Functional significance of post-myocardial infarction left ventricular hypertrophy: a beneficial response.

Hypertrophy of noninfarcted myocardium occurs as a chronic response to myocardial infarction, but no previous study has related the changes in wall thickness to serial changes in left ventricular function. Thus the functional significance of postinfarction hypertrophy is unknown. The purpose of this study was to determine the relationship between the development of postinfarction hypertrophy and the resting left ventricular ejection fraction measured by two-dimensional echocardiography. After occlusion of the proximal left anterior descending coronary artery in 11 dogs, the ejection fraction fell acutely (0.63 +/- 0.08 to 0.33 +/- 0.10, p less than 0.001) and rose at 3.5 months to 0.62 +/- 0.12. End-diastolic thickness of the noninfarcted left ventricle increased (11 +/- 1.0 mm to 13 +/- 1.4 mm, p less than 0.01) as did left ventricular mass (101 +/- 18 gm to 134 +/- 21 gm, p less than 0.0001). Restoration of the ejection fraction toward the baseline value correlated with the increases in left ventricular mass (r = 0.79, p = 0.007) and wall thickness (r = 0.71, p = 0.025). Hypertrophy of the noninfarcted myocardium correlated with the magnitude and approximately paralleled the time course of the improvement in the ejection fraction and therefore may have had a beneficial effect on resting left ventricular function as a chronic adaptation to myocardial infarction.     

Compensatory hypertrophy in the heart after myocardial infarction in the rat

Hypertrophy after myocardial infarction would be a very important process for compensation of damaged myocardium and preservation of cardiac function. Fifty-four female Sprague-Dawley rats were studied 5 weeks after randomization to infarct operation, sham operation and control groups. At sacrifice, anteroapical infarcts ranging from 1 to 51% of left ventricle were present in the infarct operated group. When classified according to infarct size, groups with the largest infarcts (greater than 15 to 30% and greater than 30%) had significant (p less than 0.001) cardiac cellular hypertrophy in the noninfarcted myocardium of the septum and anterior walls (fiber diameter 15.9 +/- 2.3 and 14.5 +/- 2.3 microns, respectively) compared with the control group (12.0 +/- 1.8 microns). Because of cardiac hypertrophy, remaining noninfarcted myocardial area, as estimated from serial histologic sections of the heart, was normal in the greater than 15 to 30% infarct group (area 1.35 cm2) compared with the control group (1.43 cm2); however, because hypertrophy plateaued in the greater than 30% infarct group, myocardial area was significantly decreased (1.06 cm2, p less than 0.001), but was still more than expected without hypertrophy. We suggest that hypertrophy accompanies large infarction in the rat and is a compensation for preserving tissue volume lost by infarction. This compensatory response appears to have limitations, such that when very large amounts of myocardium become necrotic, there is not enough hypertrophy to return myocardial volume to normal.     

Contractility and stiffness of noninfarcted myocardium after coronary ligation in rats. Effects of chronic angiotensin converting enzyme inhibition

