The "wavefront phenomenon" of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow.

The present study was done to quantitate the evolution of myocardial ischemic cell death within the framework of (1) the anatomical boundaries of the ischemic bed at risk and (2) the magnitude and transmural distribution of collateral blood flow. Myocardial ischemia was produced by proximal circumflex (LCC) occlusions in open chest dogs. Infarcts reperfused at 40 minutes, 3 hours, or 6 hours were compared with permanent infarcts. All dogs were sacrificed at 4 days. Regional myocardial blood flow was measured with 9-micrometer tracer microspheres before, and 20 minutes after, LCC occlusion. The location and size of the ischemic LCC bed at risk was determined by a dye injection technique. Infarct size was quantitated from multiple histologic sections. Necrosis involved 28 per cent, 70 per cent, and 72 per cent of the ischemic bed at risk in infarcts reperfused at 40 minutes, 3 hours, and 6 hours versus 79 per cent following permanent LCC ligation. Viable and potentially salvageable subepicardial muscle persisted for at least 3 hours after the onset of ischemia. Most of the salvageable myocardium was in the subepicardial region. In all groups, the lateral margins of necrosis were sharp in the subendocardial zone and were determined by the anatomical boundaries of the ischemic LCC bed at risk. LCC bed size ranged from 29 to 48 per cent of the left ventricle and thus contributed to variation in infarct size. However, infarct size, as a percentage of bed size, was determined by the transmural extent of necrosis within that bed (r = -0.97). This transmural extent of necrosis was related to subepicardial collateral flow after 3 hours (r = 0.92) and 6 or 96 hours (r = -0.85) but not after 40 minutes (r = -0.26) of ischemia. Thus, irreversible injury of ischemic myocardium developed as a transmural wavefront, occurring first in the subendocardial myocardium but ultimately becoming nearly transmural. Eventual transmural necrosis, and therefore over-all infarct size was determined by, and can be predicted from flow measurements obtained shortly after coronary occlusion.     

Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis.

Morphologic changes in the subendocardial myocardium that appeared to be caused by severe, chronic subendocardial ischemia were studied in patients with fatal ischemic heart disease admitted to the Specialized Center of Research for Ischemic Heart Disease at the University of Alabama in Birmingham in the period 1970--1977. Thirteen patients were selected for this report on the basis that they had the lesions in the subendocardial myocardium we believe to have been caused by subendocardial ischemia and had no evidence of acute or remote myocardial infarction or other conditions that may have contributed to their terminal illness or death. Clinical findings were unstable angina, congestive heart failure, usually no increase in plasma enzymes indicative of myocardial damage, and electrocardiographic changes consistent with subendocardial ischemia. All 13 patients had 75% or greater stenosis of the three major coronary arteries; none had acute thrombotic or embolic coronary artery occlusion. The left ventricle in all cases was hypertrophied. The subendocardial myocardium showed circumferential pallor, hyperemia, or focal fibrosis without perceptible loss of volume in papillary muscles or trabeculae carneae. Microscopically, acute lesions showed one to two layers of preserved myofibers adjacent to the endocardium, vacuolar change in the deeper fibers, and focal areas of coagulation necrosis of variable size in the myocardium external to the fibers with vacuolar change. Coagulation necrosis was extensive in some cases and usually was not associated with infiltration of neutrophils. The repair reaction involved removal of necrotic sarcoplasm by mononuclear phagocytes, resulting in a reticular-appearing tissue without evidence of stromal collapse. Granulation tissue was not seen. Collagen fibers appeared to be deposited within the area of previous sarcolemmal sheaths. The distribution and morphology of subendocardial myocardial lesions associated with severe coronary atherosclerosis are distinctive and can be distinguished from myocardial necrosis or fibrosis associated with acute total occlusion of a coronary artery.     

