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An important need in hemodialysis is a self-sealing prosthesis for vascular access with at least equivalent patency and biostability to expanded polytetrafluoroethylene (ePTFE) alternatives. The authors have developed a Corethane/polyester composite (CPC) graft with an inner blood interfacing layer of spun Corethane fibers (10-15 microns diameter; pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp-knitted polyester sheath. Twenty-six CPC grafts (6 mm internal diameter; 25-30 cm length) and eight Gore-Tex ePTFE grafts (same dimensions) were implanted as femoral artery-to-vein shunts in dogs on low dose (162 mg/day) aspirin, and subjected to weekly dialysis needle punctures for up to 52 weeks. Patency was 73% (19/26 with 15 at 52 weeks) for the CPC grafts and 63% (5/8 at 52 weeks) for the ePTFE controls, with more favorable healing (e.g., less extensive mural thrombi) of the CPC grafts. The hemostasis time per needle pair after removal (3.1 min mean for CPC versus 21.2 min mean for ePTFE) and the blood loss in achieving hemostasis (5.7 g mean for CPC versus 47.9 g for ePTFE) documented the significant (p0.0001) performance advantages of the CPC prosthesis.

We have developed a composite vascular prosthesis with the inner blood interfacing layer made of a porous elastomeric membrane of spun Corethane fibers (10-15 microns in diameter, pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp knitted Dacron sheath. Forty-eight Corethane/Dacron composite (CDC) vascular grafts, 4 mm in diameter and 5 cm in length, and 48 expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar size were implanted bilaterally as end to end interposition grafts on opposite sides in the carotid and femoral arteries in dogs on low dose (162 mg/day) aspirin. Patency at 3 months was 37/48 (77%) for the ePTFE grafts and 44/48 (91.7%) for the CDC grafts. Fisher's exact test (two-tailed comparison) indicates the probability of superior CDC graft patency to be 95.5%. In the seven pairs of grafts in which one graft was occluded and the contralateral graft of another type was patent, the CDC graft was patent and the ePTFE graft was occluded in every instance. Explant histology and scanning electron microscopy showed greater collagenization, less residual platelet-fibrin and red blood cell deposits, and more frequent mid-graft endothelialization in the CDC grafts than in the ePTFE grafts.

Polyurethane vascular prostheses offer the potential of superior thromboresistance and reduced anastomotic hyperplasia compared to existing Dacron and ePTFE alternatives, but have suffered from susceptibility to biodegradation, with resulting mechanical failure. To address this problem, the authors have developed and evaluated a composite prosthesis comprised of: 1) an inner blood interfacing elastomeric porous membrane made from Corethane, a proprietary Shore 80A polyurethane like material substantially devoid of ether/ester linkages, with superior biostability over conventional polyether urethanes, spun into a nonwoven structure with fiber diameters 10-15 microns and pore sizes 30-60 microns filled with gelatin +/- heparin; and 2) an outer soft, tissue interfacing, warp knitted Dacron mesh bonded to the inner layer to assure long-term dimensional stability. Twenty 4 mm ID x 5 cm L composite prostheses, half with heparinized gelatin (the remainder nonheparinized) were implanted as femoral interposition grafts in 10 dogs. Four of the 10 nonheparinized grafts occluded. All 10 with heparin remained widely patent, with two explanted at 6 months showing vascularized connective tissue growth through the graft, in contrast to the giant cell inflammatory response to the Dacron mesh, with a substantially endothelialized neointima and no Corethane biodegradation. Of the 10 patent grafts at 1 year follow-up, none showed aneurysm formation. This vascular prosthesis provides compliance superior to ePTFE and Dacron alternatives, with excellent suture retention and good kink resistance, while combining the superior thromboresistance and tissue ingrowth properties of polyurethanes with the proven biostability of Dacron.

