Early Coronary Artery Reperfusion Research Articles

Ozone protects cardiomyocytes against ischemia/reperfusion injury: Regulating the heat shock protein 70 (HSP70) expression through activating the JAK2/STAT3 Pathway

ABSTRACT Ischemia/reperfusion (I/R) injury causes complications in early coronary artery reperfusion for acute myocardial infarction (AMI). Ozone (O3) has been reported to be applied for protecting I/R injury, but its detailed mechanism remains unclear. Our study focused on the protective effect of O3 pretreatment on myocardial I/R injury and JAK2/STAT3 signaling and HSP70 regulation involving in the mediation. The rat hearts which were perfused and isolated as well as the cultured cardiomyocytes of neonatal rat were exposed to hypoxia/reoxygenation (H/R) and different concentrations of O3 followed by heat shock protein 70 (HSP70) siRNA treatment. The results showed O3 attenuated the suppression of cell viability induced by H/R and decreased the release of activity of creatine kinase (CK), lactate dehydrogenase (LDH) and apoptosis of cardiomyocytes in vitro. Moreover, O3 also activated the JAK2/STAT3 signaling, upregulated the expression of HSP70 both in vitro and vivo, and decreased the index of apoptosis of cardiomyocytes caused by I/R as well as myocardial infarct area in vivo. In addition, HSP70 siRNA and JAK2 inhibitor AG490 inhibited the cardioprotective effect of O3. And the expression of HSP70 increased by ozone was reduced by AG-490. In conclusion, our results demonstrated that ozone protects cardiomyocytes in I/R injury through regulation of the expression of HSP70 by activating the JAK2/STAT3 pathway.

Consecutive electrocardiographic changes during percutaneous coronary intervention for acute coronary syndrome with high-grade atrioventricular block: a case report

BackgroundAcute coronary syndrome (ACS) with high-grade atrioventricular block (HAVB) still has a poor mortality risk, even in the current percutaneous coronary intervention (PCI) era. However, early PCI for ACS with HAVB is associated with improved in-hospital survival and a 6-month survival similar to that of ACS without HAVB.Case presentationA 70-year-old man was admitted to our hospital for ACS with HAVB. ECG showed complete AV block, complete right bundle branch block (CRBBB), and left axis deviation. Cardiac enzymes were elevated. He underwent temporary pacemaker insertion and coronary angiography, which showed severe stenosis of the proximal right coronary artery (RCA), 99% stenosis of the distal RCA with Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow, and total occlusion of the proximal left anterior descending artery (LAD). We performed primary PCI in both the RCA and LAD, which resulted in TIMI grade 3 flow in both. After PCI, the HAVB recovered to normal sinus rhythm with CRBBB; a normal QRS interval returned within three days. The patient was discharged from the hospital without complications.ConclusionIn this case of ACS with HAVB, early intensive coronary artery reperfusion resulted in long-term patient survival. The blood supply to the AV node and bilateral bundle branches is complex. Multivessel ischemia may compromise both primary and collateral blood flows to the AV node and septum, resulting in severe conduction impairment. Clinicians performing PCI should be aware of this anatomy and physiology.

New and revisited approaches to preserving the reperfused myocardium.

Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.

Coronary artery reperfusion for ST elevation myocardial infarction is associated with shorter cycle length ventricular tachycardia and fewer spontaneous arrhythmias

Ventricular tachycardia (VT) induction at electrophysiological (EP) study early after ST elevation myocardial infarction (STEMI) has been a predictor of spontaneous ventricular arrhythmia. Reperfusion therapy for STEMI may have resulted in altered VT character. We attempted to determine differences in VT cycle length (CL) and VT recurrence rates, in patients who received early and late reperfusion treatment for STEMI. Of 180 consecutive patients with left ventricular ejection fraction < 40%, 77 patients had positive EP studies. Forty-nine patients receiving early reperfusion treatment (group 1, n = 49) were compared with 28 patients who received late reperfusion (group 2; n = 28). Seventy-five patients had defibrillators implanted for primary prevention of sudden death. Patients were followed for up to 6 years to assess long-term rates of spontaneous ventricular tachyarrhythmia. Patients who received early reperfusion demonstrated shorter CL inducible VT (231 ± 43 ms vs. 252 ± 56 ms; P = 0.016). They also had fewer spontaneous arrhythmias (adjusted hazard ratio of 2.94, 95% confidence interval: 1.07-8.13; P = 0.03) with shorter CL spontaneous VT (266 ± 54 ms vs. 320 ± 80 ms; P = 0.02) at 53 ± 33 months. Ventricular tachycardia CL was the only independent predictor of spontaneous arrhythmia or sudden cardiac death (1.22, 1.07-1.47; P = 0.016). Patients receiving early reperfusion for STEMI had faster inducible and spontaneous VT and fewer spontaneous recurrences. This may be due to changes in the myocardial substrate as a result of early coronary artery reperfusion.

