Clarence A. Guenter

The pulmonary ultrastructure in septic shock

Abstract The ultrastructural alterations in the lungs of the monkey after intravenously administered lethal injections of live E. coli organisms or endotoxin are markedly similar. Edema of the perivascular space was seen in all lung tissues examined. Pulmonary capillaries were engorged with polymorphonuclear leukocytes undergoing fragmentation 15 minutes after injections of endotoxin or E. coli organisms. The endothelial cytoplasm contained large vacuoles and many vesicles, but there was no evidence of actual rupture of the cytoplasmic membranes. Endothelial cellular membranes appeared fuzzy and indistinct at sites where polymorphonuclear leukocytes were adhering. Fragmentation and loss of specific granules in polymorphonuclear leukocytes were noted 1 hour postinjection. The loss of specific granules, fragmentation of polymorphonuclear leukocytes, and focal areas of pulmonary edema were observed 4 hours after the injection of endotoxin or live E. coli organisms. In marked contrast to a previous report on the primate administered endotoxin, this investigation revealed no evidence for intravascular coagulation of fibrin and platelet aggregates. The widespread morphological alterations could explain some of the functional derangements previously observed in monkeys in shock.

Antitrypsin Deficiency in Pulmonary Disease: The Significance of Intermediate Levels

Abstract Deficiency of serum alpha1antitrypsin is inherited as an autosomal recessive trait, with the homozygous state manifested by severe deficiency and the heterozygous state by intermediate lev...

Pathophysiology of the Pulmonary Circulation in Emphysema Associated with Alpha1 Antitrypsin Deficiency

Patients with homozygous alpha1 antitrypsin deficiency present a unique opportunity for evaluation of the pulmonary vasculature in primary emphysema. In five patients, the detailed angiographic appearance of small (0.2-2.0 mm diameter) muscular pulmonary arteries, shown by wedge arteriography, was correlated with the results of right heart catheterization during the control hypoxemic state (average arterial Po2 50 mm Hg), the administration of oxygen (average arterial Po2 90 mm Hg), and a constant infusion of aminophylline. In all patients, wedge arteriograms in the lower zones of the lungs showed a sparsity of arborization and a diminished background blush of capillary filling. These abnormalities were in the areas of diminished pulmonary blood flow, as indicated by the pulmonary scintiscans and the capillary phase of pulmonary arteriograms. The administration of oxygen and of aminophylline produced an increase in the diameter of arteries 0.5 to 2 mm in diameter on the wedge arteriograms of some of the patients. The average pulmonary arterial mean pressure, 30 mm Hg, and average pulmonary vascular resistance, 300 dyne-sec-cm−5, were both elevated during the control hypoxemic state and decreased in each patient during the administration of oxygen and of aminophylline. This study demonstrates abnormalities of the small pulmonary arteries in patients with alpha1 antitrypsin deficiency. These abnormalities may be responsible for pulmonary hypertension and altered regional perfusion.

Acute Changes in Oxyhemoglobin Affinity EFFECTS ON OXYGEN TRANSPORT AND UTILIZATION

It has been postulated that 2,3-diphosphoglycerate (DPG)-mediated changes in oxyhemoglobin affinity play an important role in oxygen delivery; however, the effect of an acute increase in affinity without changing red cell mass has not been systematically evaluated. This study was designed to measure changes in oxygen transport and oxygen consumption produced by an acute increase in oxyhemoglobin affinity caused by an autologous exchange transfusion using DPG-depleted stored blood. From each of 10 5-kg rhesus monkeys, 100 ml of blood was taken on the 1st and 3rd wk of the study and each stored in 25 ml of acid-citrate-dextrose storage solution. On the 5th wk, each animal underwent an exchange transfusion with 200 ml of its stored blood. Hemodynamic data were obtained before and 30 min after transfusion. The oxyhemoglobin dissociation curve shifted to the left (P(50) changed from 33.9 to 27.2 mm Hg), as mean red cell DPG decreased from 28.6 to 12.7 mumol/g of hemoglobin. No significant change was noted in pH, P(CO2), base deficit, arterial or venous percent saturation of hemoglobin, cardiac output, or oxygen consumption. However, a fall in mixed venous P(O2) from 35.3 to 27.9 mm Hg occurred.Thus, an acute shift of the oxyhemoglobin curve to the left was accompanied by a significant decrease in the mixed venous P(O2) without evidence of acidosis, decreased oxygen consumption, or a compensatory increase in cardiac output.

