Biomedical subjects

K R Walley

Publications and source records attributed to K R Walley.

66 records · Page 4Linked to original sources

PubMed1991

Effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium.

The separate effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium were compared in 10 papillary or trabecular muscles superfused using control (95% O2-5% CO2), hypoxic (18% O2), and hypercapnic (20% CO2) physiological salt solutions. This level of hypoxia did not irreversibly damage the muscles and reduced peak isometric force by 53 +/- 11%. The level of hypercapnia was chosen to match the force depression (50 +/- 12%) produced by hypoxia. Multiple force-velocity points were measured by applying critically damped isotonic force steps at 90% of the time to peak isometric force and at the time to 50% peak isometric force. These points defined the force-velocity relation and maximum velocity of shortening, the extrapolated isometric force, and the maximum power of nonpotentiated and postextrasytolic potentiated contractions. Hypoxia and hypercapnia reduced maximum force and maximum power nearly equally. Maximum velocity of shortening decreased more during hypoxia (21 +/- 12%) than during hypercapnia (12 +/- 9%) (p less than 0.01). Postextrasystolic potentiation completely reversed the reduction of maximum velocity of shortening during hypercapnia but not during hypoxia. A 6% internal load could account for the reduction in maximum velocity of shortening during hypercapnia and all but 9% of the reduction in maximum velocity of shortening during hypoxia. The relative time course of the force-velocity relation was not altered by either hypoxia or hypercapnia. We conclude that hypercapnia reduces the effect of activation because increased activation (by postextrasystolic potentiation) restored the force-velocity relation and maximum velocity of shortening to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome.

We asked whether oxygen consumption is dependent on oxygen delivery in 17 patients who had severe adult respiratory distress syndrome (ARDS), 10 of whom had increased concentrations of plasma lactate. We determined oxygen consumption using analysis of respiratory gases while increasing oxygen delivery using blood transfusion. Oxygen consumption did not change after transfusion (from 227 +/- 83 to 225 +/- 82 ml/min, p less than or equal to 0.38). Oxygen delivery increased from 1,043 +/- 468 ml/min (24%, p less than or equal to 0.001). Even in the 10 patients who had increased concentration of plasma lactate and metabolic acidosis, oxygen consumption remained constant after increasing oxygen delivery (pretransfusion, 224 +/- 101 ml/min; post-transfusion, 225 +/- 99 ml/min; p less than or equal to 0.83). These data have more than 99% power of detecting a change in oxygen consumption of 20 ml/min after transfusion. Therefore, we conclude that directly measured oxygen consumption remains constant and independent of increases in oxygen delivery in our patients with severe ARDS. Because simultaneously determined oxygen consumption calculated from variables shared with the calculation of oxygen delivery yielded a dependent relationship, we speculate that finding dependence of calculated oxygen consumption on oxygen delivery may be the result of methodologic error.

Aged↗

PubMed1990

Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study.

STUDY OBJECTIVE: To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis. DESIGN: Prospective, randomized, blinded, crossover study. Each patient sequentially received sodium bicarbonate and equimolar sodium chloride. The order of the infusions was randomized. SETTING: Intensive care unit of a tertiary care hospital. PATIENTS: Fourteen patients who had metabolic acidosis (bicarbonate less than 17 mmol/L and base excess less than -10) and increased arterial lactate (mean, 7.8 mmol/L). All had pulmonary artery catheters and 13 were receiving catecholamines. MEASUREMENTS AND MAIN RESULTS: Sodium bicarbonate (2 mmol/kg body weight over 15 minutes) increased arterial pH (7.22 to 7.36, P less than 0.001), serum bicarbonate (12 to 18 mmol/L, P less than 0.001), and partial pressure of CO2 in arterial blood (PaCO2) (35 to 40 mm Hg, P less than 0.001) and decreased plasma ionized calcium (0.95 to 0.87 mmol/L, P less than 0.001). Sodium bicarbonate and sodium chloride both transiently increased pulmonary capillary wedge pressure (15 to 17 mm Hg, and 14 to 17 mm Hg, P less than 0.001) and cardiac output (18% and 16%, P less than 0.01). The mean arterial pressure was unchanged. Hemodynamic responses to sodium bicarbonate and sodium chloride were the same. These data have more than 90% power of detecting a 0.5 L/min (7%) change in mean cardiac output after administration of sodium bicarbonate compared with that after sodium chloride. Even the 7 most acidemic patients (mean pH, 7.13; range, 6.90 to 7.20) had no significant hemodynamic changes after either infusion. CONCLUSIONS: Correction of acidemia using sodium bicarbonate does not improve hemodynamics in critically ill patients who have metabolic acidosis and increased blood lactate or the cardiovascular response to infused catecholamines in these patients. Sodium bicarbonate decreases plasma ionized calcium and increases PaCO2.