New Horizons in Cardioprotection

Coronary heart disease is the largest major killer of American men and women and accounted for 1 of every 6 deaths in the United States in 2007.1 The annual incidence of myocardial infarction in the United States is estimated to be 935 000, with 610 000 new cases and 325 000 recurrent attacks. Survivors have a much higher chance of suffering from congestive heart failure, arrhythmias, and sudden cardiac death. Prognosis after an acute myocardial ischemic injury is primarily dependent on the amount of myocardium that undergoes irreversible injury.2–4 Large transmural infarcts yield a higher probability of cardiogenic shock, arrhythmias, adverse remodeling, and development of late chronic heart failure. Although it has been known since the early 1970s that the size of a myocardial infarction can be modified by various therapeutic interventions,5 early coronary artery reperfusion by fibrinolysis or percutaneous coronary intervention, including balloon angioplasty with or without stenting, remains the only established intervention capable of consistently reducing infarct size in humans. Although reperfusion has led to significant advances in patient care and reduction in hospital mortality, delays in seeking medical attention and inherent limitations in initiating fibrinolysis or percutaneous coronary intervention dictate that additional substantive improvements in morbidity and mortality can be achieved only with the development of new adjunctive therapies coupled with reperfusion. In addition, reperfusion therapy itself may induce reperfusion injury, a phenomenon that may encompass stunned myocardium, no-reflow phenomenon, and lethal myocardial cell death. If this injury could be prevented or minimized by administration of adjunctive therapy, then the net benefit of reperfusion could be enhanced. The problem of acute ischemic injury and myocardial infarction is not limited to patients with acute coronary artery syndrome. It remains a major problem in cardiac surgery as well. It is well documented that the incidence of myocardial necrosis after surgery, as determined by creatine kinase MB enzyme release and troponin levels, ranges somewhere between 40% and 60%, and, depending on its clinical definition, the incidence of myocardial infarction after coronary artery bypass graft surgery may be as high as 19%. The intermediate and long-term implications are considerable. In a recent retrospective analysis of 18 908 patients who underwent coronary artery bypass graft surgery and in whom long-term follow-up was available, it was shown that myocardial enzyme elevation within the first 24 hours of surgery was associated with increasing mortality over the course of months to years. This study confirms earlier reports that even small enzyme elevations after surgery are associated with worse long-term outcomes.4

State of the Science of Cardioprotection: Challenges and Opportunities— Proceedings of the 2010 NHLBI Workshop on Cardioprotection

The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against ischemia and reperfusion injury. Since the early 1970s, there has been evidence that the size of a myocardial infarction could be altered by various interventions. Early coronary artery reperfusion has been an intervention that consistently reduces myocardial infarct size in animal models as well as humans. Most cardiologists agree that the best way to treat acute ST-segment elevation myocardial infarction is to reperfuse the infarct artery as soon as possible and to keep the infarct artery patent. In general, stenting is superior to angioplasty, which is superior to thrombolysis. There is no accepted adjunctive therapy to acutely limit myocardial infarct size along with reperfusion that is routinely used in clinical practice. In the Kloner experimental laboratory, some adjunctive therapies have reproducibly limited infarct size (regional hypothermia, preconditioning, cariporide, combinations of the above, remote preconditioning, certain adenosine agonists, and late sodium current blockade). In clinical trials, a host of pharmacologic adjunctive therapies have failed to either reduce infarct size or improve clinical outcome. Potential reasons for the failure of these trials are discussed. However, some adjunctive therapies have shown promise in data subanalyses or subpopulations of clinical trials (adenosine, therapeutic hypothermia, and hyperoxemic reperfusion) or in small clinical trials (atrial natriuretic peptide, ischemic postconditioning, and cyclosporine, the mitochondrial permeability transition pore inhibitor). A recent clinical trial with remote conditioning induced by repetitive inflation of a brachial artery cuff begun prior to hospitalization showed promise in improving myocardial salvage and there are several reports in the cardiothoracic literature, suggesting that remote preconditioning protects hearts during surgery. Thus, in 2011, there is hope that applying some of the body's own conditioning mechanisms may provide protection against ischemic damage.