BACKGROUND. Previous studies have shown that global left ventricular function is depressed after myocardial infarction. However, little is known about the effects of myocardial infarction on contractility and the passive-elastic properties of residual myocardium. METHODS AND RESULTS. We evaluated isometric function and passive myocardial stiffness in isolated, noninfarcted left ventricular papillary muscle from rats 6 weeks after sham operation or myocardial infarction. Maximal developed tension and peak rate of tension rise (+dT/dt) were significantly decreased in untreated rats with large myocardial infarction compared with controls (3.3 +/- 1.1 versus 4.3 +/- 0.6 g/mm2 and 49.5 +/- 17.5 versus 72.5 +/- 10.5 g/mm2/sec, respectively). Time to peak tension was prolonged (120 +/- 8 versus 102 +/- 4 msec) and myocardial stiffness was increased in untreated myocardial infarction rats compared with controls (35.2 +/- 4.9 versus 24.2 +/- 3.7). Rats with smaller myocardial infarctions differed from controls only with respect to a prolongation of time to peak tension. Papillary muscle myocyte cross-sectional area was increased by 44% (p less than 0.05), and myocardial hydroxyproline content was increased by 160% (p less than 0.05) in rats with large myocardial infarctions compared with controls. To determine whether treatment that improves left ventricular function after myocardial infarction also improves myocardial function, rats were treated with captopril beginning 3 weeks after myocardial infarction and continuing for 3 weeks. Treatment with captopril attenuated the prolongation in time to peak tension in the myocardial infarction rats; however, developed tension, +dT/dt, and muscle stiffness remained abnormal. Compared with untreated myocardial infarction rats, captopril-treated myocardial infarction rats had a 9% decrease in myocyte cross-sectional area (p = 0.1) but a persistent increase in myocardial collagen content. In summary, large myocardial infarction in rats causes contractile dysfunction, increased stiffness, myocyte hypertrophy, and increased collagen content in the residual noninfarcted myocardium. Treatment with captopril alters the process of cardiac remodeling and hypertrophy and improves one parameter of contractility in noninfarcted myocardium; however, myocardial collagen content and myocardial stiffness remain abnormal. CONCLUSIONS. These findings suggest that angiotensin converting enzyme inhibition in the rat infarct model of heart failure improves global cardiac performance via combined effects on myocardial function and the peripheral circulation.     

Infarct resorption, compensatory hypertrophy, and differing patterns of ventricular remodeling following myocardial infarctions of varying size

OBJECTIVES: We sought to identify advantages of contrast-enhanced magnetic resonance imaging (MRI) in studying postinfarction ventricular remodeling. BACKGROUND: Although sequential measurements of ventricular volumes, internal dimensions, and total ventricular mass have provided important insights into postinfarction left ventricular remodeling, it has not been possible to define serial, directionally opposite changes in resorption of infarcted tissue and hypertrophy of viable myocardium and effects of these changes on commonly used indices of remodeling. METHODS: Using gadolinium-enhanced MRI, the time course and geometry of changes in infarcted and noninfarcted regions were assessed serially in dogs subjected to coronary occlusion for 45 min, 90 min, or permanently. RESULTS: Infarct mass decreased progressively between three days and four to eight weeks following coronary occlusion; terminal values averaged 24 +/- 3% of those at three days. Radial infarct thickness also decreased progressively, whereas changes in circumferential and longitudinal extent of infarction were variable. The ability to define the circumferential endocardial and epicardial extents of infarction allowed radial thinning without epicardial expansion to be distinguished from true infarct expansion. The mass of noninfarcted myocardium increased by 15 +/- 2% following 90-min or permanent occlusion. However, the time course of growth of noninfarcted myocardium differed systematically from that of infarct resorption. Measurements of total ventricular mass frequently failed to reflect concurrent changes in infarcted and noninfarcted regions. Reperfusion accelerated infarct resorption. Histologic reductions in nucleus-to-cytoplasm ratios corresponded with increases in noninfarcted ventricular mass. CONCLUSIONS: Concurrent directionally opposite changes in infarcted and noninfarcted myocardium can be defined serially, noninvasively, and with high spatial resolution and full ventricular coverage following myocardial infarction.     

Regional myocardial blood flow in experimental myocardial infarction after pretreatment with aspirin

