George Biro - Academia.edu (original) (raw)

Papers by George Biro

Blood Substitutes and Oxygen Biotherapeutics

Postgraduate medical journal, 1972

Advances in Experimental Medicine and Biology, 1989

The size of the hypoperfused zone (area at risk) produced by occluding any given coronary artery ... more The size of the hypoperfused zone (area at risk) produced by occluding any given coronary artery shows considerable variation among untreated animals (1). Since the amount of myocardium that will infarct is, to a large extent, dependant upon the size of the area at risk (AAR) (1–3), infarct sizes also show considerable variation. Therefore, it has become conventional to express infarct size as a percentage of the AAR in order to standardize this variable.

Advances in Experimental Medicine and Biology, 1996

The role of amino groups in hemoglobin function and the effects of chemical modification of these... more The role of amino groups in hemoglobin function and the effects of chemical modification of these on the function of the protein have recently been reviewed (1). Amino groups are contributed by either the N-terminal residues of the globin chains or the lysine residues of the polypeptides. Depending on the reagents used and the conditions chosen, a variable degree of specificity towards amino groups can be achieved. Such studies can be of value in determining the role of individual functional groups in biological function and may be of use in the preparation of derivatives that have modified functional properties desirable in material to be used in a hemoglobin based oxygen carrier. We have recently developed a new method for hemoglobin amino group modification which has a much greater rate of reaction with a amino groups than with the 8 amino groups of lysines at physiological pH (2). This method utilizes the activation of exogenous carboxyl containing compounds with water soluble carbodiimides and subsequent reaction with the amino groups of proteins such as hemoglobin. We report here the effects on oxygen binding observed as a function of the extent and conditions of hemoglobin modification with citrate used as the exogenous carboxyl containing compound.

WORLD SCIENTIFIC eBooks, 2022

Angiology, Dec 1, 1990

The effects of low-dose (10-9 and 3x10-9 mole/kg/min) infusions of dopexamine HCl, a new syntheti... more The effects of low-dose (10-9 and 3x10-9 mole/kg/min) infusions of dopexamine HCl, a new synthetic catecholamine with β2-adrenergic and DA 1-dopaminergic agonostic actions, was tested in anesthetized dogs, with and without acute ligation of the left anterior descending coronary artery. The infusions caused diastolic arterial blood pressure to fall by 12±4 and 23±5 mmHg, respectively. Microsphere-estimated collateral blood flow to the ischemic myocardium did not change significantly during the drug infusions. The findings suggest that low doses of dopexamine HCl do not cause coronary "steal" from acutely ischemic myo cardium.

Canadian Medical Association Journal, Jun 1, 1997

Objective: To determine the nature and quality of the physiologic evidence regarding an "optimum"... more Objective: To determine the nature and quality of the physiologic evidence regarding an "optimum" hemoglobin concentration in anemic patients or in patients with specific diseases. Literature search and selection: Searches of MEDLINE from January 1966 to December 1996 were combined with manual searches of the bibliographies and references from experts. Citations were chosen by 2 reviewers if they were related to red blood cell transfusion practice and, more specifically, to physiologic adaptation to anemia. Disagreement was resolved through consensus. Literature synthesis: The articles selected from the literature search were classified by study design and topic areas. Evidence-based inferences were derived from the literature. Results: Of the 160 articles included in this review, 58 (36%) were human studies and 102 (64%) were laboratory studies. Most studies (84) fell into the "hemodilution" category, and were predominantly in animal models (70). Overall, 90 studies (56%) used a valid design with appropriate experimental and concurrent control groups (graded as level I or II). The distribution of grading was uniform throughout the categories. The quality of the evidence was deemed weaker for laboratory studies evaluating cardiac adaptation to anemia, largely because of a lack of reported concurrent controls in most studies. Inferences drawn from the literature were graded on a 4-point scale assessing the quality of the evidence; 13 of 18 statements were given the highest grade. The clinical significance of the Bohr effect and the shifts in the oxyhemoglobin curve following changes in pH were thought to be poorly studied and were rated lowest. The studies evaluating maximum oxygen delivery in anemia were rated as weak, partly because of conflicting reports. Of all identified studies, 56% were well designed and reported. Important adaptive responses to anemia consist of an elevation of cardiac output and its redistribution to favour the coronary and cerebral circulations at the expense of the splanchnic vascular beds; studies supporting these statements were rated highly. The evidence also suggests that patients with cardiac disease are at risk of adverse events from anemia. Conclusions: There is a significant body of evidence supporting cardiovascular adaptive responses to anemia. However, there is a remarkable lack, in both quality and quantity, of clinical studies addressing how the "normal" physiologic adaptations may be affected by a variety of diseases. The physiologic evidence alone is insufficient to inform most decisions about red blood cell transfusion. M any of the physiologic concepts in oxygen (O 2) transport and utilization were described in the early part of the century and are still widely accepted. 1 In 1920, Barcroft 2 noted that tissue oxygenation was a function of hemoglobin concentration ([Hb]), oxygenation of blood by the lungs and cardiac output. Similarly, many of the principles underlying the transfer of O 2 from the microcirculation to the mitochondria are well established and have stood the test of time. 1 Although much of the basic physiology underlying the delivery of O 2 has been extensively studied, 1,3-5 there are few, if any, systematic, comprehensive evaluations of the quality of the evidence in laboratory and clinical studies in

