Heinz O. Hirzel

Thallium-201 scintigraphy in complete left bundle branch block.

Nineteen symptomatic patients with left bundle branch block (LBBB) were examined by thallium-201 (TI-201) exercise scintigraphy and selective coronary arteriography. All elicited significant anteroseptal perfusion defects in the exercise scintigrams, but in only 4 was coronary artery disease (CAD) involving the left anterior descending coronary artery present. To further elucidate the effect of LBBB on septal TI-201 uptake in the absence of CAD, TI-201 scintigrams combined with regional myocardial blood flow measurements using radioactive microspheres were carried out in 7 dogs during right atrial and right ventricular pacing (LBBB in the ECG) at similar heart rates. During right atrial pacing, TI-201 uptake was homogeneous in the entire left ventricle, as were tissue flows. During right ventricular pacing, TI-201 activity was reduced to 69% of maximal TI-201 activity within the septum, whereas it averaged 90% in the lateral wall (p less than 0.05) in 6 dogs. Correspondingly, regional myocardial blood flow was lower within the septum as compared with that in the lateral wall, averaging 89 and 120 ml/min/100 g, respectively (p less than 0.005). In 1 dog, normal TI-201 distribution and tissue flows were found in both studies. Thus, symptomatic patients with LBBB may elicit abnormal TI-201 exercise scintigrams, suggesting anteroseptal ischemia despite normal coronary arteries. The electrical induction of LBBB in dogs results, in most instances, in a comparable reduction in septal TI-201 uptake associated with diminished septal blood flow. Therefore, exercise-induced septal perfusion defects in the presence of LBBB do not necessarily indicate CAD even in symptomatic patients, but may reflect functional ischemia due to asynchronous septal contraction.

Relationship between myosin isoenzyme composition, hemodynamics, and myocardial structure in various forms of human cardiac hypertrophy.

Hemodynamic and angiographic parameters, muscle fiber diameter, nonmuscle tissue content, and myosin light chain isoform composition were determined in the left ventricle of nine patients with primary (four with hypertrophic, five with dilated cardiomyopathy) and 27 patients with secondary hypertrophy (11 with aortic regurgitation, 16 with aortic stenosis), nine patients with coronary heart disease, and seven controls. In various forms of hypertrophy, a new atrial-like light chain 1 occurred in two-dimensional electrophoresis of total tissue homogenates amounting up to 29% of total light chain 1. Total light chain 1 content remained constant in all groups when related to tropomyosin. The mean content of this atrial light chain 1 was highest in dilated cardiomyopathy (12.1%), less in cases with pressure (6.4%) and volume overload (2.9%), but as low in hypertrophic cardiomyopathy (0.3%) as in controls (0.4%). In cases with coronary heart disease without prior infarction, it was lower (0.6%) than with infarction (1.9%). Its occurrence was not affected by digoxin administration. In ventricular myocardium, an atrial-like light chain 2 was never observed. Peptide patterns after limited proteolytic digestion of isolated myosin heavy chains from cases with pressure overload and hypertrophic cardiomyopathy were identical to those from controls. The content of the atrial-like light chain 1 was not correlated to either muscle fiber diameter or nonmuscle tissue content, both of which were increased in all hypertrophy groups. In individual cases, no firm correlation could be established between atrial-like light chain 1 content and various parameters of ventricular load and function. However, a significant correlation resulted when the mean values of atrial-like light chain 1 content of each disease group were related to the respective mean values of peak circumferential wall stress (r = 0.96). Thus, the shift of myosin light chain 1 isoforms in ventricle seems to characterize biochemically the hypertrophy process induced by mechanical stress.

Silent myocardial ischemia: Hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris

The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 +/- 4,828 [SD] versus 19,247 +/- 4,117 beats/min X mm Hg [NS] in the study and control groups without prior infarction, and 19,665 +/- 3,950 versus 17,701 +/- 4,600 beats/min X mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 +/- 4 to 36 +/- 11 and from 13 +/- 5 to 29 +/- 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 +/- 7 to 32 +/- 13 and from 19 +/- 7 to 36 +/- 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 +/- 7 to 50 +/- 15 and from 60 +/- 4 to 52 +/- 9% in the study and control groups without prior infarction and from 54 +/- 9 to 47 +/- 10 and 55 +/- 9 to 50 +/- 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction. Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion.

Hemodynamic performance and myosin light chain-1 expression of the hypertrophied left ventricle in aortic valve disease before and after valve replacement.

Previously, we have reported on the selective accumulation of an atrial-like myosin light chain-1 (ALC1) in different forms of human ventricular hypertrophy. The present study involves the determination of ALC1 content in a control group and in patients with aortic stenosis or insufficiency before and 56 +/- 23 months after valve replacement and compares the hemodynamic and angiographic parameters. ALC1 was quantified densitometrically after two-dimensional electrophoretic resolution of biopsy specimens from the left ventricle and was expressed in percent of total ventricular light chain-1. The mean ALC1 content was 11.2 +/- 9.2% in preoperative aortic stenosis and 4.5 +/- 1.4% in aortic insufficiency, both being significantly (p less than 0.001) higher than the control value of 0.3 +/- 0.3%. After valve replacement, mean ALC1 content was lower than before, 4.2 +/- 3.3% (p less than 0.05) in stenosis and 3.4 +/- 3.1% (p = NS) in insufficiency. Left ventricular systolic pressure yields a significant (p less than 0.01) linear correlation (r = 0.45) with the ALC1 content in all preoperative and postoperative patients. Patient group averages of ALC1 content correlate directly with left ventricular systolic and end-diastolic pressure and wall thickness (r = 0.94-0.98) and, in an exponential fashion, with peak systolic circumferential wall stress (r = 0.98) but not with muscle mass or any other parameter. The ventricular ALC1 binds to myosin in proportion to its occurrence in the myocardium. The content of the endogenous ventricular light chain-1 did not change under pathological hemodynamics. The response in expression of the ALC1 to pressure and volume overload suggests an adaptational process.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular isovolumic pressure decay and diastolic mechanics after postextrasystolic potentiation and during exercise

