Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation.

OBJECTIVE: The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. METHODS: Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. RESULTS: Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. CONCLUSIONS: (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.     

Functional significance of regional ischemic contraction abnormalities.

To evaluate the progression of segment function following induction of ischemia, the left anterior descending coronary artery was ligated (eight dogs) or cannulated and perfused at various pressures via a bypass-oxygenator (six dogs). Mercury-in-silastic length gauges were sutured to the anterior left ventricle, and pressure was recorded by a catheter-tipped transducer. Segment function was determined from the area of the pressure-length loop by plotting instantaneous left ventricular pressure against segment length and by evaluation of the degree of systolic shortening. Segment function decreased linearly as flow in the left anterior descending artery was decreased in a stepwise fashion by reduction in perfusion pressures from 100 to 20 mm Hg. With both left anterior descending coronary artery ligation and stepwise flow reduction, the pressure-length loop invariably showed four clearly identifiable morphologic patterns which relate conceptually to the specific left ventricular contraction patterns: dyssynchrony, hypokinesis, akinesis, and paradoxic systolic expansion. Re-oxygenation following occlusion invariably revealed return to a normal pattern in reverse order. This study demonstrates that a consistent and predictable progression of segmental contraction abnormalities occurs with ischemia.     

Effects of ischemia on myocardial function during rapid left ventricular pacing

INTRODUCTION: Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. METHODS: In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. RESULTS: Significant differences (p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1+/-1.6 vs. 10.8+/-1.6%), and QRS duration (77.3+/-4.1 vs. 85.7+/-3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences (p < 0.05) were seen for myocardial contractility dP/dt(max) (1277+/-197 vs. 1158+/-156 mm Hg/s), segmental shortening (10.3+/-1.9 vs. 8.1+/-1.7%), left ventricular end-systolic pressure (76.9+/-7.5 vs. 69.6+/-7.9 mm Hg), and QRS duration, and for myocardial contractility dP/dt(max) (1033+/-209 vs. 917+/-207 mm Hg/s) and left ventricular end-systolic pressure (69.2+/-13.5 vs. 62.2+/-15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. CONCLUSIONS: During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.     

Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion

Recent evidence suggests that oxygen free radicals generated during ischemia or reperfusion may contribute to myocardial dysfunction after brief coronary occlusion ("myocardial stunning"). Because neutrophil leukocytes represent a potential source of oxygen radicals, the concept of whether depletion of neutrophils could attenuate myocardial stunning after 10 min of ischemia was examined. In 16 anesthetized dogs, the left anterior descending coronary artery was perfused by an extracorporeal circuit, either with (n = 8) or without (n = 8) neutrophil filters in the perfusion line. The group with filters had near total absence of neutrophils in blood perfusing the left anterior descending coronary artery territory (16 +/- 8 versus 1,826 +/- 399/microliters in the control group). Systolic myocardial shortening and end-systolic pressure-segment length relations were recorded during rest conditions and during incremental intracoronary infusion of dobutamine (5 to 15 micrograms/min) before and after 10 min of coronary flow occlusion. Before coronary occlusion, systolic myocardial shortening at rest was similar in control (15.4 +/- 1.7%) and neutropenic (12.4 +/- 2.2%) groups. Dobutamine (15 micrograms/min) resulted in increased shortening in both control (18.2 +/- 1.4%, p less than 0.01) and neutropenic (15.8 +/- 1.5%, p less than 0.05) groups and in a leftward shift of the end-systolic pressure-length relation. During coronary occlusion, collateral coronary flow to the left anterior descending coronary artery territory was not significantly different in the control (0.10 +/- 0.03 ml/min per g) and neutropenic (0.18 +/- 0.06 ml/min per g) groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between left ventricular midwall function and coronary vasodilator capacity in arterial hypertension