Ischemic heart disease

Ischemic heart disease is one of the leading causes of death in Japan. Acute coronary syndrome (ACS) most commonly begins with atherosclerotic plaque rupture and intracoronary thrombus formation. Therefore, the primary goal of treatment of acute coronary occlusion is the achievement of early and complete reperfusion. To achieve this goal, detection of atherosclerosis and/or myocardial necrosis by imaging and serologic tests is important. Original diagnosis of acute myocardial infarction (AMI) was made from typical symptoms, characteristic rises in serum enzyme levels, and an atypical electrocardiographic pattern. Increasingly sensitive and specific tests have been developed in recent years and have been rapidly adopted into clinical practice. Rapid developments in technology in the field of serum biomarkers have redefined the diagnosis of AMI. The new ESC/ACC criteria place increased emphasis on cardiac biomarkers, especially troponins. However, the electrocardiogram still remains significant in the diagnosis of AMI and the ability to identify high risk subgroups by admission electrocardiogram is necessary to estimate the severity of AMI. Current practice guidelines recognize the importance of promptly restoring normal epicardial blood flow, but blood flow to the ischemic tissue may still be impeded after relief of the occlusion; a phenomenon known as no reflow. Myocardial scintigraphy is one of the methods for defining coronary microvascular injury in the acute phase of AMI. Prompt assessment of coronary perfusion and detection of coronary microvascular injury may aid in making decisions concerning the use of drugs to improve microvascular function and left ventricular function after primary coronary angioplasty.     

Continuum of the thickness of surviving myocardial wall with single myocardial infarcts

The pathologic correlate of the clinical terms subendocardial and transmural applied to myocardial infarcts is uncertain. To examine this question, we reviewed the morphology of 204 hearts with single myocardial infarcts studied at autopsy after coronary arteriography and fixation in distention. The thickness of surviving myocardium with the infarct (S) and the thickness of the adjacent noninfarcted myocardium (A) were measured microscopically and expressed as a ratio. The S:A ratios ranged from 0.00 to 0.83. Necrosis of the entire wall (S:A ratio = 0.00) was seen in 37 (18%) cases. Distribution of the remaining cases by 10% intervals of wall necrosis (ie, from 0.00 less than S:A ratio less than or equal to 0.10 through 0.90 less than S:A ratio less than or equal to 1.00) were present in 27, 33, 31, 24, 25, 12, 8, 6, 1, and 0 cases, respectively. A lower S:A ratio was correlated with infarct size, infarct expansion, infarct rupture, proximal location of the coronary artery lesion causing the infarct, recency of the infarct, and degree of endocardial mural thrombus. A higher S:A ratio was correlated with the degree of left ventricular hypertrophy. No correlation was observed between S:A ratio and several measures of coronary artery disease. Multivariate regression analysis showed that infarct expansion, infarct age, and rupture were distinct predictors of infarct thickness. The study shows that thickness of myocardium surviving with an infarct forms a continuum; there is no evidence of separate populations that would correspond to infarcts of transmural or subendocardial extent.     

Anatomic variant of the posterior interventricular coronary artery: Implications for coronary angioplasty in acute myocardial infarction

Acute thrombotic occlusion of an infarct-related artery is frequently found in patients presenting with myocardial infarction. In a patient with acute inferior wall myocardial infarction complicated by continuous chest pain and hemodynamic instability, emergency diagnostic coronary arteriography demonstrated a patent, infarct-related, “pseudo” right coronary artery while, in fact, this vessel was a rare anatomic variant of the posterior interventricular branch with very early origin from the right coronary artery and the true right coronary artery was completely occluded by a thrombotic obstruction. Accurate anatomic-angiographic interpretation of the angiogram was crucial for successful performance of emergency recanalization and revascularization of the true right coronary artery with laser and balloon angioplasty. Once antegrade flow was restored another rare coronary variant was discovered, i.e., a sinoatrial node artery arising from the middle portion of the newly patent right coronary artery. Clin. Anat. 10:303–306, 1997. © 1997 Wiley-Liss, Inc.     

Abnormal myocardial fluid retention as an early manifestation of ischemic injury.

Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity.     

Capillary perfusion patterns in reperfused ischemic subendocardial myocardium: experimental study using fluorescent dextran

The relationship between functional capillary perfusion patterns and sarcolemmal membrane permeability in localized acute myocardial ischemia was investigated in the rat model. The macromolecule dextran (MW 150,000) labeled with fluorescein (FITC) was intravenously injected. In histological sections, the label fluorescence showed those capillaries which had been perfused by the stained plasma; the blood-tissue barrier could be explored by detection of fluorescein in interstitial spaces and/or within the myocardial cells. Morphological parameters were calculated by semiautomatic image analysis. The data obtained indicate that (1) there is a great heterogeneity in the pattern of capillary perfusion within the reperfused ischemic myocardium; (2) as early as 20 min after coronary artery clamping followed by short reperfusion, the macromolecular tracer can be seen in the cytoplasm of muscle cells randomly distributed in subendocardial areas; (3) only the underperfused areas display permeated myocardial cells. It is suggested that capillary perfusion varies from site to site depending on the difference in cellular membrane permeability changes. The ischemia-induced cell changes can lead to capillary filling defects and an increase in coronary flow resistance. Whether the inadequate blood flow upon reperfusion contributes to further myocyte damage remains a matter of debate.     

