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Vol. 22, No. 1, January 1999 (Supplement I)

Intrapericardial Therapeutics and Diagnostics (IPTD): Potential Advantages, Recent Advances, Experimental Direct Therapy of Cardiac Diseases and Arrhythmias

Guest Editor

"This supplement is based on both the proceedings of an Intrapericardial Therapeutic and Diagnostics (IPTD) Workshop held in Chicago, Illinois on July 28, 1998 and previous IPTD investigations. The IPTD Workshop, prior investigations, and publications of the proceedings were supported by unrestricted grants from Chiron Corporation and Comedicus Incorporated.

To download the full supplement in PDF [3.5 mb], follow this link.
To read individual articles, follow the links below.


Direct Therapy of Coronary Disease, Myocardial Disease, and Severe Cardiac Arrhythmias

D. H. Spodick, M.D., D.Sc., FACC

Original Contributions

Microphysiology of the Pericardium in Relation to Intrapericardial Therapeutics and Diagnostics  [PDF]

D. H. Spodick, M.D., D.Sc., FACC

Intrapericardial delivery of therapeutic agents for pericardial diseases has long been available in the presence of excess pericardial fluid. Most patients with myocardial and coronary disease have no such excess so that their direct treatment requires pericardial access, for which a new instrument has succeeded in animals with induced infarctions, coronary lesions and arrhythmias. Nitric oxide donors, calcium-avid drugs, antibodies, angiogenic agents (pharmacologic coronary bypass), and hypothermic solutions have been instilled intrapericardially, and even iontophoresis has been used; gene therapy is also promising. Intrinsic pericardiogenic substances potentially may be stimulated for comparable purposes.

Function of the Normal Pericardium  [PDF]

R. Shabetai, M.D.

Using the pericardial space as a depot for cardiovascular drugs necessitated the development of techniques to instrument the normal pericardium. These techniques have the potential to be exploited to further our understanding of pericardial function. Pericardial physiology includes intrapericardial pressures and their relation to ventricular function and the ambient (intrathoracic and intrapleural) pressures, yielding transmural cardiac pressures and responses, respectively, during the respiratory cycle. A continuing point of discussion involves appropriate instrumentation for intrapericardial pressures, specifically whether an unstressed flat balloon introduced atraumatically is superior under certain circumstances to the familiar catheter techniques. Each yields about the same result with pericardial fluid exceeding 30 ml in experimental animals.

Therapeutic Myocardial Angiogenesis Using Percutaneous Intrapericardial Drug Delivery  [PDF]

R. J. Laham, M.D., D. Hung, M.D., Ph.D., M. Simons, M.D.

A number of growth factors, including the fibroblast growth factor (FGF) family and vascular endothelial growth factor (VEGF), have all been shown to stimulate blood vessel growth. However, the delivery strategies used were not applicable to patients. The pericardial space appears to play an important role in the physiologic and pathologic regulation of various myocardial processes. Intrapericardial or epicardial administration of various cytokines appear to result in functionally significant angiogenesis in animal models of chronic myocardial ischemia. A single bolus injection of basic FGF (bFGF) into the pericardial space (via a percutaneous subxyphoid access of the pericardial space) improved regional perfusion, regional left ventricular function, and microvascular reactivity, and increased angiographically visible collaterals and magnetic resonance-detected collaterals. The pericardial space, thus, offers an attractive drug delivery reservoir that might be used to deliver therapeutic substances to the heart.

Pharmacokinetics and Consistency of Pericardial Delivery Directed to Coronary Arteries: Direct Comparison with Endoluminal Delivery  [PDF]

H.-P. Stoll, M.D., K. Carlson, B.A., L. K. Keefer, Ph.D., J. A. Hrabie, Ph.D., K. L. March, M.D., Ph.D. FACC

Several proteins were delivered into the porcine pericardial space or into coronary arteries using an endoluminal (EL) delivery catheter, and their penetration into arterial tissue was compared for these two local delivery approaches. The results show that pericardial fluid contents can access coronary arteries with intramural concentrations which vary by 10–15-fold, while EL delivery results in a remarkably wide intramural concentration range with up to 33,000-fold variability. The apparent redistribution rate is more rapid following EL delivery, possibly due to sustained diffusive tissue loading from the pericardial space. Pericardial delivery appears to offer substantial advantages over EL administration with respect to residence time and reproducibility.

Intrapericardial Treatment of Inflammatory and Neoplastic Pericarditis Guided by Pericardioscopy and Epicardial Biopsy--Results from a Pilot Study  [PDF]

B. Maisch, M.D., S. Pankuweit, Ph.D., C. Brilla, M.D., R. C. Funck, M.D., B. C. Simon, M.D., W. Grimm, M.D., M. Herzum, M.D., G. Hufnagel, M.D.

