Resolution of ventricular tachycardia and endocardial tuberculoma following antituberculosis therapy.

A 23-year-old woman presented with sustained ventricular tachycardia and was found to have an endocardial mass by echocardiography and by magnetic resonance imaging. The diagnosis of cardiac endocardial tuberculoma was made, and she was treated with antituberculous therapy and an antiarrhythmic drug for one year. After a year, the mass was no longer present, and with all antiarrhythmic medications stopped, ventricular tachycardia could no longer be induced by electrophysiologic study. There has been no clinical recurrence.

Time course of creatine kinase release after termination of sustained ventricular dysrhythmias.

Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern.

The automatic implantable cardioverter-defibrillator: effect of patch polarity on defibrillation threshold.

An automatic implantable cardioverter-defibrillator (AICD) was implanted in 40 patients with sudden cardiac arrest (n = 29), sustained monomorphic ventricular tachycardia (n = 10) or recurrent syncope (n = 1) who were unsuitable for direct ablative surgery or had had unsuccessful medical therapy. The effect of patch electrode polarity on the defibrillation threshold was prospectively evaluated. Two large epicardial patches were used. Initial polarity was selected at random. Ventricular fibrillation was induced by direct current and a preestablished defibrillation protocol employed to assess the minimal energy that would reproducibly defibrillate the heart. Nineteen patients had a lower defibrillation threshold with the inferior left ventricular patch as an anode and nine patients had a lower defibrillation threshold with this patch as a cathode. In general, the defibrillation threshold was lower when this patch was used as an anode than when it was used as a cathode (18 +/- 10 versus 22.6 +/- 12.2 J; p less than 0.01). No preoperative variable predicted optimal polarity. Therefore, the effect of patch polarity on defibrillation threshold should be assessed in each patient at the time of AICD implantation so that the safety margin for satisfactory device function can be maximized.

Late results of the left subcostal approach for automatic implantable cardioverter defibrillator implantation.

A left subcostal surgical approach was used to implant an automatic implantable cardioverter defibrillator (AICD) in 48 patients with a history of nonfatal cardiac arrest or documented ventricular tachycardia/fibrillation. Electrophysiologic studies before surgery yielded induction of monomorphic or polymorphic ventricular tachycardia in 40 patients, whereas 8 were noninducible. Mean (+/- standard deviation) age was 58 +/- 12 years. Mean ejection fraction was 33 +/- 16%. Thirty patients (63%) had documented coronary artery disease; 14 patients (29%) had previous coronary bypass surgery. The mean intraoperative defibrillation threshold was 13.8 +/- 6.6 J. In 6 patients, an adjunctive right minithoracotomy was used to position 1 patch over the right atrium and thus optimize the defibrillation threshold. Patients with prior exposure to amiodarone and previous coronary bypass surgery had higher defibrillation thresholds at implantation. Two perioperative deaths occurred. There were no infections. Long-term follow-up yielded a 1- and 5-year survival of 0.88 and 0.58, respectively, and a freedom from sudden cardiac death of 1.0 and 0.97, respectively. The nonthoracotomy, left subcostal surgical approach is safe and effective, provides adequate defibrillation thresholds in most patients, and yields long-term survival comparable to other implantation techniques.

Return of atrial mechanical function following electrical conversion of atrial dysrhythmias.

The return of atrial mechanical function and its relationship to embolic events following cardioversion of atrial arrhythmias is controversial. Fourteen patients with atrial arrhythmias were evaluated with pulsed Doppler echocardiography before and after direct current (DC) cardioversion. The atrial filling fraction increased significantly: 1.14 +/- 4.3% at baseline versus 14.9 +/- 13.3%, 13.4 +/- 11.4%, and 21.9 +/- 13.5% at 5 minutes, 30 minutes, and 24 hours, respectively, following cardioversion. Absent atrial mechanical activity was noted in four patients immediately after cardioversion. Mechanical activity resumed by 30 minutes in one patient and at 24 hours in two others. Those with delayed atrial function had lower stroke volumes and atrial filling fractions following cardioversion. An embolic event occurred in one patient who had immediate return of atrial mechanical activity. This patient also had the largest atrial filling fraction of any patient at 24 hours (41%). These data suggest that the degree of atrial mechanical activity following cardioversion is variable and that embolic episodes are not necessarily related to delayed return of atrial mechanical activity following cardioversion.

Effect of human recombinant superoxide dismutase on canine myocardial infarction.