The dynamics of platelet deposition and embolization from control and heparin bonded polyurethane catheters (CPC and HBPC) was evaluated with In-111 labeled autologous platelets (IN-PLT) and 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) 24 hr after injection of 300-420 microCi of In-PLT, and imaged for 3 hr with the computerized gamma camera. The regional platelet deposition curves (RPDC) indicated multiple peaks and valleys; the curves were analyzed for early rate of thrombus formation (upswing), thrombus retention time (full width at half maxima of the RPDC-peak), and rate of embolization (downswing) on both catheters. The four parameters (mean +/- SD) of thrombosis on catheters and integral of the radioactivity time curve for the 3 hr duration of imaging were calculated from normalized counts/sec. The rate of thrombus formation and rate of embolization are higher for the control than HBPC, suggesting that heparin-bonding decreases the early rate of thrombosis and embolization. The thrombus adhesivity and retention time appear shorter for the control catheter, indicating that the control thrombogenic catheter forms multiple thrombi and emboli than HBPC. The integral appears larger for the control catheter than HBPC. In vivo (dynamic) studies, in vitro studies, and critical analyses of the radioactivity time curve were essential for complete evaluation of thrombogenicity of catheters and other cardiovascular prostheses.

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.

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.

A hydrogel basedin vivo reference electrode catheter has been developed. A simple diffusion model of ion transport was applied to study chloride ion transport through polyhydroxyethylmethacrylate (pHEMA) membranes. Based on an experimentally derived effective diffusion coefficient of Deff=4·04±0·5×10−8 cm2s−1, a reference electrode catheter was fabricated featuring a dimensionally appropriate pHEMA porous liquid junction, a gelled Ringer's solution internal electrolyte compartment and a Ag/AgCl internal half cell. The reference electrode potential is not a function of pH from pH6 to pH9 and is linearly related to temperature by 0·33 m VoC−1. In animal trials, the intravascular catheter electrodes exhibit an average stability of ±0·92mV for 6–8h. Stability in blood can be attributed to the haemocompatibility and transport properties of pHEMA.

In the brief for the Province of Nova Scotia, presented to the provincial Royal Commission inquiring into Nova Scotia's disabilities under the Canadian federal system, Professor Rogers includes an estimate of the regional incidence of the customs duties. This is the first study of its kind to be made in Canada. It may be expected to give rise to a good deal of controversy on account of the complexity of the problem and because other provinces are already beginning to make parallel estimates which do not altogether agree with those made for Nova Scotia. Professor Rogers's discussion of the burden of the tariff was condensed into a single chapter, owing to the large amount of general historical and argumentative material which it was necessary to include. It is therefore desirable to quote from the unpublished minutes of evidence in order to do full justice to the reservations which Professor Regers made in putting forward his estimates. In Halifax on August 13, 1934, he said: It is desirable to emphasize again that this table representing the provincial distribution of tariff subsidies and tariff costs is chiefly valuable as an indication of a condition. It is not an exact statement of the effects of the tariff upon the incomes of the several provinces of the Dominion. It does not indicate the tendency of the tariff to contract the income of the export industries by reason of the increase in costs of such industries. It does illustrate, however, the effect of the tariff upon the internal distribution of the national income…. Personally I would hardly suggest that this is more than an approach to a method of measuring the provincial incidence of the tariff. But I do feel convinced that the results which attend a computation of this kind bring out a condition which really exists, and that the final result in respect to the provincial incidence of the tariff is probably an under-statement rather than an over-statement. I do feel that we have reached a point where we are compelled to try to express the effects of the tariff in more complete terms.

Normothermic and hypothermic (24 C) dogs were given ethanol intravenously and the rates of accumulation and disappearance of ethanol from arterial blood were studied, with the following results: 1) The rate of decrease of ethanol concentration in the arterial blood in normo- and hypothermic dogs was similar. 2) Extrapolation of concentration vs. time curves after equilibration showed reduction in apparent total available body-water space in hypothermic dogs. 3) Equilibration took twice as long in hypothermic as in normothermic dogs. 4) A fourfold increase of tidal volume did not affect the disappearance of ethanol in a normothermic dog. 5) The disappearance rate of ethanol in hypothermic dogs was decreased by hexamethonium or a small dose of epinephrine, but normalized by a pressor dose of epinephrine. It is suggested that the effects of hypothermia on hepatic blood flow and on alcohol dehydrogenase activity tend to cancel each other out. Modification of the rate of alcohol disappearance by hexamethonium and by epinephrine probably results from changes in hepatic circulation.

