Duration Of Coronary Occlusion Research Articles

Structure and function of the ventricular tachycardia isthmus.

Catheter ablation of postinfarction reentrant ventricular tachycardia (VT) has received renewed interest owing to the increased availability of high-resolution electroanatomic mapping systems that can describe the VT circuits in greater detail, and the emergence and need to target noninvasive external beam radioablation. These recent advancements provide optimism for improving the clinical outcome of VT ablation in patients with postinfarction and potentially other scar-related VTs. The combination of analyses gleaned from studies in swine and canine models of postinfarction reentrant VT, and in human studies, suggests the existence of common electroanatomic properties for reentrant VT circuits. Characterizing these properties may be useful for increasing the specificity of substrate mapping techniques and for noninvasive identification to guide ablation. Herein, we describe properties of reentrant VT circuits that may assist in elucidating the mechanisms of onset and maintenance, as well as a means to localize and delineate optimal catheter ablation targets.

Association between duration of coronary occlusion and high-intensity signal on T1-weighted magnetic resonance imaging among patients with angiographic total occlusion

ObjectivesTo evaluate the association between duration of the coronary occlusion and high-intensity signal (HIS) on noncontrast T1-weighted imaging using a 1.5-T magnetic resonance imager among patients with angiographic coronary total occlusion.MethodsThe signal intensity of the coronary target area divided by the signal intensity of the left ventricular muscle near the target area at each site (TMR) was measured. Areas with a TMR >1.0 were defined as HIS. Thirty five lesions from 33 patients were divided into the following three groups: subacute occlusion (up to 3 months; n = 7), short-duration chronic total occlusion (SD-CTO: 3–6 months; n = 9) and long-duration CTO (LD-CTO: ≥6 months; n = 19).ResultsAll subacute occlusion lesions showed a HIS within the occlusion site. Among patients with CTO, the frequency of a HIS within the occlusion site was significantly higher in SD-CTO than in LD-CTO lesions (p = 0.013). In multivariate analyses, only an occlusion duration of less than 6 months was an independent factor associated with the presence of HIS (odds ratio 7.6, 95% CI 1.1–54.5; p = 0.044).ConclusionsThe presence of a HIS in the occlusion site was associated more with SD-CTO than with LD-CTO among patients with CTO.Key Points• All subacute occlusion lesions show a high-intensity signal on T1-weighted imaging.• HIS within occlusion sites is associated with subacute or short-duration total occlusion.• T1-weighted imaging for coronary total occlusion may be useful for intervention strategy.

Intracoronary Infusion of Thioflavin-S to Study Microvascular Obstruction in a Model of Myocardial Infarction

Introduction and objectivesMicrovascular obstruction exerts deleterious effects after myocardial infarction. To elucidate the role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction, we performed a preliminary methodological study to accurately define this process in an in vivo model. MethodsMyocardial infarction was induced in swine by means of 90-min of occlusion of the mid left anterior descending coronary artery using angioplasty balloons. Intracoronary infusion of thioflavin-S was applied and compared with traditional intra-aortic or intraventricular instillation. The left anterior descending coronary artery perfused area and microvascular obstruction were quantified in groups with no reperfusion (thioflavin-S administered through the lumen of an inflated over-the-wire balloon) and with 1-min, 1-week, and 1-month reperfusion (thioflavin-S administered from the intracoronary catheter after balloon deflation). ResultsIn comparison with intra-aortic and intraventricular administration, intracoronary infusion of thioflavin-S permitted a much clearer assessment of the left anterior descending coronary artery perfused area and of microvascular obstruction. Ischemia-reperfusion injury exerted a decisive role on the occurrence and dynamics of microvascular obstruction. The no-reperfusion group displayed completely preserved perfusion. With the same duration of coronary occlusion, microvascular obstruction was already detected in the 1-min reperfusion group (14%±7%), peaked in the 1-week reperfusion group (21%±7%), and significantly decreased in the 1-month reperfusion group (4%±3%; P<.001). ConclusionsWe present proof-of-concept evidence on the crucial role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction. The described porcine model using intracoronary injection of thioflavin-S permits accurate characterization of microvascular obstruction after myocardial infarction.

