Biomedical subjects
Publications and source records attributed to M Mirowski.
Guerin epithelioma, a highly metastatic tumour implanted to Wistar rats contains two inhibitors of fibrinolysis which can be detected with the use of zymographic techniques. The first one--with Mr about 48000 forms SDS-stable complex with urokinase. The second--with Mr about 7000 inhibits fibrinolytic and amidolytic activity of plasmin.
Explore the source record for details and available documents.
This study contains a survey of papers published in the last few years on the specific inhibitor of plasminogen activation (PA-inhibitor, or antiactivator) discovered in plasma in 1983. Molecular weight of the PA-inhibitor is ranging from 40,000 to 50,000; the antiactivator is present in very small concentration in plasma. Most probably it originates from the endothelial cells. The antiactivator inhibits both tissue plasminogen activator and urokinase, forming complexes in molar ratio 1:1 with them. Possibly, it is the main plasmic inhibitor of plasminogen activators. Its increased content in plasma of patients with tendency to develop thromboembolic disease points to a relationship between lowered fibrinolytic activity and increased concentration of the PA-inhibitor in blood.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Myocardial revascularization and implantation of the automatic implantable cardioverter defibrillator (AICD) have individually been shown to improve survival in patients after sudden cardiac death. Their combined role has not been well defined. Twenty-three survivors of sudden death underwent revascularization and AICD implantation at an average age of 59 years. The initial arrest was caused by ventricular fibrillation in 15 and ventricular tachycardia in 8. Exercise stress tests, ambulatory ECGs, and electrophysiological monitoring with programmed electrical stimulation were done preoperatively and postoperatively. Follow-up averaged 24 months with a two-year survival of 91%. Eight patients (35%) required AICD resuscitation an average of 8 months postoperatively, and electrophysiological testing did not accurately predict arrhythmia recurrence. The addition of AICD implantation to revascularization substantially improves survival of patients with sudden cardiac death.
Explore the source record for details and available documents.
Since February 1980 the automatic implantable cardioverter defibrillator has been implanted in over 1,500 patients. Sudden death rates have been reduced to 2%-4% annually. This report reviews the implantation techniques, their indications, and our clinical experience in 200 patients.
Because the automatic internal cardioverter defibrillator's long-term ability to reduce arrhythmic mortality in patients with ventricular tachycardia/fibrillation is unknown, it is important to determine whether the threshold for defibrillation changes over time. Serial defibrillation thresholds were measured in 23 patients over a mean replacement time of 24.8 +/- 7.5 months. In all cases the lead system was a superior vena cava coil to a left ventricular epicardial patch. The defibrillation threshold for the entire group increased from 12.3 +/- 4.7 J to 16.9 +/- 5.9 J (p less than 0.05). Striking increases in the defibrillation threshold were seen in the subgroup of patients taking amiodarone (from 10.9 +/- 4.3 J at implantation to 20.0 +/- 4.7 J at replacement, p less than 0.05). Defibrillation threshold decreased in patients taking no antiarrhythmic drugs or taking class I agents. Thus, the increase in mean defibrillation threshold was the result of an increase in the patients taking amiodarone. These data suggest that at initial implantation lead systems associated with the lowest defibrillation threshold should be used and the defibrillation threshold should be measured at generator change to guarantee an adequate margin of safety.