Comparison of Septic Shock Due to Gram-Negative and Gram-Positive Organisms

Summary Cardiorespiratory effects of gram-negative and gram-positive septicemia were compared in the lightly anesthetized rhesus monkey. Thirty to 60 min after the onset of infusion of organisms, the cardiac output was higher and the peripheral resistance was lower in the group that received staphylococci, as compared to the group that received E. coli. Subsequently, the cardiac output decreased, systemic pressure decreased, minute ventilation increased, alveolo-arterial oxygen tension gradients increased and arterial PCo2 and bicarbonate decreased as previously described in septic shock and to a comparable degree in both groups. These findings suggest a common host response to gram-positive and gram-negative organisms.

Rapid onset of emphysema associated with diffuse parenchymal disease

In experimental models pulmonary emphysema may be produced in hours to days; however, in human subjects emphysema commonly develops over a period of many years. In this report we document a case of severe emphysema which developed in less than six months in association with an unexplained illness characterized by dyspnea, hypoxemia and bilateral lung parenchymal disease. There was no hereditary predisposition. The diffuse alveolar injury syndrome must be considered as a potential cause of alveolar disruption.

Physiologic Effects of Passive Hyperventilation on Oxygen Delivery and Consumption

Summary Numerous recent studies have emphasized the potential adverse effects of increased oxyhemoglobin affinity on oxygen delivery. Respiratory alkalosis increases the affinity of hemoglobin for oxygen, and is also associated with increased oxygen consumption. This study was designed to evaluate the effect of increased hemoglobin affinity for oxygen on oxygen transport and consumption during a period of respiratory alkalosis in a group of animals whose oxygen delivery system was already stressed by a decrease in red cell mass. Nine rhesus monkeys were anesthetized and studied before, during and 40 min after being hyperventilated. With hyperventilation, the arterial pH increased to 7.56 while base excess decreased from 3.5 to 1.3 mequiv/liter. Oxygen consumption increased from 5.5 to 11.4 cm3/min/kg and the in vivo P 50 (the PO 2 at which hemoglobin is 50% saturated) fell from 34.8 to 27.8 mm Hg as the oxyhemoglobin dissociation curve shifted to the left. No change was observed in 2, 3-diphosphoglycerate or in P 50 when corrected to pH 7.40. The increased oxygen consumption was maintained by an increase in the arterial-venous oxygen difference; cardiac output did not change with hyperventilation. The mixed venous PO 2 fell from 44 to 29 mm Hg: approximately half of the 15 mm Hg fall was due to the increased oxyhemoglobin affinity and half to the increased oxygen consumption. Thus, in this experimental model, oxygen consumption significantly increased during hyperventilation without changes in the cardiac output or evidence of anaerobic metabolism, even though hemoglobins affinity for oxygen had also increased. This resulted in a marked fall in the mixed venous PO 2. We express appreciation to Mr. Larry Tague, Mrs. Geraldine Imundo, Mr. Earle Berrell, and Miss Jane Harris for valuable technical assistance.

The Effect of Changes in Arterial pCO2 on Isogravimetric Capillary Pressure and Vascular Resistances

Summary The study was designed to determine the effect of a changing arterial pCO2 on capillary membrane permeability and pre- and postcapillary resistances. Experiments were carried out on isolated forelimbs of dogs perfused with blood equilibrated with different CO2 pressures in an isolated lung. Gas mixtures containing 0, 5, and 10% CO2 resulted in arterial mean pCO2 values of 12, 48 and 78 mm Hg. Isogravimetric capillary pressure (Pci ) was measured using a modified Pappenheimer and Soto-Rivera technique. Results show the mean Pci rising from 13 to 14.7 mm Hg (p = 0.04) after pCO2 was increased from 48 to 78 mm Hg. When the pCO2 was lowered to 12 mm Hg, Pci fell to 10.1 mm Hg (p = 0.016). Precapillary resistance fell with an increased pCO2 and rose with a decreased pCO2. Effects of pCO2 alters the permeability of the capillaries due to a direct action on the capillary membrane. The observed changes in capillary permeability are interpreted as a protective mechanism opposed to effects of alterations of capillary hydrostatic pressure resulting from changes in blood pCO2.