Infusión intracoronaria de tioflavina-S para el estudio de la obstrucción microvascular en un modelo de infarto de miocardio

Introduction and objectivesMicrovascular obstruction exerts deleterious effects after myocardial infarction. To elucidate the role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction, we performed a preliminary methodological study to accurately define this process in an in vivo model. MethodsMyocardial infarction was induced in swine by means of 90-min of occlusion of the mid left anterior descending coronary artery using angioplasty balloons. Intracoronary infusion of thioflavin-S was applied and compared with traditional intra-aortic or intraventricular instillation. The left anterior descending coronary artery perfused area and microvascular obstruction were quantified in groups with no reperfusion (thioflavin-S administered through the lumen of an inflated over-the-wire balloon) and with 1-min, 1-week, and 1-month reperfusion (thioflavin-S administered from the intracoronary catheter after balloon deflation). ResultsIn comparison with intra-aortic and intraventricular administration, intracoronary infusion of thioflavin-S permitted a much clearer assessment of the left anterior descending coronary artery perfused area and of microvascular obstruction. Ischemia-reperfusion injury exerted a decisive role on the occurrence and dynamics of microvascular obstruction. The no-reperfusion group displayed completely preserved perfusion. With the same duration of coronary occlusion, microvascular obstruction was already detected in the 1-min reperfusion group (14%±7%), peaked in the 1-week reperfusion group (21%±7%), and significantly decreased in the 1-month reperfusion group (4%±3%; P<.001). ConclusionsWe present proof-of-concept evidence on the crucial role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction. The described porcine model using intracoronary injection of thioflavin-S permits accurate characterization of microvascular obstruction after myocardial infarction.Full English text available from:www.revespcardiol.org/en

Contribution of calpain to myoglobin efflux from cardiomyocytes during ischaemia and after reperfusion in anaesthetized rats

Calpain activation has a putative role in ischaemia-reperfusion injury of cardiomyocytes. This study clarified the in vivo contribution of calpain to disruption of cardiomyocyte sarcolemma during ischaemia and after reperfusion in anaesthetized rats. Using a microdialysis technique in the hearts of anaesthetized rats, we investigated the effects of the calpain inhibitors on myocardial interstitial myoglobin level in the ischaemic region during coronary occlusion and after reperfusion. The calpain inhibitors were administered locally via a dialysis probe. Two durations of coronary occlusion were tested. Thirty-minute coronary occlusion: dialysate myoglobin concentration increased markedly from 385 ± 46 ng mL(-1) at baseline to 3701 ± 527 ng mL(-1) at 20-30 min of occlusion. After reperfusion, dialysate myoglobin concentration further increased, reaching a peak (12 296 ± 1564 ng mL(-1) ) at 10-20 min post-reperfusion and then declined gradually. The calpain inhibitors, MDL-28170 and SNJ-1945 did not change dialysate myoglobin concentration during occlusion but attenuated the increase after reperfusion to 6826 ± 1227 and 8130 ± 938 ng mL(-1) at 10-20 min post-reperfusion (P < 0.05), respectively. Ninety-minute coronary occlusion: dialysate myoglobin concentration increased from 516 ± 33 ng mL(-1) at baseline to 5463 ± 387 ng mL(-1) at 80-90 min after occlusion. After reperfusion, there was no significant increase in dialysate myoglobin concentration. MDL-28170 did not affect dialysate myoglobin concentration during occlusion or after reperfusion. Calpain contributes to sarcolemmal disruption immediately after reperfusion following 30-min coronary occlusion, but has little effects during ischaemia and after reperfusion in 90-min coronary occlusion.

Assessment and Impact of the Human Coronary Collateral Circulation on Myocardial Ischemia and Outcome

Cardiovascular disease is the leading cause of death in industrialized countries and may become the most prevalent reason for mortality worldwide.1,2 In the vast majority of patients, death is the consequence of cerebral or myocardial infarction, both of which are characterized by acute vessel occlusion in the context of atherosclerosis.2 In this situation, outcome depends critically on the extent of infarcted tissue.3 Myocardial infarct size is reflected by the degree of ECG ST-segment elevation during the acute phase4 and is directly determined by the duration of coronary occlusion, the ischemic area at risk for infarct, the lack of collateral supply to the jeopardized region, the absence of preconditioning ischemic episodes before, and the level of myocardial oxygen consumption during the acute coronary event.5 The ischemic area at risk for necrosis is intimately related to alternative sources of blood supply to the occluded vascular region; this is to the extent that well-developed coronary anastomoses originating from a collateral supplying artery can entirely compensate for the occlusion in the collateral-receiving vessel, thus rendering its area at risk zero (Figure 1). In this event, the duration of coronary artery occlusion also becomes irrelevant. However, in the event of acute and permanent coronary occlusion, myocardium is only salvaged in the presence of a preformed collateral circulation.6 In this context, the promotion of well-functioning coronary anastomoses (arteriogenesis) in patients with chronic coronary artery disease (CAD) before a coronary event is an appealing therapeutic principle. The selection of suitable candidates for arteriogenesis should be based on sound assessment of coronary collateral function. Figure 1. Normal left ventricular angiogram ( top middle and right ) in a patient with chronic total occlusion of the proximal left anterior descending artery occlusion ( top left ). Angiography of the right coronary artery ( bottom ) shows extensive collateral supply …