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) "low-dose" h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) "high-dose" h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

Assessment of regional myocardial perfusion by contrast echocardiography. II. Detection of changes in transmural and subendocardial perfusion during dipyridamole-induced hyperemia in a model of critical coronary stenosis.

Measurements of myocardial contrast (sonicated meglumine diatrizoate) intensity were compared with myocardial flow by radioactive microspheres before and after administration of dipyridamole (0.5 mg/kg body weight intravenously) in 10 open chest dogs with a critical stenosis in the left circumflex coronary artery. Computer measurements of contrast time-intensity curves corrected for background myocardial intensity were made along 12 transmural segments of the left ventricle at mid-papillary level and for the subendocardial and subepicardial half of each segment. After administration of dipyridamole, transmural flow in the control region increased significantly (p less than 0.001), resulting in a dipyridamole/baseline flow ratio (i.e., coronary reserve ratio) of 2.54 +/- 0.95. Similar changes (p less than 0.001) were seen by contrast echocardiography; the coronary reserve ratio was 2.10 +/- 0.60 with use of peak intensity and 3.48 +/- 1.58 with use of area under the time-intensity curve. In contrast, no significant changes were observed in myocardial flow, peak contrast intensity or area under the curve in the ischemic region after dipyridamole. In the control region the ratio of subendocardial to subepicardial flow was similar at baseline and after dipyridamole administration as assessed by microspheres (1.08 +/- 0.24 versus 1.17 +/- 0.25) or by area under the time-intensity curve (1.11 +/- 0.45 versus 1.11 +/- 0.56). In the ischemic region, the subendocardial/subepicardial flow ratio decreased significantly after dipyridamole administration as measured by microspheres (1.15 +/- 0.19 to 0.82 +/- 0.25; p less than 0.001) or by area under the curve (1.10 +/- 0.28 to 0.70 +/- 0.47; p less than 0.01). Thus, myocardial contrast echocardiography appears to be a sensitive technique with which to detect changes in myocardial flow induced by dipyridamole in the various myocardial layers of normal segments as well as of segments supplied by a critically stenotic coronary artery.

Nuclear magnetic resonance imaging of acute myocardial infarction within 24 hours of chest pain onset.

The present study was intended to establish the feasibility, safety and usefulness of conventional spin-echo nuclear magnetic resonance (NMR) imaging for the detection of acute myocardial infarction within 24 hours of the onset of chest pain. Monitoring facilities were established in the NMR imaging suite that provided the same level of reliability and safety found in a standard coronary care unit. An imaging protocol was developed that allowed the acquisition of a complete study in 30 minutes while providing useful information about mechanical function and myocardial tissue contrast. Eighteen postthrombolysis patients were imaged within 21 +/- 2 hours of chest pain onset. No patient developed recurrent chest pain or arrhythmias in the NMR imaging suite. Relatively T2-weighted spin-echo images (echo time = 60 ms; repetition time = heart rate) provided interpretable images in 16 patients. Fourteen normal subjects were imaged for comparison. Thirteen of 16 patients had an increase in signal intensity in the region of the infarction. Regional wall thickening was assessed using a floating endocardial centroid technique. Wall motion abnormalities detected by NMR corresponded to those noted by 2-dimensional echocardiography and contrast angiography. Sensitivity, specificity and accuracy for the detection of infarction were 93, 80 and 87%, respectively, when signal intensity and wall thickening abnormalities were combined. In summary, NMR imaging is feasible in patients with acute myocardial infarction within 24 hours of chest pain onset. The study can be conducted safely and it provides useful information about acute myocardial infarction.

Captopril-related exfoliative dermatitis.

A patient with congestive heart failure and mild renal impairment developed exfoliative dermatitis following the addition of captopril to her therapy. The skin reaction responded to drug withdrawal and the administration of corticosteroids, though the patient subsequently succumbed to the complications of an incidental myocardial infarction. Recognition and prompt treatment of this potentially fatal dermatological crisis is stressed. The newer generation of angiotensin converting enzyme inhibitors may have a lesser propensity for cutaneous complications.

Influence of neutrophil depletion on myocardial function and flow after reversible ischemia.