Platelet/von Willebrand Factor Inhibitors to the Rescue of Ischemic Stroke

In the last few decades, there have been dramatic advances in the treatment of acute coronary syndromes, leading to a substantial reduction in the actual mortality and disability of the most frequent atherothrombotic diseases. To make brief a long story of clinical success, coronary care units initially managed to reduce mortality by controlling severe arrhythmias and heart failure. Further reduction of major adverse cardiac events was subsequently achieved through early coronary artery reperfusion by means of pharmacological thrombolysis and percutaneous coronary intervention with stent deployment. The development and improved use of anticoagulant and antiplatelet drugs has also been crucial for further clinical progress. See accompanying article on page 1949 Clinicians are well aware that progress was much smaller for ischemic stroke, the second most frequent atherothrombotic disease. Specialized intensive care units are helpful, but their impact on stroke mortality and disability is not as great as that of cardiac care units. Pharmacological thrombolysis is only effective in the limited therapeutic window of 3 to 4.5 hours after the onset of symptoms of cerebral ischemia (the sooner the treatment, the higher the efficacy), and the risk of intracerebral bleeding looms large. Moreover, antiplatelet and …

Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection

Following an acute myocardial infarction (AMI), early coronary artery reperfusion remains the most effective means of limiting the eventual infarct size. The resultant left ventricular systolic function is a critical determinant of the patient's clinical outcome. Despite current myocardial reperfusion strategies and ancillary antithrombotic and antiplatelet therapies, the morbidity and mortality of an AMI remain significant, with the number of patients developing cardiac failure increasing, necessitating the development of novel strategies for cardioprotection which can be applied at the time of myocardial reperfusion to reduce myocardial infarct size. In this regard, the Reperfusion Injury Salvage Kinase (RISK) Pathway, the term given to a group of pro-survival protein kinases (including Akt and Erk1/2), which confer powerful cardioprotection, when activated specifically at the time of myocardial reperfusion, provides an amenable pharmacological target for cardioprotection. Preclinical studies have demonstrated that an increasing number of agents including insulin, erythropoietin, adipocytokines, adenosine, volatile anesthetics natriuretic peptides and 'statins', when administered specifically at the time of myocardial reperfusion, reduce myocardial infarct size through the activation of the RISK pathway. This recruits various survival pathways that include the inhibition of mitochondrial permeability transition pore opening. Interestingly, the RISK pathway is also recruited by the cardioprotective phenomena of ischemic preconditioning (IPC) and postconditioning (IPost), enabling the use of pharmacological agents which target the RISK pathway, to be used at the time of myocardial reperfusion, as pharmacological mimetics of IPC and IPost. This article reviews the origins and evolution of the RISK pathway, as part of a potential common cardioprotective pathway, which can be activated by an ever-expanding list of agents administered at the time of myocardial reperfusion, as well as by IPC and IPost. Preliminary clinical studies have demonstrated myocardial protection with several of these pharmacological activators of the RISK pathway in AMI patients undergoing PCI. Through the use of appropriately designed clinical trials, guided by the wealth of existing preclinical data, the administration of pharmacological agents which are known to activate the RISK pathway, when applied as adjuvant therapy to current myocardial reperfusion strategies for patients presenting with an AMI, should lead to improved clinical outcomes in this patient group.