American Journal of Therapeutics, Apr 20, 2022

Biomaterials, artificial cells, and immobilization biotechnology, Dec 1, 1991

Springer eBooks, 1990

We tested the cardiovascular actions of the surfactant Pluronic F68 by infusing it into anestheti... more We tested the cardiovascular actions of the surfactant Pluronic F68 by infusing it into anesthetized dogs, in doses approximating those which would be received when Fluosol-DA were used to resuscitate moderate or severe hemorrhage (0.66 and 1.11 g/Kg). In order to alleviate the reactions to Pluronic, the surfactant was purified by treatment with activated charcoal and the dogs were pretreated with corticosterone. Pluronic F68 caused dose-dependent increments in cardiac filling pressures and in systemic and pulmonary arterial blood pressure. Heart rate and contractility remained unchanged. There was an increase in the cardiac output which was dose-dependent and unrelated to the filling pressures. Regional blood flow, as determined by radionuclide-labelled microspheres, tended to increase, but only that to the heart, kidney cortex and lung (bronchial arterial) increased to a statistically significant extent. It would appear that Pluronic F68, when purified with charcoal and after steroid prophylaxis, possesses significant hemorheologic and cardiovascular effects, indicating the need for further investigation of various purification methods and the effects of purified preparations.

PubMed, Aug 1, 1983

During the last two decades the search for alternatives to whole blood transfusions has led to pr... more During the last two decades the search for alternatives to whole blood transfusions has led to promising developments in the field of erythrocyte substitutes. Hemoglobin solutions free of fragments of erythrocyte stroma and fluorocarbon emulsions are not blood-type-specific and appear likely to satisfy some proportion of our blood requirements. Both must be modified before becoming clinically useful. The oxygen affinity of the hemoglobin solution must be reduced and its intravascular persistence improved. Fluorocarbons cannot yet contribute significantly to the oxygen supply unless the patient breathes hyperbaric oxygen. Recent advances are leading to solutions for these problems.

Advances in Experimental Medicine and Biology, 1989

Perfluoro-octylbromide-containing perfusate is capable of supporting the contractile activity of ... more Perfluoro-octylbromide-containing perfusate is capable of supporting the contractile activity of isolated hearts. Because of the high oxygen content of such perfusate, "normal" mechanical function is maintained by such hearts with substantially reduced coronary flow.

