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Biomedical subjects

M B Laver

Publications and source records attributed to M B Laver.

At least 37 records · Page 2Linked to original sources
PubMed1978

Allosteric effect of o-iodobenzoate on hemoglobin.

O-Iodobenzoate interacts non-covalently with hemoglobin and lowers the oxygen affinity of the protein. In contrast to 2,3-diphosphoglycerate or inositol hexaphosphate, its interaction does not depend upon the presence of free amino groups at the beta-chain amino terminals. Lysine beta82 is one of its oxygenation linked binding sites. As with the organic phosphates, the halogenated benzoate reacts preferentially with deoxy-hemoglobin to shift the allosteric equilibrium from R to T.

Allosteric Regulation↗
PubMed1977

Effect of sodium ortho-iodobenzoate on oxygen transport and erythropoiesis in hypoxemic dogs with a right-to-left cardiac shunt.

Eight dogs were made hypoxemic by surgical construction of a right-to-left cardiac shunt; and they were given sodium ortho-iodobenzoate (OISB) before and for 3 months after operation. The P(50) at 50% saturation) rose from 27.2 +/- 0.7 to 31.2 +/- 0.6 mm Hg (p less than 0.001) during OLSB treatment before operation and increased further to 32.2 +/- 0.8 mm Hg 3 months after creation of hypoxemia. The P(50) remained elevated for an additional 3 months after OISB was stopped. Administration of OISB before operation did not alter the red blood cell 2,3-diphosphoglycreate concentration. Hypoxemia caused an increase of this metabolite from 0.91 +/- 0.21 to 1.50 +/- 0.28 moles/moles of hemoglobin (p less than 0.05); the rise was not as great as that observed in hypoxemic dogs without OISB treatment. In spite of significant hypoxemia, hematocrit rose only slightly during the period of OISB infusion. OISB increased P50 and prevented the compensatory polycythemia regularly seen when dogs are made hypoxemic. Altering oxygen transport in this fashion may increase tissue oxygen delivery in patients with conditions which result in tissue hypoxia.

Animals↗
PubMed1976

[Cardiorespiratory problems in intensive care (author's transl)].

Prompt and aggressive support of lung and hemodynamic function are required if the incidence of recovery from acute respiratory insufficiency is to be improved. Prophylactic ventilator and inotropic therapy are required to prevent progressive deterioration of blood gas exchange and maintain myocardial function in the face of an acutely elevated right ventricular afterload. Methods for early diagnosis are now readily available; the criteria for therapeutic intervention are discussed.

Adult↗
PubMed1976

Hemodynamic response to ganglionic blockade with pentolinium during N2O-halothane anesthesia in man.

Hemodynamic and blood-gas variables were studied before and after pentolinium tartrate administration in six patients anesthetized with nitrous oxide-halothane and maintained at PaCO2 35-40 torr. Measurements were made prior to induction of anesthesia; before and 10, 20, and 60 minutes after administration of pentolinium (0.3 mg/kg); 15 minutes after return of arterial blood pressure to control values. Mean arterial blood pressure (MAP) was significantly decreased at 20 (P less than 0.02) and 60 (P less than 0.001) minutes, in association with significant decreases in systemic vascular resistance (SVR) (P less than 0.05 and P less than 0.005). At 60 minutes MAP was significantly lower than that at 10 minutes (P less than 0.01). Cardiac output (CO) was increased (P less than 0.05) after 10 minutes secondary to a significant increase in heart rate. Neither variable changes significantly thereafter. CO and HR were significantly lower (P less than 0.01) 60 minutes after pentolinium than at 10 minutes; both returned to 10-minute values after intravenous administration of atropine. Changes in stroke volume (SV) and mean right atrial pressure (MRAP) were not significant. Whole-body O2 uptake (VO2) was not significantly altered by pentolinium. However, a substantial diminution of myocardial O2 consumption (MVO2) was deduced from a significant decrease in the heart rate-arterial systolic pressure produce (HR X ASP). Fifteen minutes after return of MAP to control levels, SVR was 11.5 per cent lower, while CO was still significantly higher (P less than 0.02) than control values. Following ganglionic blockade with pentolinium during halothane-N2O anesthesia, HR is a valuable index of changes in CO, while the HR X ASP index may be utilized to evaluate changes in MVO2. Assessment of myocardial performance during controlled hypotension is possible by the use of routinely available measurements.

Adolescent↗
PubMed1976

Sodium o-iodobenzoate and hemoglobin-oxygen affinity: in vivo effects.