Fourteen patients with autoimmune and 15 with neoplastic effusions underwent pericardioscopy, epicardial and pericardial biopsy with histological, immunohistological and PCR analysis for microbial DNA and RNA. Protusions identified by pericardioscopy proved specific for neoplastic effusions. Cytology and epicardial but not pericardial biopsy identified neoplastic disorders. Cristalloid triamcinolone (lg intrapericardially) in autoreactive (PCR-negative) pericarditis effectively prevented recurrence in 13 of the 14 cases after 3 months, and in 12 of the 14 cases after one year. In neoplastic effusion 50 mg of intrapericardial cis-platin effectively prevented recurrence of a hemodynamically relevant effusion after 3 and 6 months.

Efficient in Vivo Catheter-Based Pericardial Gene Transfer Mediated by Adenoviral Vectors [PDF]

K. L. March, M.D, Ph.D., M. Woody, M.S., K. Mehdi, M.D., D. P. Zipes, M.D., M. Brantly, M.D., B. C. Trapnell, M.D.

It was hypothesized that efficient adenovirus-mediated gene expression in pericardial mesothelium could be achieved by transmyocardial vector delivery to the pericardium. Introduced percutaneously in dogs, the catheter was passed through the right ventricular myocardium. Adenoviral vectors expressing beta-galactosidase, luciferase, or secreted a1-antitrypsin reports were instilled intrapericardially, and reporter gene expression was evaluated. In animals receiving Av1nBg, beta-galactosidase activity was evident in most of the pericardial mesothelium. In animals receiving Av1Lu, luciferase activity was abundant only in the pericardium. In animals receiving Av1Aa, human a1AT was abundant (16–29 µg/ml) in pericardial fluid. The procedure was well tolerated. Thus, highly efficient, minimally invasive adenovirus vector delivery and gene transfer and expression can be induced in the pericardium, supporting the feasibility of intrapericardial gene therapy.

Initial Clinical Experience with PerDUCER® Device: Promising New Tool in the Diagnosis and Treatment of Pericardial Disease  [PDF]

P. M. Seferovic, M.D., Ph.D., FACC, FESC, A. D. Ristic, M.D., R. Maksimovic, M.D., M.Sc., P. Petrovic, M.D., Ph.D., M. Ostojic, M.D., Ph.D., FACC, FESC, S. Simeunovic, M.D., Ph.D., FACC, D. Zamaklar, M.D., D. Simeunovic, M.D., D. H. Spodick, M.D., D.Sc., FCCP, FACC

The goal of the present study was to evaluate the feasibility and safety of percutaneous pericardial access with PerDucer® in patients with pericardial disease, and to analyze our initial experience with this new technique. The procedure consists of two distinct techniques: (1) access to the mediastinal space, and (2) pericardial capture, puncture, and insertion of the guidewire. The device was studied in five patients with pericardial disease. Access to the mediastinal space and pericardial capture and probably puncture were accomplished in 4 or 5 patients. However, the authors were not able to confirm the introduction of the intrapericardial guidewire in the pericardial cavity in any of their patients (0/5).

Minimally Invasive Access of the Normal Pericardium: Initial Clinical Experience with a Novel Device  [PDF]

M. P. Macris, M.D. and S. R. Igo

Clinical trials are being conducted to evaluate a minimally invasive pericardial access device (PerDUCER). Twelve clinical trials have been completed on patients undergoing cardiac surgery. In eight patients, a median sternotomy allowed visual positioning of the device prior to pericardial puncture. Four patients underwent a closed-chest, fluoroscopy-assisted procedure. Intrapericardial guidewire insertion was successful in 10 patients (7 on first attempt, 3 on second) without adverse effects. There was no evidence of injury to the pericardium or heart. These studies suggest that the PerDUCER may provide safe, rapid, and effective percutaneous insertion of a guidewire into the normal pericardial space.

Establishment of a Clinically Correlated Human Pericardial Fluid Bank: Evaluation of Intrapericardial Diagnostic Potential  [PDF]

T. J. Dickson, M.S., V. Gurudutt, A. Q. Nguyen, M.S., K. Kumfer, W. Maxted, J. Brown, M.D., Y. Mahomed, M.D., T. Sharp, M.D., T. X. Aufiero, M.D., N. Fineberg, Ph.D. K. L. March, M.D., Ph.D

The development of a clinically correlated human pericardial fluid bank and data base is described. A unique feature of this registry is the availability of a large number of pericardial fluid samples for testing with respect to multiple factors and for correlation with angiographic findings and clinical syndromes expressed by the patients. Study of the pericardial fluid bank should lead to enhanced understanding of molecular mechanisms, as well as the reasons underlying the interpatient variability in these processes. It is further anticipated that this information might provide a foundation for the diagnostic use of pericardial fluid to individualize therapies targeting angiogenesis or plaque physiology.

The opinions expressed in this presentation are those of the panelists and are not attributable to the sponsor or the publisher, editor, or editorial board of Clinical Cardiology. Clinical judgment must guide each physician in weighing the benefits of treatment against the risk of toxicity. References made in the articles may indicate uses of drugs at dosages, for periods of time, and in combinations not included in the current prescribing information.