Gender differences in postinfarction left ventricular remodeling.

OBJECTIVE: Previous studies suggest that gender affects the adaptive responses of the heart to some forms of cardiac overload. It is unknown whether gender influences left ventricular (LV) remodeling after myocardial infarction (MI). METHODS: We performed transthoracic echocardiographic-Doppler examinations in age-matched male (n = 17) and female (n = 16) rats before, and 1 and 6 weeks after transmural MI or sham surgery. RESULTS: Following large MI (male = 45 +/- 1% LV circumference vs. female = 48 +/- 4%, p = NS), both male and female rats developed progressive LV dilatation. Infarctions caused a similar degree of global and regional LV systolic dysfunction in males and females. Male rats had significant increases in the thickness of the noninfarcted posterior wall by 6 weeks after MI. However, posterior wall thickness did not change in the infarcted female rats. Average myocyte diameter in the noninfarcted region of the heart was also greater in male than female MI rats. The combination of increased cavity size with little change in wall thickness resulted in a greater decline in relative wall thickness in the female rats compared to the males. Male rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. Female rats had less of an increase in the ratio of early to late transmitral velocities and less of an increase in the E wave deceleration rate after MI. CONCLUSIONS: Female rats showed a different pattern of LV remodeling than males with less of an increase in thickness of the noninfarcted portions of the left ventricle than males, but comparable LV cavity enlargement and systolic dysfunction. Despite similar infarct size, females developed less pronounced abnormalities of LV diastolic filling. We hypothesize that the gender-related differences in postinfarction LV remodeling may contribute to the different LV filling patterns, and might ultimately relate to differences in clinical outcome.     

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.     

Biomechanical properties of reperfused transmural myocardial infarcts in rabbits during the first week after infarction. Implications for left ventricular rupture.

Left ventricular (LV) rupture potential was studied after transmural myocardial infarction (MI) in rabbits by measuring 1) the tensile strength of infarcted tissue strips, 2) the force required to initiate a tear (tear threshold) in the central infarcted region, and 3) the intracavitary pressure required to rupture the infarcted ventricle. During the first week after MI, infarcts resulting from a permanent coronary occlusion were compared with infarcts reperfused "late" (i.e., 3 hours) after coronary occlusion with a resultant hemorrhagic transmural infarct but no reduction in infarct size. The reperfused hemorrhagic infarcted strips had less tensile strength than strips from permanently occluded infarcts in the initial 24 hours after MI (16 +/- 1 versus 24 +/- 3 g/mm2, p less than 0.05), but the tear threshold and response to increased LV pressure were not influenced by infarct reperfusion at this time. By 3 days after MI, reperfused infarcts had equal tensile strength, had greater resistance to infarct tearing, and could withstand a greater LV distending pressure compared with permanently occluded infarcts. By 5 days after MI, reperfused infarcts maintained a greater tear threshold but had less tensile strength than permanently occluded infarcts, although all infarct values were equivalent or greater than normal LV values. By 7 days after MI, reperfused and permanently occluded infarcts were equally strong by all measurements. Thus, late reperfusion of transmural infarcts increased resistance to infarct tearing and LV rupture above that of nonreperfused permanently occluded infarcts by 3 days after MI and enhanced tissue strength after an initial 24-hour vulnerable period. These findings suggest that late reperfusion may accelerate myocardial healing after MI.     

Short-term exercise has a prolonged effect on scar formation after experimental acute myocardial infarction

