Reversibility and Pathohistological Basis of Left Ventricular Remodeling in Hibernating Myocardium

The phenomenon of left ventricular (LV) remodeling with dilatation, wall thinning, and increased muscle mass has previously been reported in pigs with 7-day myocardial hibernation. This study investigated cellular and extracellular basis and reversibility of the structural LV remodeling with hibernating myocardium. Five groups of pigs were included: Group A: 7-day myocardial hibernation with a fixed coronary stenosis; Group B: 7-day hibernation with subsequent 3-week reperfusion by release of the stenosis; Group C: control group with sham operation; Group D: 24-hour myocardial hibernation to define structural mechanism of initial wall thinning in the hibernating region without confounding factors of cell loss or hypertrophy, Group E: 4-week myocardial hibernation to exclude the possibility of spontaneous regression of LV remodeling with hibernation. LAD flow decreased by 38 ± 12% (p < 0.01) with a significant decrease in systolic wall thickening at 7 days of hibernation with severe coronary stenosis (Group A). End-diastolic wall thickness decreased by 19% (p < 0.01) accompanied by a decrease in myocyte number across the wall (44%) and in myocyte density (24%), a significant increase in myocyte width (17%), a mild increase in interstitial tissues in hibernating region, and significant increases in LV diastolic volume and in LV mass at 7 days. After reperfusion (Group B), LV volume decreased, LV ejection fraction improved, and myocyte hypertrophy regressed with a decreased LV mass index without a significant change in interstitial tissue. LV remodeling progressed with further increases in LV volume, mass, and interstitial fibrosis in 4-week hibernation. In pigs undergoing 24 hours of myocardial hibernation (Group D), end-diastolic LV wall thickness decreased significantly in the hibernating region with a proportional decrease in the transmural myocyte number but without changes in myocyte width, myocyte density, or interstitial tissues. Therefore, progressive gross LV remodeling associated with hibernating myocardium is accompanied by increasing myocyte hypertrophy and interstitial fibrosis. In hibernating myocardial region, wall thinning is proportional to a decreased myocyte number across the LV wall, indicating slippage of myocytes as a preponderant mechanism for the wall thinning. Myocyte hypertrophy develops within 7 days in hibernating myocardium, causing an increase in LV mass. These changes are partially reversible after reperfusion.     

Nicardipine augments local myocardial perfusion after coronary artery reperfusion in dogs

Nicardipine is a potent coronary and systemic vasodilator without depression of ventricular function. We investigated the changes in local myocardial perfusion (LMP) according to the nicardipine administration after coronary reperfusion in a beating canine model. A Doppler probe was placed around the left anterior descending coronary artery (LAD) and thermal diffusion microprobe was implanted in the myocardium perfused by the exposed LAD. To define the nicardipine effects, we compared the two groups (control group, n=7 vs nicardipine group, n=7). In nicardipine group, 5 microgram/kg/min nicardipine was infused continuously. After the release of the LAD occlusion, LAD blood flow were increased compared to the baseline of both groups. However, there was no difference between groups in the LAD blood flow. The LMP after LAD reperfusion did not recover to the baseline level until 30 min after LAD reperfusion in control group (74%, 52% and 70% at 10, 20 and 30 min after LAD reperfusion, respectively). In nicardipine group, however, the LMP recovered to the baseline level at 20 min (99%), and increased more than the baseline level at 30 min (141%) after LAD reperfusion. Our findings suggest that the nicardipine augments the LMP following the release of a coronary occlusion.     