Myocardial injury in patients with aortic stenosis

Clinical studies of patients with aortic stenosis suggest that left ventricular myocardial injury is frequent. To examine the morphologic basis of this observation, we studied 32 patients with isolated aortic stenosis, no cardiac surgery, and hearts studied at autopsy after postmortem arteriography and fixation in distension. The patients were 46-87 years old (average 69), and 21 (66%) were male. Calcific aortic stenosis was present in 19 hearts, 12 had congenital bicuspid aortic valve, and 1 had rheumatic aortic stenosis. In 19 hearts there was moderate or marked coronary atherosclerosis, and 12 hearts had 17 myocardial infarcts. However, among 13 hearts with no or mild coronary atherosclerosis, 9 had either subendocardial myocardial contraction band necrosis, a lesion occurring when periods of no perfusion are followed by reflow, or focal replacement fibrosis. In 13 hearts there was subendocardial vacuolization of myocytes, an alteration produced by ischemia, that was not accounted for by coronary artery disease. Our results are consistent with clinical observations and show that ischemic myocardial injury may be associated with isolated aortic stenosis in the absence of coronary artery obstruction. The contraction band necrosis and vacuolated myocytes suggest that both episodic and sustained reductions of subendocardial blood flow occur in the presence of aortic stenosis.     

Contraction-band necrosis: patterns of distribution in the myocardium and their diagnostic usefulness in sudden cardiac death

Experimentally-produced acute regional myocardial infarcts of 2 or more hours duration show a characteristic pattern of myocardial cell alteration known as "contraction-band necrosis". To investigate the potential usefulness of this feature in assessing the myocardial status in sudden cardiac death, detailed histological examinations of the coronary arteries and midventricular myocardium were carried out on hearts from 70 unselected cases of sudden cardiac death. Contraction-band necrosis was frequently encountered and occurred in 3 main patterns which could be correlated with the coronary artery pathology and the case history: a regional distribution consistent with early subendocardial or transmural infarction, not yet characterized by coagulative necrosis, associated in most cases with a recent thrombotic event in the relevant supply artery (27.1%); adjacent to pre-existing infarction (recent or healed) or to subendocardial fibrosis resulting from severe coronary artery disease, consistent with recent extension of ischemic injury (18.6%); a global, full-transmural distribution, consistent with reperfusion injury from delayed resuscitation in the absence of significant coronary artery pathology (8.6%). Thus, examination of the myocardium for a specific pattern of contraction-band necrosis may frequently facilitate the definitive diagnosis of sudden cardiac death.     

Determinants of hemorrhagic infarcts. Histologic observations from experiments involving coronary occlusion, coronary reperfusion, and reocclusion.

Quantification of intramyocardial hemorrhage was performed in 69 pigs submitted to various protocols of coronary artery occlusion and reperfusion. The study groups include 1) permanent occlusion; 2) reperfusion after periods of coronary occlusion of 30, 45, 60, 90, and 120 minutes; 3) reperfusion with diltiazem and with 4) methoxamine after a 60-minute occlusion period; and 5) permanent reocclusion after a 30-minute period of reperfusion. Red blood cell counts were directly assessed by visual examination of histologic slices of myocardium and in a subgroup of animals by counts of red blood cells labeled with 99m-technetium pertechnetate. Hemorrhage occurs in infarcts reperfused after a duration of 45 minutes or more of coronary occlusion and after a period of reperfusion maintained for at least 30 minutes. Red blood cell counts were maximal in the mid portions of transmural sections of the infarcts, with decreasing values toward epicardium and endocardium. Diltiazem decreased total red blood cell counts, whereas methoxamine increased it and also caused subendocardial hemorrhage. The most powerful predictors of the severity of hemorrhage after sustained reperfusion were infarct size and higher blood pressure.     