The effects of aspirin on myocardial blood flow in an area of ischemia were studied in 12 baboons. In each, a diagonal branch of the left anterior descending coronary artery was ligated. Six of the baboons received aspirin (2 X 600 mg orally, 12 hours and 1 hour before ligation); the other six did not receive aspirin and served as a control group. The extent of myocardial ischemia was delineated with an electrode wire grid on the surface of the anterior left ventricular wall. The maximal area circumscribed by electrodes with 2 mV or more ST segment elevation was compared with the area of reduced myocardial blood flow. Myocardial blood flow was measured with the radioactive microspheres method using strontium-85-labeled carbonized spheres. Two areas of reduced myocardial blood flow were noted, one with severely reduced flow in the center of the myocardial infarct (0 to 49% of noninfarcted myocardium) and another with mild to moderately reduced myocardial blood flow at the border of the myocardial infarct (50 to 90% of noninfarcted myocardium). Myocardial blood flow in the border area (margins of ST elevation area) for the total wall was 85 +/- 8% of normal in the aspirin-treated animals and 40 +/- 4% in the control group (p less than 0.01); for the epicardium it was 67 +/- 10% of normal in noninfarcted myocardium after aspirin and 37 +/- 5% for the control group (p less than 0.05); and for the endocardium it was 78 +/- 8% of normal in noninfarcted myocardium after aspirin and 39 +/- 6% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic sequelae of chronic myocardial infarction: local refractoriness and electrographic characteristics of the left ventricle

Ventricular tachycardia (VT) has been shown to arise from ischemically damaged left ventricular myocardium, which possesses heterogeneity of refractoriness and activation. Catheter techniques were used to study left ventricular refractoriness using the strength-interval relation and activation by local electrographic characteristics in 8 patients with and 6 patients without previous myocardial infarction (MI). Noninfarcted myocardium in patients with and without previous MI was similar overall with respect to refractoriness and excitability, whereas local electrographic duration in MI patients was longer (66 +/- 2 vs 52 +/- 3 ms, p less than 0.005) and amplitude lower (3.9 +/- 2.1 vs 6.1 +/- 2.0 mV, p less than 0.05). Comparisons of infarcted and noninfarcted regions in MI patients revealed an increased threshold of excitability at infarct sites (e.g., 1.9 +/- 1.0 vs 0.7 +/- 0.4 mA, p less than 0.05) and prolongation of refractory periods (375 +/- 118 vs 275 +/- 13 ms, p less than 0.05) at the lowest level of stimulating current. Shortening of refractory period as a result of change in pacing cycle length was not affected by infarction. The local electrographic duration (95 +/- 17 ms) was significantly longer in infarcted regions than at noninfarcted sites (p less than 0.005), but the electrographic amplitude (3.4 +/- 3.0 mV) differed significantly only in noninfarct patients. It is concluded that considerable electrophysiologic disparity exists between infarcted and noninfarcted myocardium. Whether or not arrhythmogenic tissue possesses unique alterations in electrophysiologic characteristics remains to be established.     

Early and late remodeling of the left ventricle after acute myocardial infarction

This report describes early and later structural changes that occur in infarcted and noninfarcted ventricular myocardium after coronary arterial ligation in the rat. Histologic analysis was conducted of hearts subjected to 2 days (n = 22) and 21 days (n = 22) of coronary arterial occlusion, or to a sham operation (n = 22). Lengths, circumferences and areas of the left ventricle, of infarcted myocardium and of noninfarcted myocardium were obtained by videoplanimetry. Although the left ventricular (LV) endocardial circumference was similarly increased at 2 days (19 +/- 3 mm, mean +/- standard deviation) and 21 days (20 +/- 3 mm) compared with shams (13 +/- 3 mm, p less than 0.01), LV epicardial circumference was similar in all 3 groups (30 +/- 2, 31 +/- 2 and 31 +/- 2 mm, respectively). The area enclosed by the endocardial circumference was significantly (p less than 0.01) increased at 2 days (20 +/- 6 mm2) and 21 days (22 +/- 6 mm2) compared with shams (7 +/- 4 mm2); however, the area enclosed by the epicardial circumference was similar at 2 days, 21 days and in shams (70 +/- 9, 72 +/- 9 and 73 +/- 10 mm2, respectively). The total LV tissue area was similar at 2 and 21 days, but was less than that in shams (p less than 0.01). Between 2 and 21 days, 3 measures of infarcted myocardium significantly decreased: its segments of endocardial and epicardial circumference, its circumference and its area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemic myocardial mitochondrial function and ultrastructural change--influence of regional myocardial blood flow

