Long-term preservation of ischemic myocardium in the dog by hyaluronidase

The administration of hyaluronidase is a promising intervention to protect the ischemic myocardium in man, but evidence of the extent to which it may reduce the ultimate size of an infarct is not well-defined. Hence, open chest, anesthetized dogs were randomized into 10 control dogs which received saline and eight treated dogs which received three doses of hyaluronidase (500 NF units/kg I.V.) at 15 minutes, 2 hours and 24 hours after occlusion of the left anterior descending coronary artery (CAO). Regional myocardial blood flow (RMBF) assessed by the microsphere technique was measured 12 minutes after CAO. The chest was then closed and the dogs were allowed to recover. Twenty-one days after CAO, the hearts were excised, divided into 1 cm thick slices and incubated in triphenyl tetrazolium chloride. Infarct size was then determined by planimetry. The left ventricular myocardium was divided into multiple samples for RMBF analysis. In control dogs 23.2 +/- 2% of the left ventricle was infarcted, compared to only 9 +/- 2.8% (P less than 0.001) in hyaluronidase-treated dogs. RMBF in noninfarcted myocardium directly adjacent to the infarct was similar to that in the normal zone remote from the infarct in the control dogs; however, in the hyaluronidase-treated dogs, blood flow in the myocardium adjacent to the infarct was significantly reduced to 68% of normal (P less than 0.01) in the outer myocardial wall and to 86% of normal (P less than 0.02) in the inner myocardial wall, which indicates that this tissue, at least in some part, was in jeopardy, but was salvaged by hyaluronidase. Epicardial electrocardiographic data showed that three weeks after CAO, Q waves were less frequent and smaller in hyaluronidase compared to untreated dogs. Preservation of the frequency and magnitude of R waves was greater in the hyaluronidase-treated group at three weeks. We conclude that hyaluronidase resulted in long-term preservation of the ischemic myocardium.     

Effect of decreased blood flow and ischemia on myocardial thallium clearance

To determine the effect of reduced coronary blood flow on myocardial thallium-201 clearance over a range of flows, miniature radiation detectors were inserted into the left ventricular apex and positioned against the anterior and posterior endocardial walls in 21 dogs. Thallium was administered intravenously and myocardial tracer activity was monitored continuously for 1 hour in both walls. A balloon occluder was then partially inflated around the left anterior descending coronary artery in 19 dogs, producing a range of anterior wall blood flow reductions as assessed by the microsphere technique. Thallium activity was monitored continuously for 3 hours in both walls. Two dogs served as control animals and had no coronary artery occlusion at 1 hour. At the end of the 4 hour experiment, the dogs were sacrificed and the hearts counted in a well counter. The 19 dogs with coronary artery stenosis were divided into three groups (mild, moderate and severe flow reduction groups) on the basis of their poststenosis anterior/posterior wall regional myocardial blood flow ratios. The two control dogs had similar thallium clearances in the anterior and posterior left ventricular walls during the 3 hour period, as assessed by the radiation detectors, and by a final anterior/posterior wall thallium ratio near unity. All three groups of dogs with coronary stenosis had comparable fractional thallium clearances from the anterior and posterior walls before and after the balloon occluder inflation. The final anterior/posterior left ventricular wall thallium ratios were not significantly different than unity for all three groups of dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetics and imaging of indium-11-labeled autologous platelets in experimental myocardial infarction