BJA: British Journal of Anaesthesia, Jul 1, 1973

The effects of intravenous practolol 0.4 mg/kg were studied in 12 hypertensive patients during ha... more The effects of intravenous practolol 0.4 mg/kg were studied in 12 hypertensive patients during halothane/nitrous oxide anaesthesia. Practolol decreased heart rate (HR) and cardiac output (Q) from the elevated levels following atropine administration during anaesthesia, but values of arterial pressure (AP), HR and Q after the combination of atropine and practolol were not significantly different from those during anaesthesia prior to blockade. The effects of a similar anaesthetic sequence were studied in a further 11 treated hypertensive patients given practolol by mouth 1.5 mg/kg/6 hours for at least 48 hours preoperatively in addition to current anti-hypertensive therapy. By comparison with treated hypertensive patients previously studied, those pretreated with practolol had similar AP awake, but higher AP throughout anaesthesia with either spontaneous or artificial ventilation. Cardiac output was higher and systemic vascular resistance was lower both before and during anaesthesia. Both the present groups of patients showed significantly attenuated responses of tachycardia and hypertension following laryngoscopy and intubation compared with previous studies. The incidence of dysrhythmia and e.c.g. evidence of myocardial ischaemia was significantly lower (4%) in beta-blocked patients compared with those who had not received practolol (38%).

Transfusion Medicine Reviews, Apr 1, 1993

Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoi... more Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoing extensive testing. This new generation is the result of the application of physicochemical principles, applied to both the choice of the PFC itself and the emulsifier, as well as advances in emulsion-producing technology. The efficacy of PFCs in general for oxygen transporting capability has been fully recognized, as exemplified by the limited license issued to Fluosol. The latter also represents the recognition of the relative absence of major toxicity of PFCs in general. The development of new products owes much to the lessons learned during the past 20 years and to advances made in the physical chemistry of PFCs. These advances now permit the rational selection or design of the most appropriate PFC and the design of emulsifiers best suited for the purpose. Perflubron represents a clear advance over the Fluosol-DA-type formulation. It is only one but the most advanced of the second-generation products. At least three other commercial entities (Hema-Gen/PFC, Green Cross, Adamantech) are also developing products based on the above principles. Five years ago we concluded that, in spite of the enormous complexity of PFC emulsions as large volume parenterals, they have shown remarkable biocompatibility. The advances in the past 5 years have confirmed this conclusion. The advances occurring during the past 5 years show that the application of the proper technology can lead to product improvement, and that PFC preparations with significant transfusional and nontransfusional potential are, in fact, feasible. It remains to be seen whether high PFC-content emulsion can be successfully deployed in initial, prehospital resuscitation situations. The high PFC content will reduce the absolute requirement for the maintenance of FIO2 > 0.8 in the case of Fluosol-DA for optimal efficacy. The second-generation products also seem to lend themselves to intraoperative use, because they can be removed from the blood postoperatively by plasmapheresislike methods. They are also suitable in combination with autologous blood donation/transfusion. All of these potential applications are in various stages of exploration and, if found to be efficacious, will likely conserve the supply of whole blood and blood components. The nontransfusional applications, particularly those in diagnostic imaging, seem to show substantial promise. Because they involve smaller doses than transfusional applications, they may enter clinical use earlier. The applications in radiation and chemotherapy of malignant diseases represent an intermediate position between the transfusional and nontransfusional uses.(ABSTRACT TRUNCATED AT 400 WORDS)

American Heart Journal, 1980

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collate... more The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.

Springer eBooks, 1989

The Ottawa '88 meeting of the International Society for Oxygen Transport to Tissue attracted ... more The Ottawa '88 meeting of the International Society for Oxygen Transport to Tissue attracted a record number of participants and presentations. We were able to avoid simultaneous sessions and still keep the scientific program to four days by using poster sessions followed by plenary debate on each poster. To paraphrase the British physicist David Bohm, we tried to avoid an ordinary discussion, in which people usually stick to a relatively fixed position and try to convince others to change. This situation does not give rise to anything creative. So, we attempted instead to establish a true dialogue in which a person may prefer and support a certain point of view, but does not hold it nonnegotiab1y. He or she is ready to listen to others with sufficient sympathy, and is also ready to change his or her own view if there is a good reason to do so. Our Society is in its "teen" years, and there are even some arguments about its exact age. Many newer members have raised questions concerning the history of the Society. For this reason, I have asked one of the "founding fathers," D. Bruley, to prepare a brief account of the birth and early history of the Society which appears on the following page.

