Salvage of ischemic myocardium by ibuprofen during infarction in the conscious dog

Because nonsteroidal anti-inflammatory drugs differ in potency and degree of prostaglandin inhibition, they may have different effects on ischemic myocardium. The effect of ibuprofen, an agent of this type, on myocardial infarct size was measured 2 days after occlusion of the left circumflex coronary artery in conscious dogs. Treatment was randomized in dogs after occlusion: Intravenous infusions of ibuprofen (6.25 mg/kg per hour) were administered to 13 dogs and saline solution (0.9 percent) to 13 control dogs over a period of 6 hours. The boundary of the occluded coronary bed, or anatomic risk region, was defined by postmortem coronary arteriography. Masses of infarct and occluded bed were measured by planimetry of weighed transverse sections of the left ventricle. Ibuprofen decreased infarct size compared with that in control dogs, both as percent of the left ventricle (mean ± standard error of the mean 7.5 ± 1.4 versus 15.2 ± 3.1, p < 0.05) and as percent of the occluded bed (16.3 ± 2.3 versus 38.6 ± 5.7, p < 0.005). Ibuprofen also altered (p < 0.001) the relation between the size of the infarct and the size of the occluded bed, so that hearts with occluded beds of similar size had smaller infarcts than those of control dogs. Morphologically, ibuprofen salvaged myocardium in both lateral and epicardial regions of the occluded bed. Changes in arterial pressure, left atrial pressure and heart rate were similar in the two groups. Changes in regional myocardial blood flow measured with 7 to 9 μm radioactive microspheres were also similar in both groups, with an increase in flow to infarcted regions and borders between 20 seconds to 15 minutes after occlusion, but no further change from 15 minutes to 6 hours. Thus, protection of ischemic myocardium by ibuprofen was not due to changes in collateral flow or myocardial oxygen demands, suggesting that cellular and metabolic effects might be important.     

Right ventricular infarction: two-dimensional echocardiographic evaluation

Seventeen patients with predominant right ventricular infarction (RVMI) were studied with two-dimensional echocardiography (2DE). On initial 2DE all had abnormal wall motion (AWM), defined as akinesis plus dyskinesis, in the inferior right ventricle (RV), inferior interventricular septum, and inferior left ventricle (LV). The extent of RV vs LV AWM in short-axis sections at mitral, chordal, and papillary levels was 58% vs 29%, 56% vs 38%, and 59% vs 38%, respectively. The calculated topographic extent of AWM was greater in the RV than in the LV (58% vs 36%, p less than 0.05), and the RV/LV ratio (1.65) exceeded (p less than 0.001) unity. Peak creatine phosphokinase levels correlated significantly (p less than 0.001) with the topographic extent of LV AWM (r = 0.79) or RV + LV AWM (r = 0.75). Although all patients had RV dilatation, eight also had LV dilatation. Serial studies detected the cause of mechanical complications (n = 13), mural echo densities suggesting thrombi (LV in six and RV in seven), and persistent AWM in survivors. Thus, 2DE provided diagnostic data, and assessment of RV and LV AWM confirmed predominant RV involvement.     

Different relations between infarct size and occluded bed size in barbiturate-anesthetized versus conscious dogs