The effect of early short-term exercise on late scar formation of myocardial infarction is unknown. Therefore, rats anesthetized with ether underwent proximal left coronary artery occlusion. Infarct extent was assessed 24 hours later by electrocardiographic criteria (QRS morphology). Immediately after electrocardiography, the rats were divided into two groups. Group 1 rats (n = 8) were subjected to daily graded swimming (up to 45 minutes a day) starting 24 hours after coronary occlusion for a total of 7 days followed by 2 weeks of nonswimming. Group 2 rats (n = 7) served as a control group and were not subjected to swimming. Twenty-one days after coronary occlusion, the rats were anesthetized, their heart excised and wall thickness determined histologically. Noninfarcted septal wall thickness was similar in both Groups 1 and 2. A ratio for transmural infarcts was obtained from multiple measurements by dividing scar thickness by noninfarcted septal wall thickness. Ratio of scar thickness divided by noninfarcted wall thickness for the control (nonswimming) group was 0.48 +/- 0.05 (mean +/- standard error of the mean); however, in the exercise (swimming) group, there was marked scar thinning with a ratio of 0.25 +/- 0.02 (mean +/- standard error of the mean, p less than 0.001). Infarct extent assessed by planimetry as percent of left ventricular slices was similar in both groups. Thus, early short-term swimming exercise during the first week after experimental myocardial infarction even when followed by 2 weeks without swimming, has long-lasting effects on scar formation.     

Magnetic resonance tomography image of transmural myocardial infarct in comparison with 99mTc-methoxyisobutylisonitrile SPECT]

To assess the ability of magnetic resonance imaging (MRI) to identify morphologic and functional abnormalities associated with transmural anterior and inferior myocardial infarction, 18 patients with anterior myocardial infarcts and 11 patients with inferior myocardial infarcts confirmed by ECG and cine-ventriculography underwent gradient-echo MRI of transverse and short-axis imaging planes. Myocardial perfusion of corresponding imaging planes was measured by 99mTc-methoxyisobutyl-isonitrile single-photon emission computed tomography (MIBI-SPECT). Transmural scar by MRI was defined as diastolic wall thickness 2.5 SD below corresponding normal values of a healthy control group (n = 21). MIBI-SPECT scar was defined as a MIBI uptake less than 2.5 SD below mean values of a healthy control group (n = 11). By MIBI-SPECT, 231 segments contained normal tissue and 161 contained scarred myocardium. In 352/392 (90%) segments gradings based on diastolic wall thickness and MIBI-SPECT gradings were identical. Diastolic wall thickness was significantly higher in normal than in scarred MIBI-SPECT segments (10.3 +/- 1.5 vs 5.2 +/- 2 mm, p less than 0.0001). Additionally, normal segments by MIBI-SPECT showed significantly higher systolic wall thickening than scar segments (5.5 +/- 1.5 vs 0.6 +/- 1.6 mm, p less than 0.0001). The correlation between MRI and MIBI-SPECT assessed infarct size was r = 0.91 for anterior and r = 0.77 for inferior myocardial infarcts. The agreement between MIBI-SPECT perfusion defect size and regions with reduced diastolic wall thickness on MRI tomograms was significantly better for anterior myocardial infarcts than for inferior myocardial infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Increased myocardial infarct size by thiopental after coronary occlusion in the dog

The effect of a single dose (10 mg/kg) of intravenous thiopental (TP), during acute myocardial infarction, on infarct size was studied in conscious dogs randomized 10 minutes after left circumflex coronary artery occlusion to either the TP group (n = 10) or a control group given 0.9% saline solution (n = 10). During the first hour following therapy, myocardial blood flow (microspheres), arterial pressure, left atrial pressure, and arterial blood gases were similar in the two groups, but the heart rate (140 +/- 3 vs 110 +/- 3 bpm; p less than 0.001) and rate-pressure product (15,090 vs 12,210 bpm X mm Hg; p less than 0.025) were greater in the TP group. Infarct size (planimetry) and occluded bed size (postmortem coronary arteriography) measured 2 days later revealed that: the slope of the relation between infarct and occluded bed mass, as a percentage of the left ventricle (% LV) was greater with TP than with saline solution (1.10 vs 0.61; p less than 0.001); excluding hearts (four TP and three saline solution) with small occluded beds (less than 22% LV), infarcts were also larger with TP (n = 6) than with saline solution (n = 7), both as a percentage of the left ventricle (26.4 vs 12.2%; p less than 0.02) or occluded bed (61.5 vs 28.9%; p less than 0.005); and transmural and endocardial extents of the infarcts on topographic maps were greater with TP than with saline solution. In 12 other conscious dogs, increasing the heart rate between 10 and 70 minutes after left circumflex coronary artery occlusion to the average rate of the TP group (140 bpm) by atrial pacing resulted in infarcts larger than those in control dogs but similar to those in the TP group. Thus, TP therapy after left circumflex occlusion increased infarct size in dogs. This effect appeared to be due mainly to the increased heart rate, probably via increased myocardial oxygen demands.     