Canadian Journal of Physiology and Pharmacology, Apr 1, 1973

The participation of the aortic chemoreceptors in the reflex cardiac responses to acute hypoxia i... more The participation of the aortic chemoreceptors in the reflex cardiac responses to acute hypoxia is suggested only by the indirect evidence of pharmacological stimulation of these receptors. In order to assess their role more directly, the response to a 15 min period of hypoxia was determined after surgical denervation of the aortic chemoreceptors (A.D.), and compared with the response of sham-operated (S.O.) dogs, anesthetized with morphine–pentobarbital. In the control period, while breathing room air, the cardiovascular and respiratory parameters measured in the A.D. animals were not different from those of the S.O. dogs. Hypoxia (partial pressure of oxygen approximately 30 mm Hg) in the S.O. dogs was associated with a statistically significant rise in the heart rate (+71 ± 7 min−1, mean ± S.E.M.) and of the cardiac output (+25 ± 10 ml kg−1 min−1). In the A.D. animals, the significantly smaller increment in heart rate (+29 ± 6 min−1) was associated with a fall of the cardiac output (−16 ± 12 ml kg−1 min−1). The hypoxia-induced changes in heart rate and cardiac output in the S.O. animals were different (p < 0.05) from those in the A.D. group. The minute volume of ventilation was significantly augmented in both groups, and to a comparable extent. These findings indicate that the aortic chemoreceptors play a significant role in the cardiac response to hypoxia, but they do not affect, to a significant extent, the respiratory response.

Canadian Medical Association Journal, Jul 15, 1988

Canadian Journal of Physiology and Pharmacology, Oct 1, 1984

The effect of propranolol treatment was investigated in the myocardial ischemia-induced hypervisc... more The effect of propranolol treatment was investigated in the myocardial ischemia-induced hyperviscosity state in anesthetized dogs. In untreated control dogs, low shear blood viscosity rose progressively, following an acute occlusion of the left anterior descending coronary artery; this effect was partially but significantly reduced by intravenously administered propranolol (0.2 mg/kg). The effect of the in vitro addition of propranolol was also determined upon viscosity of blood samples obtained at hourly intervals from dogs subjected to similar coronary ligation. The in vitro addition of propranolol did not produce a similar reversal of the hyperviscosity state observed in the blood obtained from dogs after coronary ligation.

Blood Substitutes and Oxygen Biotherapeutics

Postgraduate medical journal, 1972

Advances in Experimental Medicine and Biology, 1989

The size of the hypoperfused zone (area at risk) produced by occluding any given coronary artery ... more The size of the hypoperfused zone (area at risk) produced by occluding any given coronary artery shows considerable variation among untreated animals (1). Since the amount of myocardium that will infarct is, to a large extent, dependant upon the size of the area at risk (AAR) (1–3), infarct sizes also show considerable variation. Therefore, it has become conventional to express infarct size as a percentage of the AAR in order to standardize this variable.

Advances in Experimental Medicine and Biology, 1996

The role of amino groups in hemoglobin function and the effects of chemical modification of these... more The role of amino groups in hemoglobin function and the effects of chemical modification of these on the function of the protein have recently been reviewed (1). Amino groups are contributed by either the N-terminal residues of the globin chains or the lysine residues of the polypeptides. Depending on the reagents used and the conditions chosen, a variable degree of specificity towards amino groups can be achieved. Such studies can be of value in determining the role of individual functional groups in biological function and may be of use in the preparation of derivatives that have modified functional properties desirable in material to be used in a hemoglobin based oxygen carrier. We have recently developed a new method for hemoglobin amino group modification which has a much greater rate of reaction with a amino groups than with the 8 amino groups of lysines at physiological pH (2). This method utilizes the activation of exogenous carboxyl containing compounds with water soluble carbodiimides and subsequent reaction with the amino groups of proteins such as hemoglobin. We report here the effects on oxygen binding observed as a function of the extent and conditions of hemoglobin modification with citrate used as the exogenous carboxyl containing compound.

