Functional infarct expansion, left ventricular dilation and isovolumic relaxation time after coronary occlusion: a two-dimensional echocardiographic study

Left ventricular dilation and infarct expansion after acute myocardial infarction are associated with an increased morbidity and mortality. The purpose of this study was to determine whether angiotensin-converting enzyme inhibition could reverse left ventricular dilation and improve the diastolic properties of the left ventricle very early after coronary occlusion. The acute time course of left ventricular dilation and infarct expansion (as determined by two-dimensional echocardiography) and early diastolic isovolumic relaxation time were studied in 20 dogs subjected to 3 h of coronary occlusion. End-diastolic area before occlusion was 8.4 +/- 0.5 and 8.9 +/- 0.7 cm2 (p = NS) in the captopril- and the saline-treated group, respectively. At 30 min after occlusion (pretreatment), end-diastolic area increased to 12.6 +/- 0.8 cm2 in the captopril-treated group (p less than 0.01) and 11.3 +/- 0.9 cm2 (p less than 0.05) in the saline-treated group. Three hours after occlusion and after captopril treatment, end-diastolic area decreased to 9.4 +/- 0.6 cm2 (p less than 0.05 versus 30 min after occlusion), whereas it was unchanged in the saline-treated group. Functional infarct expansion (as assessed by end-systolic anterior to posterior endocardial segment length ratio) occurred early after occlusion, and captopril reduced this expansion. Pretreatment values for early diastolic isovolumic relaxation time increased from 29.1 +/- 2.4 to 50.5 +/- 2.9 ms in captopril-treated dogs (p less than 0.01) and from 34.3 +/- 3.4 to 46.9 +/- 2.7 ms in saline-treated dogs (p less than 0.01) after coronary occlusion, implying a worsening of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion

Prolonged nontransmural ischemia was produced and the early and late effects of reperfusion were studied in 10 conscious dogs instrumented over the long term. Five hours of partial circumflex coronary artery stenosis was produced with a hydraulic occluder, followed by gradual release over 20 min, with measurements of left ventricular pressure, regional myocardial function (systolic wall thickening by sonomicrometry), coronary blood flow velocity (pulsed Doppler), and myocardial blood flow (microspheres). During coronary stenosis the occluder was adjusted frequently to maintain a reduction of systolic wall thickening to 50% to 75% of control (average 62.6% of control). Myocardial blood flow in the ischemic area at 4 hr of partial coronary stenosis was reduced in the inner layers of the myocardium (subendocardium, from 0.81 +/- 0.18 at control to 0.36 +/- 0.08 SD, p less than .01; midwall, from 0.77 +/- 0.20 to 0.46 +/- 0.07 ml/min/g, p less than .01), accompanied by significant ST segment elevation on the subendocardial electrogram (0.83 +/- 0.96 to 4.58 +/- 4.10 mV; p less than .05) and decreased left ventricular dP/dt (3503 +/- 462 to 2991 +/- 339 mm Hg/sec; p less than .01). Within a few minutes after complete release of partial coronary stenosis, ST segments returned to control and myocardial blood flow of the inner layers was increased (subendocardium, 1.37 +/- 0.39, p less than .01; midwall, 0.97 +/- 0.28, p less than .05), but systolic wall thickening and left ventricular dP/dt were significantly depressed and remained reduced at 24, 48, and 72 hr when myocardial blood flow was normal. By seven days, systolic wall thickening and left ventricular dP/dt had returned to control (94.1 +/- 7.0% of control, 3353 +/- 605 mm Hg/sec, respectively; NS). Histologic changes caused by ischemia constituted only 2.7% (average) of the tissue between the crystals in the ischemic wall, but ischemic damage in the posterior papillary muscle, which did not contain crystals, was 31.9%. Thus, regional myocardial dysfunction reduced by nontransmural ischemia for 5 hr persisted for at least 3 days, with only slight damage to the left ventricular free wall but considerable infarction of the posterior papillary muscle. Full recovery of regional and global contractile function of the free wall then occurred within a period of 1 week.     

Changes in isovolumic segment shortening following acute coronary occlusion: disproportionate effects of anterior versus posterior ischemia