The kinetics of accumulation and the external imaging patterns of indium-111-labeled platelets infused in a dog model of left anterior descending coronary artery occlusion with reperfusion were studied. The effects of infarct age and regional residual myocardial blood flow upon platelet accumulation were quantified, and the capacity of indium-111 platelets to image the experimental infarction was evaluated qualitatively. The endocardial accumulation of indium-111 platelets occurred primarily in infarct zones with residual blood flow less than 0.6 times normal and was maximal (24.98 +/- 2.76 times normal) in the lowest blood flow zone (less than 0.1 times normal). Indium-111 platelet accumulation in the epicardium occurred in the regions with blood flow less than 0.6 times normal and was maximal (17.83 +/- 1.20 times normal) in the lowest blood flow zone (less than 0.1 times normal). The maximal endocardial and epicardial platelet accumulation occurred 24 hours after reperfusion and was significantly decreased at 48 hours. In vivo cardiac images revealed discrete areas of increased myocardial radioactivity uptake in the anterior wall of dogs 24 hours after reperfusion. All images 48 hours after reperfusion were negative. Thus, in the experimental setting, indium-111 platelets allow quantification of platelet accumulation after myocardial infarction at a tissue level and provide a noninvasive means of in vivo imaging of reperfused infarcted myocardium.     

Inotropic stimulation of reperfused myocardium with dopamine: effects on infarct size and myocardial function

Prolonged postischemic ventricular dysfunction ("stunned myocardium") may be responsible for heart failure after myocardial reperfusion. Although inotropic stimulation can enhance the contractility of stunned myocardium, it could potentially increase infarct size and thereby impair ultimate recovery of myocardial function. In 16 anesthetized dogs, the left anterior descending coronary artery was occluded for 2 hours, and then reperfused. At 45 minutes of reperfusion, the dogs were randomized to receive a 3 hour intravenous infusion of either saline solution or dopamine (10 micrograms/kg per min), and 1 hour after the infusion was discontinued the area of necrosis and an in vivo area at risk of necrosis were determined. All dogs had serial two-dimensional echocardiograms with computer-assisted analysis and in vivo biopsies for determination of adenosine triphosphate and creatine phosphate levels. Dopamine caused an increase in the contractility of the reperfused myocardium, with systolic wall thickening increasing from -4.1 +/- 2.6 (mean +/- SEM) to +24.0 +/- 3.7% (p less than 0.002) and short-axis cross-sectional ejection fraction increasing from 27.1 +/- 4.7 to 71.6 +/- 4.4% (p less than 0.002) after 15 minutes of infusion. Regional myocardial blood flow in the previously ischemic epicardium was increased from 1.18 +/- 0.11 ml/min per g with saline to 2.95 +/- 0.36 ml/min per g with dopamine (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms and time course for the disappearance of thallium-201 defects at rest in dogs: Relation of time to peak activity to myocardial blood flow

The kinetics of thallium (Tl)-201 in ischemic myocardium was studied with a balloon constrictor to create a fixed reduction in distal left anterior descending coronary arterial pressure in 19 dogs. After 30 to 60 minutes of partial occlusion, Tl-201 was administered intravenously. Tracer activity was monitored continuously for 4 hours in both the normal and reduced flow zones using implanted miniature cadmium telluride radiation detectors. Microsphere-determined regional myocardial blood flow, heart rate, mean arterial pressure, mean left atrial pressure, mean distal left anterior descending coronary arterial pressure and sonomicrometer-determined myocardial wall thickness did not change significantly during each study. Thallium-201 time-activity curves for the normal zones (flow 1.00 ml/min per g or more) demonstrated an initial rapid increase to 80 to 90 percent of peak, an early peak (mean 20 minutes) and then a monoexponential decrease in activity (decay constant λ = 0.0013 min^?1). Thallium-201 time-activity curves for mildly and moderately ischemic zones (flow = 0.40 to 0.99 ml/min per g) demonstrated a progressive delay in the time to peak activity with progressive reductions in flow (r = 0.84). Thallium-201 time-activity curves for severely ischemic zones (flow less than 0.40 ml/min per g) demonstrated a rapid initial increase, and then no further increase in activity, probably because of cell death with a resultant decreased ability to accumulate Tl-201.When the Tl-201 activity ratio (reduced/normal flow zone) was calculated as a function of time for each dog, there was a progressive increase in this ratio over time for all dogs, although the rate of increase was slower for dogs with increasing degrees of flow reduction. This increasing ratio over time would correspond to disappearance of an initial Tl-201 resting scintiscan defect over time. The mechanism for the increasing ratio in dogs with mild or moderate flow reduction was both clearance of Tl-201 from normal zones and accumulation of Tl-201 by ischemic zones. However, the mechanism for the increasing ratio in dogs with severe flow reductions was a faster rate of Tl-201 loss from the normal compared with the reduced flow zone.     

