Biomedical subjects

M R Zile

Publications and source records attributed to M R Zile.

At least 73 records · Page 4Linked to original sources

PubMed1992

The effects of valvular regurgitation on thermodilution ejection fraction measurements.

Through the use of thermodilution principles and rapid response thermistors, it is now possible to measure right ventricular ejection fractions serially in patients. However, to our knowledge, the extent to which tricuspid regurgitation affects the accuracy of thermodilution ejection fraction measurements has not been quantified. The purpose of this study was to compare actual and thermodilution ejection fraction measurements in an in vitro model of tricuspid regurgitation over a wide range of ejection fractions. Stepwise perforation of the inlet valve resulted in regurgitant fractions ranging from 4 to 40 percent. At each increment of inlet valve regurgitation, triplicate sets of thermodilution (EFthermo) ejection fraction measurements were obtained and compared with actual ejection fractions (EFactual). The mean difference between EFactual and EFthermo significantly increased with 8 percent regurgitation and significantly increased with greater increments of inlet valve regurgitation. EFthermo consistently underestimated EFactual over the entire range of regurgitant values. Linear regression analysis revealed a significant correlation between EFactual and EFthermo for all degrees of regurgitation; however, the correlation coefficient significantly declined from control valves with 13 percent regurgitation and declined further with 33 percent regurgitation. Qualitative classification of the inlet valve regurgitation into mild, moderate, and severe regurgitation was performed using pulsed Doppler echocardiography. Mild inlet valve regurgitation resulted in a significantly increased difference between EFactual and EFthermo from control values. A significant increase in the difference between EFactual and EFthermo was observed with both moderate and severe regurgitation. In summary, thermodilution underestimated actual ejection fraction in a direct linear relationship to the degree of inlet valve regurgitation. Thus, in the presence of tricuspid regurgitation, this method may still be useful in serially measuring changes in right ventricular ejection fraction.

Cardiac Output↗

PubMed1992

Effects of chronic tachycardia-induced cardiomyopathy on the beta-adrenergic receptor system.

Chronic supraventricular (or ventricular) tachycardia causes a dilated cardiomyopathy. Effective treatment requires ablation of the tachycardia using antiarrhythmic agents, cryoablation, electroablation, or surgical interruption/excision. However, the underlying pathophysiologic mechanisms responsible for the development of supraventricular tachycardia-induced cardiomyopathy have not been fully identified. We hypothesized that chronic supraventricular tachycardia is associated with significant changes in the beta-adrenergic system that may have implications for the pathophysiology and treatment of supraventricular tachycardia-induced cardiomyopathy. Accordingly, we examined the relationship between left ventricular function, plasma norepinephrine level, beta-receptor number and affinity, and response to a beta-agonist (isoproterenol) infusion in eight control pigs and eight pigs subjected to supraventricular pacing-induced tachycardia (240 beats/min for 3 weeks). Left ventricular function was measured using simultaneous echocardiography and catheterization. Left ventricular end-diastolic dimension and pressure increased in pigs with supraventricular tachycardia (5.1 +/- 0.4 cm and 27 +/- 2 mm Hg) versus control pigs (3.8 +/- 0.3 cm and 8 +/- 2 mm Hg), p < 0.05. Left ventricular fractional shortening decreased in supraventricular tachycardia (10 +/- 1%) versus control pigs (34 +/- 1%), p < 0.05. In addition, in the pigs with supraventricular tachycardia the fractional shortening versus left ventricular end-systolic stress relationship fell below the control relationship. Plasma norepinephrine level (measured by high-performance liquid chromatography) increased in pigs with supraventricular tachycardia (3592 +/- 1606 pg/ml plasma) versus control pigs (323 +/- 74 pg/ml plasma), p < 0.05. beta-Receptor number and affinity (measured by [3H]dihydroalprenolol binding) did not change in supraventricular tachycardia (98.6 +/- 11.5 fmol/mg protein and 7.2 +/- 1.1 nmol) versus control pigs (99.1 +/- 9.4 fmol/mg protein and 6.8 +/- 0.5 nmol). The response to isoproterenol infusion (10 micrograms/kg) in supraventricular tachycardia was blunted: the absolute increase in left ventricular peak (+)dP/dt was reduced in supraventricular tachycardia (833 +/- 233 mm Hg/sec) versus control pigs (2180 +/- 139 mm Hg/sec), p < 0.05. Chronic supraventricular tachycardia caused a decreased contractile state, increased plasma norepinephrine level, and caused no change in beta-receptor number or affinity; however, the response to beta-agonist infusion was blunted. These results suggest that chronic supraventricular tachycardia is associated with uncoupling of the beta-receptor from subsequent intracellular components of the beta-adrenergic system. Therefore medical management of chronic supraventricular tachycardia-induced cardiomyopathy before and immediately after definitive ablation may require use of pharmacologic agents whose actions do not depend on an intact beta-adrenergic pathway.