We explored the role of polymorphonuclear leukocytes (PMN) in the genesis of contractile dysfunction (myocardial "stunning") and of vascular abnormalities after reversible ischemia. Open-chest dogs underwent a 15-min coronary occlusion and 4 h of reperfusion (REP); treated animals (n = 16) received intravenous goat antiserum against canine PMN, whereas controls received nonimmune goat serum (n = 10) or saline (n = 15). In treated dogs, the average blood PMN levels were 10% of those in saline controls. During ischemia, collateral flow tended to be higher, and paradoxical systolic wall thinning tended to be less in neutropenic dogs, but despite this, recovery of wall thickening after REP was not enhanced in these animals. Similarly, arrhythmias during ischemia or REP did not differ among the three groups. Four hours after REP, both resting and minimal coronary resistance (the latter assessed by adenosine infusion) were higher in the stunned compared with the nonischemic myocardium; these vascular derangements, however, were similar in all three groups. Thus profound neutropenia failed to attenuate mechanical dysfunction, to reduce arrhythmias, and to prevent vascular abnormalities after a 15-min coronary occlusion. Although previous studies have suggested that neutrophils mediate cell death during prolonged ischemia, the present findings suggest that PMN do not contribute importantly to the damage associated with brief, reversible ischemia. The duration of flow reduction may be a critical factor determining whether PMN exacerbate ischemic injury.

Prolonged abnormalities of left ventricular diastolic wall thinning in the "stunned" myocardium in conscious dogs: time course and relation to systolic function.

Myocardial reperfusion after reversible ischemia is known to be associated with prolonged abnormalities of systolic contractile function (myocardial "stunning"). However, no information is available regarding the recovery of diastolic function in the stunned myocardium in the conscious state. Accordingly, 10 conscious dogs instrumented with pulsed Doppler thickening probes underwent a 15 min occlusion of the left anterior descending coronary artery followed by 7 days of reperfusion. Regional systolic function was assessed as net systolic thickening fraction. Left ventricular regional diastolic properties were estimated from two variables: the mean rate to half end-diastolic thinning and the late diastolic thinning fraction. Both indexes of diastolic function remained severely impaired after restoration of flow. In general, the recovery of the mean rate to half end-diastolic thinning and of the late diastolic thinning fraction paralleled the recovery of systolic thickening, but the impairment of the mean rate to half end-diastolic thinning was more marked than that of the late diastolic thinning fraction. At 4 h of reperfusion, the values for the mean rate to half end-diastolic thinning and the late diastolic thinning fraction (expressed as percent of baseline) were 57 +/- 5% (p less than 0.001 versus baseline) and 79 +/- 7% (p less than 0.05), respectively, whereas systolic thickening fraction averaged 52 +/- 10% (p less than 0.001). At 24 h, the mean rate to half end-diastolic thinning and the late diastolic thinning fraction were no longer significantly different from baseline, whereas systolic thickening fraction remained decreased at 82 +/- 4% (p less than 0.001) and returned to control values by 48 h. This study demonstrates the presence of profound, prolonged abnormalities of regional diastolic wall thinning after a brief episode of ischemia in the conscious state and expands the concept of myocardial stunning from the traditional notion of impaired systolic performance to that of a global derangement in mechanical function that involves both systolic and diastolic properties.

Time course and determinants of recovery of function after reversible ischemia in conscious dogs.

The postischemic recovery of contractile function [measured as systolic wall thickening (WT)] was analyzed in 21 conscious dogs undergoing a 15-min coronary occlusion followed by 7 days of reperfusion (REP). Average WT was still depressed 24 h after REP (85% of base line, P less than 0.001) and returned to base line by 48 h. Analysis of individual dogs, however, revealed marked variability, whereby some recovered completely by 1 h of REP and others required up to 48 h. WT recovered completely within 30 min in dogs with collateral blood flow (CBF) greater than 50% of nonischemic zone flow (NZF) but was still impaired at 24 h (P less than 0.05) in those with CBF less than 25% of NZF. There was a close, curvilinear relation between WT during the first 4 h of REP and transmural CBF, which was described best by an exponential equation WT (as percent of base line) = P0-P1e-P2.CBF(as % of NZF) (r2 = 0.92 at 1 h, 0.76 at 2 h, 0.71 at 3 h, and 0.72 at 4 h), where P0, P1, and P2 are regression coefficients. Importantly, the slope of the regression line was very steep at low CBF, implying that even small differences in CBF produce large differences in postischemic function. Heart rate, systolic pressure, and rate-pressure product during ischemia were also related to WT after REP, but when the effect of CBF was taken into account, the influence of these variables became insignificant. The size of the occluded vascular bed did not correlate with postischemic WT. The presence of hypokinesis or akinesis during ischemia was associated with rapid recovery after REP, but there was no relation between ischemic and postischemic dysfunction when dyskinesis was present during occlusion. Thus, on the average, regional function remains depressed for 24 h after a 15-min ischemic episode, but there is considerable individual variability. This variable rate of recovery is determined primarily by the severity of blood flow reduction during ischemia. Systemic hemodynamics may modulate recovery of function indirectly via their effects on ischemic blood flow.

