New developments in thrombolytic therapy.

Pharmacologic lysis of occlusive, ischemia-producing thrombi has become widely accepted during the past decade. New developments in this field have centered around increasing the efficacy of the known plasminogen activators while employing methods to minimize the risk of hemorrhage and decrease the incidence of rethrombosis. Such methods have included the use of thrombus-directed antibodies linked to plasminogen activators, increased plasminogen (substrate) concentration at the thrombus site, anticoagulant and antiplatelet therapy to prevent thrombus propagation and reformation following lysis, and combination plasminogen activator therapy designed to increase efficacy and safety.

The effect of skeletal muscle ventricle pouch pressure on muscle blood flow.

Skeletal muscle powered assist ventricles (SMV) are being investigated in animal studies as a treatment for heart failure. Muscle fatigue is almost always dependent upon muscle capillary blood flow. This study examined the relationship between SMV intrapouch pressure and blood flow to the circumferential muscle in a working SMV with a mock circulation.

The impedance of a spherical monopolar electrode.

The impedance of a monopolar electrode immersed in an environmental volume conductor consists of two parts; the impedance of the active electrode-electrolyte interface, and the resistance of the environmental conductor. Two studies were carried out to quantitate these components. First, impedance-frequency data were collected for five spherical stainless-steel electrodes (ranging from 0.

Artificial respiration in the dog by percutaneous, bilateral, phrenic nerve stimulation.

Artificial respiration was produced in 11 anesthetized dogs using trains of short duration stimuli (1 msec with a frequency of 35/sec), applied to needle electrodes placed bilaterally at the base of the neck. The tips of the needles were in close proximity to the phrenic nerves. In all cases, the inspired volume increased with an increase in stimulus intensity.

Endothelial superoxide production in the isolated rat heart during early reperfusion after ischemia. A histochemical study.

This paper describes a histochemical study of superoxide generation in buffer-perfused, isolated rat hearts during the first 2 minutes of reperfusion after 60 minutes of warm ischemia. Superoxide radical production was demonstrated by a modification of Karnovsky's manganese/diaminobenzidine technique, in which superoxide oxidizes Mn++ to Mn ions, which in turn oxidize diaminobenzidine to form amber, osmiophilic polymers, observable by light or electron microscopy. Isolated hearts were rendered ischemic, reperfused with oxygen equilibrated buffer containing Mn++ and diaminobenzidine, fixed by perfusion with Trump's solution, and processed for light and electron microscopy.

Inspiration produced by bilateral electromagnetic, cervical phrenic nerve stimulation in man.

Eddy-current stimulation of both phrenic nerves at the base of the neck in human subjects was carried out to provide inspiration resulting from tetanic diaphragm contraction. The inspired volume obtained was in excess of spontaneous tidal volume.

Endothelial superoxide production in buffer perfused rat lungs, demonstrated by a new histochemical technique.

This paper describes a new approach to the histochemical demonstration of superoxide generation by pulmonary vascular endothelial cells using a supravital high manganese/diamine technique, in which nascent superoxide radicals induce formation of amber, osmiophilic polymers of diaminobenzidine (DAB), detectable by light or electron microscopy. Superoxide oxidizes Mn2+ ions to the Mn3+ valence state. In turn trivalent manganese readily initiates formation of the polymerized DAB reaction product.

Detection of ventricular fibrillation with a ventricular monopolar catheter electrode.

This report describes the use of right ventricular impedance (RVZ) sensing with a monopolar electrode to identify the cessation of pumping with the onset of ventricular fibrillation. RVZ, ECG (lead II), and femoral artery pressure were monitored in seven anesthetized dogs. An impedance recorder (10-kHz, 100-microA peak-to-peak current) was used to measure RVZ between a monopolar, catheter-mounted electrode placed in the right ventricle and an indifferent electrode (8.

Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury.

Tissue oxidases, especially xanthine oxidase, have been proposed as primary sources of toxic oxygen radicals in many experimental models of disease states. Among these, ischemia-reperfusion injury may be of the greatest clinical interest. In this paper we propose the use of methylene blue as a means of suppressing the production of superoxide radicals O2- by acting as an alternative electron acceptor for xanthine oxidase.

Effective estimation and computer control of minimum tumour temperature during conductive interstitial hyperthermia.

The goal of heat therapy in the treatment of malignant disease is to raise the temperature of all neoplastic tissue to a cytotoxic temperature for a predetermined period of time. This seemingly simple task has proved difficult in vivo in part because of non-uniform power absorption and in part because of non-homogeneous and time-varying tumour blood flow. We have addressed this difficulty first by utilizing the conceptually simple technique of conductive interstitial hyperthermia, in which the tumour is warmed by multiple, electrically heated catheters, and second by implementing on-line control of minimum tumour temperatures near each catheter, estimated on the basis of the steady-state ratio of catheter power to catheter temperature rise.

Enhancement of the thrombolytic efficacy of prourokinase by lys-plasminogen in a dog model of arterial thrombosis.

Current findings suggest that the efficacy of thrombolytic therapy may be limited by the availability of active forms of plasminogen at the thrombus site. The purpose of this study was to determine if the systemic administration of 0.5 mg kg-1 glu-plasminogen (glu-plg) or 0.

The potential power output for skeletal muscle to provide cardiac assistance.