Acidosis, Lactic↗

PubMed1990

Therapeutic use of intrinsic positive end-expiratory pressure.

A patient with acute hypoxemic respiratory failure undergoing mechanical ventilation with PEEP developed significant obstructive airway disease. We found that intrinsic PEEP, substituted for externally applied PEEP, could maintain oxygenation. The increased inspiratory/expiratory time ratio, which resulted in the development of intrinsic PEEP, beneficially reduced airway pressures.

Airway Obstruction↗

PubMed1990

Effect of lactic acidosis on canine hemodynamics and left ventricular function.

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.

Acidosis, Lactic↗

PubMed1990

Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs.

To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. Despite this, cardiac output increased (1.7 to 2.1 l/min, p less than 0.01), and heart rate increased (96 to 121 beats/min, p less than 0.05), with no change in blood pressure. Systemic vascular resistance fell by 26% (p less than 0.01). During eucapnia, propranolol reduced Emax (11.4 to 4.6 mm Hg/ml, p less than 0.01) with no change in V0. After propranolol treatment, respiratory acidosis further reduced Emax (4.6 to 3.6 mm Hg/ml, p less than 0.05) and increased end-systolic volume more than before propranolol (p less than 0.001). Now cardiac output did not increase even though heart rate increased (81 to 106 beats/min, p less than 0.001) and systemic vascular resistance fell by 20% (p less than 0.01). We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.

Acidosis, Respiratory↗

PubMed1990

The mechanism of respiratory arrest in inspiratory loading and hypoxemia.

Respiratory arrests occur in the clinical setting of respiratory failure, but the mechanism is unclear. We used a dog model with increased inspiratory resistance and hypoxemia to explore the cause. We hypothesized that respiratory muscle fatigue (RMF) played a role in these respiratory arrests, and that the combination of hypoxia and resistive loading would produce respiratory arrest by the mechanism of RMF. Our preparation had transdiaphragmatic pressures that were 40% of maximum (Pdimax = 46.3 +/- 10.0 cm H2O) and progressive hypoxia resulting in a final arterial PO2 of 38 +/- 9 mm Hg and a phrenic vein O2 content of 1.8 +/- 1.1 mg/dl. Instead of failure associated with carbon dioxide retention and RMF, we saw a rapid decrease in tidal volume and respiratory rate, leading to apnea over 30 to 60 s while the diaphragm still responded with significant pressure generation when externally stimulated. These results suggest that respiratory muscle fatigue may not be a major factor in respiratory arrests associated with inspiratory loading and hypoxia, but that suppression of central drive, induced by the combination of inspiratory loading and hypoxemia, may be important.

Acid-Base Equilibrium↗

PubMed1989

Comparison of the effects of different inotropic interventions on force, velocity, and power in rabbit myocardium.