Myocardial kinetics of thallium-201 after stress in normal and perfusion-reduced canine myocardium

Despite the emerging use of quantitative computer programs for assessing myocardial thallium uptake and clearance after exercise, little is known about the kinetics of thallium after exercise stress. Accordingly, 11 mongrel dogs with experimental left anterior descending coronary stenoses were given thallium during norepinephrine infusion to simulate exercise. The infusion was discontinued and thallium activity was monitored regionally using miniature radiation detectors for 3 hours. Heart rate, arterial pressure and double product all increased significantly during norepinephrine infusion. The mean fractional myocardial thallium clearance was lower (0.47 +/- 0.03 [+/- standard error of the mean]) for the stenosis zone than for the no-stenosis zone (0.57 +/- 0.03) (p less than 0.0001). The stress blood flow ratio (stenosis/no-stenosis zone = 0.27 +/- 0.06) was significantly lower than the final thallium activity ratio (0.68 +/- 0.07) (p less than 0.001), consistent with thallium redistribution occurring over the 3-hour period. Myocardial thallium activity in the stenosis zone peaked in a mean of 2.2 minutes, then washed out biexponentially with a final decay constant of 0.0035 +/- 0.0005 min-1. Myocardial thallium activity in the no-stenosis zone peaked within 1 minute in all dogs, then washed out biexponentially, with a final decay constant of 0.0043 +/- 0.0003 (p less than 0.001 compared with stenosis zone). In conclusion, fractional clearance of thallium can differentiate myocardium distal to a coronary artery stenosis from that supplied by a normal coronary vessel.     

Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction

To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.     

Imaging and characterization of acute myocardial infarction in vivo by gated nuclear magnetic resonance

Imaging by nuclear magnetic resonance (NMR) techniques has been shown to provide high-contrast resolution between soft tissues and characterization of normal and pathologic tissues by differences in magnetic relaxation times. The current study was designed to determine whether electrocardiogram (ECG)-gated NMR imaging of the canine heart in vivo could distinguish normal from infarcted myocardium without the use of intravenous paramagnetic contrast agents. Seven dogs were studied by ECG-gated NMR imaging in vivo (spin-echo technique) with a 0.35 Tesla superconducting magnet at 2 to 7 days after ligation of the left anterior descending coronary artery. In six of the seven dogs, signal intensity was increased in the anterior wall compared with the remainder of the left ventricle; this region of high signal intensity corresponded to the area of myocardial infarction demonstrated at postmortem examination. The signal intensity of the infarcted region was 66 +/- 27% greater than that of normal myocardium (p less than .01). The T2 (spin-spin) relaxation time was 69 +/- 3% longer in the infarcted myocardium as compared with normal myocardium (p less than .01). The NMR images from the seventh dog had uniform signal intensity throughout the myocardium of the left ventricle. An infarct was not evident on postmortem examination in this dog. Thus gated NMR imaging in vivo by the spin-echo technique displays acute myocardial infarctions as regions of high signal intensity without the use of contrast media. The infarct is characterized by a prolonged T2 relaxation time.     

Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism

Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 +/- 0.39 vs. 0.59 +/- 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 +/- 22.6% vs. 61.2 +/- 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.     