Contraction band necrosis at the lateral borders of the area at risk in reperfused infarcts

The aim of this study was to test the hypothesis that increased mechanical stress at the lateral borders of the area at risk may render this area more susceptible to ischaemia/reperfusion injury in the absence of collateral flow. The spatial distribution of myocardial necrosis within the territory of a transiently occluded left anterior descending coronary artery was investigated in 31 porcine hearts submitted to 48 min of coronary occlusion and 6 h of reperfusion. Immediately before excising the heart, the left anterior descending coronary artery was re-occluded and 10% fluorescein was injected in the left atrium. The area at risk was imaged by ultraviolet illumination of the myocardial slices, and the area of necrosis by incubation in triphenyltetrazolium chloride. The area at risk was divided in four sectors and an index of eccentricity was calculated as the percent of the area of necrosis located in the two lateral sectors of the area at risk. The area of contraction band necrosis was measured in whole heart histological sections. Infarcts were generally small, and were composed almost exclusively of contraction band necrosis. There was a good correlation between the extent of the area of contraction band necrosis and infarct size (r=0.831, P<0.0005). The area of necrosis had a patchy appearance and was predominantly distributed along the lateral borders of the area at risk. This eccentric distribution was more prominent in smaller infarcts, and the eccentricity index was inversely correlated with infarct size (r=–0.471, P=0.007), suggesting that contraction band necrosis occurres first at the interface between control and reperfused myocardium in this model. These results are in agreement with a prominet role of mechanical factors in the genesis of myocardial necrosis during transient coronary occlusion.Partially supported by Grants 92/0443 from the Fondo de Investigaciones Sanitarias de la Seguridad Social, CRHG 07-92/79 from the Institut Català de la Salut, and Concerted Action BMH1-CT92/1501, BIOMED I Program from the European Union.     

A comparison of the effects of ischemia and of selective occlusion of capillaries, pre-capillaries and terminal arterioles on coronary reperfusion

To study the 'no-reflow' phenomenon is ischemic myocardium, the effects of ischemia and selective embolic blockade of capillaries, precapillaries and terminal arterioles were compared in isolated rat hearts. Hearts received oxygenated Krebs-Henseleit buffer for 10 min via an aortic cannula, and then coronary perfusion was stopped. The pattern and extent of reperfusion after 15-90 min of global ischemia and after the injection of 9, 15 or 55 mu diameter microspheres were determined from the distribution of injected 6.7% fluorescein isothiocyanate-dextran in frozen transverse sections of the ventricles. Following ischemia, progressively larger subendocardial regions surrounding the left ventricle could not be reperfused. In contrast, embolic occlusion of capillaries, precapillaries or terminal arterioles caused a transmural reduction in perfusion and a fine linear or herringbone pattern of fluorescence. Sixty min of ischemia followed by microsphere injection had no effect on the subendocardial zone of no-reflow but much reduced the intensity of fluorescence elsewhere. Thus thrombosis, erythrocyte plugging and occlusion of capillaries, precapillaries or terminal arterioles are unlikely to be primary causes of the reperfusion defect which develops in ischemic myocardium.     

In vivo determination of acute myocardial ischemia based on photoacoustic imaging with a focused transducer

The location and ischemia extent are two important parameters for evaluating the acute myocardial ischemia (AMI). A focused-transducer-based photoacoustic imaging method was employed to assess time-dependent AMI. Our preliminary results show that the photoacoustic signal could identify the myocardium. The intensity and area of photoacoustic images of myocardium could be used for characterizing the ischemia extent and scope of myocardial ischemia. The results also imply that the intensity and area of photoacoustic images are the rapid fall of an exponential model with an increase of delaying time after the left anterior descending coronary artery (LAD) occlusion. These experimental results were consistent with the clinical characteristics. The findings suggest that the photoacoustic imaging be a potential tool for the real-time assessment of acute myocardial ischemia during surgical operation.     