Sleep-induced hypotension precipitates severe myocardial ischemia

STUDY OBJECTIVES: Epidemiologic studies have shown a high frequency of major cardiac events at night in patients with coronary artery disease. This has been attributed to the sympathetic surges accompanying rapid eye movement (REM) sleep; the role of non-REM sleep, which comprises 80% of total sleep duration, has been largely neglected. Accordingly, we evaluated the effect of non-REM sleep on contractile function in a region of the left ventricular wall supplied by a flow-limiting coronary stenosis. DESIGN: Eight domestic pigs were chronically instrumented to measure regional left ventricular contractile function (wall thickening), coronary blood flow, and systemic hemodynamic variables. Measurements were obtained: (1) during wakefulness, i.e., conscious condition, prior to imposition of coronary stenosis; (2) during wakefulness following imposition of coronary stenosis (30% reduction of baseline coronary blood flow from 40 +/- 4 to 27 +/- 3 mL/min); and (3) during non-REM sleep with coronary stenosis maintained. RESULTS: During wakefulness, coronary stenosis reduced wall thickening (from 23.3 +/- 3.4% to 15.7 +/- 2.0%), whereas mean arterial pressure and heart rate were unchanged. With coronary stenosis maintained, the onset of non-REM sleep caused 20% decreases in mean arterial pressure and coronary blood flow, accompanied by a cessation of regional wall thickening, i.e., akinesis (wall thickening = 0.2 +/- 2.8%), indicating severe myocardial ischemia. CONCLUSIONS: The arterial hypotension, and associated reduction in coronary blood flow, during non-REM sleep precipitated severe myocardial ischemia in a region of the left ventricular wall supplied by flow-limiting coronary stenosis. Such episodes would occur repeatedly during the sleep cycle and could potentially set the stage for a major cardiac event during the sympathetic activation accompanying REM sleep or morning activities.     

Gene transfer of the pancaspase inhibitor P35 reduces myocardial infarct size and improves cardiac function

Myocardial infarction and subsequent reperfusion lead to the activation of apoptosis, and the final destruction of the cell. The aim of this study was to show that broad-scale inhibition of caspases, the main executioners of apoptosis, improves functional outcome after ischemia and reperfusion in an in vivo model. Twenty male Wistar rats were directly injected with an adenovirus, encoding the baculoviral protein p35. Nineteen rats served as controls, and were injected with a virus only encoding green fluorescent protein (GFP). After 3 days, 12 animals were used for Langendorff perfusion experiments, the other 27 animals were submitted to in vivo infarction. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD) for 30 min, and reperfusion for 24 h. Echocardiographic and hemodynamic measurements were made 24 h after infarction. Infarct size was assessed in all animals histologically. In both, in vivo and Langendorff perfused hearts, myocardial infarct size was significantly reduced in the p35 group (for in vivo experiments: 0.11+/-0.03 vs 0.33+/-0.03 in the GFP group, p<0.01), as was the ratio of infarct size to area at risk (6 vs 17%, p<0.01). Left ventricular function was similar in both groups prior to infarction, but was significantly less compromised after infarction in the p35 group. The left ventricular systolic pressure after infarction was higher in the p35 group (107+/-5 vs 92+/-4 mmHg, p<0.05), as was the maximal rate of rise of left ventricular systolic pressure dp/dt (5,659+/-585 vs 4,634+/-256 mmHg s(-1), p<0.05). Adenoviral gene transfer of the caspase inhibitor p35 leads to a significant reduction of the myocardial infarct size after ischemia and reperfusion. Hemodynamic variables were significantly improved by treatment with p35. Cardiac restricted inhibition of apoptosis seems to be a promising approach for ameliorating the effects of ischemia and reperfusion.     

Intracoronary adiponectin at reperfusion reduces infarct size in a porcine myocardial infarction model

