No abstract

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.

Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.

Left ventricular filling dynamics were examined at rest and during supine bicycle exercise in 33 patients at cardiac catheterization; 23 had coronary artery disease (ischemia group), five with prior infarction had an akinetic area at rest (scar group), and five had minimal cardiovascular disease (control). Peak filling rate and mean filling rate during the first half and second half of diastole were assessed by biplane angiography. Simultaneous micromanometer pressures were used to compute the time constant of isovolumic pressure decay (T). Peak filling rate and mean filling rate during the first half of diastole increased with exercise in all groups (from 615 to 1050 and 358 to 681 ml/sec in controls and comparably in the scar group and from 697 to 1035 and 347 to 768 ml/sec in the ischemia group). However, T was greater (reduced rate of pressure decay) with exercise in the ischemia group (38 vs 26 msec in controls; p < .05). Changes in the atrial driving pressure for filling appeared to counterbalance the difference in T. Mean filling rate during the second half of diastole increased with exercise in controls and in the scar group but only modestly in the ischemia group (from 202 to 349 ml/ sec). The reduction in late diastolic filling during exercise-induced ischemia was associated with increased filling in early diastole, with a middiastolic volume increase from 160 to 186 ml and an upward shift in the diastolic pressure-volume relation. Thus left ventricular filling is not impaired at rest in patients with coronary artery disease who have normal ejection fractions. Furthermore, the augmentation of early filling induced by exercise is not blunted but is maintained during ischemia, apparently at the expense of elevated left atrial pressure. However, late filling is restricted with ischemia by an increase in impedance.Circulation 68, No. 1, 59-67, 1983.LEFT VENTRICULAR FILLING is a dynamic process involving the interaction of active and passive properties of the atria and ventricles. The rate of left ventricular pressure decay and the atrial-ventricular pressure gradient are major influences on ventricular filling in the early stages, ' and the operative stiffness of the left ventricle becomes increasingly important as filling progresses.2 Finally, the strength and timing of atrial contraction provide the end-diastolic "kick" to ventricular filling, which is frequently of importance in disease states.3-9During exercise and ischemia, cardiovascular function alters substantially. Ventricular filling must occur in an abbreviated diastole. During exercise, the rate of pressure decay in the norrmal ventricle increases sig-

Myocardial creatine phosphokinase (CPK) activity was measured as an indicator of cell viability 24 hours after ligation of the left anterior sescending coronary artery (LAD) in normal myocardium, the entire region supplied by the LAD, and individual samples from the border and center of the infarct. Tissue supplied by the LAD and delineated by dye was carefully dissected from normal tissue along the stained border, CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in normal myocardium interdigitating with ischemic tissue at the border. Normal tissue was marked prior to occlusion with microspheres injected into the left atrium, whereas the distal portion of the LAD was perfused separately with unlabeled blood from a reservoir. With this correction, the CPK activity in the ischemic tissue from the lateral border of the infarct was essentially the same as in samples from the center, whereas that in the normal tissue immediately adjacent to the stained border was equal to values in remote normal myocardium. Thus, CPK depletion throughout the entire ischemic myocardium was nearly equal to CPK depletion in the center of the infarct. The uncorrected intermediate CPK levels in the individual samples from the border of the stained region correlated with the amount of normal tissue contaminating these samples. However, differences in CPK depletion across the heart wall resulted in the most depletion in the subendocardium and the least in the epicardium. Further more, coronary collateral blood flow measured 10 minutes after occlusion correlated well with the subsequent extent of CPK depletion.