MRI in acute myocardial infarction

Although acute myocardial infarction (AMI) is still one of the main causes of high morbidity in Western countries, the rate of mortality has decreased significantly. The main cause of this drop appears to be the decline of the incidence of ST-segment elevation myocardial infarction (STEMI) along with an absolute reduction in case fatality rate once STEMI has occurred. Myocardial ischaemia progresses with the duration of coronary occlusion and the delay in time to reperfusion determines the extent of irreversibile necrosis from subendocarial layers towards the epicardium in accordance with the so-called 'wave-front phenomenon'. Coronary artery recanalization, either by thrombolitic therapy or primary percutaneous intervention, may prevent myocardial cell necrosis increasing salvage of damaged, but still viable, myocardium within the area at risk. Magnetic resonance imaging (MRI) can provide a wide range of clinically useful information in AMI by detecting not only location of transmural necrosis, infarct size and myocardial oedema, but also showing in vivo important microvascular pathophysiological processes associated with AMI in the reperfusion era, such as intramyocardial haemorrhage and no-reflow. The focus of this review will be on the impact of cardiac MRI in the characterization of AMI pathophysiology in vivo in the current reperfusion era, concentrating also on clinical applications and future perspectives for specific therapeutic strategies.

Kardioprotektive Konditionierung

The extent of myocardial infarction depends primarily on the size of the perfusion territory of the occluded coronary artery, then on the duration of coronary occlusion and on collateral perfusion, and finally on the hemodynamic situation, notably heart rate. Early reperfusion is mandatory for salvage of ischemic myocardium; however, reperfusion is a double-edged sword and causally contributes to the extent of infarction through reperfusion injury. Short cycles of ischemia and reperfusion before (preconditioning) or following (postconditioning) a sustained coronary occlusion with reperfusion reduce infarct size. Pre- and postconditioning are also operative in the human heart. Such cardioprotection is effected by a complex signal transduction, initiated by extracellular triggers (autacoids, cytokines, growth factors), which activate an intracellular mediator cascade. Intracellular mediation requires activation of protein kinases. Mitochondria are central elements of signal mediation, notably by free oxygen radical formation, but also end-effectors which are decisive for cell death or survival. Age, comorbidities, and drugs interact with cardioprotection.

Superoxygen Therapy

In North America, every 25 seconds someone will have a coronary event and every minute someone will die of one.1 ST elevation myocardial infarction (STEMI) is the most dramatic manifestation of coronary artery disease and remains as one of the most important causes of mortality in the industrialized world. Prompt and successful reperfusion therapy (either pharmacologically with use of fibrinolytic therapy or mechanically with primary percutaneous coronary intervention [PCI]) is currently the cornerstone of acute management of STEMI to salvage ischemic myocardium and limit infarct size. Although undoubtedly beneficial, reperfusion of an occluded artery represents “a double-edge sword,”2 because restoration of epicardial coronary flow initiates a series of complex biochemical and molecular phenomena, which will ultimately mitigate myocardial healing. Thus, with reperfusion comes reperfusion injury.3 Article see p 366 Although the concept of cardioprotection (myocardial salvage) was first suggested by Braunwald,4 it was the seminal works of Reimer et al who crystallized the fact that there exists a window of opportunity to act to limit myocardial injury. They postulated that a “wavefront phenomenon” of cardiac necrosis, if left unchecked, would extend the infarct from the subendocardial region to the subepicardial region by using canine models of transiently or permanently occluded coronary arteries.5 Thereafter, over the course of 3 decades, mixed and disappointing results have plagued both experimental and clinical attempts to limit the deleterious effects of early reperfusion through either pharmacological (adenosine, calcium channel blockers, Na+/H+ exchange inhibitors, KATP channel openers, and glucose-insulin-potassium infusion) or nonpharmacological (therapeutic hypothermia) means.3,6 The reasons for such inconsistent findings in cardioprotection are multifold. First, reperfusion injury encompasses numerous, overlapping mediators of cardiomyocyte death from oxidative stress and Ca2+ overload to alterations in cellular pH, as well as an inflammatory process with a central …