The relation between infarct size and occluded bed size in barbiturate-anesthetized (n = 32) and conscious (n = 34) dogs was compared using models of the left anterior descending (n = 43) and circumflex (n = 23) coronary arteries with 2 day old infarcts. Infarct and occluded bed (postmortem coronary arteriography) masses were measured by computerized planimetry of weighed left ventricular rings. For either type of occlusion, infarcts were larger in anesthetized than in conscious dogs (56 versus 33% occluded bed, p less than 0.001), with greater slopes of the linear regressions between infarct size and occluded bed size (p less than 0.001) and less epicardial sparing (p less than 0.05) on topographic mapping. Although arterial and left atrial pressures were similar in the two groups, heart rates were higher in the anesthetized dogs, both before (127 versus 88 beats/min, p less than 0.001) and after (151 versus 109 beats/min, p less than 0.001) occlusion. Myocardial blood flow distribution (radioactive microspheres, n = 33) favored the epicardium in anesthetized dogs, with lower endocardial-epicardial flow ratios pre- and postocclusion. Also, the level of total plasma catecholamines (radioenzymatic assay) was higher in barbiturate-anesthetized (n = 5) than in conscious (n = 5) dogs. Increasing the heart rate in conscious dogs (n = 18) to that of the anesthetized group (139 beats/min) by pacing produced larger infarcts and greater linear regression slopes, as seen in anesthetized dogs. Decreasing the heart rate in anesthetized dogs (n = 7) to that of the conscious group (98 beats/min) by sinoatrial node destruction and pacing resulted in smaller infarcts and lower linear regression slope, as seen in conscious dogs. Thus, the larger infarcts in barbiturate-anesthetized dogs appeared to be related mainly to the tachycardia, although transmural maldistribution of flow and increased circulating catecholamines might have contributed.     

Severe, acute disseminated intravascular coagulation. A reappraisal of its pathophysiology, clinical significance and therapy based on 47 patients.

Forty-seven patients with severe acute disseminated intravascular coagulation (DIC) were identified during a period when total hospital admissions were 115,175. Infections, shock, trauma, hepatic disease and malignancy were the common predisposing factors. Most patients were critically ill. Routine treatment included aggressive therapy of the underlying diseases and the administration of blood products, vitamin K and folic acid when indicated. Twelve patients were treated with heparin; bleeding worsened in seven (58 per cent), the DIC diminished in five (42 per cent), and 10 patients (83 per cent) died. Thirty-five patients did not receive heparin; the DIC diminished in 13 (37 per cent), and 30 patients (86 per cent) died. These deaths would probably not have been prevented by heparin therapy. Microvascular thrombi were not found in 25 patients who were examined at autopsy although infarcts possibly secondary to them were found in four. Hpwever, in three of these patients local disease was a more likely cause. Infarcts, presumably secondary to microthrombi, were diagnosed clinically in three additional patients. Acute renal failure occurred in 19 patients and acute respiratory failure in 16. Sepsis or shock was present in each of these patients; in those examined at autopsy neither microthrombi nor infarction could he implicated as the likely cause of organ failure. Eight patients had venous thromboemboli, and seven had other large vessel thrombi. All of the latter were associated with local disease. Potentially serious hemorrhage occurred in 33 patients primarily from wounds, the gastrointestinal tract and lungs. Local disease was found when adequate investigations were performed. Although bleeding (12 patients) and thrombosis (eight patients) often contributed to death, they were never the sole cause and were the immediate cause in only two patients. These findings suggest that severe acute DIC is uncommon, is not necessarily associated with microvascular thrombosis, rarely causes significant organ damage, and seldom eventuates in severe hemorrhage or large vessel thrombi unless local disease is also present. Heparin is rarely beneficial and often worsens bleeding. The high mortality associated with severe acute DIC cannot readily be attributed to it. It is perhaps best regarded as an incidental, often preterminal event, occurring in many acute catastrophic illnesses.     

A follow-up study of 48 patients with Reiter's syndrome

A follow-up study of 48 patients with Reiter's syndrome was carried out in an attempt to clarify the clinical course of the disease. The mean age at the onset of Reiter's syndrome was 27.1 years (range 15 to 52 years) and when seen at follow-up 32.5 years (range 19 to 58 years). The average time from the onset of the first attack of peripheral arthritis to the time of follow-up was six and a half years (range 0.5 to 27 years). Only three patients had diarrhea prior to the onset of Reiter's syndrome. At follow-up 22 per cent of the patients were asymptomatic, 24 per cent had recurrent minor symptoms, 24 per cent had recurrent moderate symptoms, and 30 per cent had recurrent major symptoms. However, even in the last group, all patients were in functional classes 1 or 2 between the flares of disease. No patients in the series were in functional class 3 or 4, and 30 per cent were in class 1.     

