Hypertrophic cardiomyopathies.
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Cardiomyopathies↗
Biomedical subjects
M M LeWinter
Publications and source records attributed to M M LeWinter.
Effects of oral equiblocking doses of a cardioselective and noncardioselective beta-adrenergic blocking agent on left ventricular function in the normal conscious dog.
The effects of propranolol, a noncardioselective beta-adrenergic blocking agent, and practolol, a cardioselective agent, on left ventricular function were compared in an awake dog model at an equiblocking dose range. Both agents produced modest depression of inotropic state at rest, and during volume and phenylephrine loading. No significant differences between the two agents were detected.
Animals↗
Comparison of left ventricular free wall and septal diastolic compliance in the dog.
Septal to free wall dimensions are frequently employed for the analysis of diastolic compliance. However, the diastolic properties of these anatomically distinct regions of left ventricle are not well characterized. Regional compliance was studied in eight open-chest anesthetized dogs. Pairs of 2-mm-diameter piezoelectric crystals were implanted in the left ventricular free wall or septum 1.38 +/- 0.06 cm apart at a midwall location 58% +/- 1.9 of the left ventricular endocardial-epicardial or left ventricular endocardial-right ventricular endocardial distance. Left ventricular end-diastolic pressure was increased from an average of 8.1-21.0 mmHg, with a resulting average maximum end-diastolic strain of 11% (end-diastolic (ED) segment length/control ED length). Regional stiffness was assessed at all sites based on the relationship between left ventricular end-diastolic pressure and regional strain. Neither strain nor calculated stiffness coefficients differed significantly among the three sites. Septal transmural pressure (left ventricular end-diastolic pressure--right ventricular end-diastolic pressure) was nearly constant as left ventricular end-diastolic pressure increased during volume infusion and thus did not account for the observed septal strain.
Animals↗
Alteration in heart rate response to hemorrhage in conscious dogs with volume overload.
The heart rate response to hemorrhage was studied in conscious dogs before and up to 2 mo after the establishment of volume overload due to systemic arteriovenous (a-v) fistulas. Before a-v fistula, heart rate increased markedly during hemorrhage. When hemorrhage was preceded by dextran infusion, bleeding resulted in a gradual reduction in heart rate. The a-v fistula caused marked increases in resting heart rate, central venous pressure, pulse pressure, and blood volume. During hemorrhage, heart rate initially remained constant, but then declined abruptly from the resting value of 121 +/- 3.7 beats/min to a nadir of 89 +/- 6.5 beats/min (P less than 0.01). Although mean arterial pressure decreased markedly, there was no significant change in pulse pressure, and central venous pressure tended to stabilize with the heart rate decline. The abrupt heart rate decline was prevented by atropine but unaltered by propranolol. The response was observed as early as 5 days after a-v fistula. We conclude that an alteration in the heart rate response to hemorrhage appears early during volume overload. This alteration appears to be reflex in nature and to be mediated by the parasympathetic nervous system.
Animals↗
A guide to the use of propranolol in five cardiac conditions.
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Angina Pectoris↗
The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram.
The effects of propranolol, digoxin and combination therapy (/D) on the resting and exercise ECG were studied in ten normal subjects and 20 patients with coronary artery disease (CAD) given a sequence of oral placebo, propranolol, P/D, digoxin and placebo, for two week periods. Digoxin produced a significant decrease in T-wave amplitude and often resulted in ST segment depression in the resting ECG. Propranolol, digoxin, and P/D tended to decrease the QTc interval and prolong the PR interval. However, CAD patients were more sensitive to PR prolongation than normals while receiving propranolol or digoxin alone. Propranolol therapy did not significantly affect the ST segment of the exercise ECG in the normal subjects or the CAD patients without an ischemic control exercise ECG. By contrast, 50 per cent of the normal subjects developed "false-positive" ischemic ST segment responses to exercise while receiving digoxin of P/D and three of eight CAD patients without ischemic control exercise ST segments had a similar response to digoxin or P/D. In 12 CAD patients with ischemic control exercise ST segments, propranolol did not affect the amount of ST segment depression at the onset of angina or the maximum amount of ST segment depression. Digoxin or P/D both uniformly increased the maximum amount of ST segment depression which was greater with digoxin than P/D. However, the maximum heart rate on P/D was significantly reduced as compared to that on digoxin. It is concluded that (1) CAD patients are more sensitive to propranolol or digoxin-induced AV block than normals, (2) propranolol does not change the magnitude of ischemic exercise ST segment depression, (3) digoxin increases ischemic exercise ST segment depression and results in a high incidence of false-positive exercise tests, and (4) the addition of propranolol to digoxin attenuates the effects of digoxin on the exercise ST segment.