WORLD SCIENTIFIC eBooks, 2022

Angiology, Dec 1, 1990

The effects of low-dose (10-9 and 3x10-9 mole/kg/min) infusions of dopexamine HCl, a new syntheti... more The effects of low-dose (10-9 and 3x10-9 mole/kg/min) infusions of dopexamine HCl, a new synthetic catecholamine with β2-adrenergic and DA 1-dopaminergic agonostic actions, was tested in anesthetized dogs, with and without acute ligation of the left anterior descending coronary artery. The infusions caused diastolic arterial blood pressure to fall by 12±4 and 23±5 mmHg, respectively. Microsphere-estimated collateral blood flow to the ischemic myocardium did not change significantly during the drug infusions. The findings suggest that low doses of dopexamine HCl do not cause coronary "steal" from acutely ischemic myo cardium.

Canadian Medical Association Journal, Jun 1, 1997

Objective: To determine the nature and quality of the physiologic evidence regarding an "optimum"... more Objective: To determine the nature and quality of the physiologic evidence regarding an "optimum" hemoglobin concentration in anemic patients or in patients with specific diseases. Literature search and selection: Searches of MEDLINE from January 1966 to December 1996 were combined with manual searches of the bibliographies and references from experts. Citations were chosen by 2 reviewers if they were related to red blood cell transfusion practice and, more specifically, to physiologic adaptation to anemia. Disagreement was resolved through consensus. Literature synthesis: The articles selected from the literature search were classified by study design and topic areas. Evidence-based inferences were derived from the literature. Results: Of the 160 articles included in this review, 58 (36%) were human studies and 102 (64%) were laboratory studies. Most studies (84) fell into the "hemodilution" category, and were predominantly in animal models (70). Overall, 90 studies (56%) used a valid design with appropriate experimental and concurrent control groups (graded as level I or II). The distribution of grading was uniform throughout the categories. The quality of the evidence was deemed weaker for laboratory studies evaluating cardiac adaptation to anemia, largely because of a lack of reported concurrent controls in most studies. Inferences drawn from the literature were graded on a 4-point scale assessing the quality of the evidence; 13 of 18 statements were given the highest grade. The clinical significance of the Bohr effect and the shifts in the oxyhemoglobin curve following changes in pH were thought to be poorly studied and were rated lowest. The studies evaluating maximum oxygen delivery in anemia were rated as weak, partly because of conflicting reports. Of all identified studies, 56% were well designed and reported. Important adaptive responses to anemia consist of an elevation of cardiac output and its redistribution to favour the coronary and cerebral circulations at the expense of the splanchnic vascular beds; studies supporting these statements were rated highly. The evidence also suggests that patients with cardiac disease are at risk of adverse events from anemia. Conclusions: There is a significant body of evidence supporting cardiovascular adaptive responses to anemia. However, there is a remarkable lack, in both quality and quantity, of clinical studies addressing how the "normal" physiologic adaptations may be affected by a variety of diseases. The physiologic evidence alone is insufficient to inform most decisions about red blood cell transfusion. M any of the physiologic concepts in oxygen (O 2) transport and utilization were described in the early part of the century and are still widely accepted. 1 In 1920, Barcroft 2 noted that tissue oxygenation was a function of hemoglobin concentration ([Hb]), oxygenation of blood by the lungs and cardiac output. Similarly, many of the principles underlying the transfer of O 2 from the microcirculation to the mitochondria are well established and have stood the test of time. 1 Although much of the basic physiology underlying the delivery of O 2 has been extensively studied, 1,3-5 there are few, if any, systematic, comprehensive evaluations of the quality of the evidence in laboratory and clinical studies in

American Journal of Therapeutics, Apr 20, 2022

Biomaterials, artificial cells, and immobilization biotechnology, Dec 1, 1991

Springer eBooks, 1990

We tested the cardiovascular actions of the surfactant Pluronic F68 by infusing it into anestheti... more We tested the cardiovascular actions of the surfactant Pluronic F68 by infusing it into anesthetized dogs, in doses approximating those which would be received when Fluosol-DA were used to resuscitate moderate or severe hemorrhage (0.66 and 1.11 g/Kg). In order to alleviate the reactions to Pluronic, the surfactant was purified by treatment with activated charcoal and the dogs were pretreated with corticosterone. Pluronic F68 caused dose-dependent increments in cardiac filling pressures and in systemic and pulmonary arterial blood pressure. Heart rate and contractility remained unchanged. There was an increase in the cardiac output which was dose-dependent and unrelated to the filling pressures. Regional blood flow, as determined by radionuclide-labelled microspheres, tended to increase, but only that to the heart, kidney cortex and lung (bronchial arterial) increased to a statistically significant extent. It would appear that Pluronic F68, when purified with charcoal and after steroid prophylaxis, possesses significant hemorheologic and cardiovascular effects, indicating the need for further investigation of various purification methods and the effects of purified preparations.

