Evolution Of Acute Myocardial Infarction Research Articles

Pathobiology of Myocardial Ischemia and Reperfusion Injury: Models, Modes, Molecular Mechanisms, Modulation, and Clinical Applications.

This review presents an integrated approach to the analysis of myocardial ischemia and reperfusion injury and the modulating influence of myocardial conditioning during the evolution of acute myocardial infarction (AMI) and other clinical settings. Experimental studies have involved a spectrum of in vitro, ex vivo, and in vivo models, and guidelines have been developed for the conduct of rigorous preclinical studies and for the identification of various forms of cell injury and death in evolving AMI. AMI in vivo is dominated by oncosis (cell injury with swelling) leading to necroptosis and final necrosis of ischemic cardiomyocytes (CMCs), without or with contraction band formation. Early after coronary occlusion, reperfusion salvages a significant amount of ischemic myocardium in the subepicardium while reperfusion injury contributes up to 50% of the final subendocardial infarct. AMI progression is mediated by damage (or danger)-associated molecular patterns, also known as alarmins, which activate pattern recognition receptors and initiate the inflammatory response. In preclinical studies, lethal reperfusion injury can largely be prevented with preconditioning or postconditioning by pharmacologic or physical means due to effects on both the CMC and microvasculature. Conditioning involves triggers, cytosolic mediators, and intracellular effectors. Mitochondria have a central role in the maintenance and loss of viability of CMCs. Reperfusion of severely ischemic myocardium leads to sustained opening of the mitochondrial permeability transition pore (MPTP). Once the MPTP is opened, the mitochondrial membrane potential (ΔΨm) is rapidly lost and energy production ceases. Conditioning blocks the sustained opening of the MPTP. Translation of conditioning strategies to the clinical management of patients has been challenging. The status of translation of experimental findings to approaches to modulate and ameliorate ischemic and reperfusion injury is discussed for the clinical settings of acute coronary syndromes treated with percutaneous interventions and cardiac preservation during open heart surgery and cardiac transplantation.

The current profile of the patient with atrial fibrillation

Abstract: Atrial fibrillation (AF) is the most common supraventricular arrhythmia, characterized by an irregular and extremely rapid atrial electrical activation that causes loss of atrial mechanical function and important hemodynamic consequences. AF classification is important in both the therapeutic approach and the prognosis. Several classifications based on the ECG patch, epicardial or endocavitary records have been performed over time, but no classification can take into account all the characteristics of AF and especially associated diseases, which may be both the cause and consequence of arrhythmia. Aim: The aim of the study is to establish the current profile of the patient with atrial fibrillation in the new era of oral anticoagulant therapy and sinus rhythm restoration.
 Material and methods: The trial was conducted on patients with atrial fibrillation hospitalized between 01.10.2014-31.03.2015 at Institute of Cardiovascular Diseases ”Prof. Dr. G. Georgescu”, Iasi. Patients included in the study were analyzed according to age and sex, criteria for the clinical and paraclinic definition for atrial fibrillation.
 Results: Atrial fibrillation is an extremely common cardiovascular pathology and is present in about one-third of patients admitted to our clinic. Cardiovascular diseases such as hypertension, ischemic coronary artery disease, and valvulopathy are common in patients with AF. Patients with AF are usually elderly patients with many associated diseases in whom sinus rhythm restoration treatment and anticoagulant therapy are difficult to establish. AF is one of the most common arrhythmias that complicates the evolution of acute myocardial infarction, association between dual antiplatelet therapy and anticoagulation treatment, increasing the risk of bleeding complications.
 Conclusions: Atrial fibrillation is an extremely common cardiovascular pathology and is present in about one-third of patients admitted to our hospital. The data obtained revealed that this arrhythmia occurs in a small number of cases as the only pathology of the patient, usually associated with numerous comorbidities. Cardiovascular diseases such as hypertension, ischemic coronary artery disease, valvulopathy are common in our practice. Patient with AF is a patient who requires long-term anticoagulant therapy and in whom sinus rhythm recovery therapy is dependent on the precocity of presentation to the physician, as well as on the therapeutic resources of current medicine.

Diagnostic accuracy of coronary CT angiography combined with dual-energy myocardial perfusion imaging for detection of myocardial infarction.