Administration, Oral↗
Pharmacologic and hemodynamic influences on the rate of isovolumic left ventricular relaxation in the normal conscious dog.
We studied the effects of acute pharmacologic and hemodynamic interventions on isovolumic left ventricular relaxation in 19 conscious dogs using micromanometer tip catheters. Isoproterenol (11 studies) augmented peak rate of rise of left ventricular pressure [(+) dP/dt] by 1,275+/-227 (SE) mm Hg/s (P < 0.001) and dP/dt at an isopressure point of 35 mm Hg during isovolumic relaxation [(-) dP/dt(35)] by 435+/-80 mm Hg/s (P < 0.001). Peak (-) dP/dt decreased by 467+/-89 mm Hg/s (P < 0.002). The time constant, T, derived from the logarithmic fall of pressure during isovolumic relaxation, shortened from 20+/-2.8 to 14.9+/-1.8 ms (P < 0.003). Calcium (11 studies) increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.0001); peak (-) dP/dt was unchanged. T shortened from 20.4+/-1.8 to 17.3+/-1.5 ms (P < 0.002). Volume (13 studies) did not affect either dP/dt or T. Phenylephrine (13 studies) augmented peak (-) dP/dt, but reduced (-) dP/dt(35) (both P < 0.01); T lengthened from 22.1+/-1.5 to 32.5+/-1.5 ms (P < 0.01). In 15 studies, rapid atrial pacing increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.01). In the first post-pacing beat, peak (-) dP/dt and (-) dP/dt(35) decreased (both P < 0.01), although peak (+) dP/dt increased further. T paralleled values of (-) dP/dt(35). In five dogs, beta adrenergic blockade had no significant effect on any variable after calcium, volume, or phenylephrine infusion or during or after atrial pacing when the pre-and post-propranolol states were compared. We conclude that positive inotropic interventions augment both left ventricular contraction and relaxation. The changes in isovolumic relaxation are independent of alterations in sympathetic tone produced by beta-adrenergic blockade. Peak (-) dP/dt may not be a valid measure of left ventricular relaxation rate during acute alterations in inotropic state or afterload.
Animals↗
Regional shortening patterns in canine right ventricle.
The right ventricular outflow tract (OT) is a functionally distinct area of the right ventricle. However, there is little information on the contrdingly, inflow tract (IT) and OT chords and right ventricular free wall segmental changes were measured with implanted ultrasound crystals. The timing and extent of shortening of IT and OT chords and free wall segments were determined both at rest and after stellate ganglion stimulation. At rest, IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening was 38% while OT shortening was 34%. In contrast, OT segments did not show systolic expansion. IT segment shortening was 13% while OT shortening was 21%. With stellate stimulation, IT-OT gradients of 15-25 mmHg developed. The lag between IT and OT shortening decreased to 30 ms and segmental shortening increased. We conclude that the OT is a physiologically distinct region which contracts later and remains contracted longer than the IT. Both septal and free wall movements contribute to these changes.
Animals↗
Effects of oral propranolol in normal subjects.