Sodium o-iodobenzoate (OISB) was given intravenously to 15 dogs to test the in vivo effect of this drug on the oxyhemoglobin dissociation curve. Administration of a single dose of 500 mg/kg was followed by an average increase in P50 (PO2 at 50% oxyhemoglobin saturation) of 3.6 mmHg from 26.8 +/- 0.5 to 30.4 +/- 1.8 mmHg (corrected to pH 7.4). This elevation was sustained for 7 days. During intravenous infusions of 200 mg/kg every other day for 3 wk, there was a sustained increase in P50 of 2.6 mmHg from 27.8 +/- 1.1 to 30.4 +/- 0.9 mmHg. All dogs survived the experiment and no ill effects of the drug were noted. An increase in serum lactate and pyruvate occurred in all animals following acute or chronic exposure to the drug. There was no significant change in whole blood pH, 2,3-diphosphoglycerate concentrations, intracellular pH, or serum total phosphate. Multiple infusions of sodium cyanate (50 mg/kg per day) reduced P50 by an average of 12.2 +/- 0.3 mmHg. A subsequent single infusion of OISB (500 mg/kg) failed to increase P50. Our preliminary data indicate that pharmacological manipulation of hemoglobin O2 affinity is possible with organic compounds unrelated to erythrocyte metabolism.

Animals↗
PubMed1976

Effect of sodium para-aminosalicylate on oxygen affinity in normal, sickle and fetal human blood.

Sodium para-aminosalicylate (sodium salt of 2-hydroxy-4-aminobenzoic acid, Na-PAS) lowers the oxygen affinity of normal adult human placental, heterozygous and homozygous sickle cell anemic whole blood at 37 degrees C. The reduction of oxygen affinity is related to the type of hemoglobin in the blood. The mean P50 +/- S.E. at pH 7.40 for normal, placental, heterozygoud and homozygous sickle cell anemic blood in 26.2 +/- 0.1, 20.8 +/- 0.3, 26.8 +/- 0.3 and 31.0 +/- 0.5 mm Hg; in the presence of 5.7 mmol of Na-PAS per liter of blood the P50 values are increased to 28.0 +/- 0.3, 22.9 +/- 0.8, 30.5 +/- 0.6 and 33.9 +/- 0.3 mm Hg, respectively. The Bohr effect in normal and placental blood at this Na-PAS concentration is essentially unchanged: in heterozygous and homozygous sickle cell anemic blood, the Bohr factor (deta log P50/deta pH) is reduced from -0.48 +/- 0.02 to -0.41 +/- 0.01 and from -0.53 +/- 0.03 to -0.48 +/- 0.01. The Hill constants (n) of normal and placental blood are not affected by Na-PAS. In homozygous and heterozygous sickle blood, high concentrations of Na-PAS (22.9 mmol/l) decrease the Hill constant from 2.55 to 2.35 and from 2.56 to 2.28, respectively. Na-PAS is more firmly bound to red blood cells than to plasma. The binding of Na-PAS is probably primarily ionic in nature since the drug can be almost completely removed from blood components by dialysis. The changes in oxygen affinity caused by Na-PAS are consistent with conformational changes (R leads to T) which enhance the presence of deoxyhemoglobin.

Adult↗
PubMed1975

Hemodynamic responses to mechanical ventilation with PEEP: the effect of hypervolemia.

The hemodynamic effects of prolonged mechanical ventilation with positive end-expiratory pressure (PEEP), with and without blood volume augmentation, were studied in 18 beagles anesthetized with halothane (0.7 per cent end-tidal). Addition of 12 cm H2O PEEP during mechanical ventilation in normavolemic dogs was associated with reductions of transmural cardiac filling pressures, cardiac index and stroke index to 50 per cent of control values. Circulatory adaptation did not occur. Filling pressures and flow remained unchanged during the ensuing 8 hours when PEEP was maintained. They returned to control levels when PEEP was discontinued, except for the transmural right ventricular end-diastolic pressure, which remained elevated above control levels. Systemic vascular resistance was unchanged, but pulmonary vascular resistance doubled upon addition of PEEP. Following autologous whole blood transfusion (25 ml/kg) during mechanical ventilation with PEEP, cardiac index returned to, and remained at, control levels. After PEEP was discontinued, cardiac index increased acutely and remained elevated for the remainder of the study period (as long as 7 hours). Comparable transfusion during mechanical ventilation without PEEP elevated cardiac index only transiently. Right atrial, pulmonary capillary wedge, and right and left ventricular end-diastolic pressures showed marked increases relative to atmospheric with PEEP and after transfusion. Calculated transmural pressures demonstrated clear reductions with application of PEEP, followed by increases to control levels with transfusion and further increases to above control when PEEP was discontinued. Study of ventricular function curves revealed that changes in filling pressures and not to changes in ventricular contractility. Transmural pulmonary arterial diastolic pressure rose throughout the 12 hours of study, despite return of pulmonary vascular resistance to control level with removal of PEEP. Thus, acute decreases in cardiac filling pressure, cardiac index, and stroke index persist consequent to application of PEEP, and circulatory adaptation does not occur. The apparent hemodynamic deterioration may be reversed by blood volume augmentation, but when PEEP is discontinued, hypervolemia with consequent increases in filling pressures and a move along a ventricular function curve will occur. Changes in cardiac index will depend upon the overall state of right and left ventricular contractility.