The aim of the present study was to evaluate the diagnostic accuracy of second generation dual-energy computed tomography (DECT) myocardial perfusion imaging for the detection of myocardial infarction (MI) in patients with suspected MI. In total, 56 patients underwent DECT. Among those, 40 patients had MI that was detected by catheter coronary angiography and cardiac troponin I elevation and evolution of acute MI detected by electrocardiogram changes. The diagnostic accuracy, including the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection of MI were evaluated, as well as the coronary image quality of coronary artery and radiation dose. The sensitivity, specificity, PPV and NPV for the detection of MI were 95.0, 97.0, 86.4 and 98.9%, respectively. Moreover, the image quality was rated excellent (score 1) in 90.2% (515/571), good (score 2) in 6.5% (37/571), adequate (score 3) in 1.9% (11/571) and non-diagnostic (score 4) in 1.4% (8/571) of the coronary segments. The effective radiation dose was on average 6.1±1.5 mSv (3.1–10.9 mSv). Therefore, combined DE iodine maps and coronary CT angiography using the DECT may provide a high diagnostic accuracy for detecting MI with lower radiation exposure in patients with suspected MI.

Prognostic evaluation of soluble CD40L in acute myocardial infarction: is not fancy, is science!

Acute myocardial infarction (AMI) is a critical clinical presentation of coronary artery disease (CAD). As pointed out previously by us (1), major clinical research efforts have been dedicated to the identification of patients at higher risk and to the diagnosis of CAD and AMI. Although a great pool of information concerning systemic inflammation markers have been so far collected in different cardiovascular conditions, the evolution of AMI is not well depicted (1).

Glycoproteome of human apolipoprotein A-I: N- and O-glycosylated forms are increased in patients with acute myocardial infarction

High-density lipoprotein (HDL) functionality, which is closely associated with its composition and transport capabilities, determines its role in atheroprotection. During acute phase processes, HDL seems to lose its anti-inflammatory and cytoprotective properties. In this study, we hypothesized that after an acute myocardial infarction apolipoprotein (Apo) A-I, the main protein component of HDL, might undergo changes in its molecular processing. Therefore, we have characterized theApo A-I proteome during the evolution of new-onset acute myocardial infarction (AMI). To this end, serum Apo A-I was characterized by 2-dimensional electrophoresis/mass-spectrometry in controls and AMI patients at admission (within the first 6hours after pain onset) and 8 hours, 16 hours, 24 hours, and 3days afterward. The Apo A-I glycoproteome was analyzed by lectin-based glycoprotein isolation methods and deglycosylation assays, and Apo A-I serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The Apo A-I proteomic signature (5 spots: 28kDa/pI:5-5.75) was significantly altered in AMI patients 3days after the event with respect to controls. Increased levels of N- and O-glycosylated Apo A-I forms were found post-AMI. Apo A-I serum levels measured by ELISA were significantly changed and related to left ventricular ejection fraction, troponin-T, and C-reactive protein. The Apo A-I molecule measured by ELISA corresponded to the main glycosylated spots and was specifically O-GlcNAcylated in AMI patients. Therefore, our results demonstrate that Apo A-I is both N- and O-glycosylated and that there is an increase in Apo A-I glycosylation after AMI. Furthermore, the specific increase in the O-GlcNAcylated forms could have a relevant prognostic value and a protective role in the evolution of AMI.

Selective Cyclooxygenase-2 Inhibition Protects Against Myocardial Damage in Experimental Acute Ischemia

BACKGROUNDAcute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated.GOALThe objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion.METHODS AND RESULTSThis study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow.The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I.CONCLUSIONIn a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis.

The potential of erythropoietin for conferring cardioprotection complementing reperfusion

Despite the well-recognized effects of erythropoietin (EPO) on augmenting red blood cell production, EPO exerts multiple additional effects in diverse tissues. Evidence indicating the potential for tissue protection is reviewed as is a description of a study now initiated, in which its potential benefit on the evolution of acute myocardial infarction in patients is being explored. The literature demonstrating tissue-protective effects of EPO in experimental animals and patients is cited as is the protocol of the recently undertaken Vermont/Dubai study assessing the potential benefits conferred by EPO on the evolution of infarction in patients. Compelling arguments can be made indicating that EPO and its congeners, some of which are devoid of erythropoietic effects, can protect tissue against injurious stimuli. Accordingly, the promise of EPO for favorably altering the evolution of acute myocardial infarction merits exploration. Congeners of erythropoietin or EPO itself may be beneficial in protecting the heart against injury induced by ischemia thereby favorably modifying infarct size. Rigorous testing of this hypothesis is now in progress in a study involving patients with acute myocardial infarction admitted to hospital within 6 h after the onset of chest pain in whom infarct size is being evaluated based on serial analyses of concentrations of creatine kinase in plasma and thrombolysis is induced pharmacologically as promptly as possible. EPO is promising for myocardial protection. Its potential is being delineated in a clinical study of myocardial infarction treated with tenecteplase with or without concomitant EPO.