PubMed, Aug 1, 1983

During the last two decades the search for alternatives to whole blood transfusions has led to pr... more During the last two decades the search for alternatives to whole blood transfusions has led to promising developments in the field of erythrocyte substitutes. Hemoglobin solutions free of fragments of erythrocyte stroma and fluorocarbon emulsions are not blood-type-specific and appear likely to satisfy some proportion of our blood requirements. Both must be modified before becoming clinically useful. The oxygen affinity of the hemoglobin solution must be reduced and its intravascular persistence improved. Fluorocarbons cannot yet contribute significantly to the oxygen supply unless the patient breathes hyperbaric oxygen. Recent advances are leading to solutions for these problems.

Advances in Experimental Medicine and Biology, 1989

Perfluoro-octylbromide-containing perfusate is capable of supporting the contractile activity of ... more Perfluoro-octylbromide-containing perfusate is capable of supporting the contractile activity of isolated hearts. Because of the high oxygen content of such perfusate, "normal" mechanical function is maintained by such hearts with substantially reduced coronary flow.

BJA: British Journal of Anaesthesia, Jul 1, 1973

The effects of intravenous practolol 0.4 mg/kg were studied in 12 hypertensive patients during ha... more The effects of intravenous practolol 0.4 mg/kg were studied in 12 hypertensive patients during halothane/nitrous oxide anaesthesia. Practolol decreased heart rate (HR) and cardiac output (Q) from the elevated levels following atropine administration during anaesthesia, but values of arterial pressure (AP), HR and Q after the combination of atropine and practolol were not significantly different from those during anaesthesia prior to blockade. The effects of a similar anaesthetic sequence were studied in a further 11 treated hypertensive patients given practolol by mouth 1.5 mg/kg/6 hours for at least 48 hours preoperatively in addition to current anti-hypertensive therapy. By comparison with treated hypertensive patients previously studied, those pretreated with practolol had similar AP awake, but higher AP throughout anaesthesia with either spontaneous or artificial ventilation. Cardiac output was higher and systemic vascular resistance was lower both before and during anaesthesia. Both the present groups of patients showed significantly attenuated responses of tachycardia and hypertension following laryngoscopy and intubation compared with previous studies. The incidence of dysrhythmia and e.c.g. evidence of myocardial ischaemia was significantly lower (4%) in beta-blocked patients compared with those who had not received practolol (38%).

Transfusion Medicine Reviews, Apr 1, 1993

Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoi... more Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoing extensive testing. This new generation is the result of the application of physicochemical principles, applied to both the choice of the PFC itself and the emulsifier, as well as advances in emulsion-producing technology. The efficacy of PFCs in general for oxygen transporting capability has been fully recognized, as exemplified by the limited license issued to Fluosol. The latter also represents the recognition of the relative absence of major toxicity of PFCs in general. The development of new products owes much to the lessons learned during the past 20 years and to advances made in the physical chemistry of PFCs. These advances now permit the rational selection or design of the most appropriate PFC and the design of emulsifiers best suited for the purpose. Perflubron represents a clear advance over the Fluosol-DA-type formulation. It is only one but the most advanced of the second-generation products. At least three other commercial entities (Hema-Gen/PFC, Green Cross, Adamantech) are also developing products based on the above principles. Five years ago we concluded that, in spite of the enormous complexity of PFC emulsions as large volume parenterals, they have shown remarkable biocompatibility. The advances in the past 5 years have confirmed this conclusion. The advances occurring during the past 5 years show that the application of the proper technology can lead to product improvement, and that PFC preparations with significant transfusional and nontransfusional potential are, in fact, feasible. It remains to be seen whether high PFC-content emulsion can be successfully deployed in initial, prehospital resuscitation situations. The high PFC content will reduce the absolute requirement for the maintenance of FIO2 > 0.8 in the case of Fluosol-DA for optimal efficacy. The second-generation products also seem to lend themselves to intraoperative use, because they can be removed from the blood postoperatively by plasmapheresislike methods. They are also suitable in combination with autologous blood donation/transfusion. All of these potential applications are in various stages of exploration and, if found to be efficacious, will likely conserve the supply of whole blood and blood components. The nontransfusional applications, particularly those in diagnostic imaging, seem to show substantial promise. Because they involve smaller doses than transfusional applications, they may enter clinical use earlier. The applications in radiation and chemotherapy of malignant diseases represent an intermediate position between the transfusional and nontransfusional uses.(ABSTRACT TRUNCATED AT 400 WORDS)