Progressive failure of coronary flow during reperfusion of myocardial infarction: documentation of the no reflow phenomenon with positron emission tomography

During reperfusion of a myocardial infarct, development of microvascular occlusion may result in regional hypoperfusion ("no reflow") despite a patent infarct-related artery. This study examined the extent and time course of no reflow with use of rubidium-82 positron emission tomography. In 12 anesthetized dogs, the left anterior descending coronary artery was occluded for 90 min and then freely reperfused. Regional myocardial perfusion was imaged by serial rubidium-82 positron emission tomography during coronary occlusion and every 30 min during reperfusion. After 4 h of reperfusion, infarct size and no reflow zone were measured postmortem by triphenyltetrazolium and thioflavin staining, respectively. Perfusion defects evident on rubidium-82 images during coronary occlusion rapidly resolved during the early reflow period. However, a recurrent perfusion defect appeared after 1 to 2 h of reflow in all dogs. The severity of recurrent perfusion defects progressed with time; after 5 min of reflow, relative perfusion in the left anterior descending artery territory was 97 +/- 6% of that in the normal circumflex artery region, but perfusion decreased progressively to 68 +/- 5% after 2 h (p less than 0.05) and to 55 +/- 4% after 4 h of reperfusion (p less than 0.05 versus 2 h). As measured by radioactive tracer microspheres, endocardial blood flow decreased similarly in the postischemic left anterior descending artery region from 1.2 +/- 0.2 ml/min per g after 5 min of reflow to 0.4 +/- 0.1 ml/min per g after 3 h of reflow (p less than 0.01). Residual infarct perfusion, measured by rubidium-82 after 4 h of reflow, was related to both infarct size (r = -0.88) and the extent of the no reflow zone (r = -0.84) in the postmortem left ventricular sections. Thus, serial positron emission tomography with rubidium-82 demonstrates a progressive loss of infarct perfusion, beginning 1 to 2 h after initial restoration of blood flow despite patency of the infarct-related artery. This phenomenon is probably a manifestation of progressive microvascular occlusion within the reperfused myocardium.     

Early differentiation of infarcted and noninfarcted reperfused myocardium in dogs by quantitative analysis of regional myocardial echo amplitudes

This study tests the hypothesis that ischemic but viable reperfused myocardium can be differentiated from infarcted reperfused myocardium by regional analysis of myocardial echo amplitudes. In eight closed-chest, anesthetized dogs, the left anterior descending coronary artery was occluded for 3 hours, followed by 1 hour of reperfusion, and sacrifice. Infarct size was measured by the triphenyl tetrazolium chloride technique in a 1-cm-thick mid-left ventricular transverse slice, and matched with a corresponding end-diastolic two-dimensional echo short-axis cross-section. Outlining of epi- and endocardial surfaces, along with construction of a mid-myocardial outline, allowed measurements of regional myocardial echo intensities and grey-level histograms in subendo- and subepicardial regions. In 36 eventually infarcted subendocardial segments (greater than 20% wall necrosis), average pixel intensity (arbitrary units) was 73.7 +/- 33.1 (SD) in control, 75.8 +/- 33.0 at 3 hours of occlusion, and 107.8 +/- 40.9 at 5 minutes, 105.5 +/- 38.9 at 15 minutes, and 101.1 +/- 37.6 at 60 minutes postreperfusion P less than 0.05 vs. control or occlusion); intensity in normal segments (no or less than 20% wall necrosis) was 60.0 +/- 18.6 in control, 57.4 +/- 20.3 at 3 hours of occlusion, and 63.5 +/- 14.8, 68.0 +/- 27.9, and 64.2 +/- 22.3 at 5, 15, and 60 minutes postreperfusion, respectively (no significant change). The skew of the grey-level distribution in infarcted subendocardial segments did not change from control (0.49 +/- 0.72) to 3 hours of occlusion (0.41 +/- 0.52), but decreased (shift to higher echo amplitude) significantly at 5 minutes (-0.31 +/- 0.53), 15 minutes (-0.22 +/- 0.50), and 60 minutes (-0.28 +/- 0.45) after reperfusion (P less than 0.05 vs. control or occlusion); in normal subendocardial segments, there was no significant change throughout the study. In 31 partly infarcted subepicardial segments (greater than 50% wall necrosis), changes in postreperfusion echo amplitudes were less significant. Average pixel intensity was 71.3 +/- 28.6 in control, 71.8 +/- 29.2 after coronary occlusion, and 89.2 +/- 35.3, 83.7 +/- 37.5, and 85.6 +/- 34.9 at 5, 15, and 60 minutes after reperfusion, respectively. It is concluded that reperfusion of irreversibly injured myocardium is associated with consistent early increase in regional myocardial echo intensities and changes in the grey-level distribution. Such alterations might be used to detect the extent of tissue necrosis within minutes after reperfusion.     