In systemic hypertension, depressed left ventricular midwall shortening predicts an adverse outcome and is associated with increased left ventricular relative wall thickness, which has been proposed as an independent predictor of cardiovascular risk and reduced coronary reserve. This study was designed to investigate whether depressed midwall shortening is associated with more critical impairment of coronary function and with exercise-induced myocardial ischemia. Sixty untreated hypertensive patients without coronary artery stenosis and 20 normotensive volunteers underwent exercise ECG testing, standard and transesophageal echocardiography to assess the occurrence of exercise-induced myocardial ischemia, left ventricular mass, geometry, and midwall shortening, and coronary vasodilator capacity. Compared with hypertensive patients with normal midwall shortening, those with depressed function (n=15) had higher minimum coronary resistance (1.19+/-0.27 versus 1.39+/-0.20 mm Hg/cm per second, P<0.01) and prevalence of exercise-induced myocardial ischemia (36 versus 67%, P<0.05). Within the hypertensive group, midwall shortening was inversely related to minimum coronary resistance (r=-0.42, P<0.01). Compared with patients with an exercise ECG test negative for myocardial ischemia, those with a positive test result (n=26) had higher minimum coronary resistance (1.13+/-0.21 versus 1.38+/-0.27 mm Hg/cm per second, P<0.01) and lower midwall shortening (104+/-16 versus 93+/-14%, P<0.01). We conclude that hypertensive patients with depressed midwall shortening have more severe impairment of coronary function and a higher prevalence of exercise-induced myocardial ischemia as compared with hypertensive patients with normal midwall shortening. These findings suggest that a decrease in myocardial performance may be related, at least in part, to chronic intermittent myocardial ischemia caused by a critical impairment of coronary vasodilator capacity.     

Alterations in left ventricular relaxation, early diastolic filling and passive viscoelastic properties during postpacing ischemia

Alterations in left ventricular relaxation, early diastolic filling, regional myocardial dynamics and passive viscoelastic properties during postpacing ischemia were studied in 9 patients with coronary artery disease. In all patients typical anginal pain developed during pacing tachycardia, and in the postpacing beat, left ventricular end-diastolic pressure increased from 14 +/- 4 to 26 +/- 5 mm Hg (mean +/- standard deviation, p less than 0.01), relaxation time constant increased from 44 +/- 9 to 59 +/- 7 ms (p less than 0.01) and ejection fraction diminished from 63.1 +/- 9.1 to 52.8 +/- 10.8% (p less than 0.01). However, peak rate of early left ventricular filling obtained from frame-by-frame analysis of left ventriculograms did not change significantly. The time difference from segmental peak lengthening to left ventricular peak filling increased significantly in the ischemic segment (32 +/- 30 vs 77 +/- 49 ms, p less than 0.05). Chamber stiffness constant of a viscoelastic model increased significantly from 0.0177 +/- 0.01 to 0.0354 +/- 0.015 (p less than 0.01) without change in chamber viscosity constant. In the ischemic segment, peak rate of lengthening decreased by 45% with ischemia, and peak rate of lengthening normalized for the end-diastolic segment length by 36%. However, peak rate of lengthening normalized for the extent of systolic shortening did not change. The control segment showed a tendency to increase in these 3 parameters, but the changes were not statistically significant. Thus, peak rate of segmental myocardial lengthening decreased with ischemia because of a decrease in segmental shortening.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of pacing-induced ischemia on early left ventricular filling and regional myocardial dynamics and their modification by nifedipine