Characterization of a pituitary stone

Calcification of the pituitary is unusual and functional studies of such cases have not been previously reported. We have been able to document persistent prolactin secretion both in vivo and in vitro in a patient with a severely calcified pituitary adenoma (“pituitary stone”), and have also documented prolactin granules within the calcified tissue mass. Normal menstrual function was restored after surgical removal of the “stone,” and galactorrhea subsided although the prolactin response to thyrotropin-releasing hormone (TRH) remained abnormal. Two years after surgery the menstrual cycle has remained regular, but galactorrhea has recurred, emphasizing the need for prolonged follow-up in patients with prolactin-producing adenomas, despite apparent surgical cure. The in vitro studies showed that human pituitary tissue is secretory in culture and thus may serve as a useful tool for physiologic studies of the pituitary cell.     

Anterolateral ST segment depression in acute inferior myocardial infarction: angiographic and clinical implications

We examined the relationship between coronary anatomy and anterolateral ST segment depression during inferior acute myocardial infarction (AMI) in 84 consecutive survivors of inferior AMI, who underwent prospective coronary angiography a median time of 2 weeks after AMI. Multivessel disease was defined as two or more significantly (greater than 70%) stenosed vessels. A QRS scoring system was used to estimate myocardial infarct size. Patients with ST depression had more multivessel disease compared to patients with no ST depression (53% vs 6%, p less than 0.01), more left anterior descending stenoses (36% vs 10% p less than 0.05), and higher QRS scores (5.8 +/- 3.2 vs 2.6 +/- 1.8, p less than 0.01) indicating larger infarcts. Patients with ST depression and one-vessel disease (47%) still had higher QRS scores compared to patients with no ST depression (4.8 +/- 2.9 vs 2.6 +/- 1.8, p less than 0.001) and had an increased prevalence of infarct-related vessels with a terminal branch supplying the left ventricular lateral wall or apex. We conclude that anterolateral ST depression during inferior AMI may indicate the presence of additionally stenosed vessels or that the infarct-related vessel has a large vascular territory. The absence of ST depression virtually precludes multivessel disease.     

Prophylactic quinidine for the prevention of arrhythmias after acute myocardial infarction

A selected group of 103 patients with uncomplicated myocardial infarction of less than 24 hours′ duration were randomly assigned to two different treatments: 45 patients received quinidine sulfate orally in a dose of 0.4 g every 8 hours and 58 patients received sodium lactate placebo. The period of observation was 72 hours. Ventricular tachyarrhythmias, including ventricular tachycardia, and ventricular premature beats that were multifocal or occurred at a frequency greater than 5/ min occurred in 26 of 58 patients (45 percent) receiving placebo and in 7 of 45 patients (16 percent) treated with quinidine. Quinidine effected an even more significant reduction of ventricular tachycardia; this arrhythmia was observed in 12 of 58 patients receiving placebo and in only 1 of 45 quinidine-treated patients (P < 0.01). Continuous 72 hour electromagnetic tape recordings showed no reduction In the frequency of isolated ventricular premature beats in the quinidine-treated group compared with the control group. Bradyarrhythmias including heart block warranted discontinuance of the trial in 6 of 45 quinidinetreated patients and 2 of 58 patients receiving placebo. There was no difference in mortality in the two groups during the 72 hour study period or during the entire period of hospitalization.     

Significance of reciprocal S-T segment depression in anterior precordial leads in acute inferior myocardial infarction: Concomitant left anterior descending coronary artery disease?

The reciprocal changes of S-T segment depression in the anterior precordial leads of the electrocardiogram in acute inferior myocardial infarction may be due to left anterior descending coronary artery disease and anterior wall ischemia. The electrocardiograms of 45 patients with acute inferior infarction who had subsequent cardiac catheterization (41 patients) or necropsy (4 patients) were examined to test this hypothesis.

