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Biomedical subjects

D C MacGregor

Publications and source records attributed to D C MacGregor.

At least 19 recordsLinked to original sources

The kinetics and quantitation of platelet deposition on control (CPC) and heparin-bonded polyurethane angio-catheter (HBPC) with indium-111 labeled platelets in a dog model.

The dynamics of platelet deposition on CPC and HBPC was evaluated with In-111 labeled platelets (In-PLT) with a computerized gamma camera (CGC). Ten non-heparinized dogs (18-25 kg) were catheterized in both femoral arteries with 10 cm of CPC and HBPC (5 Fr., Cordis, Inc.) 24 hours post-injection of 300-420 microcuries of In-PLT, and imaged for 3 hours with gamma camera. The regional platelet deposition on three segments of catheters and puncture site was determined. The catheters were harvested and radioactivity on the catheter segments (proximal: PROX, middle: MID, distal: DIST and puncture site: PS) of both was determined. From the platelet count in blood, radioactivity in blood and segments of catheters, adjacent artery and area of artery and catheter, the platelet-density [X10(3)] (mean +/- S.D.) on catheter and artery were calculated and tabulated: (table; see text) The large standard deviation of retained platelets is due to embolization. The platelet-density and regional counts on catheter segments were lower in the HBPC than CPC. The rate of platelet-deposition was lower in the HBPC than CPC. Most of the thrombi were lost during pullout of the catheter. Both in vivo (dynamic) and in vitro studies were necessary for evaluation of CPC thrombogenicity.

Animals

The use of silicone/polyurethane graft polymers as a means of eliminating surface cracking of polyurethane prostheses.

The long-term biodegradation of various polyurethanes with and without surface modifications was evaluated by implanting small porous filamentous patches of these materials subcutaneously in the backs of dogs for one month. Data were compared to those obtained with spun polyurethane vascular grafts of similar materials implanted in the aorto-iliac position in dogs. The extremely high surface area of approximately 7 m2/cm3 of these porous filamentous patches provided numerous sites for surface cracking and the very fine filaments (10 microns in diameter) provided an easily identifiable structure to study the cracking phenomenon. Results from numerous one month implants clearly demonstrated that the subcutaneous implant model effectively reproduced the biodegradation behavior observed in vascular graft implants. The degradation was most pronounced in the softer Shore 80A polyurethanes and less pronounced in the harder 55D and 75D polyurethanes. The degradation could not simply be stopped by stress annealing the polyurethane and the degradation did not require the presence of metallic ions. Antioxidants, surface adsorbed albumin, poly(2-hydroxyethyl-methacrylate) grafting, silicone copolymerization, tetrafluoroethylene plasma discharge and the addition of urea linkages to the polymer were also shown to be ineffective in stopping the biodegradation process. In contrast, covalent bonding or grafting of silicone polymer to the surface of the urethane successfully inhibited the biodegradation process.

Animals

Functional mechanisms of polymer-based in vivo reference electrodes.

We describe a reference electrode catheter based upon a haemocompatible porous liquid junction of poly(2-hydroxyethyl methacrylate) (pHEMA). The diffusion properties of pHEMA rapidly reach a steady state in a variety of physiological environments. To elucidate the functional mechanisms, the transport of ions through pHEMA membranes was studied in electrolyte solutions, plasma solutions and whole blood. Plasma was shown to enhance ion transport by approximately 10% whereas blood decreased transport rates by 40%. The stability of the reference electrode catheter remained within 1 mV over an 8 h period. The mechanisms of stability lie in those material properties of pHEMA which control diffusion, limit protein adsorption and respond to changes in pH, properties which may result in micromechanical fluctuations and subsequent renewal of the polymer/blood interface.

Biocompatible Materials

Intramyocardial pH as an index of myocardial metabolism during cardiac surgery.