Quantitation of myocardial infarct size from thallium-201 images: validation of a new approach in an experimental model

A new computer-based method has been developed to quantitate myocardial infarct size from the size of the regional thallium-201 deficit. The operator outlines the left ventricular myocardial activity with an ellipse. The program then plots the background-corrected activities of the highest mean value in a 3 pixel myocardial band perpendicular to and within the ellipse. The approach uses a new interpolative background correction. To determine the accuracy of this approach in assessing regional thallium deficit size, acute myocardial infarction was produced in six dogs by 24 hour occlusion of the proximal left anterior descending coronary artery. Infarct size was assessed from planar thallium images of the dog heart in three views, each with the chest opened and closed and with the heart excised and placed in a cradle. Before removal of the heart, triphenyltetrazolium chloride was infused to delineate normal from infarct tissue. Transverse slices of left ventricle were made and thallium images of the slices acquired. Infarct size delineated by triphenyltetrazolium chloride staining was expressed as a percent of the total left ventricular slice surface area (planimetric infarct size). Infarct size from whole heart and left ventricular slice thallium images was expressed as a percent of the total length of the left ventricular perimeter (perimetric infarct size). This was determined from points below a certain percent of normalized peak thallium activity in the computer-generated thallium activity curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial cell hypertrophy after myocardial infarction with reperfusion in dogs.

BACKGROUND. The potential role of myocardial cell hypertrophy in the ischemic zone in the mechanism of late recovery of regional contractile function after myocardial infarction followed by reperfusion has not been examined. METHODS AND RESULTS. Eight chronically instrumented, conscious dogs were subjected to 90-120 minutes of circumflex coronary artery occlusion followed by reperfusion. The thickness and function of the anterior (AT) and posterior (PT) walls was measured by ultrasonic gauges at control, during occlusion, and after reperfusion. After 3 weeks, cross-sectional areas of surviving cells were determined from subepicardial (epi), midwall (mid), and subendocardial (endo) regions in six dogs and compared with those from six animals without infarction, including three sham-operated control dogs. PT systolic wall thickening showed dyskinesia during occlusion but recovered after reperfusion to 48% of control at 1 week and 67% at 3 weeks. End-diastolic thickness of the PT wall increased markedly after reperfusion, but AT and PT walls were only slightly thicker (p = NS) than in control dogs at 3 weeks. Cross-sectional areas of reperfused dogs in the infarct region averaged 279 (PTepi), 291 (PTmid), and 317 microns 2 (PTendo) and were significantly larger than in control animals (237 [PTepi], 241 [PTmid], and 233 microns 2 [PTendo]). PT cell areas were significantly larger than AT cells, ENDO cell areas were larger than EPI cells (both p < 0.05), and ENDO cells of the AT wall were larger than those of noninfarcted dogs (p < 0.05). CONCLUSIONS. In dogs with myocardial infarction followed by reperfusion, the cross-sectional areas of cells in the infarcted PT wall were larger than those in the noninfarcted AT wall, and within both the infarcted and noninfarcted zones, cell areas were larger in the endocardial than the epicardial region. In all regions of the infarcted wall and in the ENDO region of the noninfarcted wall, cell areas were generally larger than those of control dogs without infarction, and the control dogs showed no transmural differences in cell areas. The mechanisms responsible for this significant remodeling of the reperfused infarcted zone, which involves myocardial cellular hypertrophy, are unknown, but it is possible that hypertrophy of surviving regions of the infarcted wall played a role in the late recovery of regional function that accompanied this hypertrophic response.     