Significant left anterior descending coronary artery disease (greater than 70 percent stenosis of luminal diameter) was observed in 31 (69 percent) of the 45 patients. The sensitivity, specificity and predictive value of S-T depression (1 mm or greater) in various anterior precordial leads singly or in combination was determined for this lesion. Left anterior descending coronary artery disease was present in 23 of 24 patients with S-T depression in one or more leads from V₁ to V₄ (predictive value 95 percent), and this index had the best combination of sensitivity (74 percent), specificity (93 percent) and predictive value in this group. Seven of 13 patients with left anterior descending coronary artery disease had S-T depression only in lead I or aVL, or both (sensitivity 100 percent, specificity 53 percent and predictive value 54 percent). S-T depression in any of leads I, aVL and V₁ to V₆ occurred in 37 patients, and 31 of these had left anterior descending coronary artery disease (sensitivity 100 percent, specificity 57 percent and predictive value 84 percent). The eight patients without anterior precordial lead S-T depression did not have left anterior descending coronary artery disease. Complications of infarction developed in 13 patients;S-T depression in at least one of leads V₁ to V₄ occurred in 12 (92 percent) of these 13 but in only 12 (38 percent) of 32 patients without complications.

Thus the predictive value of S-T depression in leads V₁ to V₄ (95 percent) for left anterior descending coronary artery disease is greater than the occurrence of the latter (69 percent) in all cases of acute inferior myocardial infarction (p < 0.05). S-T depression in these leads may be due not to reciprocal changes but rather to left anterior descending coronary artery disease with anterior wall ischemia. Such S-T depression is a sensitive marker for complications in these patients.     

Evaluation of biventricular involvement in hypotensive patients with transmural inferior infarction by two-dimensional echocardiography

Hypotension in inferior myocardial infarction (IMI) may be due to extensive involvement of the right ventricle (RV), left ventricle (LV), or both. We verified this hypothesis in 24 patients with IMI and hypotension (systolic blood pressure less than 100 mm Hg), within 48 hours of admission, by means of two-dimensional echocardiography (2DE). We measured the extent of regional RV and LV asynergy (akinesis and/or dyskinesis) in parasternal short-axis sections at mitral, chordal, midpapillary muscle, and low papillary muscle levels. Initial right heart catheterization revealed predominant RV dysfunction in 16 patients (group 1) and predominant LV dysfunction in eight patients (group 2). For all patients, the initial 2DE revealed: (1) biventricular asynergy involving the posterior RV, posterior LV, and posterior interventricular septum; (2) a wide range of values for the extent of asynergy (RV 21% to 90%; LV 19% to 48%); and (3) a direct correlation between peak creatine kinase levels and percentage of LV asynergy (r = 0.80, p less than 0.001) or percentage of RV plus LV asynergy (r = 0.72, p less than 0.001). Although the extent of LV asynergy was similar in the two groups (34% vs 34%, NS), the extent of RV asynergy was greater in group 1 than in group 2 (57% vs 30%, p less than 0.001). More important, the ratio of RV/LV asynergy was greater for group 1 than group 2 (1.75 vs 0.89, p less than 0.001), and this difference in ratios between the two groups was also found in 2DE studies at 10 days and 6 months. A RV/LV asynergy ratio value of 1.1 provided clear separation between the groups. Thus, the RV/LV asynergy ratio on an initial 2DE can clarify the clinical syndrome of hypotension in patients with IMI. An increased asynergy ratio might identify those patients with predominant RV involvement.     

Clinical implications of anterior S-T segment depression in patients with acute inferior myocardial infarction