Regional left ventricular function assessed by contrast angiography in acute myocardial infarction.

The relationship of segmental left ventricular (LV) wall motion abnormalities to LV function 2-6 days after acute transmural myocardial infarction (MI) was investigated in 45 patients by quantitative contrast ventriculography. Patients were divided into four classes according to the MIRU criteria. Segmental wall motion was assessed by determining the percentage of systolic shortening (deltaS) along nine hemiaxes and the extent of akinetic or dyskinetic abnormally contracting segments (% ACS) expressed as a percentage of end-diastolic perimeter. When compared with that in 17 normal control-subjects, the LV end-diastolic volume was increased only in patients in class III and class IV; the LV end-systolic volume increased progressively from normal through class IV. Ejection fraction had a negative linear correlation with %ACS (r = 0.97). The size of ACS was larger in anterior (34 +/- 14%) than in inferior MIs (23 +/- 7%), resulting in greater LV dysfunction. However, for a comparable size of ACS, infarct location alone did not influence LV function parameters. In the noninfarcted zone, deltaS was increased when the size of ACS was less than 25% and reduced when the size of ACS was greater than 25%. Thus, the size of ACS is a major determinant of LV dysfunction in acute MI. The compensatory mechanisms operate either through an augmented mechanical function of residual myocardium when the infarct is small, or through the Frank-Starling mechanism when the infarct is large.     

Differentiation of subendocardial and transmural infarction using two-dimensional strain rate imaging to assess short-axis and long-axis myocardial function.

OBJECTIVES: This study sought to differentiate the transmural extent of infarction (TME) by assessment of the short-axis and long-axis function of the left ventricle (LV) using 2-dimensional (2D) strain. BACKGROUND: The differentiation of subendocardial infarction from transmural infarction has significant prognostic and clinical implications. METHODS: Contrast-enhanced magnetic resonance imaging (CE-MRI) and dobutamine stress echocardiography (DBE) were performed in 80 patients (age 63 +/- 10 years) with chronic ischemic LV dysfunction. Myocardial function was assessed in the short axis at the midventricular level using peak strain rate (SR) and strain (S) in circumferential and radial dimensions, and was assessed in the long axis using longitudinal SR and S. Wall motion analysis was performed during DBE to assess for contractile reserve. RESULTS: Transmural infarct segments had lower circumferential S (-10.7 +/- 6.3) and SR (-1.0 +/- 0.4) than subendocardial infarcts (S: -15.4 +/- 7.0, p < 0.0001; SR: -1.4 +/- 0.8, p = 0.02) and normal myocardium (S: p < 0.0001; SR: p < 0.0001). Transmural and subendocardial infarct segments had similar radial S and SR. Subendocardial infarct segments showed significant reduction of longitudinal S (-13.2 +/- 5.6) and SR (-0.91 +/- 0.45) compared with normal myocardium (S: -17.8 +/- 5.4, p < 0.0001; SR: -1.1 +/- 0.41, p < 0.0001), but there were no significant differences between subendocardial and transmural infarct segments (p = 0.09). Wall motion analysis by DBE could not identify subendocardial infarction on CE-MRI (TME 1% to 50%: DBE scar 38%, DBE viable 38%, DBE ischemic 24%, p = NS). CONCLUSIONS: The combined assessment of long-axis and short-axis function using 2D strain may be used to identify TME.     