Early infarct expansion: Structural or functional?

With the onset of ischemia, the length of myocardial segments increases rapidly, distorting ventricular geometry. Permanent stretching and thinning of infarcted zones have been termed infarct expansion. Although these changes are noted within minutes in vivo, infarct expansion may not be seen for days in postmortem preparations. The apparent postmortem reversal of early infarct expansion suggests that early expansion may be a functional phenomenon, reversible in the early hours of infarction. Alternatively, reversal of expansion may be a postmortem artifact, concealing the importance of underlying structural abnormalities. Myocardial infarction was produced in five dogs by occluding the left anterior descending coronary artery. Ultrasound sonomicrometers were used to measure myocardial segment end-diastolic length in the infarct and normal zones. After 3 hours of ischemia, the heart was arrested in diastole and biopsy specimens were taken from the normal and infarct zones. Sarcomere length was measured from electron photomicrographs, and myofiber width was measured from light photomicrographs. After 3 hours of ischemia, infarct zone segment length had increased significantly more than normal zone length (116 +/- 11 [SD] versus 103 +/- 4% of control length, p less than 0.05), whereas 2 minutes after cardiac arrest, both the infarct and normal zones returned to preischemic segment length, demonstrating apparent reversibility of early infarct expansion. However, histologic study revealed that the infarct zone myofibers were significantly thinner than normal zone myofibers (7.9 +/- 0.3 versus 9.4 +/- 0.3 micron, p less than 0.001) and sarcomere length in the infarct zone was significantly longer than that in the normal zone (1.9 +/- 0.2 versus 1.5 +/- 0.2 micron, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of acute myocardial infarct scintigraphy with postmortem studies.

Acute myocardial infarct scintigraphy with technetium-99m-pyrophosphate was performed in a patient with an acute massive transmural infarct. The patient died 12 hours later, and postmortem tracer studies demonstrated a tracer concentration ratio of 13:1 between acutely infarcted myocardium and normal myocardium remote from the infarct. The concentration of tracer in tissue bordering on the infarct but without histologic evidence of acute infarction was 1.5 times that in normal tissue remote from the infarct. In vitro scintigraphy of the excised heart revealed a pattern of tracer distribution similar to that of scintiscans obtained before death. The biologic distribution of 99mTc-pyrophosphate, with large tracer concentrations only within the acutely infarcted tissue, suggests that acute myocardial infarct scintigraphy can be used to estimate the extent of an acute myocardial infarct.     

Detection of intramyocardial hemorrhage using high-field proton (1H) nuclear magnetic resonance imaging

Proton (1H) nuclear magnetic resonance (NMR) imaging has been used to define zones of myocardial infarction (MI), which appear as areas of relatively increased signal intensity (SI). However, zones of decreased SI have been observed within the areas of infarction and have been postulated to result from intramyocardial hemorrhage. To explore this phenomenon further, ex vivo spin-echo 1H NMR imaging at 1.5 Tesla was performed in 17 dogs after 24 hr (n = 9) and after 72 hr (n = 8) of coronary artery occlusion. In all dogs, a zone of increased SI (118 +/- 9% compared with normal myocardium) was observed in the distribution of the occluded coronary artery. In 12 of the 17 dogs, zones of decreased SI (92 +/- 8% compared with normal) were seen within or around the central zone of increased SI. Gross inspection and histological assessment of sliced myocardium usually disclosed hemorrhage in the regions of decreased SI. In three of the five dogs with no apparent zones of decreased SI on NMR, the infarct was small, and only minor hemorrhage was observed by gross inspection, whereas in the remaining two dogs no hemorrhage was seen. Myocardial flow in the hemorrhagic regions was significantly higher than in the necrotic core (59 +/- 29% vs. 31 +/- 24% compared with control, P less than 0.05). Image-derived calculation of T2 relaxation times in the different infarcted regions revealed a significant shortening of T2 in the infarcted hemorrhagic zones with decreased SI compared with the infarct zones with increased SI (49 +/- 8 msec vs. 66 +/- 8 msec, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of ischemic injury and early reperfusion derangements by hypothermic retroperfusion