Animals↗

PubMed1992

Left ventricular mechanics and myocyte function after correction of experimental chronic mitral regurgitation by combined mitral valve replacement and preservation of the native mitral valve apparatus.

BACKGROUND: Contractile function improves after correction of experimental mitral regurgitation, but ejection performance becomes depressed when mitral valve replacement involves chordal transection. A role for chordal transection in producing the depressed ejection performance was suspected but uncertain. Therefore, in this study, we tested two specific hypotheses: 1) that contractile function would improve and, in conjunction with chordal preservation, would allow for preserved ejection performance and 2) that improved left ventricular contractile function after surgery would be reflected in the function of myocytes isolated from the affected left ventricles. METHODS AND RESULTS: We examined ventricular contractile function and ejection performance and isolated myocyte function after correction of experimental mitral regurgitation (chordal rupture) with mitral valve replacement that involved chordal preservation. After 3 months of chronic mitral regurgitation, the average regurgitant fraction of seven dogs was 0.77 +/- 0.04. End-diastolic volume had increased from 79 +/- 5 to 132 +/- 10 cm3 (p < 0.05). At that time, all indexes of left ventricular contractile function were depressed. Three months after mitral valve replacement with chordal preservation, end-diastolic volume fell to 100 +/- 4 cm3 (p < 0.05). At this time, all indexes of contractile function had returned to normal. End-systolic stress and ejection fraction after mitral valve replacement were similar to their baseline levels. Viscosity-velocity curves (analogous to force-velocity curves) of myocytes isolated from the affected left ventricles were similar to those of myocytes isolated from normal left ventricles. CONCLUSIONS: We conclude that mitral valve replacement with chordal preservation allows ventricular contractile function to return to normal. Normal global ventricular function, in turn, is associated with normal function of the individual myocytes that compose the left ventricular chamber. Further, chordal preservation allowed for loading and ejection performance to return to premorbid levels.

Animals↗

PubMed1991

Dialysis-induced alterations in left ventricular filling: mechanisms and clinical significance.

Quantitative two-dimensional (2-D) and Doppler echocardiography were used to determine whether hemodialysis results in alterations in left ventricular (LV) diastolic filling that might contribute to dialysis-induced hypotension, as well as to assess whether any hemodynamic variables or indices of diastolic filling might be used to identify which patients were at the greatest risk of becoming hemodynamically unstable during dialysis. Sixteen male patients undergoing routine maintenance hemodialysis for end-stage renal disease were prospectively studied before and after hemodialysis. Following hemodialysis there was a significant prolongation (P less than 0.05) in LV isovolumetric relaxation time (IVRT), as well as a significant reduction in the rate and extent of early rapid ventricular filling (P less than 0.005); in contrast, late atrial-assisted filling did not change significantly. A multiple stepwise linear regression analysis of predialysis hemodynamic parameters and noninvasive indices of LV filling showed that there was a significant independent inverse relationship between the frequency of dialysis-related hypotensive episodes and the duration of early LV filling (r = -0.81; P less than 0.001). These results suggest that hemodialysis results in discrete alterations in early LV filling, with no significant compensatory increase in late atrial-assisted ventricular filling. Further, patients with the shortest early LV filling times appeared to have the greatest predilection for becoming hemodynamically unstable during dialysis.

Aged↗

PubMed1991

Left ventricular function after surgical correction of chronic mitral regurgitation.