Observation on tissue factor pathway and some other coagulation parameters during the onset of acute cerebrocardiac thrombotic diseases

It is widely recognized that thrombosis is the major event in the evolution of acute myocardial infarction (AMI) and acute ischemic stroke (AIS). But the contribution of coagulation factors to the development of ischemic arterial diseases is still not clearly established. The goal of this study was to establish the possible relationship between coagulation factors as well as anticoagulant and the onset of AMI and AIS. The study population consisted of 69 patients with AMI and 71 with AIS as well as 50 age-matched healthy volunteers. Compared with the control group, plasma tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activities and both TF and TFPI antigens were significantly higher in the AMI group; plasma TF activity and antigen in AIS group were significantly increased, but the activity and antigen of plasma TFPI were significantly decreased in the AIS group. Plasma FVII coagulation (FVII:C) activity was markedly higher in patients with AIS, but not statistically different to the control in patients with AMI. FVIII coagulation (FVIII:C) activity was remarkably higher in patients with AMI but slightly lower than the control in patients with AIS. In the AMI and AIS groups, prothrombin activity and clottable fibrinogen were significantly higher and plasma antithrombin III activity was remarkably lower than the control. The results suggested that during the onset of AMI and AIS, the initiation of TF pathway would be associated with the thrombotic events and that the blood be in hypercoagulable state. But the changes of FVII:C, TFPI and FVIII:C in AMI are different from those in AIS.

The neutrophil as a mediator of myocardial ischemia-reperfusion injury: time to move on.

Granulocytes, especially neutrophils, are recruited in myocardium during the evolution of acute myocardial infarction. Because the neutrophil reaction is most intense during reperfusion and because these cells are a rich source of toxic oxidant species and proteolytic enzymes, it has become a widely held view that neutrophils are an important mechanism of myocardial injury extension during reperfusion. However, on close examination the evidence underlying this contention is equivocal. The basic experimental situation can be summarised thus. (1) All forms of reperfusion injury (i.e., cytotoxic or lethal cell injury, myocardial stunning, endothelial dysfunction, and reperfusion-induced arrhythmias) can be observed in neutrophil-free conditions. (2) "Anti-neutrophil" interventions (e.g., anti-inflammatory drugs, adenosine, anti-neutrophil antisera, leukocyte filters and inhibitors of the various pathways of neutrophil adhesion) do not consistently prevent reperfusion injury and they certainly do not consistently limit infarct size. (3) The time course of neutrophil accumulation in post-ischaemic myocardium may be different to the time course of injury. (4) Despite more than two decades of research, no double-blind, randomised controlled clinical trial assessing an anti-neutrophil therapy in myocardial infarction has yet reported a positive benefit that is attributable to inhibition of neutrophil recruitment. The evidence weighs against a pivotal role of neutrophils as a causal factor in most forms of ischemia-reperfusion injury. An exception may be microvascular injury and capillary plugging leading to the "no-reflow" phenomenon but even here the evidence suggests that the extent of neutrophil accumulation and microvascular injury is determined by, rather than a cause of, myocyte necrosis.

Evaluation of the treadmill stress testing for risk stratification after acute myocardial infarction.