Ischemic expansion during acute myocardial infarction and reversal by coronary reperfusion.

Previous studies have shown that infarct expansion occurs at least 1 day after a large transmural infarction. To assess whether regional left ventricular expansion is evident within hours of an acute myocardial infarction, 25 adult mongrel dogs underwent left circumflex coronary artery occlusion for 2 hours and 22 of these were subsequently reperfused. Two-dimensional echocardiography was used to record left ventricular topography and function at baseline, at 2 hours of occlusion, and following reperfusion. Short-axis midpapillary echocardiograms were analyzed using a microcomputer digitizing routine by establishing a 360-degree circumferential map of the left ventricle. The central ischemic zone was defined as that region with the most depressed contractility after 2 hours of occlusion, and the normal zone was set at 180 degree away from the central ischemic zone. Endocardial and epicardial segment lengths and wall thickness were measured for both the normal zone and the central ischemic zone at end diastole. After 2 hours of occlusion, diastolic central ischemic endocardial (1.3 +/- 0.05 to 1.42 +/- 0.04 cm, p less than 0.01) and central ischemic epicardial (1.84 +/- 0.06 to 1.93 +/- 0.06 cm, p less than 0.05) segment lengths were significantly increased. There were no significant changes in segment lengths or wall thickness in the normal zone. After 2 hours of occlusion, there was significant diastolic left ventricular (LV) dilatation (LV area increased from 18.2 +/- 1.3 to 21.0 +/- 1.3 cm2, p less than 0.01). Furthermore, central ischemic endocardial and epicardial segment length changes from baseline to occlusion correlated significantly with LV dilatation (r = 0.56, p less than 0.003; r = 0.55, p less than 0.004 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nontransmural versus transmural myocardial infarction: A morphologic study

Although “nontransmural” and “transmural” are morphologic terms used widely to distinguish patients with myocardial infarction, controversy exists as to their meaning regarding clinical course. For this study, a transmural infarct was defined as one that involves essentially the full thickness of the ventricular wall, and nontransmural was defined as something less. The purpose of this study was to identify true morphologic nontransmural acute (less than 21 days old) infarcts at autopsy and compare them with transmural (full-thickness) infarcts in age-matched subjects, for clinical and pathologic similarities and differences. Among the autopsy subjects, comparing 35 nontransmural and 35 transmural infarcts, there was no significant difference with regard to subjects' race or sex, chest pain, arrhythmias, heart block, or cause of death; transmural myocardial infarctions did have a higher frequency of new Q waves (30 of 35 versus six of 35, p < 0.001) and presented more often with increasing dyspnea. At autopsy, there were no significant differences regarding heart weight, location of infarcts, severity of coronary disease, age of acute infarct, or total size of infarct (18 percent of left ventricle for nontransmural versus 22 percent for transmural). There was, however, a significantly greater tendency for those with nontransmural infarct to have evidence of prior infarction at autopsy (27 of 35 versus 19 of 35, p < 0.05). Acute coronary thrombi in the distribution of the infarct were significantly more common among transmural myocardial infarcts (32 of 35 versus 18 of 35, p < 0.001). Morphologically, the nontransmural infarcts showed mural involvement ranging from 20 to 90 percent of the left ventricle, and histologically showed more contraction band (i.e., reflow) injury (57 percent with more than 30 percent contraction band necrosis) compared with transmural infarcts (32 percent with more than 30 percent contraction band necrosis) (p < 0.05). Fatal nontransmural and transmural infarcts have major clinical and pathologic similarities, but differences in number of prior infarcts, type of necrosis, and occurrence of coronary thrombi suggest differing pathophysiology. The heterogeneity of both transmural and nontransmural infarcts likely accounts for existing differences among clinical studies regarding prognosis. Although this classification system has value in the clinical setting, that at times it represents an imprecise oversimplification of infarct type should be recognized in assessing individual patients.     