About eighteen months ago I had begun to fear that Canada might come out of the war with too low rather than too high a price level. I felt that if production and employment averaged little or no higher after the war than before it, and if prices were no higher than in 1944, the national money income would sink to the point where federal revenues would develop an enormous chronic deficit of, say, 30 to 50 per cent of current expenditures. Such might be the outcome, no matter how high the rates of taxation employed. Ultimately deficits of so great a size would lead to an expansion of bank credit and hence to a higher price level, but in the meantime the country would experience a demoralizing series of political and financial crises resembling those in France between 1920 and 1927. In the design of high policy I felt that care should be taken to avoid such an outcome, which would leave our political system and our social structure greatly weakened.

The Report of the Alberta Bondholders' Committee contains the most detailed application of Canadian national income figures yet published for purposes of argument. Owing to the difficulty of breaking down national figures for provincial purposes, and the important effect of small errors in the total income upon the residual “margin of income”, the corrections presented below are of interest. Certain deductions from Alberta's income are made to avoid double counting (table I) while the value of “necessary expenses” is estimated with more care (table II).A detailed explanation and justification of the revised estimates of income in table I is given below in section B, and of table II within the table, and in section C. It is only fair to add that there is more room for difference of opinion in the interpretation of necessary expenses than in correcting estimates of income. More than statistical technique is involved, as there must also be some value judgments.

The slowness of the industrial recovery is gradually disclosing unmanageable situations in public finance. From the standpoint of public debt, countries engaged in the export of staples fall into three classes: (1) those where widespread default occurred in 1931 or 1932 on both public and private debt and where little or no resumption of debt service has occurred, such as most of the South American republics; (2) those where a critical position appeared early in the depression, followed by collective adjustment of internal debts and measures designed to maintain the level of prices, such as Australia and New Zealand; and (3) those where little or no public default or manipulation of debts, foreign exchange, or price levels has hitherto occurred, such as the Union of South Africa and Canada. Newfoundland occupies a curious position, more like that of European countries, having undergone a political as well as a financial reorganization. The Argentine occupies a position intermediate between groups (1) and (2).

This study aims to measure the net investment or savings of individuals and enterprises in Canada. Two methods are available, the inventory or change of stocks method and the production or flow of goods method. The first compares the capital value of all durable goods at the beginning and end of the period in question, at constant prices, the difference being net saving or dissaving (inventories excepted). The sources for this approach consist of balance sheets and other data of the type used in making an estimate of national wealth. The second, the production or flow of goods method, utilizes records of retail sales of durable goods and, where sales data do not exist, figures of production, imports and exports, etc. From these sources the selling value of all durable goods sold or available to be sold, i.e. gross investment, is estimated. From gross investment is subtracted an estimate of the value of durable goods required to maintain existing capital intact. The remainder, which we shall call net investment or net saving (the additional adjective aggregate being taken for granted in both cases), represents the value of the net addition to the stock of durable goods.To the layman, net investment appears remote from net saving. It can be demonstrated, however, that it does not differ significantly from saving, at any rate for statistical purposes. By saving is meant excess of current income over current outgo. Current outgo is taken to include appropriate charges for depreciation but excludes repayment of debts. Saving or non-current outgo is defined to include many consumers' expenditures for capital goods, as indicated in Table I.

The Legislature of Alberta has distinguished itself by enacting the most drastic reform measures ever seen in Canada. Supported by a very large body of public opinion, it has reduced debts, both public and private, has attempted to take several matters out of the hands of the Courts, and has, so far as legal enactment could do so, substituted the people’s own credit—Social Credit—for the financial credit which has hitherto been relied on. It is thought that this substitution is possible and might be complete. Whether or not this belief is sound, time only can tell. The present, however, offers a good opportunity to survey the situation in the light of the circumstances of the province and the general characteristics of its people.