At present, a practical method for continuous monitoring of the state of tissue metabolism in the individual patient's heart during cardiac operations is not available. We have explored the use of miniature electrode measurements of myocardial interstitial pH to provide this monitoring capability, making comparisons with intracellular pH in left ventricular biopsy specimens and with tissue PCO2 measured by mass spectrometry. The electrode system consisted of a hydrogen ion-sensitive glass miniature electrode, housed in the beveled end of a 21 gauge (0.8 mm diameter) hypodermic needle, and a 2 mm diameter reference electrode, with an internal silver-silver chloride electrode coupled to tissue through a saline bridge (150 mM/L sodium chloride) saturated with silver chloride. Accuracy in blood at 37 degrees C was compared with conventional instrumentation (Radiometer BMS-3 MK-2 Blood Micro System) over a pH range of 7.4 to 6.4 with linear regression analysis (n = 26) revealing a high correlation (r = 0.997) and a mean difference in paired observations of only 0.01 +/- 0.004 (mean +/- SEM) pH units. In two groups of dogs on cardiopulmonary bypass, the pH needle and reference electrodes were inserted into the anterior wall of the left ventricle. Ischemic arrest of the heart at 37 degrees C was used to vary myocardial pH. In Group 1 (n = 8), intracellular pH was estimated from left ventricular biopsy specimens (400 mg each) taken over a microelectrode pH range of 7.37 to 6.37, snap frozen, and homogenized. In Group II (n = 6), tissue PCO2 in the anterior wall of the left ventricle was determined by mass spectrometry (sampling catheter 1.3 mm diameter). Miniaturized electrode (interstitial) pH exceeded biopsy (intracellular) pH under control conditions by 0.28 +/- 0.025 pH units (p less than 0.001), but below an electrode pH of 6.8 the results of the two techniques did not differ significantly. The tissue PCO2 rose from 69 +/- 2 mm Hg to a final plateau of 419 +/- 25 mm Hg, which was similar to the predicted value of 427 +/- 28 mm Hg calculated from the pH change (7.37 +/- 0.01 to 6.01 +/- 0.07), providing a further independent check on the pH electrode technique. These data indicate that our intramyocardial pH measurements do reflect intracellular metabolism during elective arrest of the heart and may have potential for clinical use.

Animals

The porous-surfaced electrode: a new concept in pacemaker lead design.

Three major problems which may be encountered with endocardial pacemaker electrodes are a lack of stable position, a chronic increase in stimulation threshold, and a diminishing magnitude of the sensed endocardial signal. These problems are particularly manifest in the atrium. Having previously shown that porous metal surfaces can support stable tissue ingrowth in both bloodstream and soft tissue environments, we set out todetermine the performance of porous-surfaced endocardial pacing electrodes in the atrial position. In two groups of six dogs each, J-shaped atrial leads with Elgiloy electrode tips (2.3 mm. in diameter, 2.3 mm. in length), having either conventional smooth surfaces (control) or porous surfaces (20 to 50 micron particle size) produced by powder metallurgy techniques, were positioned in the right atrial a-pendage. Stimulation thresholds and P-wave amplitude were repeatedly measured until the dogs were put to death 30 w-eks following implantation. The presence or absence of electrode fixation was observed and the atrial tissue reaction was examined grossly and by both light and scanning electron microscopy (SEM). The porous-surfaced electrodes demonstrated superior long-term stimulation thresholds which, at 30 weeks, averaged less then one third of those in the control group. In addition, the porous group showed a small but significant improvement in the amplitude of the sensed P wave. None of the smooth-surfaced electrodes showed fixation, and the tissue reaction consisted of a thick layer of granulation and fibrous tissue on the underlying endocardium, widely separating the electrode from the myocardium. In contrast, all of the porous-surfaced electrodes were fexed to the endocardium by fibrous tissue ingrowth into the surface pores. This tissue fixation of the electrode tip in close proximity to underlying myocytes explains their superior performance.

Animals

Left ventricular receptors inhibit brain serotonin neurons during coronary artery occlusion.

Acute coronary artery ligation in pargyline-treated rats decreased serotonin and increased 5-hydroxyindoleacetic acid in the medulla and posterior hypothalamus. Lidocaine applied topically to the left ventricle completely prevented these alterations. No changes in serotonin were observed in the other brain regions examined. These data suggest a reflex inhibition of bulbar and hypothalamic serotonergic nerves by left ventricular receptors following acute coronary artery occlusion in the rat.

Animals

Computer-assisted reporting system for the follow-up of patients with prosthetic heart valves.

The implantation of large numbers of prosthetic heart valves carries with it the responsibility for continual reassessment of all aspects of patient management. Experience with more than 2,000 prosthetic valve operations since 1963 led to the development of a comprehensive computer-assisted data collection, management and reporting system. Over a 5 year period, data forms were developed for the detailed documentation of preoperative, intraoperative and postoperative information. These were designed in the form of checklists suitable for direct computer entry with use of mark-sense document readers. Special emphasis was placed on preoperative assessment of ventricular function, valve selection, intraoperative myocardial preservation, postoperative rehabilitation and prosthetic valve-related complications. This system makes possible rapid computer generation of a variety of reports to the referring physician regarding the individual patient and to the clinical investigator in relation to patient group statistics. Also, questionnaires to patients of physicians, or both, to update patient data can be produced by the computer at appropriate intervals after valve surgery. Experience indicated that a computer-assisted methodology is the only practical way to provide adequate follow-up of large groups of patients. Additionally direct access to relevant information helps to create an environment in which essential research can be carried out in the face of a demanding clinical practice.