Wound model of myocardial infarction

ischemic heart disease is the major etiology for heart failure today ([3][1]). The initial event is frequently a large or recurrent myocardial infarction. Acute myocardial infarction starts with thrombotic occlusion of a coronary artery, develops during several hours, and terminates when necrosis

Early Monitoring of Serum Cardiac Troponin I for Assessment of Coronary Reperfusion Following Thrombolytic Therapy

The authors report the use of cardiac troponin I (cTnI) for the early, noninvasive determination of coronary reperfusion following thrombolytic therapy. Cardiac troponin I, creatine kinase (CK)-MB, and myoglobin concentrations were measured in early serum specimens at 30, 60, and 90 minutes after initiation of therapy (0 minutes) in 25 consecutive patients given front-loaded rt-PA during acute myocardial infarction. Angiography, determined at 90 minutes after therapy, was used to classify patients as follows: group I (n = 17) reperfusion (TIMI flow grade 2, 3); and group 2 (n = 8) absence of reperfusion (TIMI flow grade 0, 1). The authors calculated the ratio increase in cTnI (delta cTnI), CK-MB (delta CK-MB), and myoglobin (delta myoglobin) 90 minutes after therapy in group 1 and 2. Serum cTnI, CK-MB and myoglobin concentrations significantly increased at 60 and 90 minutes in group 1, but not in group 2. Delta cTnI, delta CK-MB, and delta myoglobin levels were significantly increased in group 1 versus group 2 at 90 minutes. Further, delta cTnI was significantly greater at 90 minutes within group 1 compared to delta CK-MB and delta myoglobin. The sensitivity for detecting reperfusion at 90 minutes angiography using threshold values of 6.0 for delta cTnI, 7.0 for delta CK-MB, and 5.0 for delta myoglobin were: delta cTnI 82.4%; delta CK-MB 64.7%; delta myoglobin 76.5%; respectively. This study indicates that early serial measurements of cTnI were a more accurate predictor of early coronary artery reperfusion 90 minutes after thrombolytic therapy compared to CK-MB and myoglobin. Larger population studies will be necessary to confirm these finding.

Cellular response of the evolving myocardial infarction after therapeutic coronary artery reperfusion

This study describes the cellular response of the evolving myocardial infarction in humans after early coronary artery reperfusion by one or more of the following therapies: streptokinase, percutaneous transluminal coronary angioplasty, tissue plasminogen activator, and/or coronary artery bypass graft surgery. Postmortem histologic changes were compared in two groups (n = 43 pairs) of human hearts with acute myocardial infarction matched for clinical age and left ventricular location of the infarct. The treatment group received one or more of the forms of reperfusion therapy. The control group received conventional therapy. The treatment group was judged to have an older histologic age infarct, P < 0.002, compared with documented clinical age. For example, infarcts that were clinically 4 days old or less were judged histologically to be 1 day older. The treatment group had a higher Cellular Response Index, P < 0.017; more hemorrhage within the infarct, P < 0.001; a greater extent of selective myocardial cell necrosis, and a lesser extent of coagulation necrosis, P < 0.05; more patchy, nontransmural distribution of necrosis, P < 0.04; and a more florid cellular response, specifically more macrophages, P < 0.034, and reactive stromal cells, P < 0.05. In infarcts less than 3 days old clinically, the treatment group had hemorrhage and a cellular response which were wide-spread throughout the lesion, P < 0.05, n = 18 pairs. In infarcts 3 to 4 days old clinically, the treatment group had a florid cellular response due to more macrophages, P < 0.05, n = 9 pairs. In infarcts 5 to 10 days old, the treatment group had more macrophages, P < 0.01; and more phagocytosis, P < 0.003. In infarcts 10 to 40 days old clinically, the treatment group had scar formation that was patchy, P < 0.05. In conclusion, this study demonstrates that early therapeutic coronary artery reperfusion after an acute myocardial infarction alters the pattern of injury and the cellular response to the evolving myocardial infarction so that the classical criteria for infarcts need to be modified.

Quantification of myocardial infarct size after coronary reperfusion by serum cardiac myosin light chain II in conscious dogs.