The recent decline in postinfarction mortality reflects the success of the most recent therapeutical proposals incorporated into clinical practice . Despite this evolutional enhancement, mostly due to the use of thrombolytic agents, an increase in the recurrence of thrombotic phenomena, such as reinfarction and unstable angina, has occurred creating the need for strategies that adequately identify the patients with higher probability of an unfavorable outcome . The current evolution of acute myocardial infarction has resulted in changes in the clinical characteristics of the patients referred for the provocative tests for ischemia. These clinical characteristics were clearly identified by the professionals involved in treating acute myocardial infarction, who needed to reassess the previously existing concepts regarding these tests . This led to the spread of the routine performance of coronary angiography after acute myocardial infarction before hospital discharge . In 1987, research carried out among American cardiologists revealed that 86% of them had adopted this management in patients who had received thrombolytic agents . The TIMI II study 5 was designed to compare the routine use of coronary angiography prior to hospital discharge with the more conservative management of only those patients who had a clinical indication. All patients were treated during the acute phase with recombinant tissue plasminogen activator (r-TPA) within the first 4 hours of pain onset. In the group undergoing the invasive procedure, 1.636 patients underwent coronary angiography and prophylactic angioplasty when it was anatomically feasible 18 to 48 hours after administration of the thrombolytic agent. In the group treated conservatively, 1.626 patients were clinically followed up and only those patients with signs of ischemia during hospital stay, either spontaneous or triggered by the treadmill stress test, were referred for coronary angiography. No statistically significant difference between the two groups was observed in regard to mortality or acute myocardial infarction and the ejection fraction at rest or during exercise on the 42 postinfarction day. In the oneyear evaluation, no difference in the rate of new infarction or mortality occurred between the groups . During this period of time, a larger number of hospital admissions due to cardiac events and coronary angiography was observed in those patients undergoing the conservative treatment, but the total number of coronary angiographies was still 40% smaller than that reported for the group undergoing the invasive treatment . Evidence obtained in the TIMI II study was fundamental in defining the results obtained in both managements, reducing the impulse to use invasive techniques in all patients.

Myocardial perfusion evolution of acute myocardial infarction following thrombolytic therapy assessed by sequential SPECT

Myocardial perfusion evolution of acute myocardial infarction following thrombolytic therapy assessed by sequential SPECT

Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.

Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.

The Influence of CLS 2210 on the Course of Myocardial Infarction: A Pilot Study in Man

To assess the effect of CLS 2210 (a new formulation of calcium dobesilate) on the evolution of acute myocardial infarction, 100 patients presenting their first infarct were distributed, according to their sequential admissions to the hospital, into CLS 2210-treated group (50 patients) or a comparison group (50 patients not receiving CLS 2210). The two groups were similar in age, sex, predisposing factors, and site of infarction. Intravenous infusion of CLS 2210 was begun within six hours of onset of chest pain and continued for seventy-two hours. Thereafter, it was given, as oral capsules, in a dose of 1,000 mg every eight hours throughout the hospitalization. Before and during the trial, blood samples were drawn for the measurements of serum concentrations of creatine kinase (CK), and twelve-lead electrocardiograms (ECGs) were obtained serially in each patient. All objective data were analyzed on a coded basis without reference to the treatment. In the comparison group, thirty-six to forty-eight hours was required for CK to fall to 50% of the baseline value, whereas in the CLS 2210-treated group it reached 50% of the baseline in eighteen to twenty-four hours. For each infarction site, a statistically significant fall was reached earlier in the CLS 2210 group. CK, the ECG index, and the sum of the ST segments showed earlier and more rapid improvement in the CLS 2210 group than in the comparison group. The consumption of narcotic analgesic agents and nitroglycerin was substantially less in the CLS 2210 group than in the comparison group.(ABSTRACT TRUNCATED AT 250 WORDS)

Early prediction of left ventricular function in streptokinase-treated acute myocardial infarction.

We administered 750,000 units of intravenous streptokinase to 121 consecutive patients experiencing their first acute myocardial infarction within 4 h of pain onset. The following information was collected: hours between pain onset and streptokinase administration (TS), hours of pain after streptokinase administration (DP), initial and peak creatine phosphokinase levels (ICK and PCK), time to peak creatine phosphokinase, time to electrocardiographic ST segment resolution. Six days after the infarction, catheterization was performed to calculate ejection fraction, infarct-related regional ejection fraction, and dysfunction index. Data was analyzed using stepwise multiple regression. In patients experiencing anterior infarctions, the following equation was obtained predicting the ejection fraction (EF) with a correlation coefficient of 0.86: EF = 69 - 0.0050(PCK) - 3.7(TS) - 1.8(DP). In anterior infarctions the infarct-related ejection fraction and dysfunction index were similarly predictable. We were slightly less accurate in forecasting the outcome of inferior infarctions. The outcome of intravenous streptokinase therapy can be predicted early in the evolution of acute myocardial infarction using routinely available information.

Increased production of arachidonate metabolites in an occlusion-reperfusion model of canine myocardial infarction.