The effect of pacing-induced ischemia on early left ventricular filling and regional myocardial lengthening was studied in 11 patients with coronary artery disease (CAD) and six control patients with normal coronary arteriograms. All of the 11 patients with CAD developed typical anginal pain during pacing tachycardia, and in the postpacing beat, the left ventricular end-diastolic pressure (LVEDP) rose from 13 +/- 4 to 26 +/- 4 mm Hg (mean +/- SD, p less than .01), the relaxation time constant increased from 43 +/- 9 to 59 +/- 7 msec (p less than .01), and the ejection fraction diminished from 62.1 +/- 6.7 to 51.6 +/- 10.6% (p less than .01). However, the peak rate of early left ventricular filling (LVPF) obtained from frame-by-frame analysis of left ventriculograms and the LVPF normalized for the stroke volume and for the end-diastolic volume did not change significantly. In the ischemic segment, the peak rate of lengthening (PL) decreased by 45% with ischemia, and the PL normalized for the end-diastolic segment length decreased by 42%. However, the PL normalized for the extent of systolic shortening did not change. In the control segment there was a tendency for these three variables to increase, but the changes were not statistically significant. The time difference from the PL to the LVPF increased significantly in the ischemic segment (31 +/- 28 vs 75 +/- 48 msec, p less than .05). Although the LVEDP rose slightly but significantly from 9 +/- 3 to 12 +/- 5 mm Hg (p less than .05) in the control patients in the postpacing beat, the other global hemodynamic variables and the variables of regional myocardial dynamics did not change. The administration of nifedipine in six patients with CAD resulted in the disappearance or diminution of anginal pain even with the same duration and rate of pacing and was associated with restoration of global systolic function and regional myocardial shortening and lengthening in the ischemic segment. In the control segment, the three variables of segmental lengthening increased with administration of nifedipine. Thus, the segmental myocardial lengthening rate decreased with ischemia due to a decrease in segmental shortening and impairment of myocardial distensibility. The LVPF did not decrease with ischemia despite impairment in isovolumetric relaxation, accentuation of asynchrony in left ventricular filling, and a decrease in the PL in the ischemic segment because of an increase in the PL in the nonischemic segment secondary to an increase in left ventricular filling pressure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Regional asynchrony during acute myocardial ischemia quantified by ultrasound strain rate imaging

OBJECTIVES: We propose a new method to easily quantify asynchronous wall motion due to postsystolic shortening (PSS). We also studied the relationship of the spatial and temporal extent of PSS to the extent of myocardium at ischemic risk after variable duration of ischemia. BACKGROUND: Postsystolic shortening is a sensitive marker of asynchrony during ischemia. Current techniques for detection of asynchrony are either subjective, or invasive and time-consuming. Strain rate imaging (SRI) can noninvasively depict PSS as prolonged compression/expansion crossover. METHODS: Nineteen open-chest pigs were scanned from apical views, before and after left anterior descending coronary artery occlusion. Strain rates were derived offline from tissue Doppler velocity cineloops. The time from electrocardiographic R-wave to the occurrence of compression/expansion crossover (TCEC) was calculated. Prolonged TCEC during ischemia was identified using a standardized analysis and both spatial (% of left ventricle) and temporal extent were quantified. The extent of myocardium at risk was measured in seven animals from dye-stained specimens. RESULTS: Prolonged TCEC was found in all ischemic segments. There was a good correlation (r = 0.91; p < 0.001) and good agreement between the spatial distributions of prolonged TCEC and myocardium at risk. The extent of myocardium at risk was better approximated by TCEC measurement (36 +/- 7% vs. 39 +/- 8%, respectively; p = NS) than by wall motion analysis (47 +/- 17%, p < 0.05). The duration of occlusion did not prolong TCEC. CONCLUSIONS: Prolonged TCEC consistently occurs in ischemic myocardium and is apparently not affected by the duration of ischemia. Standardized analysis of TCEC in SRI closely quantifies the extent of ischemic myocardium. This new method may be a useful tool in other cardiac conditions associated with regional diastolic asynchrony.     

Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia

This study evaluated the effects of transient coronary occlusion on the diameter of a nonischemic vessel or a nonischemic coronary segment proximal to the site of occlusion. Awake mongrel dogs chronically instrumented with dimension crystals, Doppler flow probes, and distal pneumatic occluders on the circumflex coronary arteries were subjected to transient 2-minute circumflex occlusions (n = 9) under constant heart rate (120 beats/min). Left ventricular end-diastolic pressure increased by 60% (from 10 +/- 1 to 16 +/- 2 mm Hg), and dP/dt decreased by 8% (from 2,048 +/- 130 to 1,885 +/- 110 mm Hg/sec); systemic hemodynamics were unaltered. Epicardial coronary diameter proximal to the site of occlusion decreased by 4.37% (from 3.62 +/- 0.25 to 3.46 +/- 0.29 mm, p less than 0.05). Constriction began 15-20 seconds after the onset of ischemia and progressed to maximum in 1-2 minutes. Combined alpha- and beta-receptor blockade (n = 8) with phentolamine (2 mg/kg) and propranolol (1 mg/kg) or cyclooxygenase inhibition (n = 5) with indomethacin (7.5 mg/kg) did not attenuate the ischemia-induced vasoconstriction response. Transient 2-minute occlusion of the left anterior descending coronary artery (n = 6) also elicited significant epicardial vasoconstriction in the circumflex coronary artery in the first minute (from 3.88 +/- 0.31 to 3.81 +/- 0.31 mm, p less than 0.05); the constriction was attenuated subsequently by an increase (25.5%) in circumflex flow. When left anterior descending occlusion was repeated (n = 6) with circumflex flow held constant, the ischemia-induced circumflex constriction was augmented; diameter decreased 3.7% (from 3.83 +/- 0.29 to 3.69 +/- 0.29 mm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Amelioration by nitroglycerin of left ventricular ischemia induced by percutaneous transluminal coronary angioplasty: assessment by hemodynamic variables and left ventriculography