Myocardial blood flow (MBF), tissue ATP content, mitochondrial respiratory function and mitochondrial ultrastructure were examined in 62 adult mongrel dogs weighing 6-14 kg in which acute myocardial ischemia had been produced under anesthesia. The left anterior descending coronary artery was dissected free for ligation before the first diagonal branch. MBF was measured before coronary ligation and 60 min following ligation. Then, samples of myocardium were taken and subjected to tissue ATP content assay, mitochondrial respiratory function measurement respiratory control index (RCI) and rate of oxygen consumption in state III (QO2III); and electron microscopic examination. Mitochondrial morphologic injury was evaluated quantitatively according to Schaper's criteria. MBF was significantly correlated with tissue ATP content, mitochondrial respiratory function and mitochondrial ultrastructural change. When MBF was less than 20 ml/min/100g, tissue ATP content (1.86 +/- 1.21 mumol/g wet weight) and mitochondrial respiratory function (RCI 2.51 +/- 0.59) were significantly lower than in the non-ischemic area (ATP 4.52 +/- 1.11, RCI 3.82 +/- 0.37), and mitochondrial ultrastructural injury had deteriorated significantly at an MBF below 40 ml/min/100 g. In conclusion, our findings show that when MBF is reduced, mitochondrial ultrastructural changes precede the depression in mitochondrial oxidative phosphorylation.     

Increased expression and regional differences of atrial myosin light chain 1 in human ventricles with old myocardial infarction. Analyses using two monoclonal antibodies.

BACKGROUND. This study was designed to examine the expression of atrial/fetal-type myosin light chain 1 (ALC1) in human ventricles with old myocardial infarction and in control hearts. METHODS AND RESULTS. The expression of immunoreactive (ir) ALC1 was examined in the subendocardial and subepicardial myocardium of the infarcted and the noninfarcted regions in the left ventricles with old myocardial infarction (n = 12) and of the control left ventricles (n = 8). For the analysis, we prepared two monoclonal antibodies, KA1 and KB1, that were specific for only ALC1 and for both ALC1 and ventricular myosin light chain 1 (VLC1), respectively. The ir-ALC1 expression ratio [ALC1/(ALC1 + VLC1), %] of the subendocardial myocardium, determined densitometrically by Western blotting with KB1, was significantly higher in the infarcted region (11.4 +/- 7.3%) than in the noninfarcted region (4.7 +/- 2.3%, p < 0.001) and the control ventricle (1.0 +/- 1.5%, p < 0.0001). In the infarcted region, the subendocardial myocardium contained a significantly greater percentage of ir-ALC1 than the subepicardial myocardium (5.8 +/- 6.7%, p < 0.005). The ir-ALC1 expression ratio had a significant negative correlation with the value of tissue protein concentration (milligrams protein per gram wet weight). The immunohistochemical study with KA1 revealed that the surviving myocytes included in the infarcted region, especially in the ventricular aneurysm, expressed ir-ALC1 strongly in comparison with those in the noninfarcted or the control ventricles. CONCLUSIONS. These results demonstrate increased expression of ALC1 and the regional differences in the failing left ventricles with old myocardial infarction. We conclude that the reexpression of ALC1 in infarcted ventricles occurs as one of the regional responses to increased load and may be a useful biochemical marker for the appearance of fetal-type myocytes.     

Relation of thallium uptake to morphologic features of chronic ischemic heart disease: evidence for myocardial remodeling in noninfarcted myocardium.