The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction.

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the mechanism by which they produce myocellular damage remains unknown. Since iron catalyzes formation of hydroxyl radicals (HO.) as well as HO.-initiated lipid peroxidation, we explored the potential role of this metal in the pathogenesis of myocardial stunning. Open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received the iron chelator desferrioxamine intravenously (10 mg/kg over 45 min beginning 30 min before occlusion, then 1.7 mg.kg-1.h-1 throughout REP, n = 19) or normal saline (n = 17). Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. After REP, however, recovery of contractile function (expressed as percent systolic thickening) as considerably greater in desferrioxamine-treated compared with control dogs: 5 +/- 3 (mean +/- SE) vs. -3 +/- 2% (P less than 0.05) at 1 h, 6 +/- 3 vs. -2 +/- 3% (P less than 0.05) at 2 h, 5 +/- 3 vs. -6 +/- 2% (P less than 0.005) at 3 h, and 6 +/- 3 vs. -6 +/- 2% (P less than 0.002) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that iron-catalyzed reactions (possibly HO. generation) play a significant role in myocardial stunning after a brief episode of reversible regional ischemia.

Lipoxygenase inhibitor nafazatrom fails to attenuate postischaemic ventricular dysfunction.

The role of lipoxygenase activation in the genesis of postischaemic myocardial dysfunction was investigated in open chest dogs undergoing a 15 min occlusion of the left anterior descending artery followed by 4 h of reperfusion. Treated animals (n = 9) received nafazatrom, a potent lipoxygenase inhibitor, 10 mg.kg-1 orally 4 h before occlusion followed by intravenous boluses of 1.5 mg.kg-1 and 0.5 mg.kg-1 5 min before occlusion and 1 min before reperfusion respectively. Control animals (n = 10) received saline. No discernible haemodynamic effects were produced by the drug. Collateral flow to the ischaemic zone (radioactive microspheres) was 0.14(0.02) ml.min-1.g-1 in the control group and 0.16(0.05) ml.min-1.g-1 in the treated group. The size of the occluded bed as determined by postmortem perfusion was 25.5(0.8)% of the left ventricle in the control and 24.3(1.3)% in the treated group. Histological examination showed a decrease in neutrophil infiltration of the non-ischaemic myocardium and, to a lesser extent, of the reperfused myocardium in nafazatrom treated animals, suggesting lipoxygenase inhibition. Systolic wall thickening (an index of regional function) was assessed using an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions. Though treated animals showed less dyskinesis during coronary occlusion (p less than 0.05), recovery of function was not enhanced over controls and in both groups the reperfused myocardium was still dyskinetic at 4 h. Thus nafazatrom failed to improve postischaemic ventricular dysfunction, suggesting that leukotrienes do not contribute importantly to this phenomenon.

Evidence for a pathogenetic role of xanthine oxidase in the "stunned" myocardium.

Recent evidence suggests that postischemic myocardial dysfunction (or myocardial "stunning") may be mediated by oxygen free radicals, but the mechanism for their production remains unknown. To explore the role of xanthine oxidase as a potential source of free radicals, open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received intravenously either allopurinol (50 mg/kg 48 h, 20 h, and 30 min before occlusion, 10 mg/kg 1 min before REP, and 6.25 mg X kg-1 X h-1 throughout REP, n = 13) or saline (n = 14). The two groups were similar with respect to occluded bed size (postmortem perfusion) and collateral flow (radioactive microspheres). In controls, the transcardiac difference in plasma uric acid (great cardiac vein - arterial concentration) increased 199 +/- 70% (means +/- SE) during ischemia (P less than 0.02) and remained elevated for 5 min after REP; no increase was observed in treated dogs. Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. Following REP, however, recovery of contractile function (expressed as percent of preocclusion values) was considerably greater in allopurinol-treated as compared with control dogs: 57 +/- 14 vs. -22 +/- 16 (P less than 0.01) at 1 h, 70 +/- 13 vs. -15 +/- 15 (P less than 0.001) at 2 h, 65 +/- 14 vs. -28 +/- 13 (P less than 0.001) at 3 h, and 68 +/- 13 vs. -17 +/- 14 (P less than 0.001) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that xanthine oxidase is a source of the oxygen free radicals responsible for myocardial stunning following a brief episode of reversible regional ischemia.