Increasingly longer balloon inflation times during coronary angioplasty can create significant left ventricular ischemia, amelioration of which was attempted in this study using nitroglycerin. Hemodynamic variables were assessed during inflation of an angioplasty balloon in the proximal left anterior descending coronary artery of 10 patients. Regional wall motion was assessed by left ventriculography during a separate balloon inflation. Nitroglycerin (200 micrograms) was then administered intravenously, and hemodynamic and ventriculographic assessments during balloon inflations were repeated. Balloon inflation resulted in a marked increase in left ventricular end-diastolic pressure (from 9.2 +/- 2.1 to 19.4 +/- 2.9 mm Hg) and time constant of left ventricular relaxation (from 44.2 +/- 6.2 to 62.3 +/- 11.3 ms) and a decrease in distal coronary artery perfusion pressure (from 54 +/- 9 to 33.1 +/- 4 mm Hg). Time to onset of angina was 29 +/- 3 seconds and time to ST segment depression of 1 mm or greater was 30 +/- 3 seconds. Regional wall motion analysis 30 seconds after onset of balloon inflation revealed marked hypokinesia and akinesia in the anteroapical segments with graduated depression of inferior wall motion, greatest at the apex. After the administration of nitroglycerin, balloon inflation resulted in a smaller increase in end-diastolic pressure (from 5.0 +/- 2.7 to 8.3 +/- 2.6 mm Hg) and time constant (from 47.9 +/- 4.7 to 54.4 +/- 9.2 ms; both p less than 0.01 versus standard balloon inflation). Distal coronary artery pressure remained similar to standard balloon inflation (32 +/- 3 mm Hg) despite lower mean arterial pressure (89 +/- 5 mm Hg, p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular pressure-length relation during exercise-induced ischemia

The pressure-length relation in normal and ischemic segments was analyzed with use of left ventriculography and simultaneous micromanometry during supine exercise in 9 normal subjects and 12 patients with effort angina. Segmental analysis was done in the right anterior oblique projection using a long axis with three perpendicular, equidistant chords. The apical segment in the 12 patients with coronary artery disease represented the ischemic region. In 5 of the 12 patients with coronary artery disease, the basal segment that showed no exercise-induced deterioration in wall motion was used as an intrapatient control (nonischemic segment). In the 12 patients with coronary artery disease, left ventricular ejection fraction decreased (from 65% to 50%, p less than 0.001), end-diastolic pressure increased (from 24 to 40 mm Hg, p less than 0.001) and the lowest diastolic filling pressure increased (from 9 to 22 mm Hg, p less than 0.001) during exercise-induced ischemia. In normal subjects, ejection fraction increased (from 64% to 70%, p less than 0.01) with unchanged end-diastolic pressure, whereas the lowest diastolic filling pressure decreased during exercise (from 9 to 3 mm Hg, p less than 0.01). Global left ventricular diastolic pressure-volume curves showed an upward and rightward shift during exercise-induced ischemia. Regional pressure-length curves of both nonischemic (n = 5) and ischemic (n = 12) segments were shifted upward in early diastole, but moved to a higher portion of the rest pressure-length curve without an upward shift during mid- to end-diastole. In contrast, the apical segment in normal subjects showed a downward shift during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of improving regional and global ventricular function by preload alterations during acute ischemia in the canine left ventricle