To define the role of arachidonate metabolites in evolving ischaemic myocardial damage 10 anaesthetised open chest dogs underwent 90 min occlusion of the left anterior descending coronary artery followed by 5 h reperfusion. Tissue extracts from ischaemic myocardium incubated in vitro were subjected to high pressure liquid chromatography for analysis of lipoxygenase products such as mono hydroxyeicosatetraenoic (HETE) acids and to radioimmunoassay for determining a cyclooxygenase product, thromboxane B2. In ischaemic myocardium the production of 12-HETE (120(35) ng.g-1, mean (SEM)) and thromboxane B2 (18.3(2.4) ng.g-1) was significantly higher than that in normal myocardium (13(2) ng.g-1, p less than 0.01, and 4.2(0.5) ng.g-1, p less than 0.001, respectively). 12-HETE production was linearly correlated with thromboxane B2 production in ischaemic myocardium (r = 0.718, p less than 0.02). The increased production of 12-HETE and thromboxane B2 was in proportion to infarct size as measured by a percentage risk area infarcted (r = 0.732, p less than 0.02, and r = 0.942, p less than 0.001, respectively). Similarly, the increase in production of these eicosanoids was related to the degree of leucocyte infiltration in ischaemic myocardium. These results indicate that altered arachidonate metabolism is strongly associated with the progression of ischaemic myocardial damage, suggesting important roles for these eicosanoids, which may be produced by blood corpuscles during the evolution of acute myocardial infarction.

Calcium-blocker withdrawal phenomenon: Increase in affinity of alpha 2 adrenoceptors for agonist as a potential mechanism

Precipitation of myocardial ischemia after withdrawal of calcium channel blocking drugs has been observed in some patients, but the mechanism of this phenomenon is not known. Among 15 patients with coronary artery disease who had been treated with nisoldipine, onset of severe unstable angina was observed in 2 and evolution of acute myocardial infarction in 1 patient after abrupt withdrawal of nisoldipine therapy. To determine a mechanism of myocardial ischemia after cessation of nisoldipine therapy, the status of α 2 adrenoceptors and platelet sensitivity to epinephrine was examined in 5 patients. After 6 weeks of therapy, there were no changes in the number of α 2 adrenoceptors (199 ± 45 vs 188 ± 35 fmol/mg protein, mean ± standard error of the mean) or affinity for antagonist (dissociation constant 5.78 ± 0.99 vs 4.70 ± 0.87 n M), but there was a significant (p < 0.01) increase in the affinity of α 2 adrenoceptors for agonist epinephrine. In vitro platelet sensitivity to epinephrine, but not ADP, also increased markedly. It is postulated that an increase in α 2-adrenoceptor affinity for agonist may relate to platelet hyperactivity, which may result in severe myocardial ischemia upon withdrawal of calcium blocking drugs in some patients.

Acute myocardial infarct size reduction by timolol administration

A multicenter, randomized, double-blind study was performed to evaluate the effects of timolol administered early during the evolution of acute myocardial infarction. Of 144 patients entered into the trial, 73 were assigned to timolol and 71 to placebo. The 2 groups were well matched at baseline. The timolol group had reduced myocardial ischemia and infarct size as measured by an accelerated reduction of ST-vector magnitude, a significant reduction of creatine kinase (CK) release and significantly smaller changes in QRS vector variables. The predicted maximal QRS vector change and cumulative CK release for any given initial ST-vector magnitude was significantly reduced in the timolol-treated patients. Furthermore, QRS evolution time and CK release time were significantly reduced after intravenous timolol, as were the need for analgesics and the pain scores. Timolol treatment was well tolerated overall.

Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction.

We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.

Prolonged electrical systole in acute myocardial infarction

Electrical systole duration has been studied in two groups of 23 patients (39 M and 7 F) admitted in the coronary care units of two different hospitals for documented acute myocardial infarction (AMI). The mean QT interval duration corrected for heart rate (QTc) was obtained from three measurements of non consecutive complexes in five different leads and compared to the ideal electrical systole duration of a normal population with the same cardiac cycle length. During the evolution of AMI, QT interval increased in both groups of patients (11.5% and 14.8% respectively) and was prolonged (17.6% and 21.5% respectively) at the 48th hour. Prolongation of electrical systole can be best measured using the ratio: QTc (according to Bazett)/normal QT (according to Ashman).

Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs

A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.