The effects of early coronary artery reperfusion on the relation between the extent of myocardial infarction and serum levels of cardiac myosin light chain II or plasma creatine kinase levels were evaluated in the conscious dog. Hydraulic occluders were placed on the left anterior descending arteries of 38 dogs. Seven to 10 days later, myocardial infarction was produced. Coronary reperfusion was performed 3 hours (group A1, n = 13) and 6 hours (group A2, n = 12) after the occlusion. In the other 13 dogs, coronary occlusion was sustained throughout the course of the experiment (group B). Seven days after the occlusion, the heart was cut from the apex to the base into 4-mm slices, and infarct size was determined macroscopically. Rapid appearance and early peaking of creatine kinase were observed in group A. Cumulative release of creatine kinase significantly correlated with infarct size in group A (infarct size ranged from 0.1 to 20.1 g, r = 0.90) and group B (from 0.6 to 26.8 g, r = 0.91). However, since creatine kinase release in group A was greater in comparison with that from infarcts of the same size in group B, the slope of the regression line for group A was significantly steeper (p less than 0.05). Cardiac myosin light chain II appeared as early as creatine kinase did and continued to be elevated for 7 days. A very close relation was observed between infarct size and total cardiac myosin light chain II release (r = 0.87 for group A, and r = 0.88 for group B) or peak level of light chain II (r = 0.85 for group A, and r = 0.81 for group B). In addition, the slopes of the regression lines for infarct size and both peak and total release of light chain II did not differ between group A and group B. On histological examination, viable myocardium was frequently observed in the epicardium of the ischemic area in group A1; therefore, infarct size was greater in group B than in group A1 (p less than 0.05). Also, myocardial creatine kinase content in the epicardium of the center of the ischemic area in group A1 was greater than that in group B. Cardiac myosin light chain II release in group A1 was less than that in group B, whereas no difference was found in plasma creatine kinase release among groups A1, A2, and B.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular topographic alterations in the completely healed rat infarct caused by early and late coronary artery reperfusion

Topographic changes in the completely healed (6 weeks) left ventricle of the rat, caused by early (30 minutes) and delayed (90 minutes) coronary artery reperfusion, were examined. With early reperfusion the extent of the scar, as a percentage of left ventricular (LV) circumference, was reduced compared to the extent of the scar in rats with permanent occlusion (27 ± 3% vs 42 ± 2%, p < 0.01). Early reperfusion also preserved LV topography by preventing dilation of the LV cavity and thinning of the healed free wall. Late reperfusion (90 minutes) did not reduce the extent of the scar (35 ± 3% vs 42 ± 2% of LV circumference, p = NS) or prevent dilation of the LV cavity compared with permanent occlusion. However, the healed free wall/noninfarcted septum ratio was significantly greater in rats with late reperfusion than in those with permanent occlusion (0.98 ± 0.06 vs 0.73 ± 0.07, p < 0.05). Thus early reperfusion completely inhibited scar thinning and dilation of the LV cavity, maintaining normal LV topography. Late reperfusion, too late to reduce infarct size, still contributed to improved healing of the myocardium by resulting in a thicker scar.

Effect of reperfusion on electrocardiographic and enzymatic infarct size: Results of a randomized multicenter study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase in acute myocardial infarction

The effect of early coronary artery reperfusion on ECG and enzymatic parameters was examined in 240 patients with acute myocardial infarction. These patients had participated in a randomized trial comparing intravenous anisoylated plasminogen streptokinase activator complex (APSAC) (n = 123) and intracoronary streptokinase (n = 117) therapy. Reperfusion occurred in 59 of 115 (51%) patients receiving APSAC and 67 of 111 (60%) patients receiving streptokinase ( p = NS). There was greater early resolution of ST segment elevation in the reperfused than in the nonreperfused patients ( p ≤ 0.003) and more rapld Q wave evolution ( p ≤ 0.03). ΣQ was lower in reperfused than in nonreperfused patients at 8 hours (1.41 ± 1.18 versus 2.11 ± 2.10 mV; p ≤ 0.05) and at 24 hours (1.43 ± 1.25 mV versus 2.08 ± 1.88 mV; p ≤ 0.02). Time to peak level was shorter in the reperfused patients for creatine kinase (CK) (10.7 ± 5.5 hours versus 14.9 ± 5.9 hours; p < 0.0001) and lactic acid dehydrogenase (LDH) (29.6 ± 13.6 hours versus 34.4 ± 10.5 hours; ≤0.03) enzymes. Peak LDH-1 was lower in the reperfused group (274 ± 149 U/L versus 341 ± 173 U/L; p ≤0.04). Reperfusion at a mean of 3.9 hours after the onset of infarction was associated with more rapid resolution of ST segment elevation, faster Q wave evolution, smaller ECG infarct size, earlier cardiac enzyme release, and smaller enzymatic infarct size than later or no reperfusion.