The purpose of the present study was to examine at autopsy the effect of multiple defibrillations on the myocardium and the pathologic consequences of short- and long-term placement of the intravascular and interpericardial leads of the automatic implantable cardioverter-defibrillator. Twenty-five patients were examined at autopsy; 8 of them underwent lead implantation only and 17 received both leads and the automatic implantable cardioverter-defibrillator. Twelve patients (48%) died of ventricular tachycardia or ventricular fibrillation; seven (28%) died of other causes. Acute pericarditis occurred in all patients, resulting in a localized, progressive fibrosis around the apical patch lead without giving rise to pericardial restriction. Thrombus formation was associated with the superior vena cava spring electrode in four patients (17%) and the right ventricular rate-sensing electrode in one patient (4%). Asymptomatic pulmonary emboli occurred in two patients (8%). In one patient who underwent defibrillation 59 times, superior vena cava changes consisted of vein wall destruction, fibrosis and thrombus formation. Pathologic changes under the apical patch related to defibrillation were observed in seven patients; two of these had fewer than 5 defibrillations, one had 8 defibrillations and four had 21 to 74 defibrillations. These changes consisted of contraction band necrosis in four patients, vacuolar cytoplasmic clearing and loss of myocytes confined to the myocardium under the patch electrode in five patients who had multiple defibrillations. The observed pathologic changes were estimated to affect less than 2% of the total myocardial mass. Thus, the automatic implantable cardioverter-defibrillator lead system and multiple defibrillations result in localized myocardial injury confined to the tissue under the patch electrode.(ABSTRACT TRUNCATED AT 250 WORDS)
Although ventricular resection guided by endocardial mapping has been a successful treatment for drug-refractory ventricular arrhythmias, 20 to 30 percent of patients still have postoperative sustained ventricular tachycardia or sudden death. To improve the outcome of the procedure, we implanted an automatic cardioverter-defibrillator in conjunction with endocardial resection in 28 patients, all of whom had had previous myocardial infarctions and between one and five cardiac arrests. There were three perioperative deaths. During follow-up of 8 to 51 months (mean, 25), 4 of the 25 survivors had recurrences of hypotensive ventricular tachycardia, which in all instances were automatically terminated by the implanted device. One patient, whose automatic cardioverter-defibrillator was not functional, died suddenly. We conclude that patients undergoing mapping-directed endocardial resection can be provided with additional protection against recurrent ventricular tachyarrhythmias or sudden death by implantation of an automatic cardioverter-defibrillator.
The clinical experience with the Automatic Implantable Cardioverter-Defibrillator (AICD) now extends to over 800 patients suffering from malignant ventricular arrhythmias, most of them survivors of sudden cardiac death. This device monitors cardiac rhythm for long periods of time, identifies ventricular fibrillation and life-threatening ventricular tachycardias, and then restores normal heart action with effective electrical discharges. The AICD practically eliminates the need for trained personnel and the time constraints associated with conventional out-of-hospital resuscitation, significantly decreasing the arrhythmic and total mortality rates of the implantees. Through August, 1985, 130 consecutive patients underwent implantation of the AICD at The Johns Hopkins Hospital in Baltimore; the one-year mortality due to arrhythmias was 1.7%. These results are similar to those reported by other centers. Thus, the growing clinical experience with the automatic implantable cardioverter-defibrillator has demonstrated a marked reduction of the mortality rate of the implantees.
Two patients with the prolonged QT syndrome and recurrent ventricular tachyarrhythmias are presented, one of them refractory to combination antiarrhythmic drug therapy and bilateral stellate ganglion blockade. We implanted and tested in vivo an automatic cardioverter-defibrillator to provide a cardiac monitoring system with the capability of delivering a 25 J electrical discharge to the heart if rapid ventricular tachycardia or ventricular fibrillation is detected. Arrhythmia induction in the electrophysiology laboratory confirmed the appropriate recognition of the arrhythmias in each patient, with prompt discharge of the device and resultant termination of the tachycardias. We suggest that implantation of such a device may provide an effective adjunct to antiarrhythmic drug therapy in the management of infrequent, but potentially lethal, ventricular arrhythmias occurring in patients with the prolonged QT syndrome.
