Background Diabetes mellitus causes the deterioration of smooth muscle cells and interstitial matrix proteins, including collagen. Collagen and smooth muscle cells are abundant in the lungs, but the effect of diabetes on airway function and viscoelastic respiratory tissue mechanics has not been characterized. This study investigated the impact of diabetes on respiratory function, bronchial responsiveness, and gas exchange parameters. Methods Rats were allocated randomly to three groups: a model of type 1 diabetes that received a high dose of streptozotocin (DM1, n = 13); a model of type 2 diabetes that received a low dose of streptozotocin with a high-fat diet (DM2, n = 14); and a control group with no treatment (C, n = 14). Forced oscillations were applied to assess airway resistance (Raw), respiratory tissue damping (G), and elastance (H). The arterial partial pressure of oxygen to the inspired oxygen fraction (PaO2/FiO2) and intrapulmonary shunt fraction (Qs/Qt) were determined from blood gas samples at positive end-expiratory pressures (PEEPs) of 0, 3, and 6 cmH2O. Lung responsiveness to methacholine was also assessed. Collagen fibers in lung tissue were quantified by histology. Results The rats in groups DM1 and DM2 exhibited elevated Raw, G, H, and Qs/Qt, compromised PaO2/FiO2, and diminished airway responsiveness. The severity of adverse tissue mechanical change correlated with excessive lung collagen expression. Increased PEEP normalized the respiratory mechanics, but the gas exchange abnormalities remained. Conclusions These findings indicate that diabetes reduces airway and lung tissue viscoelasticity, resulting in alveolar collapsibility that can be compensated by increasing PEEP. Diabetes also induces persistent alveolo-capillary dysfunction and abnormal adaptation ability of the airways to exogenous constrictor stimuli.

No abstract

Changes in lung mechanics are frequently inferred from intact-chest measures of total respiratory system mechanics without consideration of the chest wall contribution. The participation of lungs and chest wall in respiratory mechanics has not been evaluated systematically in small animals commonly used in respiratory research. Thus, we compared these contributions in intact-chest mice, rats, and rabbits and further characterized the influence of positive end-expiratory pressure (PEEP). Forced oscillation technique was applied to anesthetized mechanically ventilated healthy animals to obtain total respiratory system impedance (Zrs) at 0, 3, and 6 cmH2O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Zrs into pulmonary (ZL) and chest wall (Zcw) components. A model containing a frequency-independent Newtonian resistance (RN), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Zrs, ZL, and Zcw spectra. The contribution of Zcw to RN was negligible in all species and PEEP levels studied. However, the participation of Zcw in G and H was significant in all species and increased significantly with increasing PEEP and animal size (rabbit > rat > mice). Even in mice, the chest wall contribution to G and H was still considerable, reaching 47.0 ± 4.0(SE)% and 32.9 ± 5.9% for G and H, respectively. These findings demonstrate that airway parameters can be assessed from respiratory system mechanical measurements. However, the contribution from the chest wall should be considered when intact-chest measurements are used to estimate lung parenchymal mechanics in small laboratory models (even in mice), particularly at elevated PEEP levels. NEW & NOTEWORTHY In species commonly used in respiratory research (rabbits, rats, mice), esophageal pressure-based estimates revealed negligible contribution from the chest wall to the Newtonian resistance. Conversely, chest wall participation in the viscoelastic tissue mechanical parameters increased with body size (rabbit > rat > mice) and positive end-expiratory pressure, with contribution varying between 30 and 50%, even in mice. These findings demonstrate the potential biasing effects of the chest wall when lung tissue mechanics are inferred from intact-chest measurements in small laboratory animals.

Diabetes mellitus involves a group of chronic metabolic disorders with elevated blood glucose concentrations. Since this disease needs lifelong treatment and care, the medical and social aspects present major public health concerns and pose a global challenge for health care providers. The number of aged patients with degenerative diseases undergoing surgical procedures is continuously increasing, resulting in an overwhelming dominance of diabetes in the perioperative care. There is a particular need for an increased awareness of diabetic patients in cardiovascular units, where the incidence of this disease reaches as high as 30–40%. The main hallmarks of the pathologic metabolic milieu of diabetes are hyperglycaemia, insulin resistance and pathologic lipid metabolism. The biochemical, cellular and organ-level pathophysiological changes lead to endothelial dysfunction including a low-grade prothrombotic balance, inflammatory state and, as a consequence, impaired micro- and macrocirculation. Diabetes is also followed by platelet dysfunction resulting from intracellular hyperglycaemia, because thrombocytes have insulin-independent glucose transporters in their cell membrane. The levels of the coagulation factors of the plasma are increased, and these factors are also modified by oxidation and glycation. Diabetes mellitus is a prothrombotic condition resulting from direct and indirect tendencies of the endothelial platelet and the plasma coagulation factors. The basic “bench to clinical basics” knowledge of the endothelial dysfunction and prothrombotic balance in diabetes may contribute to the better understanding of the clinical focuses in the perioperative care of patients with diabetes mellitus. Orv Hetil. 2018; 159(33): 1335–1345.