American Heart Journal, 1980

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collate... more The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.

Springer eBooks, 1989

The Ottawa '88 meeting of the International Society for Oxygen Transport to Tissue attracted ... more The Ottawa '88 meeting of the International Society for Oxygen Transport to Tissue attracted a record number of participants and presentations. We were able to avoid simultaneous sessions and still keep the scientific program to four days by using poster sessions followed by plenary debate on each poster. To paraphrase the British physicist David Bohm, we tried to avoid an ordinary discussion, in which people usually stick to a relatively fixed position and try to convince others to change. This situation does not give rise to anything creative. So, we attempted instead to establish a true dialogue in which a person may prefer and support a certain point of view, but does not hold it nonnegotiab1y. He or she is ready to listen to others with sufficient sympathy, and is also ready to change his or her own view if there is a good reason to do so. Our Society is in its "teen" years, and there are even some arguments about its exact age. Many newer members have raised questions concerning the history of the Society. For this reason, I have asked one of the "founding fathers," D. Bruley, to prepare a brief account of the birth and early history of the Society which appears on the following page.

Canadian Journal of Physiology and Pharmacology, Apr 1, 1973

The participation of the aortic chemoreceptors in the reflex cardiac responses to acute hypoxia i... more The participation of the aortic chemoreceptors in the reflex cardiac responses to acute hypoxia is suggested only by the indirect evidence of pharmacological stimulation of these receptors. In order to assess their role more directly, the response to a 15 min period of hypoxia was determined after surgical denervation of the aortic chemoreceptors (A.D.), and compared with the response of sham-operated (S.O.) dogs, anesthetized with morphine–pentobarbital. In the control period, while breathing room air, the cardiovascular and respiratory parameters measured in the A.D. animals were not different from those of the S.O. dogs. Hypoxia (partial pressure of oxygen approximately 30 mm Hg) in the S.O. dogs was associated with a statistically significant rise in the heart rate (+71 ± 7 min−1, mean ± S.E.M.) and of the cardiac output (+25 ± 10 ml kg−1 min−1). In the A.D. animals, the significantly smaller increment in heart rate (+29 ± 6 min−1) was associated with a fall of the cardiac output (−16 ± 12 ml kg−1 min−1). The hypoxia-induced changes in heart rate and cardiac output in the S.O. animals were different (p < 0.05) from those in the A.D. group. The minute volume of ventilation was significantly augmented in both groups, and to a comparable extent. These findings indicate that the aortic chemoreceptors play a significant role in the cardiac response to hypoxia, but they do not affect, to a significant extent, the respiratory response.

Canadian Medical Association Journal, Jul 15, 1988

Canadian Journal of Physiology and Pharmacology, Oct 1, 1984

The effect of propranolol treatment was investigated in the myocardial ischemia-induced hypervisc... more The effect of propranolol treatment was investigated in the myocardial ischemia-induced hyperviscosity state in anesthetized dogs. In untreated control dogs, low shear blood viscosity rose progressively, following an acute occlusion of the left anterior descending coronary artery; this effect was partially but significantly reduced by intravenously administered propranolol (0.2 mg/kg). The effect of the in vitro addition of propranolol was also determined upon viscosity of blood samples obtained at hourly intervals from dogs subjected to similar coronary ligation. The in vitro addition of propranolol did not produce a similar reversal of the hyperviscosity state observed in the blood obtained from dogs after coronary ligation.