Effect of early coronary artery reperfusion on infarct development in a model of low collateral flow.

To characterise collateral blood flow patterns after coronary artery occlusion in the rat and to determine whether tissue can be salvaged by reperfusion in this model, anaesthetised rats were subjected to 20, 30, 40, 60 min of coronary occlusion followed by 24 h of reperfusion or 24 h of permanent occlusion. Relative regional blood flow was measured by radioactive microspheres after 10 min of occlusion in rats undergoing 30 min of occlusion plus reperfusion and in those undergoing 24 h of permanent occlusion. The area at risk was determined by in vivo injection of fluorescent microspheres and necrosis delineated by in vitro tetrazolium staining. Tracings of heart slices were planimetered and the area of necrosis and transmural extent of the infarct measured. Blood flow in the area at risk during occlusion was similar in both the reperfused and permanent occlusion groups. In the 30 min group mean(SEM) subendocardial flow was reduced to 13(5)% of normal and subepicardial flow to 9(3)% and in the permanent occlusion group to 11(2)% and 8(3)% respectively. As delineated by fluorescent microspheres the area at risk was transmural in all rats; however, infarct size expressed as a percentage of the area at risk increased as the duration of occlusion increased. In rats reperfused up to 30 min after occlusion the area of necrosis as a percentage of the area at risk was significantly decreased compared with that in the permanent occlusion group (36.4(9.2)% in rats with 30 min occlusion plus 24 h reperfusion and 78.6(7.4)% in rats with permanent occlusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative effect of early coronary artery reperfusion in baboons. Extent of salvage of the perfusion bed of an occluded artery.

We examined the extent to which ischemic myocardium was salvaged by reperfusion using a method that allowed expression of the volume of infarction as a percentage of the volume of the perfusion bed of the occluded artery (region at risk of infarction). In eight baboons, the left anterior descending coronary artery (LAD) was occluded for 2 hours, after which perfusion was restored. A control group of eight baboons underwent an identical protocol, but perfusion was not restored. Twenty-four hours after occlusion, microvascular dyes were injected into the LAD and adjacent arteries to delineate the perfusion bed of the occluded artery. The volume of infarction and volume of the perfusion bed were determined planimetrically. The mean percentage of the perfusion bed infarcted in the control baboons was 94.2 +/- 3.5% and 50.1 +/- 5.8% in the reperfused baboons. Hence, the mean percentage of the perfusion bed infarcted was reduced by 44.1% in the reperfused group compared with the control group (p less than 0.001). In reperfused baboons, hemorrhage occurred in the region of infarction but did not result in infarct extension. We conclude that reperfusion after 2 hours of coronary occlusion results in substantial salvage of ischemic myocardium in the baboon.

The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation.

The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation.

The electrophysiologic time-course of acute myocardial ischemia and the effects of early coronary artery reperfusion.

Bipolar potentials were recorded from intramural electrodes located within areas of acute myocardial ischemia in dogs. Alterations in bipolar potential electromotive force (EMF) and local activation times were measured at predetermined intervals up to 12 hours after coronary occlusion. Histochemical stains were used to correlate structural-biochemical changes with sites of electrophysiologic changes. In severely ischemic areas, bipolar potentials lost 50% of their preocclusion EMF within 30 min and 95% within six hours at which time all parameters stabilized. Lesser decreases in bipolar potential EMF were recorded in the peripheral areas of the infarct. Bipolar potential EMF increased at the junction of ischemic and normal myocardium. Activation time was delayed in ischemic areas but no correlation between the magnitude of delay and the degree of tissue ischemia could be established. Coronary reperfusion after 30 min, one hr, two hr and six hr of occlusion resulted in some return in bipolar potential EMF, decreasing as a function of duration between occlusion and reperfusion. Variation in the degree of ischemia of different zones of injury within an acute myocardial infarction, as well as a different response of those zones to the return of blood flow, was shown.