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.

SUMMARY Left ventricular pressure (LVP) decay and early diastolic pressures were studied at rest and during exercise in three groups of patients. Patients in the ischemia group (n = 15) had coronary artery disease and developed new regional wall motion abnormalities documented by biplane LV cineangiography during exercise. Patients in the control group (n = 4) had a normal exercise response. Patients in the scar group (n = 5) had prior.infarction, akinetic scars and no ischemia with exercise. Isovolumic pressure data were. used to compute the time constant (T) of LVP decay (from the linear relation of LVP and negative dP/ dt) and an extrapolated baseline pressure (PB) at dP/dt = 0. During exercise in the ischemia group, minimal LV diastolic pressure (PL) increased from 9 + 3 to 21 ± 5 mm Hg (p < 0.001), end-systolic volume increased from 38 7 to 55 ± 8 ml/m2 (p < 0.001) and PB rose from -10 ± 7 to 11 ± 8 mm Hg (p< 0.001); T decreased (from 55 ± 9 to 37 ± 8 msec, p < 0.001), although inadequately, compared with the decrease in the control group (from 49 ± 15 to 22 ± 2 msec, p < 0.01). Relaxation at PL during exercise was incomplete in the ischemia group (2.2 ± 0.4 T) and complete in the control group (3.8 ± 0.7 T, p < 0.05). The time course of LVP fall was extrapolated from the isovolumic period into the passive LV filling phase. The extrapolated pressure at the time PL occurred (PE) rose from 0 ± 4 to 20 ± 7 mm Hg with ischemia (p < 0.001). Thus, the characteristics of LVP decay can account for the elevated early diastolic pressures during ischemia.In contrast, the scar group maintained a low PL during exercise (11 3 to 8 ± 3 mm Hg), even though T decreased inadequately (from 66 ± 10 to 36 ± 5 msec, p < 0.01), because PB did not shift upward. Ischemia-related pressure elevations involve both delayed relaxation and a pressure baseline shift.During exercise, LVP decay is normally adjusted to maintain low diastolic pressures; with exerciseinduced ischemia, LVP decay is abnormal and early diastolic pressures are severely elevated.DIASTOLIC PRESSURES frequently increase dramatically during -ischemia. The mechanism for the pressure increase has attracted much attention in both clinical and experimental studies.'"3 Impaired relaxation, ventricular interaction, viscous effects, and intrinsic myocardial compliance changes are only some of the proposed mechanisms. Because late as well as early diastolic pressures rise with ischemia, different mechanisms may be operative at different times. Late diastolic pressures are believed to reflect the ventricle's passive properties. Ventricular interaction would be increasingly important later in diastole. Early diastolic pressures would be expected to reflect the decay of pressure from the preceding systole. This study de-

Left ventricular systolic and diastolic function were studied before and after surgical revascularization in Hg at rest and 6 mm Hg during exercise. All patients had an upward shift in the diastolic pressurevolume relationship during preoperative exercise. After revascularization there was no upward shift in some patients and a much smaller shift in others. The postoperative increase in left ventricular enddiastolic pressure was due to increased end-diastolic volume, not altered compliance. There was an increase in mean right atrial pressure during exercise either before (6 to 1 1 mm Hg) or after surgery (4 to 10 mm Hg). These increases were quite variable, suggesting no consistent role of pericardial restraint during exercise. Early diastolic peak filling rate during exercise was greater after surgery ( 1260 vs 950 ml/sec, p < .001). In fact, during postoperative exercise early diastolic filling rates were greater than normal, reflecting the persistence of abnormally high atrial pressures for filling. As at preoperative study, late diastolic filling during exercise was restricted after revascularization when compared with that in a control group. Postoperatively patients undergoing bypass procedures with a good clinical result showed significantly improved left ventricular diastolic and systolic function. Persistent elevation of end-diastolic and atrial pressures and other abnormalities of diastolic function may reflect chronic structural changes and need to be taken into account when evaluating patients after bypass surgery.

SUMMARY Forty-nine patients in whom percutaneous transluminal coronary angioplasty (PTCA) was attempted were evaluated by thallium-201 myocardial scintigraphy after exercise and at rest before the intervention. After successful PTCA of a single stenosis in a native vessel (30 of 44 patients) and of a stenosis in an aortocoronary bypass graft (three of five patients), scintigraphy was repeated within 3 weeks in 30 patients. Long-term follow-up studies by scintigraphy at 5-6-month intervals up to more than 2 years (mean follow-up 18 months) were performed in 16 patients.Before PTCA, clear-cut regions of decreased thallium-201 activity were observed in 43 of 49 patients. Thallium-201 activity within this zone was reduced to 74 ± 1% (SEM) of maximal myocardial thallium-201 activity after exercise, but returned to normal (> 80%) at rest (88 ± 1%, p < 0.001). After PTCA, no distinct defects were recognizable in the region of previously decreased thallium-201 activity, and the respective values were 89 ± 1% after exercise at identical work loads (p < 0.001 compared with the corresponding values before PTCA) and 94 + 1% (p < 0.01) at rest. These results paralleled the angiographic findings, which showed an increase in luminal diameter in the stenotic segment of the treated vessel from an average of 15 ± 2% of the pre-and poststenotic vessel diameter before PTCA to 67 ± 3% (p < 0.001) after PTCA. During long-term follow-up, thallium-201 activity remained normal after exercise in the entire heart in 13 of 16 patients. In three patients, a new defect in the same location as before treatment reappeared 4½/2, 6 and 29½/2 months after PTCA because the stenosis recurred, as documented by angiography.We conclude that thallium-201 exercise scintigraphy permits the best documentation of the ongoing changes in myocardial perfusion after PTCA.THE FEASIBILITY of instrumental exploration of the coronary arterial tree through a transaortic approach and its implications for removal of atheromatous tissue by retrograde curettage was first studied in dogs and human cadavers by May' and Absolon et al.2 Eight years later, Dotter and Judkins3 described a new nonoperative technique to dilate arteriosclerotic obstructions of the femoral arteries by means of tapered catheters of different outer diameters. In 1976, Gruentzig4' 5 reported encouraging results in the treatment of femoropopliteal and iliac artery obstructions using a double-lumen catheter with a nonelastic balloon at its tip. Once placed in the stenotic lesion, high pressure inflation of the balloon compressed the obstructing atheromatous material against the vascular wall, thereby enlarging the lumen. With miniaturization of the dilating catheter and with the development of appropriate guiding catheters adapted from the Judkins-type catheters for selective coronary arteriography, the system became suitable for the treatment of coronary artery stenoses.8