To assess various factors associated with anterior S-T segment depression during acute inferior myocardial infarction, 47 consecutive patients with electrocardiographic evidence of a first transmural inferior infarction were studied prospectively with radionuclide ventriculography an average of 7.3 hours (range 2.9 to 15.3) after the onset of symptoms. Thirty-nine patients (Group I) had anterior S-T depression in the initial electrocardiogram and 8 (Group II) did not have such “reciprocal” changes. There was no difference between the two groups in left ventricular end-diastolic or end-systolic volume index or left ventricular ejection fraction. Stroke volume index was greater in Group I than in Group II. There were no group differences in left ventricular total or regional wall motion scores. A weak correlation existed between the quantities (mV) of inferior S-T segment elevation and reciprocal S-T depression. No relation between anterior S-T segment depression and the left ventricular end-diastolic volume index could be demonstrated; the extent of left ventricular apical and right ventricular wall motion abnormalities, both frequently associated with inferior infarction, did not correlate with the quantity of anterior S-T depression.These data show that anterior S-T segment depression occurs commonly during the early evolution of transmural inferior infarction, is not generally a marker of functionally significant anterior ischemia and cannot be used to predict left ventricular function in individual patients. Anterior S-T segment depression may be determined by reciprocal mechanisms.     

Mechanism of inferior electrocardiographic ST-segment depression during acute anterior myocardial infarction in a baboon model

Controversy exists concerning the mechanism of electrocardiographic (ECG) ST-segment depression in leads remote from an area of acute myocardial infarction. Thus, 13 baboons were studied during ligation of the distal third of the left anterior descending coronary artery. The morphologic pattern of the ECG limb leads in the supine baboons resembled that of an asthenic human and did not change when the chest was opened. The visually apparent infarct area of the distal anterior wall was confirmed by epicardial ECG mapping 30 minutes after ligation, and by tissue creatine kinase and histologic study at 24 hours. All 13 baboons had ST depression in leads III and aVF of 0.1 to 1.2 mV at 30 minutes, and 11 of 13 had similar changes in lead II. Also, all 13 baboons had ST elevation in lead aVL (n = 10) or aVR (n = 11), suggesting that the ST vector from the infarct area was directed away from the inferior leads. In no baboon did inferoposterior wall ventricular epicardial mapping show evidence of myocardial ischemia, and mean creatine kinase content from the infarct sites was markedly lower than that from posteroinferior sites (12.7 +/- 2.8 vs 20.6 +/- 2.1 IU/mg protein, p less than 0.01). In addition, the inferoposterior myocardium was normal histologically. In conclusion, acute myocardial infarction often results in reciprocal ST depression at sites distant from the area of acute necrosis and need not represent "ischemia at a distance."     

The Multiple Causes of Stroke in Atrial Fibrillation: Thinking Broadly

Atrial fibrillation (AF) is numerically the most important risk factor for stroke. It is well established that patients with AF have a 5-fold increased risk of stroke relative to those without and that anticoagulation reduces the risk of stroke by approximately two-thirds. Definitively attributing the mechanism of an individual stroke to AF is more problematic, however. In fact, there is no way to reliably establish the etiology of any ischemic infarction. This necessitates screening for all potential stroke risk factors and treating accordingly. The pattern of infarction is often used to classify the presumed mechanism of infarction as thrombotic or embolic, although even this is approach is based on association and increasingly is recognized as not completely reliable. Furthermore, it should not dictate management—patients with perforating arterial territory infarcts with AF also require and benefit from anticoagulation. Likewise, if other potential embolic sources beyond AF are identified, anticoagulation remains the standard of care. The traditional conceptual model of the mechanistic link between AF and cardioembolic infarction is likely oversimplified. Long-term cardiac rhythm recording studies indicate an inconsistent temporal relationship between AF and infarction. This suggests that cardioembolic stroke in patients with AF may result from the underlying atrial cardiopathy, rather than the rhythm disturbance leading to atrial stasis and thromboembolism. We reviewed traditional and current concepts, as well as evidence for the role of AF in ischemic stroke.     

A transparent overlay for reading pediatric electrocardiograms

A transparent overlay depicting images of the QRS complex drawn between the upper normal limits and the baseline in precordial leads in three age categories is described. By placing such images over corresponding QRS complexes in the child's record it is possible to determine in a matter of seconds whether R and S deflections are within normal limits.     