We evaluated the changes in left ventricular pressure and isovolumic segment shortening in both the ischemic and nonischemic areas following acute coronary occlusion in 12 conscious dogs instrumented for the measurement of subendocardial segment lengths perfused by the left circumflex coronary artery and left anterior descending coronary artery, and left ventricular pressure. An externally inflatable pneumatic occluder was placed around the left circumflex coronary artery. In 6 dogs, another occluder was installed around the proximal left anterior descending coronary artery. Under the resting conditions, the isovolumic segment shortening in the areas supplied by the left anterior descending coronary artery and the left circumflex coronary artery were 2.1 +/- 0.5% (SE) and -0.1 +/- 0.5% (P less than 0.01; versus values in the area of the left anterior descending coronary artery), respectively. During a 1-min occlusion of the left circumflex coronary artery, the isovolumic shortening in the anterior segment increased to 3.8 +/- 0.5% (P less than 0.001; versus values in the basal state), while the posterior segment produced isovolumic elongation (-2.2 +/- 0.5%, P less than 0.001; versus values in the basal state). By contrast, during a 1-min occlusion of the left anterior descending coronary artery, the extent of isovolumic bulge in the anterior segment and the augmentation in the isovolumic shortening in the posterior segment was less prominent compared with the occlusion of the left circumflex coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacologic and behavioral effects on arrhythmias that immediately follow abrupt coronary occlusion: a canine model of sudden coronary death

We have developed and studied a chronically instrumented canine model in which occlusion of a major coronary artery by an implanted balloon occluder promptly leads to arrhythmias that are reasonably reproducible on successive occlusions. Dogs were studied while conscious, and the electrocardiogram and electrograms from ischemic and nonischemic ventricular epicardium were recorded. Either the left anterior descending or circumflex coronary artery was occluded for up to 5.5 minutes. Experiments were performed in a carefully controlled environment at intervals sufficient for full recovery between occlusions. The arrhythmias that occurred were single or multiple premature ventricular depolarizations, runs of ventricular premature depolarizations or ventricular fibrillation. We measured the time from the onset of occlusion to the onset of arrhythmia (latency) and the severity of the arrhythmia (grade). Latency increased with successive occlusions in the same environment until no arrhythmia occurred during an occlusion of 5.5 minutes. In this state, addition of behavioral stress usually led to recurrence of arrhythmia. Stress decreased latency (P < 0.02) and increased grade. We also studied the effects of tolamolol (a beta blocking agent), UM-272 (an analog of propranolol) and diazepam. Tolamolol increased latency (P < 0.02) and tended to decrease grade. UM-272 had variable effects, but it clearly did not exert a protective action. The severity of arrhythmia was inversely related to latency, and latency decreased with increases in heart rate. The results obtained indicate that the model is useful for studies on arrhythmias that follow soon after the onset of ventricular ischemia, and they emphasize the relation between stress, enhanced sympathetic activity and ventricular arrhythmias.     

Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs

The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise.     

First seconds after acute experimental ischemic: changes in isovolumic contraction and relaxation

The purpose of this study was to answer the following questions: 1) are isovolumic contraction and relaxation affected in a different way by LAD occlusion? 2) Does proximal and distal LAD coronary occlusion induce different changes in isovolumic contraction and relaxation? In 22 pigs, LAD coronary artery was dissected free right after the first or third diagonal branch and occluded by ligation. The following variables were evaluated: left ventricular systolic and end-diastolic pressure; peak - and + dP/dt, mean arterial and pulmonary pressure. All our data were obtained in the first minute following the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion

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

Prostaglandin E1 attenuates postischemic contractile dysfunction after brief coronary occlusion and reperfusion

We have previously demonstrated that administration of the prostacyclin analogue iloprost improved postischemic functional recovery in reversibly injured ischemic-reperfused myocardium. The present study investigated the effects of administering an endogenous vasodilator prostanoid, prostaglandin E1 (PGE1), in the stunned myocardium (15 minutes of coronary artery occlusion and 3 hours of reperfusion) of anesthetized dogs. The percentage of regional myocardial segment shortening (%SS) after administration of PGE1 by two routes, intravenously (1 microgram/kg/min) or intraatrially (0.1 microgram/kg/min), to avoid pulmonary metabolism, 15 minutes before and throughout the period of occlusion, was compared to %SS in a control group treated with saline solution. Nearly equivalent reductions in mean arterial pressure during occlusion compared to pretreatment control (PTC) values were produced by intravenous (33%) or intraatrial (25%) PGE1. There was no difference in transmural myocardial blood flow (radioactive microsphere technique) in the ischemic region between the PGE1-treated and control groups at any time. Although there were no differences in %SS in the nonischemic region between groups throughout the experiment, postischemic recovery of segment function in the ischemic-reperfused area was significantly improved (p less than 0.05) at all times during reperfusion by intravenous PGE1 (%SS of PTC: 30 minutes = 65 +/- 8; 3 hours = 58 +/- 7) or intraatrial PGE1 (%SS of PTC: 30 minutes = 57 +/- 12; 3 hours = 50 +/- 4) compared to the control group (%SS of PTC: 30 minutes = 25 +/- 13; 3 hours = 10 +/- 13). Thus treatment with PGE1 attenuates postischemic contractile dysfunction in the stunned myocardium.2+ both.     

Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary stenosis and coronary occlusion

OBJECTIVES: The aim of the study was to assess whether and how the high-cholesterol diet (HCD)-related worsening of heart failure differs between coronary stenosis (CS)-induced myocardial ischemia and coronary occlusion-induced myocardial infarction (MI). BACKGROUND: An HCD, a risk factor for coronary artery disease, also worsens ischemic heart failure. Although accelerated coronary plaque formation may be a cause of this, other mechanism(s), such as its effects through the coronary microcirculation, remain to be clarified. METHODS: In rats fed a normal chow diet or HCD, CS or MI was created surgically, and we assessed left ventricular (LV) function by echocardiography and myocardial inflammation by histopathology. In the CS groups, CS severity by histopathology, myocardial perfusion by microspheres, myocardial protein kinase C (PKC) translocation by Western blotting, and myocardial endothelial nitric oxide (NO) function were also investigated by the in vitro myocardial oxygen consumption method. RESULTS: Coronary stenosis impaired myocardial endothelial NO function and reduced coronary flow reserve, evoking myocardial ischemia, as shown by PKC- activation, myocardial inflammation, fibrosis, cardiac dysfunction, and remodeling. By itself, HCD greatly augmented such CS-induced myocardial abnormalities without modulating the CS severity. Such detrimental effects of HCD were ameliorated by supplying a cofactor of endothelial NO synthase-tetrahydrobiopterin. In contrast, MI-induced heart failure was not aggravated by HCD. CONCLUSIONS: The CS-induced ischemic myocardium seems to be more susceptible to the pro-inflammatory effect of HCD than infarcted myocardium, leading to aggravation of LV dysfunction and remodeling via modification of the coronary circulation downstream of the epicardial CS site, partly through impairment of endothelial NO.     

Contractile and biochemical effects of coronary reperfusion after extended periods of coronary occlusion.

The effects of coronary reperfusion on recovery of regional myocardial contractility and high energy pegmental changes in myocardial contractility were measured by means of a strain gauge-tipped, two-pronged catheter probe that measures myocardial fiber shortening. The curves of contraction are sensitive to the effects of ischemia. Coronary occlusion resulted in a rapid replacement of fiber shortening by passive fiber lengthening. If coronary occlusion was released and blood flow restored within 45 minutes, myocardial contractility returned promptly; adenosine triphosphate and creatine phosphate values were restored to normal. With coronary occlusion of 1 hour or longer, contractility failed to return in the immediate postperfusion period, but delayed return was recorded after 2 weeks of reperfusion. The extent of such recovery varied with the duration of preceding occlusion. Thus, reperfusion after 1 hour of occlusion was followed by return of fiber shortening over the entire reperfused region. With 2 hours of occlusion, recovery occurred over 75 percent of the reperfused myocardium. With 3 hours of occlusion followed by reperfusion, recovery of contractility was only partial, comprising approximately 60 percent of the reperfused region. High energy phosphate content of the reperfused myocardium showed a similar pattern of recovery. With occlusion of longer duration, reperfusion failed to restore contractility to any significant extent. These findings indicate that reperfusion after coronary occlusion of 1 to 3 hours may restore contractility over a period of 2 weeks, but the extent of such recovery diminishes with the increase in the duration of occlusion.     

Comparative effects of ionic and nonionic contrast materials on indexes of isovolumic contraction and relaxation in humans

The effects of contrast media on left ventricular (LV) relaxation as assessed by the time constant of isovolumic relaxation have not previously been studied. A new nonionic contrast agent (iohexol) has been shown to have fewer deleterious effects than standard ionic agents. Nineteen patients received iohexol and sodium meglumine diatrizoate (Renografin-76) in a double-blind, crossover study during left and right coronary arteriography and with simultaneous high-fidelity micromanometer measurements of LV pressure. Neither agent induced significant changes in LV end-diastolic pressure after right or left coronary arteriography. After right coronary arteriography, neither agent produced significant deterioration of peak positive dP/dt or (dP/dt)/DP40 (dP/dt at a developed pressure of 40 mm Hg). However, after right coronary arteriography both agents caused a transient deterioration in peak negative dP/dt and the time constant of isovolumic relaxation (p less than 0.05 at 20 seconds after arteriography). After left coronary arteriography, sodium meglumine diatrizoate induced deterioration of systemic blood pressure (p less than 0.05), peak positive dP/dt (p less than 0.01), (dP/dt)/DP40 (p less than 0.05), peak negative dP/dt (p less than 0.01) and the relaxation time constant (p less than 0.01). These effects were not induced by iohexol. Thus, nonionic contrast media exert negligible alterations on LV function when used for coronary arteriography. The findings are of potential clinical importance in view of the large number of patients with depressed LV function who undergo coronary arteriography.     