We examined the influence of left ventricular end-diastolic pressure (LVEDP) on the mechanical interaction between ischemic and nonischemic areas during acute myocardial ischemia. Circumferentially oriented ultrasonic segment gauges were implanted in the midwall of the anterior apex and posterior apex of the left ventricle in seven anesthetized dogs. Stroke volume was measured with a flow probe around the ascending aorta in five of these animals. We varied LVEDP with vena caval occlusion and dextran infusions to three matched levels (7, 12, and 19 mm Hg) before and 30 min after complete occlusion of the mid left anterior descending coronary artery. With acute ischemia, the anterior apex or ischemic zone demonstrated marked segmental lengthening during isovolumetric systole (end-diastole to aortic valve opening) and akinesis during the ejection phase (aortic valve opening to closure). In the posterior apex or nonischemic area, isovolumetric shortening increased and ejection phase shortening decreased during acute ischemia when compared with those under control conditions at the same LVEDP. Thus, a portion of the shortening generated by the nonischemic area was expended in stretching the ischemic zone during isovolumetric systole, thereby reducing the amount of ejection phase shortening. As LVEDP was increased, there was a parallel decrease in both the amount of isovolumetric lengthening in the ischemic zone and the isovolumetric shortening in the nonischemic area. As a result, acute ischemia produced less of a reduction in ejection phase shortening in the nonischemic area and in stroke volume at high as compared with low LVEDP. We conclude that the ischemic zone imposes a mechanical disadvantage on the nonischemic area, the magnitude of which is directly proportional to the amount of isovolumetric lengthening or bulge in the ischemic zone. An increase in LVEDP during acute ischemia improves regional and global ventricular function by both the Frank-Starling mechanism in the nonischemic (but not the ischemic) area and by reducing the mechanical disadvantage that the ischemic zone imposes on the nonischemic area.     

Comparative effects of pacing-induced and balloon coronary occlusion ischemia on left ventricular diastolic function in man

BACKGROUND. Effects of pacing-induced and coronary occlusion myocardial ischemia on left ventricular (LV) function have been compared only in anesthetized dogs. Diastolic properties of the same LV anterior wall segment were therefore compared in 12 patients with single-vessel proximal left anterior descending coronary artery stenosis at rest, immediately after 7 +/- 1.2 minutes of pacing, and at the end of a 1-minute balloon occlusion of coronary angioplasty (CO). METHODS AND RESULTS. Shifts of the diastolic LV pressure-length relation, derived from simultaneous tip-micromanometer LV pressure recordings and digital subtraction LV angiograms, were used as an index of regional diastolic LV distensibility of the anterior wall segment. Immediately after pacing, LV end-diastolic pressure rose from 13.5 +/- 3.5 to 23.8 +/- 7.0 mm Hg (p less than 0.01 versus at rest) without a significant change of the LV end-diastolic volume index (83.1 +/- 18.9 versus 88.4 +/- 16.5 ml/m2), percentage systolic shortening (%SS) of the ischemic segment fell from 40.1 +/- 10.6% to 25.2 +/- 8.6% (p less than 0.01), and the diastolic LV pressure-radial length (P-RL) plot of the ischemic segment was shifted upward by 7.1 +/- 5.0 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. At the end of CO, LV end-diastolic pressure rose to 20.8 +/- 7.8 mm Hg (p less than 0.01 versus at rest) and the LV end-diastolic volume index rose to 95.6 +/- 16.3 ml/m2 (p less than 0.05 versus at rest, p less than 0.05 versus after pacing). Ejection fraction and %SS of the ischemic segment fell respectively from 76.6 +/- 6.8% to 46.6 +/- 11.4% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing) and from 40.1 +/- 10.6% to 6.4 +/- 8.6% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing). The diastolic LV P-RL plot of the ischemic segment was shifted upward by 3.1 +/- 2.3 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. This upward shift at the end of CO was significantly smaller (p less than 0.05) than that immediately after pacing. At the end of CO, a correlation (p less than 0.03) was observed for the ischemic segment between %SS and upward shift of the diastolic LV P-RL plot. CONCLUSIONS. The upward shift of the diastolic LV P-RL plot, which was used as an index of decreased regional diastolic LV distensibility, was larger immediately after pacing than at the end of CO. Persistent systolic shortening of ischemic myocardium seems to be a prerequisite for a decrease in diastolic distensibility of the ischemic segment because of the higher %SS of the ischemic segment immediately after pacing, and because of the correlation at the end of CO between the upward shift of the diastolic LV P-RL plot and %SS of the ischemic segment.     