The natural history of regional dysfunction in a canine preparation of chronic infarction

We used a canine preparation of experimental infarction to study the natural course of echocardiographically defined regional wall motion abnormalities in the 6 weeks after acute coronary ligation. Eight dogs underwent serial short-axis echocardiographic evaluation and microsphere blood flow determinations at control, and 30 min, 48 hr, 1 week, 3 weeks, and 6 weeks after acute coronary artery ligation. Wall motion analysis and blood flow calculations were applied to 10 degree radial segments of the left ventricle (short axis) and correlated to the size and extent of infarction as defined histologically at 6 weeks. All animals had at least 50% transmural histologic infarction. The ratio of flow in infarcted tissue vs noninfarcted myocardium fell to 0.40 +/- 0.13 for endocardium and 0.56 +/- 0.13 for epicardium at 30 min after ligation, but recovered to 0.83 +/- 0.15 for endocardium and 1.12 +/- 0.11 for epicardium by 6 weeks. The maximum circumferential extent of abnormal regional wall motion was observed at 48 hr after infarction (mean circumferential extent = 51%), but was resolved to a significant extent by 6 weeks (circumferential extent = 21%, p less than .001). Four animals had virtually normal wall motion by 6 weeks after infarction. Segment-by-segment regional dysfunction correlated highly with the regional transmural reduction in blood flow of 20% )r = .89, p = .0001) for the experiment as a whole, but the echocardiogram tended to underestimate the size of the histologic infarct at 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inferior myocardial infarction as a cause of asymmetric septal hypertrophy. An echocardiographic study.

The diastolic thickness of the septum and posterior left ventricular wall were measured with M mode echocardiography in 68 patients 2 or more months after a single transmural myocardial infarction. In 42 patients with inferior wall infarction, the septal thickness of 12.4 +/- 0.6 mm (mean +/- standard error of the mean) was larger than the mean measurement in 26 patients with anterior wall infarction (9.6 +/- 0.6 mm, P less than 0.01). Twenty-five of these 42 patients (59 percent) had increased septal thickness (greater than 11 mm), including 12 (48 percent) who had hypertension and 11 (26 percent) who had decreased posterior wall thickness. The ratio of septal to posterior wall thickness was greater in the patients with inferior infarction than in those with anterior infarction (1.36 +/- 0.06 versus 0.89 +/- 0.06, P less than 0.001). This ratio exceeded 1.3 in 22 patients with an inferior infarction (52 percent) but was increased in only 1 patient with an anterior infarction. Hypertension did not predict the presence or absence of an abnormal ratio. Increased septal thickness on echocardiography may occur after interior infarction and result in an abnormal septal to posterior wall thickness ratio that meets current echocardiographic criteria for asymmetric septal hypertrophy.     

The effects of nitroglycerin-methoxamine combination on infarct size in conscious dogs

The effect of nitroglycerin combined with methoxamine in reducing infarct weight was studied in conscious dogs. Ten minutes after permanent left anterior descending (LAD) coronary artery occlusion, 10 dogs received nitroglycerin (450 micrograms bolus IV, then 300 micrograms/min for 4 hours) and methoxamine as needed to maintain blood pressure and heart rate. No dogs in heart failure. Ten control dogs received saline solution. Dogs were sacrificed 3 days later. The region at risk of infarction was delineated by simultaneously perfusing the aortic root with Evans blue and the distal LAD artery with saline solution under equal pressures. Slices of stained hearts were incubated with tetrazolium to identify infarct. Total weight of left ventricle (LV), risk region, and infarct was measured. Nitroglycerin-treated dogs showed no difference from control dogs in infarct weight (26.2 +/- 5.9 gm +/- SE vs 27.7 +/- 5.6 gm), percent risk region/LV (36.0 +/- 1.4% vs 37.9 +/- 3.1%), or present infarct/LV (23.5 +/- 5.2% vs 24.8 +/- 4.9%). In a subgroup with risk region/LV less than or equal to 35%, nitroglycerin reduced infarct weight by 45% (8.8 +/- 8.5% vs 15.9 +/- 7.9%), percent infarct/LV by 49% (7.1 +/- 6.8% vs 13.8 +/- 6.6%), and percent infarct/risk region by 41% (23.0 +/- 22.0% vs 38.9 +/- 15.9%). Because of the small number of dogs in the study, differences were not significant. In dogs with risk region/LV greater than 35%, nitroglycerin had no effect. Thus, in dogs without overt heart failure, nitroglycerin may salvage ischemic tissue within small areas at risk of infarction, but the results are not definitive. However, our results clearly demonstrate that in the absence of failure, nitroglycerin does not reduce the size of large infarcts.     