Follow-Up Studies

Self-conversion of supraventricular tachycardia by rapid atrial pacing.

The use of pacemakers in the treatment of tachycardias is one of the most exciting and rapidly expanding applications of cardiac pacing. One of the more recent developments in this field has been the use of patient-activated radio frequency transmitted rapid atrial stimulation (RAS) in the treatment of paroxysmal supraventricular tachycardia (PSVT). Based on the previously established ability of asynchronous atrial pacing to interrupt a variety of re-entrant supraventricular rhythm disturbances, this modality of treatment is gaining increasing applicability in patients with PSVT associated with debilitating symptoms or other severe cardiovascular consequences in whom standard pharmacological regimens have either failed or are impossible to maintain for indefinite periods. This report describes our experience with five patients who underwent implantation of RAS units. The detailed electrophysiological studies required to ensure success and avoid any possible future complications are described. Over a follow-up period of four months to four years (mean 16 months) very few problems arose in the use of these units which have immeasurably improved the quality of life of the recipients. Our experience with RAS units has led to a few suggestions for future improvement and these are outlined in this report. The excellent patient acceptance and the reliability of this technique in terminating episodes of PSVT should, in the future, render RAS the treatment of choice in certain selected patients suffering from this common disorder.

Adult

Permanent transvenous atrial pacing.

Atrial pacing has electrophysiologic and hemodynamic advantages for patients with symptomatic bradyarrhythmias and intact atrioventricular conduction or with certain refractory tachyarrhythmias. Permanent atrial pacing has been achieved in 29 patients followed up for periods of up to 7 years at two institutions. At Sunnybrook Medical Centre, Toronto, 16 patients have had coronary sinus electrodes introduced pervenously using standard bipolar or special unipolar catheters. Initial pacing thresholds were acceptably low (mean, 2.0 mA); chronic thresholds in three patients were similar. At the Toronto General Hospital, 13 patients had endocardial J-electrodes, bipolar or tined unipolar, inserted in the right atrial appendage. Initial thresholds were low (mean, 1.3 mA) and P-wave voltage was adequate (3.4 mV) for pacemakers with standard sensitivity. In both series, conventional R-inhibited, asynchronous or rate-programmable units have been employed. Radiofrequency self-conversion pacemakers were used in three patients. Preliminary His bundle studies were done in 10 patients; the others were tested by rapid atrial pacing during insertion of electrodes. Early and late electrode stability in both series was excellent; one electrode became dislodged from the coronary sinus position and one from the right atrial appendage.

Adult

Aortocoronary bypass graft in dogs: late histological changes.

Late histological changes occurring in aortocoronary bypass vein grafts were studied by lignt and electron microscopy in three dogs killed one, two and three years after grafting. The changes consisted of intimal thickening due to a proliferation of modified smooth muscle cells (myointimal hyperplasia) and replacement of most of the medial smooth muscle by fibrocytes. Serial angiography in the dogs did not reveal progression of the intimal thickening after one month.

Animals

Cardiorespiratory failure secondary to peripheral pulmonary emboli. Survival following a combination of prolonged extracorporeal membrane oxygenator support and pulmonary embolectomy.

A 19-year-old woman developed cardiorespiratory failure from multiple, peripheral pulmonary emboli apparently developing over the preceding 3 weeks. She was not considered to be an operative candidate. However, when 3 days of intravenous heparin infusion and 30 hours of membrane oxygenator support failed to improve the pulmonary pathology, pulmonary embolectomy was performed. The membrane oxygenator support had to be continued for 34 hours following the operation before it was successfully discontinued. The patient made a complete recovery.

Adult

Ischemic contracture of the left ventricle. Production and prevention.

Ischemic contracture of the left ventricle ("stone heart") is a recognized complication of prolonged periods of interruption of the coronary circulation during open-heart surgery. We have examined the effects of moderate hypothermia (28 degrees C.) and preoperative beta-adrenergic blockade (propranolol, 0.5 mg. per kilogram; 1.0 mg. per kilogram) on contracture development during ischemic arrest of the heart. Four groups of 8 dogs each were placed on total cardiopulmonary bypass, and ischemic arrest of the heart was produced by cross-clamping the ascending aorta and venting the left ventricle. Intramyocardial carbon dioxide tension was continuously monitored by mass spectrometry. When anaerobic energy production ceased, as indicated by a final plateau in the intramyocardial carbon dioxide accumulation curve, the ischemic arrest was terminated and the contractile state of the heart observed. These results are given in the text. We conclude that beta-adrenergic blockade delays, but does not prevent, the onset of ischemic contracture of the left ventricle under normothermic conditions. Moderate hypothermia appears to prevent this complication completely.

Animals