Myocardial infarction: a paradigm of success in modern medicine

Hospital mortality for acute myocardial infarction declined from 30% to 10% in the last 30 years, thanks to coronary care units and early revascularization with thrombolysis, angioplasty, and stent implantation. Pathologists played a major role by establishing plaque rupture and coronary thrombosis as the major cause of acute myocardial infarction and by discovering that ischemic myocardium necrosis progresses from endocardium to epicardium as a “wave front” phenomenon, with potential reversible injury if the reperfusion is accomplished within 3 h. Long-term mortality following myocardial infarction is mostly due to sudden electrical death, which may be prevented by pharmacologic (antiarrhythmic drugs) and nonpharmacologic (implantable cardioverter defibrillator, pacemaker) therapy. Ventricular assist devices may support the left ventricle as a bridge to transplantation. Long-term mortality at distance from acute myocardial infarction declined from 10% to 2% per year.Despite these indisputable achievements, there are still pending questions: in vivo identification of vulnerable plaque, mechanisms of thrombosis by plaque erosion, prompt treatment on the spot of instantaneous cardiac arrest by external defibrillation, adverse effect of myocardial reperfusion, fate of bare- and drug-eluting coronary stents.With these limitations and challenges well in mind, nowadays myocardial infarction does not represent a nightmare as it was in the past. The achievements in its prevention, diagnosis, and treatment should be considered as a pride of cardiovascular medicine.     

Intimal injury in a transiently occluded coronary artery increases myocardial necrosis. Effect of aspirin

 This study tested the hypothesis that intimal injury in a transiently occluded coronary artery limits myocardial salvage. The effect of intimal injury on reactive hyperaemia was investigated in 17 pigs submitted to a 30-min occlusion of the left anterior descending coronary artery (LAD), not resulting in myocardial infarction. Catheter-induced intimal damage increased local platelet deposition (^99mTc) and reduced hyperaemia, but did not modify myocardial platelet or polymorphonuclear leucocyte content (myeloperoxidase activity) after 6 h reperfusion. To investigate the influence of intimal injury on the extent of myocardial necrosis secondary to a more prolonged coronary occlusion, and the role of platelets on this influence, 52 pigs were submitted to a double randomization (2×2 factorial design) to 250 mg i.v. aspirin vs. placebo and to coronary intimal injury vs. no coronary damage before a 48-min occlusion of the LAD and 6 h of reperfusion. After excluding 12 animals with reocclusion, coronary intimal injury was associated with larger infarcts (triphenyltetrazolium reaction) in animals receiving placebo (36.2±7.0% of the area at risk in animals with intimal injury vs. 10.8±3.9% in animals without coronary injury, P=0.006) but not in those receiving aspirin (20.3±6.5 vs. 21.7±6.5% of the area at risk in animals with and without intimal injury respectively). These results suggest that coronary intimal injury in the reperfused artery may have adverse effects on myocardial salvage by mechanisms other than reocclusion or embolization of platelet aggregates. Recieved: 19 December 1995 / Received after revision: 25 March 1996 / Accepted: 29 April 1996     

Verapamil in two reperfusion models of myocardial infarction. Temporary protection of severely ischemic myocardium without limitation of ultimate infarct size

The ability of verapamil to protect severely ischemic myocardium was assessed in dogs using 40 minutes of temporary coronary occlusion. Reperfusion was established for 4 days after which infarcts were sized histologically. Untreated dogs developed subendocardial infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with verapamil reduced the size of these subendocardial infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed at risk (identified by postmortem perfusion of the previously occluded and unoccluded arteries with different dyes). Thus, verapamil prevented cell death in the severely ischemic subendocardial region for the 40-minute test period. In a second study to establish whether verapamil could delay cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion was used. This period of occlusion caused infarcts averaging 60 +/- 6% of the ischemic area at risk in untreated dogs. Dogs treated with verapamil 15 minutes postocclusion and throughout the remaining 165 minutes of the 3-hour test period had no limitation of infarct size (53 +/- 3% of the area at risk). In this 3-hour study, the effect of variation in collateral blood flow on infarct size was evaluated by plotting infarct size versus subepicardial collateral flow. Verapamil neither improved collateral flow nor altered the relationship between infarct size and baseline collateral flow. Thus, pretreatment with verapamil prevented necrosis of severely ischemic myocytes, when reperfusion was established at 40 minutes, but failed to prevent necrosis of moderately ischemic myocardium and thus failed to limit infarct size when the period of coronary occlusion was prolonged to 3 hours and treatment was started 15 minutes after the onset of ischemia.     

