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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↗

Multidose blood versus crystalloid cardioplegia. Comparison by quantitative assessment of irreversible myocardial injury.

The relative efficacy and safety of blood-based potassium cardioplegic solutions compared to crystalloid arresting solutions has been a major controversy in the field of intraoperative myocardial protection for cardiac operations. In this study multidose potassium (K+ = 30 mEq/L) blood cardioplegia was compared to multidose potassium crystalloid cardioplegia in a dog model in which hearts were arrested for periods of 4 1/2 and 6 hours. The cardioplegic solution was given as an initial bolus of 500 ml and then as 250 ml doses every 30 minutes of arrest. In the 4 1/2 hour arrest group, six animals received blood cardioplegia, six received a low-sodium crystalloid cardioplegia (modified Roe's solution), and 10 received a high sodium crystalloid cardioplegic solution of our own design. In the 6 hour arrest group, four animals received blood cardioplegia, four received the low-sodium solution, and four received the high-sodium solution. Myocardial temperature was precisely controlled at 27 degrees +/- 1 degree C in all groups. The hearts were reperfused for periods of 2 to 4 hours after the arrest periods and then examined morphologically for injury. The extent of myocardial damage was quantified in 5 mm thick transverse sections through the ventricles by using a tetrazolium enzyme-mapping technique. In the crystalloid groups the hearts arrested for 4 1/2 hours were significantly injured. The percentage (+/- SEM) of necrosis was 12.3 % +/- 5.6% in the low-sodium cardioplegic (modified Roe's) group and 9.3% +/- 3.4% in the high-sodium group. In the 6 hour arrest group the hearts were severely injured, with contracture occurring in all cases. The percentage of necrosis was 56.5% +/- 13% in the low-sodium cardioplegic group and 71.3% +/- 12% in the high-sodium group. In striking contrast all hearts protected with blood cardioplegia failed to show any evidence of tissue damage either on tetrazolium staining or on electron microscopic examination. We conclude that blood cardioplegia offers superior protection to the arrested heart at moderate hypothermia compared to crystalloid cardioplegia.

Animals↗

A novel process for the manufacturing of porous grafts: process description and product evaluation.

A novel process has been developed for the manufacture of porous vascular grafts from solutions or melts of polymers. It allows the manufacture of grafts with controllable porosity, pore size, and mechanical properties. In this process, the polymer melt or polymer solution is extruded through fine orifices; the fibers are then stretched and wound on a rotating mandril. Fiber-fiber bonding takes place, resulting in the formation of stable porous tubes. The effects of the process variables on the physical properties of the resulting graft have been studied and preliminary in vivo evaluation in dogs has demonstrated graft patency with a thin, stable neointima in both small (4 mm) and large (10 mm) caliber configurations.

Animals↗

Effect of pore size on the peel strength of attachment of fibrous tissue to porous-surfaced implants.

Twenty-four rectangular metal plates were fabricated with surface regions in three different pore size ranges (5-20 microns, 20-50 microns, 50-200 microns). The plates were implanted into the dorsal subcutaneous tissue of 12 adult mongrel dogs for periods of 4, 8, 12, and 16 weeks. After animal sacrifice, the fibrous tissue which adhered to the porous-surfaced regions of each plate was mechanically peeled off to give an indication of the strength of tissue attachment. The tissue was examined by both transmitted light and scanning electron microscopy. At each time period, the tissue that contacted the porous regions was found to be collagenized fibroconnective tissue. The mechanical tests indicated an increasing strength of tissue attachment with increasing implantation time and pore size range. The largest pore size range of approximately 50-200 microns produced a mean peel strength of attachment of 27.5 g/mm at the 16-week period.

Animals↗

Myocardial pH during regional ischemia: evaluation of a fiber-optic photometric probe.

The relationship between the decrease in intramyocardial extracellular pH and the degree of stenosis of the left anterior descending (LAD) coronary artery was studied in eight dogs pretreated with propranolol. Intramyocardial pH was measured with a miniature glass pH electrode and with a new photometric pH probe that uses fiber-optic filaments to measure the color change of an indicator substance in a small permeable chamber. The LAD was cannulated and perfused from the axillary artery. Cannula flow was measured with an electromagnetic flow probe, and regional myocardial blood flow (RMBF) was measured with radioactive microspheres before and at the end of a period of critical stenosis, 2/3 reduction of flow, or total occlusion of the LAD cannula. In the region of the glass electrode, the mean RMBF (+/-SE) decreased by 16.3 +/- 3.3, 52.7 +/- 7.3, and 84.8 +/- 6.5% during the three levels of stenosis, and the pH correspondingly decreased by 0.05 +/- 0.01, 0.29 +/- 0.10, and 0.94 +/- 0.17 units. In the region of the photometric probe, the RMBF decreased 19.1 +/- 1.3, 47.2 +/- 6.7, and 84.3 +/- 6.0%, and the pH decreased by 0.05 +/- 0.02, 0.14 +/- 0.04, and 0.76 +/- 0.18 units. There was no statistically significant difference between the two types of pH sensor.

Animals↗

Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis.