Left ventricular contraction, relaxation, and diastolic mechanics were examined in subjects after postextrasystolic potentiation and compared with results during supine bicycle exercise. Twelve patients had ventricular extrasystoles induced during biplane left ventricular cineangiography (PES Group). Six patients with no or minimal cardiovascular disease underwent exercise (Exercise Group). From simultaneous high-fidelity pressure curves the time constant of relaxation (T), a theoretical baseline for isovolumic pressure decay (PB), and the lowest diastolic pressure (PL) were determined. Frame-by-frame volume analysis was completed in 6 patients from the PES Group and 4 in the Exercise Group to quantitate filling rates and to construct diastolic pressure-volume relations. In the PES Group, the ejection fraction increased from 65 to 74% (p In the Exercise Group, the ejection fraction increased from 65 to 75% (p Postextrasystolic potentiation, like dynamic exercise, enhances shortening and augments restoring forces by producing a smaller end-systolic chamber. Yet, postextrasystolic potentiation delays inactivation and prolongs relaxation. Diastolic mechanics (early diastolic pressure, filling, pressure-volume relation) are not subsequently altered, suggesting that enhanced restoring forces counterbalance the delayed inactivation. With exercise, diastolic filling is enhanced both by more rapid pressure decay and by increased restoring forces. Thus, diastolic mechanics can be dissociated from systolic and are determined by the nature of the inotropic stimulus.

Effects of ischemia, bypass surgery and past infarction on myocardial contraction, relaxation and compliance during exercise

Abnormalities of left ventricular function during ischemia have been described in animal models and in humans. Exercise, while a physiologic means of inducing ischemia, has a complex effect on left ventricular function by itself. In addition, patients with coronary artery disease have a diversity of chronic changes in myocardial structure and function. Therefore, with use of micromanometer left ventricular pressure measurements and ventricular volumes, calculated from biplane cineangiograms, left ventricular function at rest and during exercise was studied in 57 patients. Exercise-induced ischemia produced a decrease in ejection fraction, an increase in end-systolic volume, dramatic increases in diastolic pressures and an upward shift in the diastolic pressure-volume relation. Central to these changes was abnormal myocardial contraction and relaxation, with reduced regional shortening and impaired left ventricular pressure decay. However, nonischemic areas were capable of augmented shortening, and global pressure decay did accelerate slightly. These findings demonstrate that exercise-induced adjustments in contraction and relaxation are intertwined with ischemia-related abnormalities. Exercise studies in patients after bypass surgery and in patients with scars from distant myocardial infarction were useful in clarifying confounding factors. For example, asynchrony of contraction and relaxation, and chronic changes in passive chamber properties, also compromise systolic and diastolic function during exercise. In patients with coronary artery disease without ischemia during exercise, left ventricular end-diastolic pressure, but not early diastolic pressure, increased during exercise. The increase in pressure was appropriate for a slight increase in end-diastolic volume in a ventricle with a steep pressure-volume relation. Furthermore, end-systolic volume, while maintained during exercise, was not reduced, as occurs normally.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural variants of heavy and light chains of atrial and ventricular myosins in hypertrophied human hearts

In human cardiac hypertrophy the myosin light chain complement varies in its relative composition as well as in its tissue-specific composition in both atrium and ventricle. In support of recent results (P. Cummins [1982] Biochem. J., 205,195-204), we also found ventricular VLC-2 and to a lesser extent VLC-1 to occur in hypertrophied atrium in addition to its own light chain complement. Our new findings concern the additional occurrence of atrial ALC-1 in hypertrophied ventricle. We further observed a large predominance of light chain of type-1 over that of type-2 in both ventricle and atrium of adult hypertrophied hearts. On the other hand, no differences were observed in the peptide patterns containing a total of around 180 distinguishable peptides produced by two different proteinases from the isolated myosin heavy chains, between normal and hypertrophied ventricular or atrial tissues. However, a number of differences in the peptide patterns from normal atrium and ventricle indicates different primary structures of the myosin heavy chains in these two heart tissues.

Electrophoretic analyses of atrial and ventricular cardiac myosins from foetal and adult rabbits

1. Rabbit cardiac myosins from atrium and ventricle were found to differ in their native form in pyrophosphate gel electrophoresis as well as in their light chain pattern in one- and two-dimensional electrophoretic systems. 2. The myosin light chain pattern in sodium dodecylsulfate gel electrophoresis differs between atrial and ventricular tissues in the mammalians (rabbit, dog, human, pig, sheep and rat) but not in the chicken. 3. In foetal rabbit ventricle an additional light chain is observed which, in two-dimensional electrophoresis with adult cardiac light chains, was found to be the same as atrial light chain-1.