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Biomedical subjects

M B Laver

Publications and source records attributed to M B Laver.

At least 19 recordsLinked to original sources

Cardiovascular adjustments to pulmonary vascular injury in dogs.

The hemodynamic effects of blood volume augmentation and mechanical ventilation (MV) with positive end-expiratory pressure (PEEP) were studied in nine Beagles anesthetized with halothane before and after thrombin-induced pulmonary hypertension. The effect of therapy with dopamine, norepinephrine with and without nitroglycerin (NTG), and intraaortic balloon pumping (IABP) were studied in a second series of six Beagles. Before thrombin, dextran (35 ml.kg-1) caused a significant increase in right and left ventricular end-diastolic and end-systolic volumes (RV and LVEDV, and RV and LVESV). However, RV and LV performance, as estimated by ejection fraction, was unchanged during volume loading and MV with PEEP when the pulmonary vasculature was intact. The response to volume loading and MV with PEEP was altered significantly once PVR had been increased with the administration of thrombin. Stroke volumes were decreased, and remained so, despite volume loading and MV with PEEP. LVEDV decreased without a decrease in LVEDP, indicating a decreased LV compliance. Dopamine and norepinephrine with and without NTG increased stroke volumes and RV ejection fraction in contrast to IABP. Assessment of LV performance, according to the Frank-Starling mechanism, requires a measure of end-diastolic volume when diffuse pulmonary vasoconstriction leads to RV distension and LV hypovolemia secondary to septal shift. Measurement of LV filling pressures can provide misleading values to estimate changes in LV volume in this setting. Measurement of ventricular volumes is required for optimal management of patients with severe acute respiratory failure and pulmonary hypertension.

Animals

Dependency of O2-affinity effects on O2 consumption in the isolated rat heart.

We have studied the effect of a decrease in hemoglobin-O2 affinity (increased P50) on O2 delivery in the non-paced, isolated, blood-perfused rat heart before and after coronary vasodilatation with and without an increase in myocardial O2 consumption (MVO2) produced with isoproterenol. Changes in perfusate P50 were produced with orthoiodosodium benzoate (OISB). Low concentrations of isoproterenol (0.74 micrograms/liter) caused no significant changes in coronary blood flow (QCOR) or MVO2 per beat. Perfusion with OISB-treated (8 mM) blood increased P50 from 29 to 33 mmHg at constant pH. MVO2 per beat increased significantly, QCOR did not change, and the ratio QCOR/MVO2, a reflection of the flow/metabolism distribution, decreased to values obtained in the absence of isoproterenol. With high doses of isoproterenol (5.0 micrograms/liter), MVO2 per beat and QCOR/MVO2 increased. Addition of OISB (13 mM) increased P50 from 29 to 39 mmHg, with no significant reduction in either QCOR or the QCOR/MVO2 ratio. Our data suggest that a decrease in blood-O2 affinity affects myocardial O2 delivery depending on the initial metabolic requirement: at basal MVO2 changes in the distribution of myocardial blood flow are probably secondary to the effects of PO2 on vessels that supply metabolically less active regions; at high MVO2 and following a maximum increase in capillary density, changes in vascular PO2 appear less effective than locally generated metabolic vasodilators, and distribution of blood flow is unaffected.

Animals

Accuracy of serial myocardial perfusion scintigraphy with thallium-201 for prediction of graft patency early and late after coronary artery bypass surgery. A controlled prospective study.

To assess the accuracy of serial myocardial perfusion scintigraphy with thallium-201 (201Tl) to predict graft patency early and late coronary artery bypass surgery, rest and exercise 201Tl and coronary arteriography were performed preoperatively and 2 weeks and 1 year after operation. The scintigraphic results were compared with graft patency, symptoms, left ventricular function and physical work capacity in a consecutive series of 55 patients with a total of 154 grafts. Serial 201Tl had an 80% sensitivity, 88% specificity and 86% overall accuracy in detecting or excluding graft occlusion, which was predicted by reversible ischemia as well as persistent "new scar" segments. Occluded grafts were correctly localized by 201Tl scintigraphy in 61%. Postoperative apical 201Tl defects were frequent (two-thirds of cases), and were the result of intraoperative transapical venting of the left ventricle. After coronary bypass graft surgery, ejection fraction at rest was unchanged. Left ventricular end-diastolic pressure and physical work capacity improved significantly. In the presence of new perfusion defects detected postoperatively, physical work capacity was reduced significantly. New 201Tl defects in addition to typical or atypical angina provided a high probability of graft occlusion, while in the absence of new 201Tl defects all grafts were patent in more than 90% of patients, all of whom had no or only atypical chest pain. We conclude that serial 201Tl imaging after coronary artery bypass surgery is an accurate noninvasive method that can be used routinely to assess graft function, to localize spatially occluded grafts and to identify patients with a high likelihood of graft occlusion who may need invasive studies.

Angina Pectoris

[Hemodynamic changes in acute respiratory insufficiency: the role of the right ventricle].

Acute respiratory failure, particularly if associated with sepsis, results in diffuse changes in pulmonary vascular geometry and the afterload characteristics against which the right ventricle must perform. Therapy in these patients frequently requires replacement of intravascular volume which, if pulmonary vascular resistance is abnormally elevated, may cause a substantial enlargement in right ventricular (RV) end-diastolic volume. The low compliance characteristics of the RV invalidate the use of filling pressure (CVP) as a guide to RV size. We have examined RV volume in critically ill patients by means of the gated 99TAc scan and noted a substantial increase in RV volume despite filling pressure in the upper normal range. This enlargement appears to encroach upon LV function because the ejection fraction of the LV remained high despite elevation of pulmonary capillary wedge pressure (PCWP). Older patients with "silent" right coronary artery disease may become hemodynamically limited during therapy for acute respiratory failure and sepsis due to RV enlargement, increased wall tension and RV ischemia, a condition not readily diagnosed at the bedside with the usual monitoring techniques.