Reperfusion injury (RI) remains an important limitation of myocardial revascularization. The aim of the present study was to evaluate the influence of the intracoronary injection of adiponectin on RI and cardiomyocyte death in a porcine myocardial infarction model. Acute infarction in 14 Polish domestic pigs was induced by inflation of an over the wire balloon (OTW) catheter in the medial left anterior descending artery for 60?min. The study group consisted of 7 pigs in which intracoronary adiponectin (50?μg) was infused through the OTW catheter immediately before reperfusion. The control group (n=7) was administered placebo. Animals were sacrificed after two days of follow-up. The infarct area (IA) was stained with tetrazoline and the area at risk (AAR) with intracoronary administration of Evans Blue dye before euthanasia. Hearts in each group had similar AARs (46.2±9.9% vs. 48.4±6.2% of the whole myocardium, p=ns). The IA/AAR% and IA were smaller in the study group when compared to the control (24.7±4.0% vs. 45.3±22.5%, p=0.005; and 11.7±4.9% vs. 20.5±5.6%, p=0.01, respectively). These outcomes corresponded well with the peak troponin levels after 12?h (109.9±60.9 ng/ml vs. 185.5±39.4 ng/ml, p=0.017). After two days there was a significantly higher LVEF in the study group (51.4±8.5% vs. 33.9±8.6%, p=0.002). There was also a trend toward lower apoptosis enhancement in the viable myocardium in the study group (3.11±2.3 vs. 8.92±6.3; p=0.07). The administration of adiponectin into the infarct- related artery is safe and feasible. The treatment significantly reduced the infarct size.     

Segment stroke work and metabolism depend on coronary blood flow in the pig

We determined the mechanical and metabolic effects of graded myocardial ischemia in 23 open-chest, anesthetized pigs. By connecting the midportion of the left anterior descending artery (LAD) to the carotid artery via a constant volume, calibrated pump, we reduced the flow in the LAD to 0, 25, 50, and 75% of control rates for periods of 1 h. Flows of 100% and 150% were also examined. Using pairs of ultrasonic crystals to measure segment dimensions, we calculated segment shortening and thickening, and total and systolic stroke work in the ischemic and normally perfused segments. Blood gases, pH, and lactate and inosine balances were determined from the regional coronary venous blood. At coronary blood flows of 0, 25, 50, and 75% of normal resting flow, total segment work was 8 +/- 8, 25 +/- 4, 51 +/- 5, and 80 +/- 6% of control, respectively, while systolic segment work was -2 +/- 5, -10 +/- 5, 40 +/- 5, and 86 +/- 7% of control, respectively (means +/- SE). Thus, the decrease in total segment stroke work is proportional to the decrease in flow over the range 0-100%. However, no useful work (i.e., systolic work) is done until flow exceeds 25%. Segment shortening and thickening are significantly depressed with flows diminished by only 25%. Segmental inosine production correlates with lactate production and parallels decreased mechanical performance.     

Cardiac accumulation of citrate during brief myocardial ischaemia and reperfusion in the pig in vivo

Citrate is a key intermediate in energy metabolism and an inhibitor of phosphofructokinase of the glycolytic pathway. During myocardial ischaemia glycolysis is the main source of cardiac ATP. The aim of the present study was to determine if myocardial ischaemia and reperfusion alter cardiac tissue levels of citrate. Open-chest, anaesthetized pigs were subjected to 10 min of regional myocardial ischaemia by occlusion of the left anterior descending coronary artery, with and without reperfusion, and to 10 min of global ischaemia by circulatory arrest. Citrate, amino acids, glucose and NH₃ were measured in biopsies. Ischaemia, whether regional or global, caused a 60–70% increase in tissue levels of citrate. During 1 min of reperfusion following regional ischaemia the level of citrate increased 460%, to ≈600 nmol g^?1 wet weight. The level of glutamate decreased by 20–33% (corresponding to 1300–2200 nmol g^?1 wet weight), indicating net consumption of this amino acid during ischaemia. The level of aspartate decreased 50% indicating conversion of aspartate to oxaloacetate for the synthesis of citrate. Theoretically, the accumulation of myocardial citrate during brief ischaemia and early reperfusion is large enough to significantly inhibit phosphofructokinase activity and could therefore affect the ability of the myocardium to increase the glycolytic rate in response to ischaemia. This could, however, be partly compensated by the metabolism of myocardial glutamate.     