Hypothermic synchronized retroperfusion was applied during coronary artery occlusion to determine its ability to alleviate junctional derangements of reperfusion and to reduce infarct size. The proximal left anterior descending coronary artery was occluded in 25 closed chest dogs for 3 hours and then reperfused for 7 days. Thirteen dogs with no reperfusion pretreatment served as a control group (Group A). In 12 dogs, hypothermic retroperfusion was applied from 30 minutes up to 3 hours of the occlusion period (Group B). Sequential two-dimensional echocardiographic and hemodynamic as well as metabolic measurements were performed. Compared with untreated control dogs, dogs with hypothermic synchronized retroperfusion had significantly reduced heart rate and rate-pressure product, decreased left ventricular volumes and improved ejection fraction during the occlusion period. Two-dimensional echocardiographically-derived ischemic zone systolic fractional area change and systolic wall thickening indicated significantly improved function as a result of retroperfusion. During the reperfusion period, untreated control dogs (group A) had more severe derangements in hemodynamics and wall motion than dogs treated by hypothermic retroperfusion (group B). Mortality was 30.7% in group A, 16.7% in group B and 7th day infarct size as percent of the left ventricle was 12.0 +/- 6.5 (mean +/- standard deviation) and 4.2 +/- 5.9, respectively (p less than 0.02). It is concluded that hypothermic synchronized retroperfusion applied after coronary occlusion and before reperfusion significantly improves cardiac function during occlusion, minimizes complications of reperfusion and reduces the ultimate infarct size. Because this form of circulatory assistance helps maintain cardiac function and delays the evolution of myocardial necrosis, its application may be beneficial during an evolving acute myocardial infarction before achievement of surgical or nonsurgical reperfusion.     

Is the shortening of the QTc interval in Q-wave leads showing ST segment shift during exercise testing a new ECG marker of myocardial ischemia and viability in patients with previous anterior myocardial infarction?

PURPOSE: To evaluate whether the shortening of the QTc-interval, measured in Q-wave leads showing ST segment elevation during exercise testing may be a marker of stress-induced transmural ischemia (and indirectly of myocardial viability) in the infarct zone in patients with prior Q-wave anterior myocardial infarction. METHODS: We evaluated 15 consecutive patients (Group A) with previous anterior myocardial infarction presenting these peculiarities: 1) ST segment elevation over Q waves during exercise testing; 2) critical (> 75%) stenosis of LAD; 3) evidence by echocardiography and stress-redistribution-reinjection 201thallium myocardial scintigraphy (SRR201TIMS) of viable myocardium in the infarct zone (akinetic segments with normal echo-reflectivity plus > 7 mm end-diastolic wall thickness and significant 201thallium redistribution after reinjection). The study control group (Group B) consisted of 15 patients with previous myocardial infarction, critical stenosis of LAD and evidence of scarring by imaging techniques (increased echo-reflectivity associated with an end-diastolic wall thickness < 6 mm and no 201thallium redistribution in infarcted areas). The QTc interval was measured at rest and at peak stress in all leads, and particularly in infarct-related leads showing ST-T changes, and the lead-by-lead fractional difference percentage between the QTc intervals (delta QTc) was calculated. The delta QTc was measured again during exercise testing in 11 patients from Group A (Group A1) who showed significant contractility recovery three months after complete myocardial revascularization. A delta QTc shortening < -10% was considered "significant". RESULTS: In 14/15 patients from Group A, a significant delta QTc shortening was measured, while in 14/15 patients from Group B no significant delta QTc shortening was detected (sensitivity = 93.3%; specificity = 93.3%) (p < 0.0001). The mean delta QTc in Group A was -18.1 +/- 8.5%; the mean delta QTc in Group B was -4.2 +/- 7.8% (p < 0.0001). No patient from Group A1 showed a significant delta QTc shortening in Q-wave leads (mean delta QTc group A1 = +6.9 +/- 14.8%). CONCLUSIONS: delta QTc shortening in infarct-related leads during exercise testing is a simple ECG marker of transmural ischemia and, indirectly, of myocardial-viability. This sign is no more evident after myocardial revascularization and may be useful in identifying "hibernating-myocardium".     