It is generally believed that mitral regurgitation (MR) creates a systolic 'unloading' effect by providing a low-resistance ejection into the left atrium; this is thought to increase the left ventricular ejection fraction (EF), and thus to mask a reduced contractile state. Similarly, mitral valve replacement (MVR), by removing the low-resistance regurgitant leak, has been thought to increase left ventricular afterload (systolic wall stress) and thereby cause the decrease in EF that is often seen postoperatively. These concepts have never been confirmed in patients with chronic MR. Accordingly, we evaluated systolic wall stress before and after MVR and assessed stress-shortening relations in two groups of patients with chronic MR (those with compensated and those with decompensated MR). Calculated values for circumferential and meridional wall stress were found to be normal or high in patients with chronic MR. This indicates that chronic MR is not associated with an unloading effect. In decompensated MR, systolic wall stress tends to increase after MVR; this can contribute to a postoperative decline in myocardial fibre shortening and a lower EF. By contrast, patients with compensated MR exhibit a decline in systolic wall stress after MVR; despite this postoperative decline in afterload, fibre shortening falls. This indicates that the fall in fibre shortening after MVR is not the result of increased systolic loading. In such patients, the valve replacement (with loss of integrity of papillary muscles and chordae, and a tethering of posterobasal wall motion by the prosthesis) is most likely responsible for the postoperative decline in fibre shortening and EF.

Chronic Disease↗

PubMed1991

Tachycardia-induced cardiomyopathy: effects on blood flow and capillary structure.

Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy. A potential factor contributing to the development of SVT-induced cardiomyopathy is abnormal myocardial blood flow (MBF). The purpose of this study was to relate changes in left ventricular (LV) function, MBF, and capillary structure with the development of SVT-induced cardiomyopathy. LV function and MBF were measured in two groups of conscious pigs: sham control (CON; n = 8) and after 3 wk of atrial pacing (SVT; 240 beats/min; n = 8) using echocardiography-catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) during rapid atrial pacing (240 beats/min), and 3) during adenosine infusion (1.5 microM.kg-1.min-1) without pacing. LV capillary density, diameter, wall thickness, and capillary-myocyte distance were measured in four additional pigs from each group. LV fractional shortening was lower, and left atrial pressure was significantly higher in the SVT group compared with CON at rest, during pacing, and with adenosine (P less than 0.05). In the CON group, average LV-MBF at rest was 2.0 +/- 0.2 ml.min-1.g-1, increased with pacing to 3.0 +/- 0.2 ml.min-1.g-1 (P less than 0.05), and increased further with adenosine to 4.1 +/- 0.3 ml.min-1.g-1 (P less than 0.05). In all states, SVT LV-MBF was significantly reduced vs. CON (P less than 0.05); SVT LV-MBF was 0.8 +/- 0.2 ml.min-1.g-1 at rest, increased to 1.3 +/- 0.3 ml.min-1.g-1 with rapid pacing (P less than 0.05), and remained unchanged during adenosine (1.3 +/- 0.4 ml.min-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1991

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.

Animals↗

PubMed1991

Load-dependent left ventricular relaxation in conscious dogs.

Load-dependent relaxation was studied in eight conscious dogs by inflating an intra-aortic balloon during late systole. Initially, the balloon was inflated at the aortic dicrotic notch and deflated before the next systole; subsequently, the inflation time was moved progressively earlier in 30-ms steps. This intervention produced an abrupt increment in left ventricular (LV) systolic pressure. The contraction duration was assessed by measuring the time required for LV pressure to fall by 50% of its maximum value (P50). The rate of LV pressure decline was assessed by measuring its peak negative first time derivative (-dP/dt) and the time constant of relaxation (tau). When the balloon was inflated during late systole (50 +/- 5 ms before aortic dicrotic notch), the time to peak -dP/dt fell, P50 fell, peak -dP/dt increased, and tau was unchanged. Thus the initial rate of LV pressure decline was accelerated, and the duration of the contraction was abbreviated. These data indicated that myocardial relaxation in the intact conscious dog is load dependent. Late systolic balloon inflations were performed after treatment with propranolol, verapamil, or caffeine. During propranolol and verapamil, the rate of LV relaxation (peak -dP/dt and tau) was slowed; however, the effects of balloon inflation on LV pressure transients were qualitatively similar to that seen in the baseline state. By contrast, caffeine prevented the abbreviation in the contraction duration caused by late-systolic balloon inflation. Thus LV relaxation remained load dependent when myocardial relaxation was slowed by propranolol or verapamil; load-dependent relaxation was attenuated by caffeine, presumably due to its influence on the sarcoplasmic reticulum.

Animals↗

PubMed1991

Effects of left ventricular volume overload produced by mitral regurgitation on diastolic function.