It is clear that autologous skeletal muscle offers a potential power source, free of invasive tubes and wires and without the need for immunosuppressive or antibiotic therapy, with the capability of assuming at least 25% to 50% of the natural heart's workload. The application of this power source as either a heart wrap in CMP procedures or as an assist ventricle in SMV designs is not only possible, but in fact, reality in the case of CMP procedures. Optimization of these applications requires continued research, but offers renewed hope for patients with CHF who currently depend on indefinite pharmacologic therapy, the total artificial heart, or the too few donor hearts for transplantation.

Comparison of canine skeletal muscle power from twitches and tetanic contractions in untrained muscle: a preliminary report.

Power output and blood flow were determined in dogs for four muscles (gastrocnemius, latissimus dorsi, rectus abdominis, and triceps) to determine effects of choice of muscle, tetany or twitch rates, force loading of the muscle, and blood flow on muscle power output. Total power for a 20-Kg dog was greatest for triceps at 0.77 watts (W) and least for rectus at 0.

Use of electrical impedance for continuous measurement of stroke volume of a skeletal muscle-powered cardiac assist device.

This study describes the use of electrical impedance Z to continuously measure the stroke volume SV of a skeletal muscle-powered ventricle (SMV). An SMV was constructed surgically in four anaesthetised dogs. The rectus abdominis (two dogs) or latissimus dorsi (two dogs) muscle was wrapped around a compressible pouch, the ends of which were connected to a saline-filled (0.

Design and evaluation of closed-loop feedback control of minimum temperatures in human intracranial tumours treated with interstitial hyperthermia.

The dynamic nature of blood flow during hyperthermia therapy has made the control of minimum tumour temperature a difficult task. The paper presents initial studies of a novel approach to closed-loop control of local minimum tissue temperatures utilising a newly developed estimation algorithm for use with conductive interstitial heating systems. The local minimum tumour temperature is explicitly estimated from the power required to maintain each member of an array of electrically heated catheters at a known temperature, in conjunction with a new bioheat equation-based algorithm to predict the 'droop' or fractional decline in tissue temperature between heated catheters.

The polarization impedance of common electrode metals operated at low current density.

The objective of this study was to characterize the polarization impedance (resistance and capacitance) of several common metal/0.9% saline interfaces operated at low-current density and to thereby provide a useful reference for those wishing to calculate the impedance of such electrodes. The series-equivalent resistance (R) and capacitive reactance (Xc) of stainless steel, platinum, silver, MP35N, palladium, aluminum, rhodium and copper electrodes, all having a surface areas S = 0.

History of magnetic stimulation of the nervous system.

The use of a time-varying magnetic field to induce a sufficiently strong current to stimulate living tissue was first reported by d'Arsonval in 1896. Since then, there have been many studies in what is now called magnetic stimulation. This paper traces the history of this field from d'Arsonval to its present use in neurophysiology.

Computer-aided design and evaluation of novel catheters for conductive interstitial hyperthermia.

Conductive interstitial heating is a modality in which heating elements are implanted directly into the treated tissue. One implementation of such therapy employs electrically heated catheters that are implanted in staggered, parallel rows. To explore strategies for maximising the uniformity of tissue temperature distributions achieved with heated catheters, a two-dimensional computer model with cylindrical co-ordinates was used to evaluate radially and longitudinally the temperature distributions produced by a typical interior catheter surrounded by other similar catheters.

Power capability of skeletal muscle to pump blood.

This article describes the various ways in which an electrically stimulated, muscle-wrapped pouch can be used to pump blood. The fundamental equations that allow calculation of the output and input power are developed. The output power in watts is 23.

The beneficial effect of lys-plasminogen upon the thrombolytic efficacy of urokinase in a dog model of peripheral arterial thrombosis.

The efficacy of thrombolytic therapy may be limited by local availability of plasminogen near a poorly perfused thrombus. The purpose of this study was to determine if the local (i.e.

Guidelines for energy-efficient coils: coils designed for magnetic stimulation of the heart.

Magnetic stimulation of the heart requires high magnetic field energy and results in considerable Joulean dissipation. Energetically efficient and mechanically robust coils were designed for magnetic stimulation of the canine heart. Circular coils with rectangular cross section oriented either parallel or perpendicular to the skin were employed.

Intravascular lead extraction using locking stylets, sheaths, and other techniques.

Unlabelled: Septicemia necessitates extraction of chronic pacemaker leads. Using locking stylets and sheaths to extract leads via the implantation vein (subclavian, cephalic, or jugular) and maneuvering devices, sheaths, and retrieval baskets via the femoral approach, extraction of 228 leads implanted 5 days to 240 months (mean 55 months) was attempted in 136 patients (mean 62 years) at 34 institutions. In addition to septicemia (9%) and infection (39%), total 48%, indications included prophylaxis/replacement (40%), and other (12%).

The protective effect of heparin in a dog model of rethrombosis following pharmacologic thrombolysis.

Rethrombosis is an important clinical problem for patients who have benefitted from pharmacologic thrombolysis. The present study describes a dog model of arterial thrombosis, which includes endothelial denudation, intimal damage, and stenosis, and is suitable for studying the phenomena of both thrombolysis and subsequent rethrombosis. The model was used to determine the effect of tissue-type plasminogen activator (t-PA), high and low dose heparin, and saline upon the incidence of rethrombosis after t-PA-induced thrombolysis.