The effects of oral propranolol were evaluated in 10 normal volunteers. The resting heart rate decreased from the mean control value of 68 plus or minus 3.3 (SE) to 56 plus or minus 2.8 beats per minute (bpm) on propranolol (p smaller than 0.001, paired test). Mean systolic blood pressur also decreased from 125 plus or minus 5.0 to 114 plus or minus 4.2 mm Hg (p smaller than 0.03). Resting systolic time intervals were unaffected by propranolol. Mean maximal treadmill exercise tolerance time was not significantly altered by propranolol although the mean heart rate systolic blood pressure product a maximal exertion was markedly decreased (1.91 plus or minus 0.17 vs 2.62 plus or minus 0.17 times 10-4, p smaller than 0.004) . The nonsignificant effect of oral propranolol on resting systolic time intervals and maximum exercise tolerance despite significant changes in heart rate and blood pressure at rest and duringexercise stand in contrast to the reported effects of intravenous propranolol. Explantations for this difference between the effects of oral and intravenous propranolol in normal subjects are examined.
Administration, Oral↗
Regional differences in myocardial performance in the left ventricle of the dog.
To determine whether significant regional differences in shortening exist in the canine left ventricle, the shortening characteristics of small segments of the circumferentially oriented hoop axis fibers and the more longitudinally oriented fibers near the epicardium were examined using pairs of ultrasound crystals placed at three levels of the left ventricular free wall in the open-chest dog. Mean control shortening of the hoop axis fibers near the apex of the left ventricle averaged 20% of the end-diastolic length, significantly greater than shortening at the midventricular (13%) or basal (14%) levels. During transient periods of aortic constriction, end-diastolic length increased significantly and the extent of shortening was maintained for the hoop axis fibers at the apical and midventricular levels; end-diastolic length did not change and shortening decreased at the basal level. The epicardial fibers shortened an average of 5.6% of their end-diastolic length during control conditions at all three sites and showed small, parallel changes in shortening and end-diastolic length during aortic constriction. We conclude that significantly greater hoop axis shortening occurs near the apex of the left ventricle and that at this level a uniformly contracting model is inappropriate. In addition, the response of the hoop axis fibers to increased aortic impedance is not homogeneous, with a significant reduction in shortening occurring only at the base of the left ventricle where end-diastolic length does not increase.
Animals↗
Combined propranolol and digoxin therapy in angina pectoris.
The effects of oral propranolol and digoxin and digoxin alone and in combination on angina frequency, heart size, systolic time intervals and treadmill exercise tolerance, were assessed in 20 patients with coronary heart disease. Oral propranolol alone reduced the average frequency of angina pectoris from 16 to 7 attacks per week (P less than 0.02). However, the mean duration of exercise was not significantly improved because 8 patients with abnormal left ventricular function exhibited a decrease in exercise tolerance. Combined propranolol and digoxin improved exercise tolerance in these patients, and, consequently, mean exercise duration in all patients increased significantly from the control value of 390 +/- 42 to 458 +/- 46 s (P less than 0.01). Propranolol alone also resulted in a significant increase in left heart size from 46.5 +/- 1.3 to 47.7 +/- 1.5 mm/m2 (P less than 0.001), which was reversed by the addition of digoxin. Therefore, oral propranolol combined with digoxin is advantageous in patients with angina pectoris who have abnormal ventricular function or large hearts.
Administration, Oral↗
Prolapsing mitral valve leaflet syndrome.
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Angina Pectoris↗
Phenylephrine-induced atypical chest pain in patients with prolapsing mitral valve leaflets.
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Amyl Nitrite↗
Diastolic dysfunction: pathophysiology, clinical features, and assessment with radionuclide methods.