Duration of Symptoms Is Not Always the Key Modulator of the Choice of Reperfusion for ST-Elevation Myocardial Infarction

Fibrinolytic therapy (FT) and primary percutaneous coronary intervention (PCI) are both well-accepted reperfusion therapies in ST-segment elevation myocardial infarction (STEMI). The evidence of randomized clinical trials indicates a relatively modest difference in 30-day mortality (≈1%) in favor of primary PCI over fibrin-specific FT and was based on very timely primary PCI (ie, a primary PCI–related delay of 40 minutes [door-to-balloon less door-to-needle time]).1 Longer delays to primary PCI, which are far more frequent in clinical practice,2 are associated with attenuated benefit or no benefit at all, particularly when compared with fibrin-specific FT.3,4 The benefit of timely primary PCI over FT is likely to especially apply to higher-risk patients.5,6 Irrespective of the method of reperfusion, the potential for myocardial salvage and better clinical outcome is inversely proportional to ischemic time or its only available clinical surrogate, symptom duration.7–12 These considerations underpin the notion expressed in the American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of STEMI that timely reperfusion therapy is likely more important in determining outcome than whether FT or primary PCI is the chosen reperfusion method.13 Response by Armstrong et al p 1310 The ACC/AHA STEMI guidelines highlight the time point of 3 hours of symptom duration in guiding the choice of reperfusion therapy. They state that if symptom duration is <3 hours, no preference exists between FT and primary PCI provided that treatment is timely (for FT, door-to-needle time <30 minutes; for primary PCI, door-to-balloon time <90 minutes and ≤60 minutes between estimated needle time and estimated balloon time). However, if symptom duration exceeds 3 hours, these guidelines favor primary PCI over FT, again provided that primary PCI can be performed in a timely fashion.13 This article reexamines the evidence that may or may not be the basis …

The antiarrhythmic effect and clinical consequences of ischemic preconditioning

Potentially hazardous short ischemic episodes increase the tolerance of myocardium to ischemia paradoxically. This condition decreases the infarct area markedly caused by a longer duration of coronary occlusion. This phenomenon is known as 'ischemic preconditioning' and its powerful cardioprotective effect has been shown in experimental and clinical studies. Ischemic preconditioning decreases cardiac mortality markedly by preventing the development of left ventricular dysfunction and ventricular and supraventricular arrhythmias after acute myocardial infarction. Ischemia-induced opening of ATP-sensitive potassium channels and synthesis of stress proteins via activation of adenosine, bradykinin and prostaglandin receptors seem to be the possible mechanisms. By understanding the underlying mechanisms of ischemic preconditioning, it may be possible to develop new pharmacologic agents that cause ischemic preconditioning with antiischemic and antiarrhythmic properties without causing myocardial ischemia.

Effects of Transient Myocardial Ischemia on the Ventricular Defibrillation Threshold

Acute myocardial ischemia and the mode of ventricular fibrillation (VF) induction influence the ventricular defibrillation threshold (DFT). The purpose of this study was to determine the effects of transient regional left ventricular (LV) ischemia on the DFT. Ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT), and DFT were measured under nonischemic conditions (control) in 26 pigs weighing 25-35 kg. Myocardial ischemia was then induced by occlusion of the mid left anterior descending coronary artery, and measurements of ERP and VFT were repeated after 2 minutes of occlusion. The coronary artery ligation was released immediately after the onset of VF and DFT was measured. LV ERP was unchanged by ischemia (199 +/- 19 ms at control vs. 200 +/- 22 ms under ischemic conditions, P = 0.799), whereas VFT was significantly lower during coronary occlusion (10.7 +/- 5.4 mA vs. 37.7 +/- 13 mA, P = 0.000). Brief myocardial ischemia caused a significant increase in DFT (13.5 +/- 12.6 J after coronary occlusion vs. 6.8 +/- 6.8 J at control, P = 0.023). The duration of coronary occlusion was not correlated with the amounts of energy required to defibrillate (P = 0.526). This experimental study shows that transient myocardial ischemia markedly increases the DFT, suggesting that specific defibrillation algorithms should be designed for recipients of implantable defibrillators at risk of myocardial ischemia.