The combination of L-arginine and ischaemic post-conditioning at the onset of reperfusion limits myocardial injury in the pig

Aim: To investigate whether ischaemic post‐conditioning (IPoC) combined with i.v. infusion of the nitric oxide (NO) substrate l ‐arginine at the onset of reperfusion exerts cardioprotective effect that is superior to either treatment given separately. Methods: Twenty‐six anesthetized pigs were subjected to coronary artery (left anterior descending artery, LAD) ligation for 40 min followed by 4 h reperfusion. The pigs were randomized into five different groups receiving either i.v. vehicle, i.v. l ‐arginine, IPoC 4 × 60 s together with i.v. vehicle or IPoC together with i.v. l ‐arginine and a group with IPoC 8 × 30 s. All infusions were started 10 min before reperfusion. Results: The infarct size of the vehicle group was 82 ± 4% of the area at risk. l ‐Arginine alone (79 ± 8%), IPoC 4 × 60 s vehicle (86 ± 3%) or IPoC 8 × 30 s vehicle (94 ± 7%) did not affect infarct size. l ‐Arginine together with IPoC significantly reduced infarct size to 59 ± 4% (P < 0.01). Except for higher LAD flow during early reperfusion in the IPoC l ‐arginine group, haemodynamic parameters did not differ between the four main groups. Heart rate and rate pressure product were lower during ischaemia and reperfusion in the IPoC 8 × 30 s vehicle group. In comparison with the vehicle group, there were no changes in the expression of Akt, phosphorylated Akt Ser⁴⁷³, inducible NO synthase, endothelial NO synthase (eNOS) or phosphorylated eNOS Ser¹¹⁷⁷ in the ischaemic/reperfused myocardium. Conclusion: l ‐Arginine given systemically at the onset of reperfusion protects the pig heart against ischaemia and reperfusion injury only when combined with IPoC. These results indicate that the combination of the two treatment strategies exerts cardioprotection.     

Selective thromboxane A2 receptor blockade in experimental exercise-induced myocardial ischaemia in dogs

Thromboxane A2 receptor stimulation induces blood platelet aggregation and vasoconstriction, both potential causes of impaired perfusion of ischaemic myocardium. To study the potential role of thromboxane A2 receptor blockade in exercise-induced myocardial ischaemia and post-exercise myocardial dysfunction, nine conscious chronically instrumented dogs with single-vessel coronary artery stenosis (ameroid constrictor) were studied before, during and after steady-state treadmill runs which induced regional myocardial ischaemia. Three hours after a control run, the dogs were exercised again after the infusion of a selective thromboxane A2 receptor blocker: BM 13.177 (10 mg kg-1 i.v.). In the control run, systolic wall thickening (WTh, sonomicrometer) in the post-stenotic myocardium decreased from 22.1 +/- 9.1% at rest to 8.8 +/- 5.2% (mean +/- SD). Subendocardial blood flow (microspheres) in the ischaemic area decreased from 0.75 +/- 0.25 to 0.45 +/- 0.27 (ml min-1 g). The WTh in the ischaemic region remained depressed at 20 min after the run. BM 13.177 reduced peak left ventricular (+) dP/dt (micromanometer) and WTh in both control and post-stenotic myocardium at rest, during and after the run. WTh in the ischaemic area was reduced to approximately the same levels during running with BM 13.177 (not significantly different from control exercise) and remained depressed for at least 30 min after the run. Regional myocardial blood flow was not affected by BM 13.177. Thus, selective thromboxane A2 receptor blockade with BM 13.177 had a modest negative inotropic effect and did not improve regional function or blood flow in post-stenotic ischaemic subendocardium.     

低浓度11,12-EET预干预对大鼠心肌缺血/再灌注损伤的影响

目的:观察外源性低浓度 11,12-EET预干预对大鼠在体心肌缺血/再灌注损伤的影响。方法:雄性Wistar大鼠,开胸,结扎和松开冠状动脉左前降支,复制心肌缺血/再灌注模型;采用缺血 5min/再灌注 5min两次造成缺血预处置。实验分 3组:对照组;缺血预处置组;外源性 11,12-EET预干预组。每组再分为A、B 2小组:A组动物心肌缺血 10min/再灌注 10min,主要观察缺血/再灌注各时程之心律失常;B组动物缺血 6 0min/再灌注 30min,主要观察缺血期心律失常、心功能的变化及再灌注后心肌梗死范围。结果:缺血预处置和 11,12-EET(6 2 4× 10^-8mol/L)预干预均可减轻缺血/再灌注心律失常及心功能的变化,降低心肌梗死范围。结论:11,12-EET预干预具有类缺血预处置样的心肌保护作用.     