Impaired sarcolemmal membrane permeability in reperfused ischemic myocardium

Summary Sarcolemmal membrane permeability to intravenously injected horseradish peroxidase HRP (MW=40,000) was examined in 8 Wistar rats which had temporary ischaemia produced by left coronary artery ligation. HRP reaction product was identified following 6 min of circulation time by light and electron microscopy. Controls included 4 uninjected animals with coronary ligation, 2 uninjected animals without myocardial ischaemia and 2 injected non operated rats.In normal myocardium, the tracer permeated endothelial plasmalemmal vesicles, intercellular spaces and intracellular vesicles of the T-tubule system, but never permeated the cytoplasm of myocardium cells.As early as 15 min after coronary artery ligation followed by 6 min of reperfusion with circulation of the tracer, HRP product could be seen in the cytoplasm of muscle cells randomly distributed in the subendocardial area. The quantity of permeated cells increased when the ischaemic myocardium is reperfused during 10 min before injecting the tracer.These data indicate that sarcolemmal membrane alteration is an early event in myocardial ischaemic injury and precede the irreversible cellular degenerative changes.This work was supported by research grant from INSERM (ATP 78-95)     

Harmful immune reactions during acute myocardial infarction

Acute coronary syndrome, including myocardial infarction, can occur as a result of ischaemia-reperfusion injury caused by acute occlusion of the coronary vessel/s following the rupture of an atherosclerotic plaque. Superimposed thrombosis at the lesion obstructs blood supply to the myocardium causing myocardial necrosis and ischaemic inflammation. Although not fully described, researchers believe that this process is initiated by a dysfunctional endothelium that activates the nearby leukocytes in the blood stream, thus attracting them to the arterial wall and initiating a cascade of complex mechanisms that lead to myocardial infarction. Interestingly, this process is two sided as the leaking soluble factors from a damaged and/or necrotic myocardium enter the systemic circulation, activating the innate and adaptive cell-mediated immune responses, which include increasing cytotoxic mediators. We hypothesize that this unwanted side effect of increase in proinflammatory mediators can lead to harmful systemic immune reactions directed towards various dysfunctional endothelia. Additionally, a strong inflammatory response, caused by myocardial damage, can impair ventricular function, on top of baseline necrosis. To evaluate this hypothesis, we propose to use in vivo tests to measure endothelial dysfunction, as well as ventricular dysfunction by ultrasound methods, and their correlation with immunological and/or biochemical parameters. These tests will be useful in assessing the risk and therapeutic outcome in patients with acute coronary syndrome.     

Primary percutaneous coronary intervention for acute myocardial infarction with idiopathic thrombocytopenic purpura: a case report

Acute myocardial infarction (AMI) is rare in patients with idiopathic thrombocytopenic purpura (ITP). We describe a case of an AMI during thrombocytopenia in a patient with chronic ITP. A 47-yr-old woman presented with anterior chest pain and a low platelet count (21,000/microliter) at admission. Urgent coronary angiography revealed total occlusion of proximal right coronary artery and primary percutaneous coronary intervention (PCI) was performed successfully. This case suggests that primary PCI may be a therapeutic option for an AMI in patients with ITP, even though the patient had severe thrombocytopenia.     

Is postsystolic shortening area always a marker of myocardial ischaemia?

Postsystolic shortening area has been shown to be a sensitive marker of myocardial ischaemia in a one-vessel model. We tested whether postsystolic shortening provoked by interaction between ischaemic and nonischaemic regions is reduced in a two-vessel model, one vessel occluded and one subjected to coronary artery stenosis. Regional function in the left ventricular anterior wall was studied by orthogonal sonomicrometry during left coronary underperfusion in 14 pentobarbital-anaesthetized cats with an acute circumflex coronary artery occlusion. Left coronary underperfusion in two discrete steps decreased subendocardial blood flow in the left ventricular anterior wall to on average 60% (P < 0.001) and 20% (P < 0.001) of control value, while subepicardial flow did not change. End-diastolic lengths of longitudinal segments increased markedly even during mild subendocardial underperfusion, whereas end-diastolic lengths of circumferential segments only increased during severe subendocardial underperfusion with concomitant increase of left ventricular end-diastolic pressure. Systolic shortening, pressure-length loop area and shortening velocity of circumferential segments did not change. In contrast, systolic shortening and total pressure-length loop area of longitudinal segments decreased progressively approaching zero values during severe coronary underperfusion. Shortening velocity of longitudinal segments also decreased progressively during experimental protocol whereas postsystolic shortening area did not change. Conclusions: postsystolic shortening area is not a marker of subendocardial ischaemia in a two-vessel model which indicates that postsystolic shortening is primarily a phenomenon related to model of ischaemia. End-diastolic lengthening is predominant in the longitudinal axis of the heart during subendocardial ischaemia.