Determinants of infarct size after thrombolytic treatment in acute myocardial infarction

Both experimental and single-center clinical studies have shown that myocardium at risk, residual collateral flow, and duration of coronary occlusion are important determinants of final infarct size. The purpose of this study was to replicate these results on a multicenter basis to demonstrate that perfusion imaging using different camera and computer systems can provide reliable assessments of myocardium at risk and collateral flow. Sequential tomographic myocardial perfusion imaging with technetium-99 (Tc-99m) sestamibi was performed in 74 patients with first time myocardial infarction, who were enrolled in a multicenter, randomized, double-blind, placebo-controlled pilot study of poloxamer 188 as ancillary therapy to thrombolysis. All patients underwent thrombolysis within 6 hours of the onset of chest pain. Tc-99m sestamibi was injected intravenously at the initiation of thrombolytic therapy, and tomographic imaging was performed 1 to 6 hours later to assess myocardium at risk. Collateral flow was estimated noninvasively from the acute sestamibi images by 3 methods that assess the severity of the perfusion defect. Final infarct size was determined at hospital discharge by a second sestamibi study. Myocardium at risk (r = 0.61, p <0.0001) and radionuclide estimates of collateral flow (r = 0.58 to 0.66, all p <0.0001) were significantly associated with final infarct size. These associations were independent of the treatment center. On a multivariate basis, myocardium at risk (p = 0.003), the radionuclide estimate of collateral flow (p = 0.03), and treatment arm (p = 0.04) were all independent determinants of infarct size. Time to thrombolytic therapy showed only a trend (p = 0.10). The treatment center was not significant (p = 0.42). Myocardium at risk and collateral flow are important determinants of infarct size that are independent of treatment center. Tomographic imaging with Tc-99m sestamibi can provide noninvasive assessments of these parameters in multicenter trials of thrombolytic therapy.

Attenuation of heat shock protein expression by coronary occlusion in hypertrophied hearts.

Hearts hypertrophied by pressure-overload are more susceptible to ischemia than nonhypertrophied hearts, which may result from the attenuation of self-protective responses. Because heat shock proteins (HSPs) are reported to protect against ischemic injuries, we hypothesized that HSP expression by coronary occlusion may be attenuated in hypertrophied hearts. We banded the ascending aorta to develop ventricular hypertrophy and put a snare around the left coronary artery in rats. After 4 wk, coronary occlusion was applied by tightening the snare for 5 or 10 min in rats with and without aortic banding. The hearts were excised 0, 0.5, 1, 2, 4, 8, 12, and 24 h after coronary occlusion. Ischemic and nonischemic myocardial tissues were obtained after the snare was tightly tied, and dye was infused from the aorta. The mRNAs and protein of 72-kDa HSP (HSP 72) and/or 73-kDa HSP (HSP 73) were detected by Northern and Western blot analyses. Protein and mRNA levels of HSPs expressed by 5-min coronary occlusion in hypertrophied hearts (left ventricular weight, 577 +/- 16 mg) were lower compared with those in control hearts (462 +/- 9 mg). A longer period of coronary occlusion (10 min) elevated the attenuated expression to a level similar to that in control hearts. Treatment with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril, 10-15 mg.kg(-1).day(-1)) for 4 wk preserved HSP mRNA expression even in hearts with ascending aortic banding. In hypertrophied hearts, HSP 72 and 73 expression by coronary occlusion was attenuated and was modulated by the duration of coronary occlusion and by ACE inhibitor treatment.

Determinants of infarct size in acute myocardial infarction in patients treated with reperfusion therapy

Infarct size after reperfusion therapy is determined by the extent of myocardium at risk, the degree of residual blood flow within the jeopardized zone, and the duration of coronary occlusion. This review article will explore the noninvasive methods that have been used to measure these variables. Recent advances in nuclear cardiology techniques will be discussed in detail, because new agents have the ability to accurately quantify these variables.

Increase of Adenosine Release by Adenosine Antagonists in Hearts with Coronary Occlusion and Reperfusion

In isolated perfused rat hearts with coronary occlusion and reperfusion, the effect of adenosine antagonists on the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated. An antagonist with high selectivity for the A1 receptor, 8-phenyltheophylline, was applied and compared with the relatively unspecific antagonist theophylline, used in its water-soluble form aminophylline. Depending on the duration of coronary occlusion, more or less severe tachyarrhythmias occurred during the myocardial ischemia, and particularly during the subsequent coronary reperfusion. Large amounts of the nucleosides and oxypurines were released after reopening the coronary artery. The release was particularly, high in hearts with ventricular fibrillation. Both adenosine antagonists increased the release in a highly significant way. The findings let assume that adenosine has perhaps a modulating effect on its own release, which can be blocked by adenosine antagonists.