OBJECTIVES: The aim of this study was to investigate the disparity between the extent of myocardial injury as assessed by thallium and the severity of left ventricular (LV) dysfunction in chronic ischemic heart disease. BACKGROUND: Although it is believed that thallium differentiates between viable and nonviable myocardium, in some patients with chronic ischemic heart disease, viable regions by thallium may fail to improve function after revascularization. METHODS: Thirteen transplant candidates with chronic ischemic heart disease (LV ejection fraction = 14 +/- 6% at rest) were studied prospectively with stress-redistribution-reinjection thallium single-photon emission computed tomography. We examined pretransplantation quantitative thallium uptake and post-transplantation extent and the histological distribution of collagen replacement in infarcted and noninfarcted myocardium and in 13 age-matched control hearts. RESULTS: The volume fraction of collagen varied inversely with wall thickness (r = -0.70, p < 0.001) and was higher in irreversible (30.9 +/- 15.8%) compared with reversible (20.2 +/- 12.6%, p < 0.001) or normal thallium segments (15.0 +/- 8.7%, p < 0.001). The irreversible thallium segments had lower wall thickness and more severe coronary artery narrowing (9.7 +/- 2.8 mm and 95 +/- 8%) compared with reversible (11.7 +/- 2.7 mm and 87 +/- 13%, p < 0.001) and normal thallium segments (12.8 +/- 2.6 mm and 80 +/- 14%, p < 0.001). Mean volume fraction of collagen was significantly lower in noninfarcted than it was in infarcted segments (13 +/- 6% vs. 36 +/- 13%, p < 0.001) but exceeded that in the control hearts (4 +/- 2%, p < 0.001). Noninfarcted segments had predominantly interstitial fibrosis with either microscopic or patchy areas of replacement fibrosis. CONCLUSIONS: In chronic ischemic heart disease with severe LV dysfunction, patterns of normal, reversible and irreversible thallium uptake correlated with the magnitude of collagen replacement, segmental wall thickness and severity of coronary artery narrowing. The finding of scattered areas of replacement fibrosis in noninfarcted myocardium may explain the observed disparity between LV contractile dysfunction and the extent of myocardial injury assessed by thallium.     

Topographic changes in the left ventricle after experimentally induced myocardial infarction in the rat

The factors that determine the thickness of transmural myocardial infarcts are unknown. Therefore, the relation between the size and thickness of transmural infarcts in 67 rats 21 days after occlusion of the left main coronary artery was studied. On examination of histologic sections, infarct size was determined by planimetry and expressed as a percentage of the left ventricular (LV) area, and thickness was expressed as a percentage of noninfarcted ventricular septal wall thickness. The circumferential length of the infarcted ventricle was measured in millimeters, as well as the circumferential length of the noninfarcted ventricular septum. Septal wall thickness was similar in rats with transmural infarcts and in sham-operated rats. No significant correlation was observed between infarct size and thickness (r = 0.10) or between circumferential length of the infarct and infarct thickness (r = 0.17). However, large (greater than or equal to 20% of the left ventricle, n = 37) and small (less than 20% of the left ventricle, n = 30) infarcts which were similarly thin (37 +/- 1% and 34 +/- 2% of septal wall thickness, respectively) affected LV topography differently. Large infarcts resulted in a 23% greater loss of myocardium (p less than 0.001), greater expansion of the LV cavity (18 +/- 9 mm2 compared with 14 +/- 1 mm2 in small infarcts, p less than 0.005), and lengthening of the septal wall (7.2 +/- 1.1 mm and 6.7 +/- 1.0 mm in large and small infarcts, respectively [p less than 0.05], and 6.3 +/- 0.1 mm in shams). Increase in cavity area and septal length in infarcted ventricles suggested a volume overload hypertrophy, which at 3 weeks was nonetheless inadequate to provide as much normal muscle as was present in sham-operated rats. In an additional 9 rats with subendocardial infarctions (involving less than 75% of the LV wall from endocardium to epicardium), the LV walls were thicker (94 +/- 5% of septal wall thickness, compared with 35 +/- 1% for transmural infarcts, p less than 0.001) and an inverse correlation was observed between infarct size and thickness. In conclusion, neither the size of a transmural infarct in rat nor the circumferential length of infarction determines the thickness of the infarct; however, infarct size does affect LV topography by increasing LV cavity area and the length of the noninfarcted septal wall. Subendocardial infarcts result in less myocardial thinning than do transmural infarcts.     

Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans

Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exercise ejection fraction (r = 0.48, p less than 0.001) at the follow-up study. Of the 32 patients who increased their left ventricular mass index greater than 7%, 18 improved their rest ejection fraction greater than 0.05 units and 17 improved their exercise ejection fraction greater than 0.05 units. Conversely, of the 13 patients who failed to increase their left ventricular mass index, only three improved their rest ejection fraction and one improved the exercise ejection fraction (Fisher's exact test, p less than 0.05). We reached three conclusions. First, in humans, significant hypertrophy of the noninfarcted myocardium can be detected by two-dimensional echocardiography, 9 months postmyocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytochemistry and ultrastructure of canine myocardium undergoing global ischemia and reperfusion injury

In order to highlight severity of myocardial injury during the course of global ischemia and reperfusion, cytochemistry of glycogen and succinate dehydrogenase (SDH) as well as hematoxylin and eosin staining (H & E) and electron microscopy were observed in canine myocardium. Seven mongrel dogs were selected for reperfusion injury after global ischemia in this study. Myocardial biopsies were taken from the anterior wall of the left ventricle (a) after cardiopulmonary bypass (the first biopsy); (b) at the end of the aortic crossclamp (the second biopsy); and (c) 30 minutes after crossclamp removal (the third biopsy). All biopsies were cytochemically assessed, and the latter two, for electron microscopic studies. The averages of myocardial necrotic rate and surface to volume ratio of myocardial mitochondria were calculated under electron microscopy and in electron microscopic slices, respectively. Myofibrillae were of normal morphology in the first biopsy; in wave-shape and partly vacuolated, with large and deformed nuclei in the second one; and in wave-shape and severely vacuolated in the third one, in H & E. Glycogen granules were variously stained in moderate, weak and intensive positive reactions in the three biopsies respectively in glycogen staining. SDH was stained in intensive, weak, and moderate positive reactions in three, respectively. By electron microscopy, Z bands twisted severely, and local dissolution of cristae and matrix occurred in a minority of the mitochondria in the second biopsy; and majority of the Z bands in necrotic region had disappeared, the myofibrillae were obscure and patchily dissolved. Clustered and deformed mitochondria could be found in the third biopsy. Significant difference could be noted between the averages of the second and third biopsies (14.88 +/- 3.09% vs. 60.25 +/- 8.55%, p < 0.001). The surface to volume ratio of the ischemic mitochondria was much bigger than that of the reperfused (3.95 +/- 1.09 micron-1 vs. 2.77 +/- 0.93 micron-1, p = 0.041). Myocardial injury was more severe in reperfusion than in ischemia myocardium. There were correlations between histobiochemical and ultrastructural alterations in damaged canine myocardium.     

Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction

Nitric oxide (NO) is an important modulator of cardiac performance and left ventricular (LV) remodeling after myocardial infarction (MI). We tested the effect of cardiomyocyte-restricted overexpression of one NO synthase isoform, NOS3, on LV remodeling after MI in mice. LV structure and function before and after permanent LAD coronary artery ligation were compared in transgenic mice with cardiomyocyte-restricted NOS3 overexpression (NOS3-TG) and their wild-type littermates (WT). Before MI, systemic hemodynamic measurements, echocardiographic assessment of LV fractional shortening (FS), heart weight, and myocyte width (as assessed histologically) did not differ in NOS3-TG and WT mice. The inotropic response to graded doses of isoproterenol was significantly reduced in NOS3-TG mice. One week after LAD ligation, the infarcted fraction of the LV did not differ in WT and NOS3-TG mice (34+/-4% versus 36+/-12%, respectively). Four weeks after MI, however, end-systolic LVID was greater, and fractional shortening and maximum and minimum rates of LV pressure development were less in WT than in NOS3-TG mice. LV weight/body weight ratio was greater in WT than in NOS3-TG mice (5.3+/-0.2 versus 4.6+/-0.5 mg/g; P<0.01). Myocyte width in noninfarcted myocardium was greater in WT than in NOS3-TG mice (18.8+/-2.0 versus 16.6+/-1.6 microm; P<0.05), whereas fibrosis in noninfarcted myocardium was similar in both genotypes. Cardiomyocyte-restricted overexpression of NOS3 limits LV dysfunction and remodeling after MI, in part by decreasing myocyte hypertrophy in noninfarcted myocardium.     