Healing after myocardial infarction in the dog: changes in infarct hydroxyproline and topography

Temporal changes in infarct collagen and left ventricular topography during healing after myocardial infarction were studied in 132 dogs with coronary artery ligation: 8 sham dogs and 13 with no infarction (controls) and 111 with infarction (3 at 1 day, 54 at 2 days, 25 at 7 days, 3 at 2 weeks, 9 at 4 weeks and 17 at 6 weeks). Myocardial hydroxyproline (a marker of collagen) was measured by spectrophotometry and pathologic infarct size, arteriographic occluded bed size and topography by computerized planimetry of weighed left ventricular rings. Over 6 weeks, hydroxyproline was unchanged in normal regions (average 4.20 mg/g dry weight) but increased progressively between 7 days and 6 weeks (9.94 versus 55.55 mg/g, p less than 0.001) in infarct zones. Progressive infarct contraction occurred over 6 weeks, with infarct size at 6 weeks being 40% less than at 2 days (9.7 versus 16.3% of the left ventricle, p less than 0.001), although total infarct hydroxyproline was directly related to infarct size at each time period (r = 0.73 to 0.81, p less than or equal to 0.05). Significant (p less than or equal to 0.05) left ventricular topographic changes in infarct hearts compared with control hearts included: 1) increase in cavity area (5.0 versus 3.9 cm2), endocardial circumference (8.8 versus 7.4 cm) and expansion index (infarct/normal endocardial segment length, 1.21 versus 1.02) by 7 days; and 2) decrease in thinning ratio (infarct/normal wall thickness, 0.71 versus 0.98) by 6 weeks. Also, compared with 2 day infarcts, by 6 weeks infarct area was decreased (1.8 versus 3.4 cm2) and the noninfarcted segment length increased (6.9 versus 5.4 cm). Changes in hydroxyproline and topography were similar for anterior (n = 54) and posterior (n = 57) infarcts. Thus, healing in canine infarcts is associated with cavity dilation and infarct expansion within 7 days followed by infarct contraction and thinning by 6 weeks, whereas collagen increases between 7 days and 6 weeks. Collagen deposition in expanded and thinned infarct segments explains the permanent regional shape distortion associated with ventricular aneurysms.     

Extent of myocardial infarction and reverse remodeling assessed by cardiac magnetic resonance in patients with and without right bundle branch block following alcohol septal ablation for obstructive hypertrophic cardiomyopathy

Percutaneous alcohol septal ablation (ASA) is an established technique for the relief of refractory symptoms in patients with obstructive hypertrophic cardiomyopathy. Most subjects develop right bundle branch block (RBBB) after ASA, but it is not known whether these patients have similar infarct characteristics, which may influence left ventricular (LV) pressure gradient reduction and reverse remodeling, compared with those without RBBB. Twenty-seven consecutive patients (15 men, 12 women; mean age 62 +/- 16 years) were studied with electrocardiography and cardiac magnetic resonance imaging at baseline and 1 and 6 months (n = 25) after ASA. Infarct size and location were determined at 1 month by delayed contrast-enhanced cardiac magnetic resonance imaging. The 17 subjects who developed RBBB tended to have larger infarcts (creatine kinase-MB 251 +/- 92 vs 148 +/- 97 IU, p = 0.03; cardiac magnetic resonance imaging mass 22.5 +/- 9.3 vs 16.6 +/- 8.3 g, p = 0.1) and were more likely to have sustained anterior and inferior septal transmural infarctions (9 of 17 vs 1 of 10, p = 0.03) than those without RBBB. Those who developed RBBB had greater LV mass reductions at 6 months (46 +/- 26 vs 29 +/- 13 g, p = 0.04) despite similar reductions in LV pressure gradients (64 +/- 31 vs 56 +/- 32 mm Hg). In conclusion, patients who develop RBBB after ASA tend to have more extensive transmural septal infarctions and greater reverse remodeling than those without RBBB.     