Aggressive interventional treatment of acute myocardial infarction. Lessons from the animal laboratory applied to the catheterization suite.

Myocardial necrosis progresses with the duration of coronary occlusion in the early stages of acute myocardial infarction. Prompt recanalization of the infarct-related artery resulting in effective and sustained reperfusion of jeopardized myocardium is the goal of modern therapy. Clinical thrombolysis trials have demonstrated a significant survival advantage for treated patients, but only a modest recovery of global or regional systolic left ventricular function. Accelerated regimens of administering currently available thrombolytic agents are associated with early coronary patency rates approaching 85%, although effective coronary perfusion is restored in only slightly better than one half of patients treated. Primary angioplasty without antecedent thrombolytic therapy has resulted in high patency rates with superior coronary flow when performed in some experienced centers. Treatment of cardiogenic shock requires immediate mechanical or surgical intervention to reestablish coronary perfusion often following placement of a circulatory assistance device. Future trends toward very early initiation of thrombolytic therapy, improvements in adjunctive therapy and advances in the noninvasive detection of recanalization should permit selective use of aggressive interventional therapy for failed thrombolysis in a minority of patients with acute myocardial infarction.

Time course of technetium-99m sestamibi myocardial distribution in dogs with a permanent or transient coronary occlusion

The influence of duration of coronary occlusion and reperfusion on technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi) myocardial redistribution between necrotic, salvaged and non-ischaemic myocardium was investigated in dogs submitted either to a 90-min or a 24-h permanent left descending coronary artery occlusion (groups 1 and 2) or to a 90-min occlusion followed by 30 min, 6 h or 22.5 h of reperfusion (groups 3, 4 and 5). In all groups, 99mTc-sestamibi and radiolabelled microspheres were injected at 45 min of occlusion. After delimiting the area at risk and the infarct by Evans blue perfusion and triphenyltetrazolium chloride staining, radioactivity of heart slices from normal, viable-ischaemic and necrotic myocardium was measured in a gamma counter. A significant (P < 0.001) linear relationship between 99mTc-sestamibi distribution and myocardial blood flow was observed in the area at risk of groups 1 (r = 0.92), 2 (r = 0.84), 3 (r = 0.90), 4 (r = 0.93) and 5 (r = 0.58). In all groups, the mean percentage of 99mTc-sestamibi uptake in the ischaemic over normal zone overestimated significantly (P < 0.05) the mean percentage of the ratio in myocardial blood flow measured with microspheres (group 1: 13.3 +/- 1.4 vs. 7.7 +/- 1.2; group 2: 15.9 +/- 2.0 vs 5.6 +/- 1.2; group 3: 14.9 +/- 1.6 vs 6.2 +/- 1.0; group 4: 20.9 +/- 1.7 vs 10.9 +/- 1.8; group 5: 51.0 +/- 2.7 vs 14.0 +/- 2.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Pathobiology of sudden death: coronary causes

The single most common cause of sudden death in the western world is coronary artery disease. Sudden death from coronary causes occurs equally in asymptomatic patients, patients with angina, and patients with a known history of myocardial infarction. The mechanism of sudden coronary death in most patients is ventricular fibrillation secondary to ischemia. Microthrombi in intramyocardial coronary arteries may also play a role. Instability of atherosclerotic plaques, in terms of thrombosis and vasoreactivity, underlies the syndrome of unstable angina as well as many cases of acute myocardial infarction. Sudden coronary death falls within this spectrum of ischemic heart disease. Development of these syndromes depends on the abruptness of onset and the completeness and duration of coronary occlusion. Thus a rapidly evolving coronary artery lesion, with plaque fissure, rupture, and luminal thrombosis, can lead to myocardial ischemia, with fatal electrical instability of the myocardium as the first clinical manifestation. The diagnosis of sudden coronary death in the absence of myocardial infarction is determined by the degree of coronary artery narrowing and the exclusion of other causes of death. The presence of acute coronary artery lesions, which may be present in a significant number of sudden coronary death patients, lends support to the pathologic diagnosis. Thus the coronary arteries in victims of sudden coronary death may exhibit established atherosclerotis or acute lesions, whereas the myocardium may appear normal or show healed or acute infarction or hypertrophy. Although less common, nonatherosclerotic coronary artery diseases can account for sudden death as well, particularly in younger patients. Therefore, when sudden death occurs in children and young adults, coronary causes related to congenital anomalies, fibromuscular dysplasia, arteritis, or metabolic diseases should be considered.

Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig.

Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.