Geometry of capillary networks in volume overloaded rat heart.

Volume overload cardiac hypertrophy was induced in male Sprague-Dawley rats by experimental aortocaval fistula. This procedure resulted in considerable increases in left ventricular mass (70%) by 21-23 days. Our objective was to study the effect of volume overload on the geometry of coronary capillaries in the left ventricular midmyocardium. Tissue sections were stained according to a protocol that distinguished arteriolar (AC) and venular (VC) capillary regions by color. Morphometric data were then collected and compared between AC and VC regions. In sham-operated controls (CON; n = 8), the tissue area (capillary domain) supplied by a single capillary decreased from AC to VC regions (AC = 505 +/- 5 microns 2: VC = 452 +/- 7 microns 2; P less than 0.01; mean +/- SE). In volume overloaded hearts (VOL; n = 8), only VC domain areas were reduced from control values (P less than 0.01) and the differences between AC and VC regions were preserved (AC = 480 +/- 5 microns 2; VC = 395 +/- 6 microns 2; P less than 0.01). Minimal capillary length was significantly longer in volume overloaded hearts (VOL = 723 +/- 18; CON = 581 +/- 20 microns; P less than 0.01). In the control group, AC segment length was longer than VC segment length (AC = 93 +/- 2 microns: VC = 74 +/- 2 microns; P less than 0.01). In volume overload, AC segment length was also longer than VC segment length, but the divergence between AC and VC regions was increased (AC = 108 +/- 3 microns; VC = 71 +/- 2 microns; P less than 0.01). These changes in capillary geometry may be secondary to specific changes in the arrangement and dimension of myocytes in the left ventricular wall following volume overload hypertrophy.     

Changes in cardiac ultrastructure and myofibrillar proteins during ischemia in dogs, with special reference to changes in Z lines

This study was designed to examine whether or not coronary ligation produces changes in myofibrillar proteins, especially Z line proteins including alpha-actinin and the 55 kDa protein, in the dog. Changes in ultrastructure of the myocardium after coronary ligation were also studied. A branch of the left anterior descending coronary artery was ligated for a period of 3, 6, 24 or 72 h. Coronary ligation produced ultrastructural changes in Z lines (characterized by broader and wavy Z lines) as well as changes in glycogen granules, mitochondria, and nuclei. Myofibrils were isolated from the myocardium that had been made ischemic by coronary ligation. The yield of myofibrils was reduced as the ischemic period was increased. Phase microscopic examination of the isolated myofibrils from the ischemic myocardium revealed that there were spread Z lines with wider I bands, these changes being essentially the same as those observed by the electron microscope in the ischemic myocardium. The effect of coronary ligation on the myofibrillar proteins was studied by means of polyacrylamide gel electrophoresis. In the isolated myofibrils from the myocardium 3 h after coronary ligation, there were decreases in the percentage of actin, alpha-actinin and the 55 kDa protein, and these changes progressively increased with lengthening of the ischemic period. These results suggest that coronary ligation decreases actin, alpha-actinin and the 55 kDa protein, in association with ultrastructural changes of the Z lines.     

Clinicopathological study of left ventricular remodeling after first acute myocardial infarction