Postsystolic shortening of acutely ischemic canine myocardium predicts early and late recovery of function after coronary artery reperfusion

Postsystolic shortening and thickening of ischemic and postischemic myocardium are well-recognized phenomena, but their significance is controversial. To discover whether postsystolic shortening and thickening might represent an active process and to establish their place as possible predictors of functional recovery during and after recovery from ischemia, we examined correlations in severely ischemic dyskinetic myocardial segments in 14 open-chest anesthetized dogs (90 minutes' ischemia, n = 9; 180 minutes' ischemia, n = 5) between the magnitudes of postsystolic shortening and thickening during ischemia and either the magnitudes of systolic shortening and thickening in the same segments before coronary occlusion or the magnitudes of shortening and thickening at 30-60 minutes and at 2-3 weeks after reperfusion. We found positive correlations between preocclusion shortening and postsystolic shortening (r = 0.44, n = 33 myocardial segments; p less than 0.02) and between preocclusion thickening and postsystolic thickening (r = 0.73, n = 13 segments; p less than 0.01), both measured at 5 minutes after onset of ischemia. Strong correlations were found also between postsystolic shortening and thickening measured immediately before reperfusion and systolic shortening and thickening measured after recovery at 2-3 weeks (r = 0.73, n = 28; p less than 0.001 for shortening; r = 0.79, n = 12; p less than 0.01 for thickening). Significant but less-exact correlations were found between postsystolic shortening and thickening measured immediately before reperfusion and early recovery of shortening and thickening at 30-60 minutes after reperfusion (during the "stunned myocardium" period). Postsystolic shortening and thickening persisted early after reperfusion in dogs that had had 90 minutes of ischemia, and this predicted further significant return of function at 2-3 weeks. However, dogs that had had 180 minutes of ischemia did not have postsystolic shortening or thickening during early recovery and showed no further return of function at 2-3 weeks. The magnitudes of postsystolic shortening and thickening immediately before reperfusion were better predictors of late return of function than the histological appearance of the ischemic segments at 2-3 weeks or the magnitude of their blood flow during ischemia (15 +/- 3 micron microspheres). From correlations made immediately before reperfusion with those at functional recovery after reperfusion, we conclude that postsystolic shortening and thickening of dyskinetic myocardial segments are markers of their potential for recovery.(ABSTRACT TRUNCATED AT 400 WORDS)     

Regional nonischemic performance as assessed by end-systolic measures of shortening and thickening

Objectives. Nonischemic contractile segmental performance was characterized by the end-systolic pressure-length and pressure-thickness relations during regional ischemia induced by proximal left anterior descending and left circumflex coronary artery occlusions.Background. The increases in shortening and thickening of the nonischemic myocardium during acute ishemia have been attributed to alterations in the regional loading conditions. However, it is uncertain to what extent ischemia affects the contractile performance of the nonischemic zone.Methods. Twenty-seven beagle dogs were instrumented with sonomicrometers and micromanometer pressure gauges. End-systolic pressure-length and pressure-thickness relation data were obtained during vena cava balloon inflation. Control data were obtained in both left anterior descending and left circumflex regions. Then, in random order, either the left anterior descending or left circumflex coronary artery was occluded for 90 s, and hemodynamic and nonischemic end-systolic pressure-length and pressure-thickness data were obtained. After a 45-min recovery period, the other artery was occluded, and the same recordings were obtained.Results. The end-systolic pressure-length relation exhibited variable degrees of rightward and downward shifts and the end-systolic pressure-thickness relation variable degrees of leftward and downward shifts. Left circumflex coronary artery occlusion was associated with a greater downward displacement (decreased slope) of the nonischemic end-systolic pressure-length relation than left anterior descending coronary artery occlusion. The baseline slope was the best predictor of the change in slope of the end-systolic pressure-length and pressure-thickness relations. The left circumflex coronary artery supplied a larger proportion of left ventricular myocardial mass than the left anterior descending coronary artery.Conclusions. Acute ischemia profoundly affects the end-systolic performance of the nonischemic segment. Furthermore, the site, and probably size, of the ischemic zone may be important determinants of nonischemic contractile performance.     

Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist

To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion. The dogs were randomized into three treatment groups: control (n = 13), dipyridamole (n = 10) or WEB-2086 (n = 12), an antagonist of the effects of the endogenous platelet-activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 +/- 0.14, 0.38 +/- 0.13 and 0.68 +/- 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 +/- 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 +/- 0.28 ml/min per g; p less than 0.03) or dipyridamole (3.00 +/- 0.83 ml/min per g; p less than 0.01). Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 +/- 11 to 124 +/- 27 mm Hg/(ml/min per g) (p less than 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic area remained unchanged in dogs receiving WEB-2086 (77 +/- 8 to 79 +/- 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 +/- 8 to 44 +/- 8 mm Hg/(ml/min per g); p less than 0.01). Regional function after 24 h remained depressed in all three groups. These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, but they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation.     

Differential effects on right ventricular function of transient right, left anterior descending and left circumflex coronary occlusions during percutaneous transluminal coronary angioplasty

Right ventricular function was studied by means of a thermodilution catheter before, during and after percutaneous transluminal angioplasty of the proximal right (group 1, n = 8), left anterior descending (group 2, n = 8) or left circumflex (group 3, n = 8) coronary artery. All patients had evidence of myocardial ischemia, with single-vessel disease affecting the proximal segment of one of the three major coronary arteries; no patient had had a previous myocardial infarction and all had normal cardiac function at baseline study. Cardiac index decreased during balloon inflation. Mean pulmonary artery pressure was unaffected in group 1 but increased in group 2 (from 19 +/- 5 to 31 +/- 11 mm Hg, p less than 0.01) and in group 3 (from 19 +/- 2 to 22 +/- 5 mm Hg, p less than 0.05). Right ventricular ejection fraction decreased from 62 +/- 9% to 52 +/- 10% (p less than 0.01) in group 1 and from 64 +/- 7% to 44 +/- 10% (p less than 0.005) in group 2, and returned to normal within 2 min after balloon deflation in both groups. In group 3, right ventricular ejection fraction was unchanged during balloon inflation (58 +/- 5% at baseline, 58 +/- 9% at 60 s, p = NS). Therefore, brief occlusion of the proximal segments of the left anterior descending or right coronary artery results in marked alteration of right ventricular performance that is probably caused by right ventricular free wall ischemia in the right coronary group and by the concomitant effects of septal ischemia and increased right ventricular afterload in the left anterior descending artery group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of pacing-induced and balloon coronary occlusion ischemia on left atrial function in patients with coronary artery disease

OBJECTIVES: The aim of this study was to compare left atrial (LA) function in 16 patients with distal left anterior descending (LAD) and in 16 patients with proximal left circumflex (LCx) coronary artery stenosis at rest and immediately after pacing-induced tachycardia (LAD-pacing [P] and LCx-P) or coronary occlusion (LAD-CO and LCx-CO). BACKGROUND: During left ventricular (LV) ischemia, compensatory augmentation of LA contraction enhances LV filling and performance. The left atrium is supplied predominantly by branches arising from the LCx. Therefore, we hypothesized that one mechanism for the loss of atrial contraction may be ischemic LA dysfunction. METHODS: Left ventricular and LA pressure-area relations were derived from simultaneous double-tip micromanometer pressure recordings and automatic boundary detection echocardiograms. RESULTS: Immediately after pacing or after coronary occlusion, LV end-diastolic pressure, LV relaxation, LA mean pressure and LV stiffness significantly increased in all patients. However, the area of the A loop of the LA pressure-area relation, representing the LA pump function, significantly decreased in groups LCx-P and LCx-CO (from 14+/-3 to 9+/-2, and from 16+/-4 to 9+/-2 mm Hg.cm2, respectively, p < 0.05), whereas it increased in groups LAD-P and LAD-CO (from 12+/-3 to 54+/-10, and from 16+/-3 to 49+/-8 mm Hg.cm2, respectively, p < 0.001). CONCLUSIONS: In patients with LAD stenosis, LV supply or demand ischemia is associated with enhanced LA pump function. However, in patients with proximal LCx stenosis who develop the same type and degree of ischemia, LA branches might have been affected, rendering the LA ischemic and unable to increase its booster pump function.     