To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that it would be unlikely to cause substantial chemical changes in the contractile proteins and that most of the effects would be due to changes in the level of activation. The effects of a digitalis analogue (acetylstrophanthidin), an adrenergic agent (isoproterenol), and a methylxanthine (caffeine) were then compared with those of postextrasystolic potentiation. The conditions were chosen so that each agent caused a twofold increase in twitch force. Acetylstrophanthidin and postextrasystolic potentiation caused twitch force to increase with only a slight (11%) decrease in time to peak force. Isoproterenol caused the peak of the twitch to occur substantially (40%) earlier with marked abbreviation of the twitch. Caffeine had the opposite effect: time to peak force was delayed (by 60%), and the twitch was markedly prolonged. In contrast to the marked differences in the time course of the twitch, there was no significant difference between the instantaneous force-velocity curves obtained with the different interventions. All four interventions caused maximum velocity to increase slightly (1-9%) and maximum power to increase only slightly more than twitch force (5-21%). All of the changes observed can be accounted for by changes in activation, either by an increase in the amount of calcium released into the myofilament space or by a change in the sensitivity of the myofilaments to calcium. There was no need to postulate direct changes in the contractile machinery to account for these results.

Animals↗

PubMed1988

Progressive hypoxemia limits left ventricular oxygen consumption and contractility.

To study the cardiac effects of progressive hypoxemia, we measured the left ventricular end-systolic pressure-volume relation (ESPVR), myocardial oxygen consumption (MVO2), and myocardial oxygen delivery (MQO2) in eight thoracotomized dogs anesthetized with fentanyl and droperidol. We specifically looked for evidence of oxygen supply limitation of MVO2 and depressed contractility (altered ESPVR) during stepwise decreases in inspired oxygen fraction. We hypothesized that the reported relation between MVO2 and left ventricular pressure-volume area (PVA) may hold when inadequate MQO2 determines MVO2, which then may limit PVA, manifested partly as a change in the ESPVR. Initially, as arterial oxygen saturation was decreased from 95 +/- 3% to 64 +/- 14%, coronary blood flow increased so that MQO2 was maintained with no change in myocardial extraction ratio (ERm = MVO2/MQO2). During this first phase, lactate utilization, PVA, and ESPVR did not change. When oxygen saturation was further reduced, coronary blood flow rose no higher and ERm increased, but not enough to maintain MVO2. Lactate consumption decreased and ST segments rose, signaling a change from aerobic metabolism. MVO2 decrease was associated with a fall in PVA, which was due to a fall in blood pressure and a significant depression of the ESPVR. Specifically, the volume intercept of the ESPVR increased in all dogs (6.5-20.1 ml, p less than 0.0001), accounting for two thirds of the increase in end-systolic volume. The slope of the ESPVR decreased during hypoxia (13.3-6.1 mm Hg/ml, p less than 0.02), accounting for only one third of the observed increase in end-systolic volume. We believe that the evidence of anaerobic metabolism, the decrease in PVA, and the depression of the ESPVR demonstrates onset of oxygen supply limitation of MVO2. Our data are consistent with the hypothesis that limited MVO2 may limit PVA. The hypoxic volume intercept alteration of the ESPVR is different from changes in the slope of ESPVR seen with other interventions. This may be analogous to recent observations in isolated muscle that show hypoxic depression in contractility to be different from other interventions.

Animals↗

PubMed1984

Ventilatory muscles during exercise in air and oxygen in normal men.

To determine whether normal ventilatory muscles fatigue during short-term high-intensity exercise, we measured diaphragmatic electromyogram (EMG, esophageal electrode), and pleural (Ppl), gastric (Pga), and transdiaphragmatic (Pdi) pressures in seven normal young men. On separate days, the subjects performed exercise to exhaustion at a constant work load (80% maximum power output) inspiring air or 40% O2. Before and after exercise, Pdimax and maximum expiratory pressure at the mouth (PEmax) were measured. At 0.5-2 min postexercise, there was a decrease in Pdimax in both air (P less than 0.02) and O2 studies (P less than 0.05). There was some recovery in Pdimax from 2-5 min postexercise in air (P less than 0.05) and complete recovery 2-5 min postexercise in O2. PEmax did not change postexercise. During exercise in air, the EMG predicted diaphragmatic fatigue in five subjects using a 20% fall of the ratio of high-frequency (150-350 Hz) to low-frequency) (20-46 Hz) power (H/L) as the criterion. Further evidence of diaphragmatic fatigue during exercise in air in two subjects was the decrease in end-inspiratory Pdi toward end exercise. There was an increase in exercise time with O2 (P less than 0.05). The improved performance in O2 was associated with a delay in the fall in H/L and the absence of the decrease in end-inspiratory Pdi in those subjects in whom such changes were observed in air.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1982

