Robert C. Eberhart

Influence of endogenous albumin binding on blood-material interactions.

A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid binding of albumin from single and binary protein solutions, from plasma, and apparently, from whole blood. The bound albumin resists fluid shear or chemically induced desorption. Fibrinogen adsorption is inhibited in vitro and in vivo. Complement protein C3 activation from plasma is inhibited. Fibrin formation and platelet aggregation is inhibited in short-term in vivo experiments. Long-term catheter implant studies suggest that the C18 alkylation is more effective than most, if not all, currently available treatments for the retention of a clean, biocompatible, blood-contacting surface. No data have been obtained to date that conflict with the hypothesis that a renewable albumin layer, so formed, blocks the adsorption or conformational alteration of plasma proteins that otherwise might initiate or participate in various host defenses.

Thermal dilution methods: estimation of tissue blood flow and metabolism.

Detailed knowledge of the rates of tissue blood flow and metabolism in tumorbearing tissue and adjacent normal tissue is essential for continuing progress in the diagnosis and treatment of tumors by hyperthermia and/or chemotherapy and radiotherapy. Indicator dilution methods have been developed and used widely for estimation of organ perfusionI4 and may be applied for this purpose in tumors. The general method follows from the Fick relation in which the net transport of indicator into a region of interest is balanced by the transient buildup or removal of the indicator. Indicators that have been used for organ blood flow analysis include: injected radioactive and other diffusible gases,’ locally generated hydrogen ion: and injected or locally generated heat.’ Trappcd indicator methods, in which radio-labeled microspheres or aggregated albumin are distributed to a capillary bed in proportion to the local flow rate.’ are currently receiving much attention. The subject of tissue blood flow measurement has recently been reviewed by Paradise and Fox.‘ Measurement of the local heat generation rate due to metabolism or frictional heating has been much less successful. Metabolic measurements have been limited to direct calorimetry on small sample preparations, or have been inferred from local measurement of oxygen consumption? This review focuses on the heat clearance methods, since the estimation of local metabolic rate as well as perfusion is possible with an appropriate analysis, and the heat clearance methods offer an inherent experimental simplicity. As a matter of interest, approximate methods for estimation of perfusion by heat clearance as originally developed by Gibbs 50 years ago” are treated briefly. More attention is given to heat clearance methods that follow from solution of a more complete equation describing the tissue energy balance (the bio-heat transfer equation). Studies will be presented for flow estimation in several organs, emphasizing those works in which independent validation of the tissue blood flow estimate is provided. The limitations of the perfusion estimate by solution of the bio-heat transfer equation are considered in detail. Sources of error derived from heat transport mechanisms not included in the bio-heat transfer equation, e.g., arteriovenous heat exchange, will be outlined and

Intraaortic Balloon Counterpulsation: Its Influence Alone and Combined with Various Pharmacological Agents on Regional Myocardial Blood Flow during Experimental Acute Coronary Occlusion

We investigated the separate and combined effects of pharmacological and intraaortic balloon pump (IABP) support on regional myocardial blood flow in an experimental model of acute myocardial ischemia. Chloralose-anesthetized dogs were ventilated with an oxygen-air mixture, and cardiac output, arterial pressure, and heart rate were held constant. Treatment was begun 20 minutes following permanent ligation of the left anterior descending coronary artery (LAD). We evaluated the following pharmacological interventions: 25% hypertonic mannitol, isosorbide dinitrate, methyl-prednisolone sodium succinate, and propranolol. We measured left ventricular hemodynamics and intramyocardial blood flow by the radioactive microsphere technique prior to treatment and at 15-minute intervals thereafter. Compared with control measurements 20 minutes following LAD ligation, collateral blood flow to ischemic myocardium tended to decrease with no treatment. Treatments with the four pharmacological interventions and with IABP alone produced no significant improvement in collateral blood flow to ischemic myocardium 15 minutes following treatment. In contrast, mannitol, isosorbide dinitrate, and propranolol, each combined with IABP support, produced significant improvements in collateral flow within the same time periods. In nonischemic myocardium, combined pharmacological and IABP treatment did not enhance myocardial blood flow above that obtained with the pharmacological agents alone. The most effective combination of mechanisms for improving the ischemic regions myocardial blood flow appeared to be a reduction of extravascular coronary flow resistance coupled with a simultaneous increase in diastolic arterial pressure.

Indwelling Blood Compatible Chemical Sensors

Progress in surgery has frequently been preceded by progress in technology. Thus positive clinical results may be anticipated with the emerging use of catheter-tip chemical probes. In these devices, the sensor is based on fluorometric or colorimetric sensing, coupled via a fiberoptic light guide to the external environment, or the potentiometric determination of ionic species via catheter-tip ISFET devices. The stages of development for these devices range from laboratory formulations, with some in vitro testing, to limited clinical experience with production prototype models. Advantages reported for the fiberoptic-based devices include no electrical interference, no reference electrode requirement, potentially low-cost fabrication, O2 tension analysis capability, and the possibility of multi-wave-length determinations to improve stability. Disadvantages of the fiberoptic-based probes include ambient light and temperature sensitivity, long-term instability of some reagents, halocarbon anesthetic sensitivity, slow response time, limited dynamic range, and trade-offs between amount of reagent phase, quenching of probe radiation, and stability. The semiconductor-based devices respond only to ionic species but feature the possibility of determining multiple species in a single-chip, low-cost fabrication, on-chip signal processing, clinically useful frequency response, robust design, and long shelf life. Disadvantages are as follows: long-term instability in situ, requirement for a reference electrode, ambient light and temperature sensitivity, and interference (in some cases) by competing ions, necessitating signal compensation. Both types of probes require treatment to avoid fouling of the probe surface and danger to the patient from thromboembolism. Some approaches to resolution of the outstanding problems are outlined. It appears that, given the current pace of industrial development, several of these probes will become a clinical reality in the near future.

FET Ion-Sensitive Sensors

FET based ion sensors appear promising as monitoring and diagnostic aids in clinical medicine. The principles underlying these miniaturized probes are outlined. The fifteen year development period, since their original description, is related to problems with reliability, biological compatibility, and incorporation of reference electrodes. Possible solutions to these problems are outlined. Some results of in vivo experimental and clinical measurements are reviewed which demonstrate their promise.

Sensitivity Analysis of Errors Induced in the Determination of Tissue Perfusion

One of the important tasks in physiology and medicine is estimating tissue blood perfusion rate and heat generation rate due to metabolism and other sources. This information is required for experimental studies as well as for clinical purposes and has been the subject of numerous ingenious efforts. The difficulties in performing these measurements are mainly due to (1) the complex anatomical structure of the tissue and interwoven blood supply network of vessels of various sizes and (2) the lack of noninvasive techniques that are capable of directly measuring these quantities. As a result, indirect methods have been devised in which the required information is inferred from measurements of related physical and physiological parameters. Due to these difficulties, the time and spatial resolution of the estimated parameters is compromised and one must accept lower accuracy and precision with these methods.