The automatic implantable cardioverter-defibrillator continuously monitors the heart, identifies malignant ventricular tachyarrhythmias and then delivers electrical countershock to restore normal rhythm. There are two defibrillating electrodes which are also used for waveform analysis; one is located in the superior vena cava and the other is placed over the cardiac apex. A third bipolar right ventricular electrode is used for rate counting and R wave synchronization. When ventricular fibrillation occurs, a 25 J pulse is delivered; when ventricular tachycardia faster than the preset rate is detected, the discharge is R wave-synchronized. The clinical evaluation study of this therapeutic method began in February 1980 in patients with recurrent refractory life-threatening ventricular tachyarrhythmias. So far, the device has been implanted in nearly 500 patients with a follow-up period of up to 59 months. The risks and complications associated with this treatment were found to be moderate. Actuarial analysis has demonstrated significant impact on the survival rate of the patients receiving implants with 1 year arrhythmic mortality rate reduced to 2% or less in all groups analyzed. The available data indicate that the automatic cardioverter-defibrillator can reliably identify and correct potentially lethal ventricular tachyarrhythmias, leading to a substantial improvement in survival in properly selected high risk patients.
The automatic implantable cardioverter-defibrillator is an electronic device designed to monitor the heart continuously, identify ventricular tachycardias and ventricular fibrillation, and terminate the life-threatening arrhythmias with an internal countershock. This device has been proved to be safe and effective, and its use has led to a significant decrease of arrhythmic mortality in the implantees.
Since February 1980, worldwide, over 400 survivors of sudden arrhythmic death have been treated with the automatic implantable defibrillator. Recently, the device has been further improved; it is now a cardioverter-defibrillator (AICD), able to treat ventricular tachycardias as well as ventricular fibrillation. There are two defibrillating electrodes which are used also for waveform analysis; one is located in the superior vena cava, the other is placed over the cardia apex. A third bipolar right ventricular electrode serves for rate counting and R-wave synchronization. When ventricular fibrillation occurs, a 25-joule pulse is delivered; when ventricular tachycardia faster than a preset rate is detected, the discharge is R-wave synchronized. Special batteries can deliver over 100 shocks or provide a three-year monitoring life. Implantation of the device can be achieved through a thoracotomy or by a subxiphoid or a subcostal approach. Thus far, the longest follow-up period has been 58 months. Actuarial analysis shows the one-year mortality attributed to arrhythmias reduced to less than 2%. Thus, the automatic cardioverter-defibrillator can reliably identify and correct potentially lethal ventricular tachyarrhythmias, leading to a substantial increase in survival in properly selected high-risk patients.
Fourteen patients with refractory ventricular tachyarrhythmias were treated with combined endocardial resection and implantation of the automatic defibrillator. There were 11 men and 3 women with a mean age of 53 years (range, 41 to 58 years). All patients had coronary artery disease; the mean ejection fraction was 26%, and the mean number of cardiac arrests was 2.6. Programmed electrical stimulation induced sustained ventricular tachycardia in 13 patients and nonsustained ventricular tachycardia in 1. Operative endocardial mapping in the 13 patients with sustained ventricular tachycardia demonstrated a septal focus of early activation in 9 patients and a nonseptal site in 4. Following resection, sustained ventricular tachycardia could not be reinduced. There was 1 operative death. Programmed electrical stimulation performed one month after operation induced ventricular tachycardia in 5 patients, but tachycardia could not be induced in the other 8 survivors. The longest follow-up was 32 months; the average was 17 months. There were 2 late deaths. One patient died of myocardial infarction and 1 of pulmonary edema following a routine cholecystectomy. In another patient, late ventricular tachycardia developed but was automatically terminated by the implanted defibrillator. These results suggest that endocardial resection combined with implantation of the automatic defibrillator may offer the greatest protection yet available to patients with malignant ventricular tachyarrhythmias.
Technical advances now permit permanent implantation of devices such as antitachycardia pacemakers, cardioverters and cardioverter-defibrillators for control of ventricular tachyarrhythmias. Despite the fact that these devices have been implanted only in patients resistant to conventional medical and surgical management, their effectiveness has been very encouraging. While improved designs are anticipated, preliminary studies have clearly indicated that one of the major challenges for successful clinical use will be appropriate interfacing of the device with the pathophysiology of the patient. Failure to recognize this fact will likely lead to unsuccessful clinical application. Moreover, these new instruments appear to be complementary to, rather than a replacement for, existing medical and surgical approaches to the patient with life-threatening ventricular tachyarrhythmias.