Dependency of location of salvageable myocardium on type of intervention

The purposes of this study were (1) to determine the location of the salvageable border zone in relation to the ischemic coronary bed, and (2) to determine whether the location of salvaged tissue differs depending on the mechanism of salvage and the type of intervention. Forty-four open chest dogs were subjected to either 6 hours of occlusion of the left anterior descending coronary artery or 4 hours of occlusion of this artery followed by 2 hours of reperfusion. Dogs with 6 hours of occlusion received either saline solution (Group I, n = 9), ibuprofen, 12.5 mg/kg body weight, (Group II, n = 7), flurbiprofen, 1 mg/kg (Group III, n = 10), or L-hydroxyphenyl-glycine, 10 mg/kg (Group IV, n = 8) intravenously 30 minutes and 3 hours after coronary occlusion. Dogs in Group V (n = 10) were subjected to 4 hours of coronary occlusion followed by 2 hours of reperfusion, but received no drugs. Although from 17 to 42 percent of the myocardium at risk did not become infarcted in Groups II through V compared with only 6 percent in Group I, the location of salvaged tissue was different in dogs receiving reperfusion (Group V) from that of dogs receiving drug interventions (Groups II, III and IV). In Group V, the salvaged tissue was primarily subepicardial with virtually no lateral zone of salvaged tissue (ratio of salvaged subepicardium to salvaged subendocardium 14.8 ± 1.9 to 1). In Groups II, III and IV, there was a portion of the myocardium at risk at both lateral margins that did not become infarcted, as well as a portion of subepicardial tissue (ratio of subepicardium to subendocardium salvaged 3.3 ± 0.4 in Group II, 2.5 ± 0.1 in Group III and 2.0 ± 0.2 in Group IV).Thus, infarct size reduction by ibuprofen, flurbiprofen and L-hydroxy-phenylglycine is accompanied by lateral and subepicardial zones of salvage, whereas tissue salvaged by reperfusion is located primarily in the subepicardium. These observations should help to resolve the controversy regarding the existence and location of the various zones of ischemic myocardium that can be salvaged by drugs or reperfusion.     

Response of reperfusion-salvaged, stunned myocardium to inotropic stimulation

The purpose of this study was to determine whether myocardium salvaged by reperfusion following coronary occlusion could respond to inotropic stimulation by dopamine. Mongrel dogs underwent a 2-hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for 5 or 28 hours. Dopamine (5 to 10 micrograms/kg/min) or dextrose was administered 1 hour or 24 hours after the onset of reperfusion. Serial, computer-assisted, two-dimensional echocardiographic determination of percentage of systolic wall thickening (%SWT) and cross-sectional ejection fraction (% delta area) were used to evaluate the response to treatment. Myocardium in the region of central ischemia contracted poorly after 1 hour of reperfusion (mean %SWT = 1.3 +/- 13.3% [mean +/- SD] compared to preocclusion value of 43.6 +/- 18.5%, p less than 0.001) and tended to thin at 24 hours of reperfusion (mean %SWT = -6.0 +/- 12.3%, p less than 0.001). After 1 hour of reperfusion, dopamine produced a greater than fourfold improvement in %SWT within the reperfused zone (to 15.3 +/- 7.3%, p less than 0.05). After 24 hours of reperfusion, dopamine again produced an improvement in %SWT (to 5.8 +/- 12.5%, p less than 0.05). There were no significant changes in %SWT with dextrose infusion. Thus, dopamine stimulates the reperfusion-salvaged but noncontracting (stunned) myocardium to contract as early as 1 hour after reperfusion.