We hypothesized that the left ventricle's ability to compensate for the volume overload produced by mitral regurgitation (MR) depends, at least in part, on associated changes in left ventricular (LV) diastolic function. Indexes of the rate of LV pressure decline, the rate and extent of early diastolic filling, and LV diastolic stiffness were measured with simultaneous echocardiography and catheterization in the baseline state (baseline), immediately after creation of MR (acute MR), and 3 mo after creation of MR (chronic MR). Data are means +/- SD. MR caused LV dilation; end-diastolic dimension increased from 4.3 +/- 0.4 in baseline to 4.7 +/- 0.5 in acute MR and 5.8 +/- 0.1 cm in chronic MR (P less than 0.05 vs. baseline for both). Chronic MR caused eccentric LV hypertrophy; LV-to-body weight ratio increased from 3.6 +/- 0.3 in baseline to 4.5 +/- 0.2 g/kg in chronic MR (P less than 0.05 vs. baseline). Acute MR increased LV end-diastolic pressure from 8 +/- 4 in baseline to 15 +/- 3 mmHg (P less than 0.05 vs. baseline); chronic MR did not further increase LV end-diastolic pressure (14 +/- 4 mmHg). MR increased the transmitral pressure gradient from 5 +/- 1 in baseline to 14 +/- 3 in acute MR and 20 +/- 6 mmHg in chronic MR (P less than 0.05 vs. baseline for both). MR increased LV early diastolic filling rate; peak rate of increase in minor axis dimension increased from 11 +/- 2 baseline to 18 +/- 2 in acute MR and 19 +/- 2 cm/s in chronic MR (P less than 0.05 vs. baseline for both). Acute MR did not change LV stiffness constants. Chronic MR decreased LV stiffness; the modulus of chamber stiffness decreased from 7.1 +/- 2.8 in baseline to 2.9 +/- 1.6 in chronic MR (P less than 0.05 vs. baseline). Thus MR caused compensatory changes in LV diastolic function. These changes resulted from an increased transmitral pressure gradient and increased LV distensibility.

Animals↗

PubMed1991

Changes in left ventricular volume, mass, and function during the development and regression of supraventricular tachycardia-induced cardiomyopathy. Disparity between recovery of systolic versus diastolic function.

Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man. Terminating this tachycardia appears to result in symptomatic improvement; however, its effects on left ventricular (LV) volume, mass, and function have not been fully examined. Accordingly, hemodynamic studies using simultaneous echocardiography and catheterization were performed in three groups of pigs: 1) those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n = 8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham-operated controls (CTR, n = 10). Systolic pump function was assessed using fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate of pressure development [peak (+)dP/dt]. Diastolic function was assessed using the time constant of isovolumic pressure decline (tau), peak early diastolic filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the myocardial stiffness constant (Km). Supraventricular tachycardia caused LV dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to 4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to-body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in SVT, p less than 0.05). There were no significant changes in Kc or Km. After terminating the supraventricular tachycardia, LV volume fell but remained greater than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR) and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p less than 0.05 versus CTR). Systolic function returned to normal (FS was 31 +/- 5% in PSVT) but diastolic function remained abnormal. In PSVT, tau remained prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/- 1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5 in CTR to 13.9 +/- 9.7 (p less than 0.05). Thus, the improvement in systolic function that occurs after the termination of supraventricular tachycardia is associated with the development of LV hypertrophy and persistent diastolic dysfunction.

Animals↗

PubMed1991

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↗

PubMed1991

Myocardial oxygen consumption and the left ventricular pressure-volume area in normal and hypertrophic canine hearts.

BACKGROUND: To assess and compare the energy demands of normal and hypertrophic hearts, we defined the relation between myocardial oxygen consumption (MVO2, an index of the energy consumed by contraction) and the left ventricular pressure-volume area (PVA, an index of the total mechanical energy generated by contraction) in eight normal and eight hypertrophic (aortic band model) dog hearts; MVO2 was also measured in the nonworking (empty beating) and basal (potassium arrest) states. METHODS AND RESULTS: The hearts were studied in an isolated, blood-perfused heart apparatus. The slope of the MVO2-PVA relation (the inverse of which reflects myofibrillar efficiency) was similar in normal and hypertrophic hearts (3.89 +/- 1.91 and 4.19 +/- 1.25 ml O2/mm Hg.ml.10(5), p = NS). The MVO2 in empty beating (0.038 +/- 0.006 and 0.041 +/- 0.015 ml/beat/100 g, p = NS) and potassium-arrested (1.95 +/- 0.06 and 1.98 +/- 0.20 ml/min/100 g, p = NS) hearts was likewise similar in the two groups. CONCLUSIONS: Basal and nonworking energy demands and working efficiencies of hypertrophic hearts are equivalent to those of normal hearts.