Basic to our understanding of heart failure is the distinction between systolic and diastolic ventricular dysfunction. Diastolic dysfunction implies that the ventricle cannot accept blood at normally low pressures. The ventricular filling pattern and the relation between ventricular diastolic pressure and volume reflect a dynamic interaction between time course of relaxation, conversion of elastic forces into elastic recoil, and the passive properties of the ventricle. In the early part of diastolic filling, the pressure-volume relationship is influenced primarily by relaxation; in the latter part of diastole, passive filling properties are important. Mitral inflow patterns reflect these time-varying filling dynamics and are commonly assessed with echocardiography. Disorders of diastolic filling are observed in patients with heart failure with normal ejection fraction, myocardial ischemia, and even dilated cardiomyopathy. Patients with concentric ventricular hypertrophy, normal ejection fraction, and heart failure are the prototype of patients with diastolic dysfunction. In this article we review the physiology and pathophysiology of diastole and the main clinical disorders associated with diastolic dysfunction, and we outline in brief the application of radionuclide techniques in the assessment of diastolic dysfunction.
Cardiomyopathies↗
Opacification phase effects of angiographic contrast medium on left ventricular size and function: influence of initial ventricular volume and the pericardium.
Prior studies of the opacification-phase effects of left ventricular (LV) injection of angiographic contrast medium (CM) on LV size and function have yielded discrepant results. A sensitive ultrasonic technique was used to measure LV dimension (Di) in 10 open-chest dogs with physiologic heart rates, and injection of saline (S) was compared with injection of CM. The influence of initial LV volume (LVVi) and that of the pericardium were analyzed. Changes in contractile state (CS) were assessed from the end-systolic (ES) pressure-Di relation. With both low and high LVVi, S and CM produced indistinguishable early (beat 5) increases in end-diastolic (ED) Di and ESDi. EDDi and ESDi subsequently returned to baseline after S but remained elevated through beat 12 after CM. The latter increase was progressive only with low LVVi. Depression of CS was evident by beat 7 after CM, while pericardiectomy did not alter the response to CM. Thus, CM produces opacification-phase depression of CS and increases in LV size which are in part dependent in LVVi.
Animals↗
Mechanoenergetic alterations during the transition from cardiac hypertrophy to failure in Dahl salt-sensitive rats.
BACKGROUND: The time course and mechanisms of altered mechanoenergetics and depressed cross-bridge cycling in hypertrophied and failing myocardium are uncertain. METHODS AND RESULTS: We studied mechanoenergetics in Dahl salt-sensitive (DS) rats fed high-salt diet (HS) for 6 (HS-6) and 12 (HS-12) weeks to produce compensated hypertrophy and failure. The slope of the end-systolic pressure-volume relation (E'max) was similar in HS-6 and low-salt controls (LS-6), but reduced in HS-12 compared with controls (LS-12). Efficiency [1/slope of oxygen consumption (&f1;O2)-pressure-volume area (PVA) relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (59+/-16% versus 44+/-7%, P<0.05). Economy [1/slope of the force-time integral (FTI)-&f1;O2 relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (218+/-123 versus 74+/-39x10(3) g. s. mL O2-1. g; P<0.05). Compared with controls, myofibrillar ATPase activity was reduced by 24% in HS-6 and 44% in HS-12. V3 Isomyosin was increased in HS-6 (40+/-12% versus 9+/-8%; P<0.05) and further increased in HS-12 (76+/-10% versus 22+/-18%; P<0.05). Hypothyroid LS-12 rats had 100% V3 isomyosin, yet efficiency, economy, and ATPase values were intermediate between LS-12 and HS-12. HS-12 rats demonstrated increased troponin T3 isoform (17+/-2 versus 23+/-2%, P<0.05). There were no changes in troponin I or tropomyosin isoforms. However, the proportion of phosphorylated troponin T was reduced in HS-12 versus LS-12 hearts (P<.001). CONCLUSIONS: In DS rats, the transition to failure is associated with depressed E'max and increased efficiency and economy. These findings are linked to myofibrillar ATPase activity and suggest that mechanisms other than isomyosin switching are important determinants of ventricular energetics. A troponin T isoform switch is one potential mechanism.
Adenosine Triphosphatases↗