Left ventricular dynamic geometry in the intact and open chest dog.

No approach to describing the heart's dynamic geometry has been widely adopted, probably because all require questionable assumptions of chamber shape, symmetry, or placement of the measuring devices. In other words, these approaches require assumptions about shape to reach conclusions about shape. We present an analysis that avoids such assumptions and provides an objective description of how the left ventricle deforms and rotates during the cardiac cycle. We only assume that the deformation of the left ventricular cavity is homogeneous, and explicitly validate this assumption. Our analysis yields the following new information about the contracting left ventricle: three principal directions of deformation and the relative length change alone these directions: the axis and angle of rotation, and relative volume. All these changes are referenced to the ventricle's configuration at end-diastole. We instrumented 13 dogs with tantalum screws without opening their chests. During systole, the three principal directions of deformation essentially are aligned along apex-base, anterior-posterior, and septum-free wall directions. There is little length change in the apex-base direction. The anterior and septal principal directions do not remain fixed with respect to the heart's anatomy during systole. During isovolumic relaxation and early filling, systolic shape changes are reversed. During slow filling, only small shape changes occur. Opening the pleura or performing a sternotomy and pericardiectomy makes the heart change orientation within the chest, but does not alter the magnitude of shortening, relative to the left ventricle's end-diastolic configuration.

Animals↗

PubMedDate not supplied

Potential deleterious effect of beta-adrenergic stimulation during warm-blood cardioplegia in rabbit hearts.

We hypothesized that beta-adrenergic stimulation with isoproterenol during continuous normothermic cardioplegic arrest would enhance the regenerative and regulatory function of the myocardium, resulting in improved cardiac function. We studied isolated rabbit hearts paced at approximately 200 beats per minute (bpm) and perfused by a support rabbit. We measured ventricular pressure over a range of ventricular volumes to determine maximal elastance (Emax) at baseline and 20 and 45 min after discontinuation of cardioplegia. Myocardial oxygen consumption (MVO2) measurements were performed simultaneously and during cardioplegic arrest. Hearts were prospectively randomized to receive either isoproterenol at 0.1 M or control in blinded fashion for 10 min during a 1-h continuous warm-blood cardioplegic arrest. Compared to control hearts, isoproterenol-treated hearts had trends toward longer time to first spontaneous heartbeat (control 141 +/- 43 vs. isoproterenol 200 +/- 74 s, p = .07), and longer time to capture of atrial pacing (control 214 +/- 52 vs. isoproterenol 288 +/- 91 s, p = .06). There was no difference observed in the MVO2 between isoproterenol-treated and control groups of hearts. MVO2 decreased during cardioplegia (p < .01), but there was no significant change in MVO2 during isoproterenol infusion during cardioplegic arrest. There was a significant reduction in Emax compared to baseline 20 min after discontinuation of cardioplegic arrest in both groups (control 7.3 +/- 1.7 mm Hg/microL vs. 9.0 +/- 1.7 mm Hg/microL, p = .02, isoproterenol-treated 6.8 +/- 2.8 mm Hg/microL vs. 8.2 +/- 2.6 mm Hg/microL, p = .01, respectively), with recovery of Emax by 45 min in control hearts only. We conclude that exposure of hearts to isoproterenol during warm cardioplegic arrest has a deleterious effect that may be mediated through mechanisms independent of increased myocardial oxygen consumption.

Adrenergic beta-Agonists↗