Opposite effects of coronary artery disease and hypertrophic cardiomyopathy on left ventricular long axis function during dobutamine stress

BACKGROUND: The mechanism for reduced early diastolic long axis lengthening velocity in hypertrophic cardiomyopathy (HCM) is not known. METHODS: We measured simultaneous septal long axis amplitude and early lengthening velocity in 23 patients with HCM, 23 normal subjects and 22 patients with coronary artery disease (CAD) of left anterior descending artery. RESULTS: Resting amplitude and lengthening velocity were reduced in HCM 0.9+/-0.2 cm, 3.5+/-1.9 cm/s but equally in CAD 1.0+/-0.3 cm, 4.1+/-2.5 cm/s vs. 1.3+/-0.2 cm, 6.3+/-1.7 cm/s in normals, p < 0.01 for both vs. normal. With dobutamine stress, lengthening velocity increased by 2.7+/-1.9 cm/s (p < 0.001) in normals, by 2.8+/-2.5 cm/s (p < 0.001) in HCM but not in patients with CAD 0.5+/-2.1, p = NS. Increment in total long axis amplitude was subnormal in CAD and HCM. However, increment in lengthening velocity was higher with stress for corresponding change in amplitude in HCM compared with CAD (chi2) = 16.5, p < 0.001). An increase in early lengthening velocity by 2 cm/s was 77% sensitive and 70% specific in discriminating between HCM and CAD. Post-ejection shortening developed or worsened in all CAD patients indicating ischemia but not in any with HCM. CONCLUSIONS: Reduced peak early lengthening velocity is not specific for HCM but also occurs in CAD. Unlike CAD, lengthening velocity increases in HCM with stress and there is no aggravation of post-ejection shortening, suggesting that the abnormal relaxation is not due to subendocardial ischemia in HCM. The greater recoil velocity per unit deformation in HCM compared with CAD, indicates elastic mechanism with increased passive muscle stiffness due to fibrosis or fibre disarray.     

Relation of intramyocardial and intracavitary pressure to regional myocardial asynergy in the canine left ventricle

The purpose of this study was to investigate the relation between abnormalities of left ventricular (LV) wall thickening during systole in ischemic regions and the interaction of LV pressure and regional intramyocardial pressure. Wall thickness was measured in 10 open-chest dogs with ultrasonic dimension gauges. LV pressure, aortic pressure, and intramyocardial pressure in the subendocardium were measured with catheter-tip micromanometers. Regional ischemia was produced by occlusion of the left anterior descending coronary artery. During the control period, peak subendocardial pressure exceeded LV pressure by 44 +/- 6 mm Hg. With hypokinesia, defined as a 50% to 89% reduction of systolic wall thickening, peak subendocardial pressure exceeded peak LV pressure but to a lesser extent (15 +/- 1 mm Hg). During akinesia, defined as a 90% to 100% reduction of systolic wall thickening, there was less than 1 mm Hg difference between peak subendocardial pressure and peak LV pressure. During dyskinesia, defined as systolic thinning of the ischemic wall, peak LV pressure exceeded peak subendocardial pressure by 29 +/- 6 mm Hg. These observations indicate that regional changes of LV wall thickness characterized by hypokinesia, akinesia, and dyskinesia are associated with pressure gradients between the LV cavity and the LV wall that are compatible with the abnormalities of wall motion.