Experimental study on size-limitation of myocardial infarct in swine produced by a coronary balloon-catheterization. I. Preliminary report; morphometry of infarct size

Experimental myocardial infarction was produced in 15 subject swine using a balloon catheter to occlude the left anterior descending coronary artery (LAD). After 30 minutes obstruction, the LAD was reperfused, and then the animals were sacrificed at 3 hours, 6 hours, 24 hours, and 48 hours after the onset of coronary occlusion, respectively. During and after the experiment they were investigated physiologically and pathomorphologically to measure the size of myocardial infarct, and the obtained results are as follows; Experimentally produced myocardial infarcts could be detected histopathologically by routine gross and light-microscopical means in the group which had suffered from ischemia for over 24 hours till sacrifice. Ischemic areas could not be distinguished from normal areas of the myocardium by routine techniques, but could be identified enzyme-histochemically in the groups observed for less than 6 hours. The mean weight ratio of infarcted myocardium to total ventricular myocardium was 25 +/- 3.6%. This method was useful for measuring infarct size.     

Real-time myocardial glucose measurement using biosensors

During ischemia, myocardial fatty acid metabolism ceases, rapidly depleting the other primary fuel, glucose. No technique has existed to continuously monitor myocardial glucose. Needle-tip enzymatic glucose biosensors have been developed for subcutaneous use in diabetic management. To study the utility of these sensors for real-time myocardial glucose monitoring in clinically relevant applications, 40 kg Yorkshire swine were cannulated for cardiopulmonary bypass. Biosensors were placed in the left anterior descending artery distribution (LAD) and posterior descending artery distribution (PD), and a third in the liver. Selective ischemia was induced by ligation of the LAD artery. Glucose levels were monitored during ischemia and reperfusion in the setting of cardioplegic arrest (n = 7) and in the normal beating heart (n = 14). In the normal beating heart, glucose levels fall to 6.5% +/- 7.4% baseline at 1 minute and 29.0% +/- 23.0% at 5 minutes of ischemia. In both arrested and beating heart scenarios, biosensors show distinct metabolic states in specific regions of the heart and liver. Biosensors can track regional glucose metabolism in the beating and arrested heart. This novel application of these sensors allows real-time determination of myocardial glucose levels to guide cardioplegia administration and monitor ischemic states for clinical and experimental use.     

丹参对急性缺血后再灌注心肌磷脂肌醇系统变化的影响

本文首镒报道采用大鼠在体心肌缺血后再灌注模型观察丹参对急性短时间缺血后再灌注心肌磷脂肌醇代谢的影响。结果显示：急性缺血１０ｍｉｎ后灌注１０ｍｉｎ，心肌磷脂肌醇信息传递系统功能明显增强，其磷脂酰肌醇－４，５－二磷酸和肌醇－１，４，５－三磷酸水平显著高于非缺血对照组和缺血组；丹参能显著抑制急性缺血后再灌注心肌磷脂肌醇系统的高功能状态，其ＰＩＰ２和ＩＰ３水平明显低于缺血组和缺血再灌注组。     

钙敏感受体在大鼠心肌缺血/再灌注损伤的表达变化及与心肌损伤关系

目的： 观察钙敏感受体（CaSR）在大鼠心肌缺血/再灌注时的表达变化，揭示其与心肌缺血/再灌注损伤的关系。方法： Wistar大鼠随机分为5组：假手术组（sham组）、缺血再灌注1、2、4和6 h组（I/R 1 h、2 h、4 h、6 h组）。采用冠状动脉结扎和松结的方法，复制大鼠在体心肌缺血/再灌注损伤模型，记录左室收缩压（LVSP）和左室内压最大变化速率（±dp/dtmax），测定血清LDH、SOD活性和MDA含量，透射电镜观察心肌超微结构变化， RT-PCR法检测心肌组织中CaSR mRNA的表达变化。结果：LVSP、左室内压±dp/dtmax及SOD活性随再灌注时间延长而减低，LDH活性和MDA含量在再灌注2 h时最高；心肌超微结构损伤在再灌注1 h、2 h较重，随再灌注时间延长而减轻；大鼠心肌缺血/再灌注1 h、2 h心肌组织CaSR的mRNA表达升高，再灌注4 h、6 h后降低。结论： CaSR mRNA表达多时心肌损伤较重，CaSR可能参与了心肌缺血/再灌注损伤。     