The surgical technique of cardiopulmonary bypass with either an empty beating or an empty fibrillating ventricle produces marked changes in the regional blood flow and oxygen demand of the left ventricle. This paper describes the changes which occurred in the regional perfusion of both the normal and the hypertrophied left ventricle during these conditions and relates them to the known changes in oxygen demand. It also correlates the changes in flow with the measurable changes in myocardial tissue pressure-systolic when the heart is beating and continuous when fibrillating. The various types of filbrillation had identical effects on both regional tissue pressure and regional flow. The subendocardial blood supply was adequate or more than adequate under each of these conditions so long as the coronary perfusion pressure was maintained at an adequate level. A low perfusion pressure during ventricular fibrillation of any type led to a marked reduction in flow to the subendocardial portion of the left ventricle: The presence of ventricular hypertrophy accentuated this danger.

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.

The dynamics of platelet deposition on control polyurethane catheters (CPC) and heparin-bonded polyurethane catheters (HBPC) were evaluated with In-111 labeled platelets (In-PLT) using a computerized gamma camera (CGC). Ten nonheparinized dogs (18-25 kg) had both femoral arteries catherized with 10 cm of CPC and HBPC (5 Fr.) 24 hr postinjection of 300-420 microcuries of In-PLT, and imaged for 3 hr with a gamma camera. Regional platelet deposition on three segments of catheters and the puncture site was determined. 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, and 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 was calculated and tabulated. Proximal values were cath (CPC), 1289 +/- 1125; artery, 1355 +/- 587; cath (HBPC), 125 +/- 113; artery, 1149 +/- 1620. The middle values were cath (CPC), 1102 +/- 1109; artery, 1512 +/- 625; cath (HBPC), 132 +/- 108; artery, 1011 +/- 942. Distal values were cath (CPC), 780 +/- 584; artery, 132 +/- 108; cath (HBPC), 227 +/- 194; artery, 1457 +/- 1309. The puncture site values were cath (CPC), 106 +/- 382; artery, 1011 +/- 942; cath (HBPC), 164 +/- 135; artery, 1498 +/- 1240. The large standard deviation in retained platelets is due to embolization. The platelet-density and regional counts on catheter segments were lower with HBPC than CPC, as was the rate of platelet-deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

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.

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.

A mathematical model and conceptualization of membrane ion transport by diffusion and phase transfer as coupled to adsorbed protein associated ion specific adsorption has been developed. The model is verified by monitoring K+ transport through poly-(2-hydroxyethyl methacrylate) membranes in the presence of plasma in concentrations of 20, 50, 80 and 100% by volume. The transport data can be adequately described by the model where the surface oriented K+ is assumed to be constant and related to bulk protein content. Control studies provide a baseline value for an effective diffusion coefficient for K+, Deff, of 2.82 x 10−8 cm2/sec. The addition of plasma to the transport study solutions shows an increase in the transport of K+ such that the rate is exponentially related to plasma percent. Since the dimension of the albumin molecule is appropriate to reside in the surface convection layer (100 A) and albumin itself is the majority protein in plasma, values of known albumin bulk concentrations and published surface concentrations are useful for extended analysis. The surface concentration of K+ at 100% plasma is 12.9 nEq/cm2 and the ratio of ion to protein is 4.3 Eq K+/mM albumin. These results provide insight into the role of protein adsorption to biomaterials as they relate to ion transport. The transport chamber approach is ideally suited to modification of the biomaterial interfacial microenvironment where, as in this study, the effects of plasma protein interactions are separated from cellular interactions. In medical devices, this phenomenon is important in the design of electrochemical blood chemistry sensors and artificial kidney membranes.

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.

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.

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.

Three series of 10 dogs each were used to study the effects of intravenously administered ethanol, propanol-1, and butanol-1. In normothermic dogs, with supported respiration and nitrous oxide anaesthesia (after induction), the mean lethal doses for ethanol, propanol-1, and butanol-1 were 4.90, 2.42, and 1.26 g/kg respectively. At a constant infusion rate, the blood alcohol levels increased almost linearly with time. Relationships between ethanol, propanol-1, and butanol-1 blood levels and blood pressure, pulse, and electrocardiogram were established. Two minutes cardiac standstill occurred at the following blood levels: ethanol, 1499 mg/100 ml; propanol-1, 713 mg/100 ml; butanol-1, 279 mg/100 ml.