Opioids in myocardial ischaemia: potentiating effects of dynorphin on ischaemic arrhythmia, bradycardia and cardiogenic shock following coronary artery occlusion in the rat

The endogenous opioid peptide (EOP) dynorphin and opioid receptorshave been found in the heart. This opioid system plays importantroles in cardiovascular regulation and is involved in the pathophysiologyof shock, heart failure and myocardial ischaemia. The aim ofthis study was to evaluate whether the EOP dynorphin modulatesor potentiates ischaemia-induced arrhythmias and whether itseffects are prevented by the opiate antagonist naloxone. Followingcoronary artery occlusion, all rats in the control group developedischaemia-induced arrhythmias, bradycardia and hypotension,which were significantly potentiated by pre-treatment with dynorphinand attenuated by treatment with naloxone. The results clearlyindicate that EOPs may be released when myocardial ischaemiaoccurs, thus causing arrhythmias, bradycardia and hypotension.Dynorphin and naloxone, by virtue of their opioid agonisticand antagonistic actions, respectively, potentiate and attenuatethese fatal complications secondary to myocardial ischaemia.This suggests that EOPs play an important part in ischaemicheart disease.     

Morphologic and functional effects of piroxicam on myocardial scar formation after coronary occlusion in dogs

To determine whether piroxicam, a widely used, long-acting anti-inflammatory agent, causes scar thinning after acute myocardial infarction (MI), MI was produced in 16 anesthetized, open-chest dogs by ligation of the proximal left anterior descending coronary artery. The dogs were randomized into 2 groups and treated in a blinded fashion, 8 with piroxicam, 1 mg/kg i.v. at 15 minutes and at 3 hours after ligation (Group 1) and 8 with saline solution (Group 2). Two-dimensional echocardiograms were performed 7 days and 6 weeks after ligation. At 6 weeks, the dogs were killed and the hearts examined. Scar thickness was 7.1 +/- 0.3 mm in control dogs and 5.2 +/- 0.4 mm in piroxicam-treated dogs (p less than 0.01). The ratio of scar thickness to noninfarcted wall thickness was 0.87 +/- 0.03 (mean +/- standard error of the mean) in the control group, and was significantly lower (0.62 +/- 0.04) in the piroxicam-treated group (p less than 0.001). Regional function, expressed as the percent change in the area of the left ventricular cavity (% delta A) from short-axis 2-dimensional echocardiograms, was 42 +/- 3% 7 days after occlusion in the control group and was not significantly different in the treated group (34 +/- 5%). At the end of 6 weeks % delta A had improved in the piroxicam-treated group to 44 +/- 3% (p less than 0.05 compared with the value after 7 days), and was similar to % delta A of the control group at 6 weeks (43 +/- 3%). Thus, clinical doses of piroxicam administered early after MI caused moderate scar thinning, which was not associated with impairment of regional left ventricular function 6 weeks later.     

Consequences of coronary arterial occlusion on remote myocardium: effects of occlusion and reperfusion.

Focal necrosis (microinfarcts) and regional lactate derangements were observed in closed chest dogs in the nonoccluded (remote) posterior segments of the left and right ventricles after acute occlusion of the proximal left anterior descending coronary artery. Focal infarcts in the remote areas were observed in five of the six dogs with 7 days of occlusion of the left anterior descending artery and in six of seven dogs with 7 days of reperfusion after 3 hours of occlusion. There was a good correlation between the finding of microinfarcts and myocardial lactate derangements in the corresponding remote myocardium. No significant lactate derangements or microinfarcts were found in sham experiments. These findings suggest that ischemia of the remote myocardium frequently accompanies an acute coronary occlusion and may result in irreversible focal lesions.     

冠状动脉闭塞血运重建术后存活心肌对心功能的影响

目的观测冠状动脉闭塞血运重建术后存活心肌的情况,分析其对心功能恢复的影响。方法选择30例冠状动脉闭塞的患者,分别于血运重建术前、术后6月行99mTc-M IB I结合18F-FDG心肌代谢的双核素心肌灌注显像方法检测存活心肌;根据灌注代谢情况来评价存活心肌的程度,术前心肌灌注代谢均减低者为无存活心肌（A组,n=12）,心肌灌注减低而代谢正常者为有存活心肌（B组,n=18）,通过超声心动图观察两组心功能的变化,并且对比评价术前、术后运动耐量的变化特点。结果血运重建术后存活的心肌增加至180个节段;B组血运重建术后6月心功能恢复显著,左心室射血分数（LVEF）为（52±4）%vs（64±4）%（P<0.01）;心肌显像缺血程度较术前有明显改善,血运重建术后运动时间延长,运动距离增加;A组变化不明显。结论冠状动脉闭塞血运重建术后存活心肌的数量与心功能的恢复密切相关。