Regional contractile blockade at the onset of reperfusion reduces infarct size in the dog heart

An important mechanism of lethal myocardial reperfusion injury is the development of cellular hypercontracture at the onset of reperfusion. Hypercontracture can lead to cytolysis by mutual mechanical disruption of myocardial cells. 2,3-Butanedione monoxime (BDM) inhibits myofibrillar cross-bridge cycling and may therefore reduce infarct size in ischaemic reperfused myocardium. This study investigated whether a temporary presence of BDM protects against myocardial reperfusion injury in an intact-animal preparation. Anaesthetized open-chest dogs (n=10) underwent 1 h of left anterior descendent artery (LAD) occlusion and received intracoronary BDM (25 mM, n=5) or vehicle (n=5) for 65 min starting with an anoxic local infusion 5 min before reperfusion. Infarct size was assessed by triphenyltetrazolium staining after 6 h reperfusion. The infusion of BDM was accompanied by a transient reduction of left ventricular systolic pressure from 84.3±11.2 mm Hg during occlusion to 66.4±9.9 mm Hg at 30 min reperfusion (mean±SD, P<0.01 vs. control). LAD-flow and regional wall motion in the area at risk showed no difference between groups. Infarct size (% of area at risk) was reduced from 24.4±8.7 (control) to 6.6±2.0% (BDM) (P<0.01). The results demonstrate that development of necrosis in reperfused myocardium can be greatly reduced by temporary presence of the contractile inhibitor BDM at the onset of reperfusion.     

Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia

The mechanism underlying cardiac arrest in patients with hypertrophic cardiomyopathy (HC) is intriguing. In the clinical setting, myocardial ischemia has long been incriminated, particularly in the young. Among 274 cardiovascular sudden deaths in the young (< or = 35 years), 19 (7.0%), 14 males and 5 females, median age 23 years, had HC. Familial occurrence of HC was ascertained in 3 (16%). SD occurred on effort in 6 (31%). Previous syncope occurred in 5 and palpitations in 3. Basal electrocardiogram (ECG) was abnormal in 7 of 8 available cases. Hypertrophy was septal asymmetric in 14. Gross examination showed large isolated or multiple septal scars in 11 (58%); at histomorphometry, the mean percent area of fibrosis of the septal myocardium was 18.6 +/- 6. Four showed a deep intramyocardial course of the left anterior descending coronary artery. At histology, myocardial disarray involved 30 +/- 16% of the septal myocardium; evidence of acute-subacute myocardial necrosis was present in 14 (74%), 1 of them with a regional acute myocardial infarction. By comparing hearts with (n = 11) and without (n = 8) areas of scar-type fibrosis, we found a statistically significant difference in terms of age (25.5 +/- 5.4 v 15.5 +/- 12.4 years, P = .04), septal thickness (25.4 +/- 5.4 v 15.4 +/- 4.9 mm, P < .001), percent increase of septal thickness versus normal value for age and sex (46.2 +/- 15 v 25.2 +/- 13.6%, P < .01) and mean score of small vessel disease (1.7 +/- 0.4 v 1.2 +/- 0.4, P = .04). Linear regression analysis showed a positive correlation of percent area of replacement fibrosis with septal thickness (P = .01) and with mean score of small vessel disease (P < .01). In conclusion, our pathologic findings of ischemic damage, either acute-subacute or in the form of fibrotic scars, support the clinical evidence that ischemia occurs in the natural history of HC and may contribute to life-threatening electrical instability.     