Animals↗

PubMed1991

Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Termination of SVT appears to reduce LV size and improve function. However, changes in myocyte structure and morphology that accompany the development and regression of SVT-induced cardiomyopathy have not been studied. Accordingly, we measured LV function using echocardiography and catheterization in three groups of six pigs each: 3 weeks of atrial pacing (SVT; 240 beats/min), 4-week recovery from SVT (PST), and sham-operated controls. At each of these three end points, isolated myocyte dimensions and nuclear number were measured using fluorescence, and the volume percent of myocytes and myofibrils was computed from tissue sections using stereological techniques. SVT resulted in reduced LV fractional shortening (15 +/- 3% versus 31 +/- 2%, p less than 0.05), increased end-diastolic dimension (5.6 +/- 0.8 versus 3.8 +/- 0.2 cm, p less than 0.05), and no change in mass (2.6 +/- 0.1 versus 2.6 +/- 0.2 g/kg, p = NS) compared with controls. Myocyte length significantly increased with SVT (171 +/- 9 versus 109 +/- 11 microns, p less than 0.05), without significant changes in cell width (28 +/- 2 versus 26 +/- 2 microns). Nuclear number did not change with SVT; however, nuclear area/myocyte area significantly increased compared with controls (9.5 +/- 0.8 versus 8.7 +/- 0.8 x 10(-2), p less than 0.05). The volume percent of myocytes within the ventricular wall and the volume percent of myofibrils within myocytes decreased with SVT compared with controls (72 +/- 3% versus 80 +/- 3% and 45 +/- 5% versus 63 +/- 4%, respectively, p less than 0.05), with no change in total myocyte volume (54.2 +/- 2.7 versus 54.3 +/- 1.8 microns3 x 10(12)). In the PST group, LV fractional shortening returned to control values; however, there was persistent dilatation (end-diastolic dimension: 4.2 +/- 0.1 cm, p less than 0.05), and LV hypertrophy developed (3.3 +/- 0.3 g/kg, p less than 0.05). Increased myocyte length (158 +/- 5 microns, p less than 0.05) and width (33 +/- 2 microns, p less than 0.05) were observed in the PST group. The volume percent of myocytes and myofibrils returned to control values, with total myocyte volume significantly increased in the PST group compared with the control and SVT groups (74.5 +/- 2.6 microns3 x 10(12), p less than 0.05). In addition, the number of nuclei per myocyte in the PST group significantly increased from control values (5.1 +/- 0.1 versus 4.0 +/- 0.1, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload.

Animals↗

PubMed1991

Anesthetic and postoperative protocols for a canine model of reversible left ventricular volume overload.

The purpose of this study was to develop anesthetic and postoperative methods that could be used in a canine model of reversible left ventricular volume overload (LVVO). LVVO was created by inducing mitral regurgitation (MR) in adult conditioned dogs. Using fluoroscopy, MR was induced by passing urologic grasping forceps into the left ventricle through a carotid artery and rupturing one or more chordae tendinea. Cardiac catheterization was performed after significant cardiac dysfunction developed (3 months after creation of MR) in order to collect data to confirm reduced contractile function. The MR was repaired by replacing the damaged valve with a bovine pericardial xenograft. Dogs were followed with sequential cardiac catheterizations to determine if the valvular replacement reversed the cardiac dysfunction. To develop this model, unique anesthetic and post-operative care protocols had to be instituted. In order not to exacerbate the existing cardiac dysfunction, a high dose narcotic anesthetic regimen using a sufentanil infusion at 9-13 microgram/kg h-1 was developed in association with cardiopulmonary bypass and hypothermia for the mitral valve replacement surgery. Intensive postoperative care protocols that involved major personnel and pharmaceutic interventions were necessary. Using our methods 11/17 dogs survived the procedure and were included in the protocol for study of mechanisms involved in reversal of cardiac dysfunction.

Anesthesia↗

PubMed1991

Chronic aortic and mitral regurgitation. Choosing the optimal time for surgical correction.

Valvular surgery for chronic aortic and mitral regurgitation is indicated when symptoms of congestive heart failure have advanced to New York Heart Association class III or when definite and reproducible evidence of left ventricular systolic dysfunction has developed, even in the absence of severe or limiting symptoms. The presence of left ventricular systolic dysfunction can be detected using both invasive and noninvasive measurements of left ventricular end systolic volume (or dimension), end systolic wall stress, and ejection fraction (or fractional shortening). Post-operative results can be optimized when corrective surgery is performed before or soon after the development of left ventricular systolic dysfunction or the development of advanced symptoms.