Animals↗
PubMed1975

The effect of pre-existing pulmonary vascular disease on the response to mechanical ventilation with PEEP following open-heart surgery.

The effects of mechanical ventilation with and without positive end-expiratory pressure (PEEP) on hemodynamic performance and blood-gas exchange were studied in ten patients following open-heart surgery. Ventilation at constant tidal volume (15 ml/kg body weight) with 10 cm H2O PEEP following aortic valve replacement (AVR) IN FIVE PATIENTs without pulmonary vascular disease was associated with the following significant changes: a rise in arterial Po2, a fall in the alveolar-arterial Po2 gradient when Fio2 = 1.0, decreases in calculated Qs/Qt and cardiac index. Using a similar pattern of ventilation following mitral valve replacement (MVR) in patients with elevated pulmonary vascular resistance, we found a significant decrease in cardiac index (but less than in the AVR group), a significant elevation of calculated physiologic deadspace (Vd/Vt) and no change in Qs/Qt. An hour after removal of PEEP, intravascular pressures, blood flow and blood-gas exchange values of all patients with AVR had returned to control levels; patients with MVR had persistently significantly low cardiac indices, while Vd/Vt returned to pre-PEEP values. These findings suggest that evaluation of responses to different ventilation patterns must take into account pre-existing V/Q abnormalities secondary to pulmonary vascular disease, particularly when these are secondary to chronic congestive heart failure. Following AVR, Qs/Qt changed in the same direction as cardiac index (CI) irrespective of ventilatory pattern: CI decreased and rose as CI increased. The authors conclude that with increasing severity of pulmonary vascular disease, changes in airway pressure will have an unpredictable effect on cardiac index unless the level of myocardial competence is taken into account. In the presence of ventricular failure, changes in pleural (and therefore transmural) pressures will be minimal compared with the high filling pressures and exert no influence on stroke volume. Although pulmonary venous hypertension was more pronounded in the MVR than in the AVR group, there was no significant difference between the postoperative values for Qs/Qt (Fio2 = 1.0), a condition probably fostered by marked differences in pre-existing V/Q.

Aged↗
PubMed1975

Filling pressures of the heart and pulmonary circulation of the patient with coronary-artery disease after large intravenous doses of morphine.

Filling pressures of the heart and hemodynamic responses were studied before, during, and after administration of morphine, 2 mg/kg, intravenously (5 mg per minute) in eight patients with coronary-artery disease and normal ventricular contractility requiring myocardial revascularization. Left-heart filling pressure (LHFP) was estimated by measuring balloon-occluded pulmonary arterial pressure via a Swan-Ganz catheter, and right-heart filling pressure (RHFP) by right atrial pressure measurements. LHFP and RHFP were unchanged until 1.5 mg/kg morphine had been administered; after 2 mg/kg, LHFP had risen from a control level of 6.9 plus or minus 0.8 to 10.6 plus or minus 1.1 mm Hg (P less than .01) and RHFP from 2.9 plus or minus 0.4 to 4.9 plus or minus 0.8 mm Hg (P less than .05). Heart rate (P less than .02) and rate-pressure product (P less than .05), an indirect index of myocardial oxygen consumption, decreased throughout the study period. Systemic arterial pressure, cardiac index, and left ventricular stroke work decreased significantly only at the 0.5 mg/kg dose level, while systemic vascular resistance and stroke index remained unchanged. Mean pulmonary arterial pressure increased (P less than .05) after 1.5 mg/kg morphine, but pulmonary vascular resistance was unchanged. PaC02, pH, base excess, and hematocrit were constant throughout the study period. These data indicate that doses of morphine to 2 mg/kg, iv, are well tolerated by, and, presumably, decrease the myocardial oxygen consumption of, patients with coronary-artery disease. The hemodynamic response resembles that seen in man without hear or lung disease.