Changes in local wall thickness correlate with pathologic lesion size following radiofrequency catheter ablation: an intracardiac echocardiographic imaging study

INTRODUCTION: High-resolution intracardiac echocardiographic (ICE) imaging can accurately assess wall thickness during radiofrequency (RF) catheter ablation procedures. This study investigated the correlation of changes in wall thickness at the ablation site with pathologic lesion size. METHODS AND RESULTS: ICE image-guided 31 RF applications (30-50 W, up to 120 sec) were performed in five anesthetized closed chest swine (n = 5, body weight 35-60 kg). Twenty-four lesions were delivered in the right and left atria with standard RF; seven lesions were delivered in the left ventricle (LV) with irrigated (30-40 ml/min) RF. Wall thickness and tissue echo density measured by ICE imaging (pre- and 1-minute post-RF delivery) with increased focal echo density following RF deployment in the atria (4.5 +/- 1.5 vs 2.3 +/- 1.0 mm pre-RF) and the LV (9.8 +/- 2.3 vs 6.8 +/- 2.2 mm pre-RF; P < 0.01). The observed changes in wall thickness (DeltaWT) following ablation in the LV were greater than in the atria (3.0 +/- 1.4 vs 2.2 +/- 1.2 mm; P < 0.05). A significant correlation between DeltaWT and lesion depth (ventricular: r = 0.85, P < 0.05; atrial: r = 0.82, P < 0.01) was demonstrated at all ablation sites. Local wall thickness measured post-RF also significantly correlated with lesion depth (r = 0.89, P < 0.01), especially with that of transmural lesions (r = 0.95, n = 23, P < 0.001) at atrial and LV sites. CONCLUSION: Therapeutic RF ablation results in mural swelling and increased echo density. These changes can be detected by ICE imaging and correlate with pathologic lesion size. ICE imaging may be useful in online quantification of lesion size, especially for transmural lesions during clinical catheter ablation procedures.     

Effect of prednisolone on myocardial infarct healing: characteristics and comparison with indomethacin.

OBJECTIVE: To characterize retardation of myocardial infarct healing by corticosteroid administration, and to examine the role of suppression of prostaglandin production in its effect. DESIGN: The left circumflex coronary artery of the rabbit was occluded for 30 mins and reperfused for 72 h. Rabbits were divided into four groups: a control group, a low dose prednisolone group (L-PSL) that was treated with 5 mg/kg/24 h prednisolone, a high dose prednisolone group (H-PSL) that was treated with 10 mg/kg/24 h prednisolone, and an indomethacin group that received a 5 mg/kg intravenous bolus of indomethacin followed by 10 mg/kg/24 h. The status of infarct healing and infarcted wall thinning was assessed 72 h after ischemia by the percentage of infarct mass organized (%O/I) and the ratio of infarcted wall thickness to noninfarcted wall thickness (thinning ratio). MAIN RESULTS: The %O/I was 61.4 +/- 4.2% (mean +/- SEM) in the control group. The L-PSL and H-PSL groups had %O/Is of 48.3 +/- 3.7% and 29.1 +/- 2.1%, respectively, which were significantly lower than the control value. The difference in %O/I between the H-PSL and L-PSL groups was also significant. However, the %O/I of the indomethacin group (55.1 +/- 3.3%) was not significantly different from control. When the myocardial infarcts were retrospectively subgrouped into small infarcts (infarct volume less than 0.31 cm3) and large infarcts (greater than or equal to 0.31 cm3), infarct healing delay in large infarcts was evident only for H-PSL and not for L-PSL, while both L-PSL and H-PSL treatment retarded healing of small infarcts. No significant difference was observed in the thinning ratio for any group. CONCLUSION: Infarct healing delay by prednisolone is dosage dependent, and smaller infarcts may be more sensitive to its effect. Retardation of infarct healing by prednisolone is unlikely to be mediated by suppression of prostaglandins from the cyclo-oxygenase pathway.     