Aortic Valve Insufficiency↗

PubMed1990

Preload does not affect relaxation rate in normal, hypoxic, or hypertrophic myocardium.

To determine whether isolated changes in preload (end-diastolic force) can influence myocardial relaxation rate in normal or abnormal (hypoxic or hypertrophic) hearts, isolated LV papillary muscles from normal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were studied using physiologically sequenced contractions. While total (systolic) load and late (lengthening) load were held constant, maximum isometric force decline (peak -dT/dt) and maximum isotonic lengthening rate (peak +dL/dt) were measured at seven levels of preload that varied from 115 to 55% of the resting tension at maximum length-tension curves (Lmax). Muscles from normal rats were studied in the oxygenated state (95% O2-5% CO2) and in the hypoxic state (95% N2-5% CO2). Preload did not effect peak -dT/dt or peak +dL/dt in either oxygenated or hypoxic muscles. During hypoxia, peak -dT/dt and peak +dL/dt were 9.5 +/- 1.0 g.mm-2.s-1 and 0.3 +/- 0.1 muscle length/s, respectively, at a preload of 115% compared with 9.0 +/- 1.2 g.mm-2.s-1 and 0.2 +/- 0.1 at a preload of 55%. In separate experiments, the effect of preload on relaxation rate was studied in WKY and SHR rats. In neither group did preload have an independent effect on relaxation rate. In the SHRs, peak -dT/dt and peak +dL/dt were 24.3 +/- 5.3 g.mm-2.s-1 and 0.7 +/- 0.1 muscle length/s, respectively, at a preload of 115% compared with 24.7 +/- 6.6 and 0.8 +/- 0.1 at a preload of 55%. Thus, in hypoxic and hypertrophic myocardium, as in normal muscle, an acute isolated change in preload did not influence the rate of force decline or muscle lengthening.

Animals↗

PubMed1990

Tolerance of the hypertrophic heart to ischemia. Studies in compensated and failing dog hearts with pressure overload hypertrophy.

Tolerance of the canine heart to prolonged ischemic arrest was studied in 10 hearts from normal control dogs and 15 hearts from dogs with left ventricular hypertrophy (LVH); experiments were performed 1 year after banding the aorta in 8-week-old puppies. At 1 year, hemodynamic studies revealed decreased left ventricular (LV) fiber shortening and elevated end-diastolic pressure (EDP) in five dogs (group with LVH failure); 10 dogs exhibited normal shortening and normal EDP (group with LVH compensation). The left ventricle-to-body weight ratio (g/kg) was 4.4 +/- 0.8 in the control group of dogs, 7.7 +/- 1.0 in the group with LVH compensation, and 10 +/- 2.5 in the group with LVH failure. The tolerance to 60 minutes of global ischemia (37 degrees C) followed by 90 minutes of reperfusion was studied in an isolated blood-perfused heart apparatus (isovolumic left ventricle, coronary perfusion pressure of 100 mm Hg). In the baseline (preischemic) state, coronary blood flow, myocardial oxygen consumption, lactate extraction, and myocardial high-energy phosphate content were essentially equal in the three groups; with LV volume adjusted to produce a systolic pressure of 100 mm Hg, there were no significant differences in LVEDP among the three groups. During ischemia, the diastolic (asystolic) pressure increased from 11 +/- 3 to 28 +/- 16 mm Hg (p less than 0.05) in the group with LVH failure; however, it did not increase in the control or the LVH compensation groups. Myocardial ATP levels declined equally in all three groups. During early reperfusion, lactate washout was lowest in the group with LVH failure. By 90 minutes of reperfusion, there were no significant differences in coronary blood flow, myocardial oxygen consumption, lactate extraction, or high-energy phosphate levels. High diastolic pressure persisted at 90 minutes of reperfusion in the LVH failure group (EDP was 34 +/- 19 mm Hg); however, there was no significant change in EDP during reperfusion in the control or with LVH compensation groups. After 90 minutes of reperfusion, developed pressures in the control (54 +/- 9 mm Hg), the LVH compensation (49 +/- 18 mm Hg), and the LVH failure (67 +/- 17 mm Hg) groups were not significantly different. These data indicate that hearts with compensated LVH do not exhibit an impaired tolerance to ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