Multidose administration of cardioplegic solution during cardiac operation is intended to maintain both electromechanical arrest of the heart and myocardial hypothermia as well as to remove accumulated metabolites of anaerobic glycolysis. This study was conducted to assess the effect of multidose infusion of three different types of cardioplegic solution on tissue acidosis during global myocardial ischemia. Three groups of five dogs each were placed on cardiopulmonary bypass and the aorta was cross-clamped for 3 hours. The hearts were maintained at a constant temperature (20 degrees C) and cardioplegic solution was infused at an initial dose of 500 ml and five supplementary doses of 250 ml administered every 30 minutes. Group 1 received a crystalloid solution weakly buffered with sodium bicarbonate, Group 2 received a blood-based solution, and Group 3 received a crystalloid solution strongly buffered with histidine (Bretschneider's solution). The buffering capacities of the solutions used in Groups 2 and 3 were 40 and 60 times, respectively, that of the solution used in Group 1. The average myocardial tissue pH at the end of 3 hours of ischemia was 6.54 +/- 0.07 in Group 1, 7.23 +/- 0.05 in Group 2, and 7.19 +/- 0.06 in Group 3 (Group 1 significantly lower than Groups 2 and 3). Multidose infusion of a cardioplegic solution with low buffering capacity was unable to prevent the progressive development of tissue acidosis during 3 hours of ischemia. However, the multidose infusion of either blood-based or crystalloid solutions with high buffering capacity completely prevented any further reduction of tissue pH after the first 30 minutes of ischemia.

Acidosis↗

Regional and transmural myocardial temperature distribution in cold chemical cardioplegia: significance of critical coronary arterial stenosis.

There is a growing recognition of discrepancies in myocardial temperatures during cold chemical cardioplegia. This study was designed to determine the extent to which coronary arterial stenosis just sufficient to abolish vasodilatory reserve in the working heart, but still compatible with myocardial viability ("critical stenosis"), limits heat transfer from the heart during cardioplegic infusion compared to complete coronary occlusion and no stenosis (control). In nine dogs, temperatures were measured from the subepicardium, midwall, and subendocardium of the left ventricle in the distributions of the circumflex (CCA) and left anterior descending (LAD) coronary arteries plus the aortic root, septum, mediastinum, and ventricular cavities. Cardiopulmonary bypass was instituted with core cooling to 28 degrees C. Three infusions of cold (4 degrees C), radioactive microsphere-labeled, potassium chloride arresting solution were periods of reperfusion. The data (mean +/- SEM) indicate that myocardial cooling was transmurally uniform under all conditions, but was significantly impaired (p less than 0.01) in the CCA region by both critical stenosis (17.4 degrees +/- 1.2 degrees C) and occlusion (23.6 degrees +/- 0.4 degrees C) compared to control (8.3 degrees +/- 0.5 degrees C), because of reduced perfusate flow to regional tissues (4 = 0.62, p less than 0.001). These findings show that coronary artery lesions, including those compatible with myocardial viability, impose a severe constraint on myocardial heat transfer and point to a need for improved cardioplegic technique.

Animals↗

Intramyocardial pH during elective arrest of the heart: relative effects of hypothermia versus potassium cardioplegia on anaerobic metabolism.

Using an intramyocardial pH needle probe (21 gauge) to monitor myocardial metabolism during ischemia, we determined the effect of potassium cardioplegia at both moderate and deep hypothermia. Five groups of 5 dogs each were placed on cardiopulmonary bypass and the pH probe was inserted approximately 10 mm into the left ventricular free wall. Cardiac ischemia was achieved by cross-clamping the ascending aorta at 37 degrees C (Group 1), 27 degrees C (Group 2), or 17 degrees C (Group 3). In the remaining two groups, aortic cross-clamping was followed by the infusion of 600 to 800 ml of potassium cardioplegic solution adjusted to cardiac temperatures of 27 degrees C (Group 4) or 17 degrees C (Group 5). In each group, myocardial temperature was maintained constant, electrical and mechanical activity observed, and pH recorded until a plateau was reached or for 3 hours. Our results show a progressive and significant decrease in the metabolic rate with reduction in temperature over the 37 degrees to 17 degrees C range. By abolishing contractile activity, potassium cardioplegia markedly reduces the rate of hydrogen ion accumulation at 27 degrees C, but at 17 degrees C the additive effect of cardioplegia is much less pronounced. These observations support the principle of reducing contractile activity to a minimum during elective arrest of the heart but indicate that potassium cardioplegia does little to further reduce the rate of anaerobic metabolism, as shown by the measurement of intramyocardial pH, under conditions of deep hypothermia.

Animals↗

Computer-assisted reporting system for the follow-up patients with cardiac pacemakers.

The implantation of large numbers of permanent cardiac pacemakers carries with it the responsibility for continual reassessment of all aspects of patient management. Experience with more than 4,000 pacemaker implants and replacements since 1963 has led to the development of a comprehensive computer-assisted data collection, management, and reporting system for the follow-up of patients with cardiac pacemakers. Over a seven-year period, data forms have been developed for the detailed documentation of pre-operative, intraoperative and follow-up information. These were designed in the form of checklists suitable for direct computer entry using mark-sense document readers. Special emphasis has been placed on pre-operative indications, selection of appropriate pacing systems, reliable follow-up methodology, and monitoring the performance of various pulse-generators. This system makes possible the rapid computer production of hospital records and reports to involved physicians and can be used to schedule follow-up assessments as required. The information also can be used for hospital statistics, billing, research, and pacemaker registration at the provincial, state of federal level. Experience has shown that a computer-assisted methodology is the only practical means of providing adequate follow-up for a large group of patients. In addition, direct access to relevant information helps to create an environment in which essential research can be carried out in the face of demanding clinical practice.

Computers↗

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↗