Hypertrophy of surviving myocytes overlying the infarct in human old myocardial infarctions with abnormal Q waves.

The time course of hypertrophy of surviving myocytes overlying the infarct after the onset was examined and the hypertrophy was analyzed in relation to the transmural extent of infarct in 34 autopsied hearts with Q wave infarction. The 34 hearts were divided into 4 groups according to the length of time between the onset of infarction and death. This was less than 5 days in group 1 (n = 10), 20-30 days in group 2 (n = 7), 40-60 days in group 3 (n = 7), and 12-24 months in group 4 (n = 10). To clarify the regional hypertrophy of myocytes overlying the infarct, the size of the surviving myocytes in the outer third of the left ventricular wall in the 1-cm wide central zone of the infarct was compared with that of the myocytes in the outer third of the left ventricular wall without infarction (control wall) in the same heart. To exclude factors which stimulate the hypertrophy of the whole left ventricle, the ratio of the monocyte diameter in the infarcted wall to that in the control wall was examined. It was 1.0 +/- 0.0 (mean +/- SD) in group 1, 1.0 +/- 0.1 in group 2, 1.2 +/- 0.1 in group 3, and 1.3 +/- 0.1 in group 4. The ratio was significantly higher in group 3 than in group 1 and 2, and was highest in group 4. In group 4, the corrected percentage transmural extent of infarct indicating the original transmural extent of infarct at the acute stage was 63 + 8%, and this transmural extent correlated positively with the ratio of myocyte diameter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Importance of venodilatation in prevention of left ventricular dilatation after chronic large myocardial infarction in rats: a comparison of captopril and hydralazine

In rats with large myocardial infarctions, we compared the effects of captopril, a presumed arterial and venous vasodilator, with hydralazine, which is thought primarily to be an arterial vasodilator. To determine if the effects of captopril were dependent on the pathophysiological consequences of heart failure, we also studied a group of noninfarcted rats treated with captopril. In noninfarcted rats treated with captopril, left ventricular (LV) systolic and mean aortic pressures decreased from 132 +/- 12 to 107 +/- 15 mm Hg and 122 +/- 1 to 100 +/- 2, respectively (p less than 0.01). In noninfarcted rats, captopril decreased LV weight, LV weight/body weight, and total heart weight/body weight but produced no effects on the peripheral venous circulation. Rats subjected to coronary artery ligation were selected by ECG criteria to have large myocardial infarctions and were treated for 4 weeks with captopril (n = 8), hydralazine (n = 5), or placebo (n = 9). In infarcted rats treated with captopril, LV systolic, mean aortic pressures and LV end-diastolic pressure (LVEDP) decreased (p less than 0.01) from 115 +/- 4 to 86 +/- 3 mm Hg, 106 +/- 4 to 74 +/- 3 mm Hg, and 23 +/- 2 to 11 +/- 2 mm Hg, respectively. Mean circulatory filling pressure decreased (p less than 0.05) from 11.2 +/- 0.6 to 8.7 +/- 0.8 mm Hg and venous compliance increased (p less than 0.05) from 2.04 +/- 0.07 to 2.70 +/- 0.20 ml/mm Hg/kg. Blood volume decreased (p less than 0.05) from 67.3 +/- 0.9 to 58.2 +/- 1.8 ml/kg.(ABSTRACT TRUNCATED AT 250 WORDS)