The morphological characteristics of post-infarction ventricular remodeling were determined by comparison of infarct location and histological changes of noninfarcted myocardium at autopsy. A total of 94 cases of first acute myocardial infarction with clinical courses of 0 to 37 days were studied. Hearts were sliced on the short axis at the level of 1/3 of the distance from the atrioventricular ring to the apex. Wall thicknesses of the infarcted and noninfarcted areas, and the endocardial and epicardial perimeter lengths of the left ventricle were measured. Myocyte diameter and number of myocytes in the noninfarcted area were measured. Infarcts were classified into 3 groups based on infarct location (51 anterior, 22 posterior, and 21 nontransmural circumferential) and each group was further divided according to the clinical course of less than 72 hours or longer. Fifty two patients died within 72 hours. Cardiac rupture was the most common cause of death in the anterior group. Patients in the posterior group chiefly died due to cardiogenic shock and in the circumferential group chiefly died to pump failure. According to the number of stenosed coronary arteries, cardiac rupture was the most common cause of death in single-vessel disease in both anterior and posterior groups (62.1% and 55.6%, respectively). In double-vessel disease, the most common cause of death in the anterior group was still cardiac rupture (50.0%). On the other hand, 50.0% of the posterior group died of cardiogenic shock in double-vessel disease. Patients with triple-vessel disease mainly died due to heart failure in all groups. Wall thickness of the infarcted myocardium was decreased in the anterior group after 72 hours (11.8 +/- 3.5 vs 7.8 +/- 2.5 mm). Endocardial perimeter length was increased in the anterior and circumferential groups (83.6 +/- 25.6 vs 116.3 +/- 29.5 mm, 75.2 +/- 12.0 vs 117.6 +/- 3.1 mm, respectively). Endocardial/epicardial perimeter length ratio increased with longer clinical course in the anterior group. No specific change in wall thickness or perimeter length was found in the posterior group. Noninfarcted wall thickness was preserved in both the anterior and posterior groups. Myocyte diameter and number of myocytes in the noninfarcted area showed no significant difference after 72 hours. The nature of ventricular remodeling differs with infarct location. Ventricular dilation occurred during the clinical course in the anterior group. The transmural and adjacent areas are more important than the remote noninfarcted area in post-infarction remodeling within this period.     

Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.     

约氏疟原虫感染大鼠和小鼠的红外期研究

约氏疟原虫约氏亚种的子抱子经尾静脉接种大鼠和三株小鼠(ICR/JCL,C57BL,KM株)后42h,在大鼠和小鼠的肝连续切片中均查见红外期裂殖体(EE裂殖体),但在KM鼠株的切片中,正常的EE裂殖体甚少。不论宿主同否,EE裂殖体均大小不等,呈圆形、椭圆形或其他形状,分化程度不同,发育不完全同步。大鼠肝中的EE裂殖体可看到明显的外膜,周围并出现细胞反应。ICR/JCL、C57BL鼠株和大鼠肝中的EE裂殖体均较KM鼠株发育良好,数量较多,但大鼠中的红内期迅速消失。结果表明;ICR/JCL和C57BL鼠株用作约氏疟原虫—斯氏按蚊系统鼠疟模型的宿主较合适。     

Effects of regional myocardial ischaemia on coronary artery calibre in the rabbit

Microangiographic and electron microscopic studies were undertaken in isolated, perfused rabbit hearts to examine the effects of acute regional myocardial ischaemia on coronary artery calibre, vascular resistance and ultrastructure. Selective left coronary angiograms were recorded prior to, after 90 min of acute regional myocardial ischaemia induced by occlusion of the marginal left ventricular branch of the circumflex artery, and after reperfusion for 5 min. Vasodilation occurred in the proximal left anterior descending artery (9 +/- 1%, P less than 0.01) and the unoccluded part of the marginal branch (21 +/- 1%, P less than 0.001) during ischaemia which reversed on reperfusion. During reperfusion, coronary vascular resistance increased by 43 +/- 10% (P less than 0.001) despite mild vasodilation of vessels in the ischaemic zone (up to 10 +/- 1%, P less than 0.01). Failure of reperfusion occurred in vessels smaller than 30 microns in diameter (terminal arterioles) and was associated with ultrastructural damage in the ischaemic zone which was particularly prominent at the apex. These findings suggest that failure of reperfusion following 90 min of acute regional myocardial ischaemia in the rabbit is associated with damage to terminal arterioles and capillaries and that the calibre of the larger coronary vessels is maintained. Failure of reperfusion after prolonged myocardial ischaemia may occur despite arterial dilatation in the ischaemic zone.