Animals

Right ventricular dysfunction in acute thermal injury.

The elevated cardiac output (CO) and pulmonary artery hypertension (PAH) observed in thermal injury offers a unique opportunity to study the effects of a combined pressure-flow load on the right ventricle in previously healthy persons. Potential responses include a diminished right ventricular ejection fraction (RVEF), increased right ventricular end-diastolic volume index (RVEDVI), and augmented myocardial oxygen consumption because of increased systolic wall tension. We investigated these factors in 15 nonhypoxic patients without sepsis having 15--75% body surface area burns using flow directed catheters and the thermodilution technique. All patients increased their CO in response in fluid resuscitation, but six patients with an elevated mean pulmonary artery pressure (greater than 20 mmHG and increased pulmonary vascular resistance (greater than 1.2 mmHg/min/L) had right ventricular dysfunction as evidenced by an increase (188 +/- 15 ml/M2) in RVEDVI and a decreased (0.26 +/- 4 ml/M2) RVEF. Patients without PAH had a smaller RVEDVI (115 +/- 4 ML/M2) and larger RVEF (0.39 +/- 0.02). Patients with PAH and RV dysfunction were older, had larger body surface area burns, lower systemic diastolic artery pressures (63 +/- 4 mmHg) and higher heart rates (114 +/- 7 beats/min); RV end-diastolic pressures were minimally elevated (9.5 +/- 1.4 mmHg). The decrease in RVEF and increase in RVEDVI may limit the hemodynamic response to fluid volume replacement and survival.

Acute Disease

Effects of chronic changes in hemoglobin-O2 affinity in rats.

We have assessed the characteristics of oxygen transport following chronic intraperitoneal administration of sodium cyanate (NaCNO, 90 mg/kg; P50 decreased), o-iodosodium benzoate (OISB, 300 mg/kg; P50 increased), or sodium chloride (NaCl; P50 unchanged) to rats at a rate of 5 times/wk for 16 wk. At the end of this period, the animals were exposed to a low inspired O2 concentration and were subjected to exercise stress. Hill's n50 at pH 6.90-7.60, hematocrit, and the saturation dependency of the Bohr effect (PCO2 constant) were altered by NaCNO only. Cyanate-treated rats gained less weight, probably due to a toxic side effect of the drug. Hypoxemia-induced lactatemia was greatest with a high P50 (OISB). Physical effort (swimming) was tolerated poorly at normal arterial PO2 when P50 was low (NaCNO). Although a left-shifted curve appears beneficial when FIO2 is reduced, reasons for the physiological advantage may be the result of other characteristics of the O2 dissociation curve, not P50 alone.

Animals

Ventricular pump performance during hypocalcemia: clinical and experimental studies.

We have compared indices of ventricular function during rapid transfusion of citrated (1.5 ml/kg/min) or heparinized (1.5 ml/kg/min) autologous blood in six patients following discontinuation of cardiopulmonary bypass. Infusion of citrated blood was associated with a lowering of plasma ionized calcium concentration ([Ca++], from 0.90 +/- 0.04 to 0.71 +/- 0.4 mM, p less than 0.001) and an increase in pulmonary artery balloon-occluded pressure (PA0, from 9.4 +/- 2.6 to 15.5 +/- 1.7 mm Hg, p less than 0.u1), without a change in left ventricular stroke work index, stroke index, or cardiac index. Transfusion of heparinized blood caused no change in plasma [Ca++]. A rise in PA0, which was similar in magnitude to that observed during citrated blood transfusion, was associated with increased left ventricular stroke work index, stroke index, cardiac index, and mean arterial pressure. Although data obtained during citrated blood transfusion suggest the presence of transient left ventricular dysfunction, its magnitude is not readily expressed in terms of ventricular function curves when accompanied by a simultaneous change in [Cized closed-chest dog by volume loading during hypocalcemia, when mean arterial pressure, heart rate, and [Ca++] were in a steady state, both prior to and following beta blockade with propranolol. Function curves obtained during severe hypocalcemia ([Ca++] = 0.43 +/- 0.02 mM) were shifted significantly to the right and downward, when compared to those obtained during normocalcemia ([Ca++] = 1.06 +/- 0.03 mM). Hypocalcemia combined with beta blockade resulted in severe left ventricular failure, as demonstrated by a flat ventricular function curve.

Aged

The effect of hemodilution with albumin or Ringer's lactate on water balance and blood use in open-heart surgery.

To determine the effect of intraoperative albumin administration on blood use, water balance, and postoperative clinical course, we studied two groups of adult cardiac surgical patients. Group I (30 patients) received 25 gm of albumin during withdrawal of 2 units of blood prior to cardiopulmonary bypass (CPB) and 50 gm of albumin in the oxygenator prime. Group II (32 patients) received no albumin prior to the end of CPB. No difference in clinical course could be identified, nor was there a significant difference in blood use. Group I patients had lower hematocrit values intraoperatively from the time of blood withdrawal until the conclusion of operation. Coronary artery bypass operations were associated with greater positive water balance than were heat valve operations. Forty-three percent of the patients having coronary artery bypass grafting had a positive water balance greater than 5 liters, whereas 50% of those undergoing valve procedures had a balance less than 3 liters. We conclude that the principal effect of withholding albumin under these circumstances is to increase net positive water balance. The greater positive water balance does not appear to be detrimental.

Adult

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