Anterior ST segment depression during acute inferior myocardial infarction: evidence for the reciprocal change theory

We evaluated the recently proposed concern that ECG anterior ST segment depression in patients with acute inferior wall myocardial infarction represents an additional area of ischemia and therefore implies worsened prognosis. We studied patients enrolled in the Aspirin Myocardial Infarction Study (AMIS), ages 30 to 69 years, who sustained an inferior myocardial infarction within 6 months from the start of the study. Two hundred nineteen patients who met those criteria were followed for an average of 38.2 months. One hundred ten patients had significant anterior lead ST depression (greater than or equal to 0.1 mV) during their acute inferior infarction and their 3-year mortality rate was 9.1%. One hundred nine patients had no anterior ST abnormality and a mortality rate of 10.1% (p = ns). Only one patient with significant depression had a subsequent anterior wall myocardial infarction. Anterior ST depression correlated closely with the magnitude of inferior ST segment elevation. Since ST depression does not alter long-term mortality but relates to magnitude of ST elevation, it probably represents a reciprocal change.     

Electrocardiographic and coronary arteriographic correlations during acute myocardial infarction

One hundred fifty-two patients underwent cardiac catheterization and coronary arteriography within 6.3 ± 6.0 hours from the onset of acute myocardial infarction (AMI). All had standard 12-lead electrocardiograms recorded within 1 hour of cardiac catheterization. The electrocardiographic abnormalities present were correlated with the infarctrelated artery as determined by coronary arteriography. ST-segment elevation was the most common finding in patients with the left anterior descending (LAD) or right coronary artery as the infarct-related artery. ST-segment depression was the most common abnormality in patients with the left circumflex (LC), artery as the infarct-related artery. A classic pattern of anteroseptal AMI was seen in 93% of all patients with the LAD as the infarct-related artery. A classic pattern of inferior AMI was seen in 53% of patients with right or LC narrowing taken as 1 group. The pattern of true posterior and isolated lateral wall AMI in the absence of classic changes in the inferior leads was highly specific and predictive of LC narrowing. In contrast, the pattern of an inferior wall AMI, in the absence of true posterior or lateral wall changes, was highly specific and predictive of right coronary artery narrowing. Fifty-six percent of patients with LC artery as the infarct-related artery presented with non-classic electrocardiographic abnormalities. The electrocardiographic patterns in patients with subtotal occlusions were similar to those of patients with total occlusions. Thus, the electrocardiogram obtained in the first few hours of AMI is reliable in localizing the LAD as the infarct-related artery. Certain patterns are specific but not sensitive in localizing the right coronary artery as opposed to the LC artery as the infarct-related artery. Presentation with signs and symptoms of AMI and a nonclassic electrocardiogram is suggestive of LC narrowing.     

Anterior S-T segment depression in acute inferior myocardial infarction: Indicator of posterolateral infarction

Although patients with acute inferior myocardial infarction often manifest S-T segment depression in precordial electrocardiographic leads, the pathophysiologic abnormalities associated with this finding are poorly understood. To examine this problem, electrocardiographic findings on admission were compared with results of radionuclide cineangiography performed within 38 hours of the onset of symptoms in 25 patients with inferior infarction. Summation of S-T depression in leads V₁ through V₄ permitted the separation of patients into two groups: Group A (11 patients with 0.20 mV or less of S-T depression) and Group B (14 patients with 0.45 mV or more of S-T depression). The radionuclide cineangiogram revealed inferior wall dysfunction in all patients. Additional posterolateral dysfunction was seen in 13 patients, all in Group B. Patients in Group B had a relatively larger infarction (peak creatine kinase units = 756 ± 358 in Group A versus 1,566 ± 983 units in Group B, p < 0.01) and greater functional impairment (ejection fraction = 45 ± 12 in Group A versus 33 ± 12 in Group B, p < 0.01). The relation between precordial S-T segment depression and posterolateral dysfunction appears to be largely independent of electrocardiographic evidence of “true posterior infarction.” Thus moderate or severe anterior precordial S-T depression in patients with acute inferior infarction is a sensitive and specific indicator of relatively extensive myocardial damage, primarily involving the posterolateral region.