nifedipine suggested that an alteration of Ca2+ movement may play an important role in the increase in left ventricular stiffness under these conditions.