Myocardial segment shrinkage during coronary reperfusion in situ

We have investigated the changes in myocardial segment length induced by reperfusion, and their relation to myocyte hypercontracture and contraction band necrosis. Regional wall function was monitored by ultrasonic gauges in 39 pigs submitted to 48-min occlusion of the left anterior descending coronary artery (LAD) and 6 h of reperfusion. Infarct size (triphenyltetrazolium reaction), the extent of contraction band necrosis (quantitative histology) and myocardial water content (desiccation) were measured. Reperfusion induced a marked reduction in end-diastolic length of the LAD segment in all animals, maximal within 15 min after reflow. After 30 min of reperfusion, end-diastolic length of the LAD segment remained below the basal value in 15 animals. The 15 animals that showed shrinkage of the reperfused segment did not differ from the remaining animals in heart rate, aortic pressure, or control segment variables, but had larger infarcts (mean ± SEM: 32.1 ± 5.4 vs 12.1 ± 3.2% of the area at risk,P = 0.003). There was an inverse correlation between end-diastolic length of the LAD segment after 30 min of reperfusion and infarct percentage (r = -0.72) or the extent of contraction band necrosis (r = -0.71). End-diastolic length reduction was more pronounced in larger infarcts despite a more severe myocardial oedema. Neither systolic shortening of the LAD segment nor end-diastolic length or systolic shortening of the control segment, or haemodynamic variables after 30 min of reperfusion correlated to infarct percentage or to the extent of contraction band necrosis. It is concluded that myocardial segment shrinkage during reperfusion reflects myocyte hypercontracture leading to contraction band necrosis.     

Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium

To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.     

Early detection of successful reperfusion by analysis of serum myoglobin in patients with acute myocardial infarction

We examined the changes of serum myoglobin (Mb) levels after reperfusion therapy (PTCR, PTCA) in 24 patients with acute myocardial infarction by latex agglutination turbidimetry. In the cases of 13 patients successfully reperfused, significantly higher Mb levels was observed and they disappeared rapidly from blood after the therapy. On the other hand, serum Mb levels disappeared slowly in the cases of patients unsuccessfully reperfused. The disappearance rate of Mb (23.4 +/- 6.7%) in successful reperfused patients was higher than that in unsuccessful reperfusion (5.3 +/- 6.8%) (p less than 0.001), the cut-off value of serum Mb levels in the decision regarding success or failure of reperfusion was set at 17% of disappearance rate, the predictive values for successful and unsuccessful reperfusion were 92% and 91% respectively. The maximum peak time of CK, CK-MB activities and Mb levels after onset of chest pain were also observed. Only the maximum peak time of CK-MB was significantly fasten than others in the cases of patients sera with successful reperfusion (p less than 0.05). We conclude that the measurement of serum Mb levels was useful and suitable for rapid judging on success or failure of reperfusion therapy by use of the disappearance rate of it.     

Overestimation of myocardial infarct size by histologic measurement in a model of occlusion followed by reperfusion.

We studied 32 transverse left ventricular slices of myocardium from 16 pigs after 45 to 100 minutes of coronary artery occlusion followed by 180 minutes of reperfusion. Infarct area for each slice was determined as follows: (1) grossly, by triphenyl tetrazolium chloride staining of each slice, and (2) microscopically, by complete histologic sectioning of the triphenyl tetrazolium chloride-stained surface of each slice. Planimetry of necrotic and nonnecrotic areas was performed from tracings and photographs of triphenyl tetrazolium chloride-stained slices and from actual histologic sections. When triphenyl tetrazolium chloride and histologic measurements were compared, necrotic tissue area had decreased 11.4% +/- 15.0% (2.59 +/- 1.04 vs 2.09 +/- 0.86 cm2). Nonnecrotic tissue area decreased 20.6% +/- 24.0% (8.31 +/- 3.79 vs 5.16 +/- 2.73 cm2). In this model of ischemia followed by reperfusion, with fixation and processing, viable tissue shrank almost twice as much as necrotic tissue. This differential shrinkage introduces an error resulting in overestimation of infarct size by histologic quantitation.