Blood Pressure↗
PubMed1975

Left ventricular performance and pulmonary circulation following addition of nitrous oxide to morphine during coronary-artery surgery.

The effects of nitrous oxide on ventricular performance and pulmonary circulation were studied in 12 patients with angiographically demonstrated coronary-artery disease and normal ventricular contractility who had received 2 mg/kg morphine intravenously. Seventeen studies were performed intraoperatively, five before and 12 after cardiopulmonary bypass and myocardial revascularization. Recordings were obtained during oxygen breathing and during nitrous oxide administration. Fifty per cent nitrous oxide significantly decreased mean arterial pressure (P less than 0.05), cardiac index (P less than 0.01), stroke index (P less than 0.01), left ventricular stroke work index (P less than 0.01), peak left ventricular dP/dt (P less than 0.05) and dP/dt/P (P less than 0.01), and heart rate-systolic arterial pressure product (P less than 0.01). Mean pulmonary arterial pressure (P less than 0.05), pulmonary artery occluded pressure (P less than 0.01), left ventricular end-diastolic pressure (P less than 0.01) and pulmonary vascular resistance (P less than 0.05) increased. Heart rate, right atrial pressure and systemic vascular resistance remained unchanged. When nitrous oxide was discontinued, all variables returned to control except mean pulmonary arterial pressure and pulmonary vascular resistance. Responses were similar before and after cardiopulmonary bypass and myocardial revascularization. These findings suggest that nitrous oxide depresses left ventricular performance when administered intraoperatively to patients who have received large doses of morphine for coronary-artery surgery. Nitrous oxide also increases pulmonary vascular resistance, possibly via alpha-adrenergic stimulation.

Anesthesia, Inhalation↗
PubMed1975

Low plasma ionized calcium and response to calcium therapy in critically ill man.

Marked lowering of plasma ionized calcium concentrations [Ca++] occurred in eight patients (2 days to 54 years old) who required extensive pharmacologic support of the circulation. [Ca++]'s ranged from 0.21 to 0.53 mM. Only one patient survived. The hypocalcemia occurred in the absence of massive transfusion of citrated whole blood or well after such transfusions had been discontinued. These abnormally low concentrations of ionized calcium were not readily corrected by intravenous administration of calcium salts in doses generally recommended. The process responsible for inadequate hemodynamic function appeared to be associated with a severe disturbance in calcium metabolism. Contribution of the latter to the severity of hemodynamic deterioration is unclear, and little benefit from intravenous calcium therapy was found. In two patients, normal [Ca++] could not be restored by administration of CaCl2 alone, but [Ca++] rose to normal following continued calcium replacement therapy in conjunction with increased isoproterenol infusion. There was no predictable relationship between total and ionized plasma calcium concentrations. Thus, measurement of total calcium provided no indication of the level of the biologically active moiety. [Ca++] was low with both normal and low plasma pH values. The data suggest that a very high infusion rate of CaCl2 may required to restore [Ca++] to normal and that hypocalcemia occurring during low-flow states often cannot be corrected by calcium therapy alone. It is recommended that calcium replacement therapy be undertaken only with close monitoring of [Ca++].

Adolescent↗
PubMed1975

Effects of acid-base changes, hypoxia, and catecholamines on ventricular performance.

Extracellular pH changes were produced in dogs with tris (hydroxy-methyl)-aminomethane (Tris) or NaHCO3 in the presence or absence of hypoxemia and before and after beta-adrenergic blockade with propranolol. Ventricular performance (VP) was evaluated by measurement of maximum rate of rise of left ventricular pressure (dp/dt max) and left ventricular end-diastolic pressure in the canine right heart bypass preparation with aortic pressure, heart rate, and cardiac output held constant. Low pH diminished VP. Hypoxemia did not alter VP within the pH, suggesting that decreased V observed with acidosis before propranolol was due primarily to decreased myocardial response to catecholamines. Increase of pH with Tris increased VP significantly more than with NaHCO3. Beta blockade diminished the response of VP to Tris at a high pH;prior administration of reserpine abolished the inotropic effect of Tris. The data suggest that Tris can influence VP independent of its effect on pH. This effect is probably mediated by the interaction between endogenous catecholamines and myocardial beta receptors.

Acid-Base Equilibrium↗