Chronic Upper Airway Obstruction Produces Right but Not Left Ventricular Hypertrophy in Rats

Abstract

With airway obstruction there is a decrease in inspiratory intrathoracic pressure. This could lead to increased venous return to the right ventricle (RV) and increased afterload imposed on the left ventricle (LV). Chronic upper airway obstruction, caused by either upper airway lesions or obstructive sleep apnea, is a cause of congestive heart failure because of a chronic resistive load imposed on the respiratory system. To determine the effects of chronic upper airway obstruction on RV and LV in adolescent rats, we chronically obstructed the trachea so as to considerably increased inspiratory esophageal pressure excursion (-3.7 +/- 2.2 to -29.4 +/- 10.1 cm H2O). Rats were studied at 7 wk (Group 1) and at 1 yr (Group 2) after tracheal banding. Sham-operated time-matched rats served as controls. In neither group was there evidence of arterial hypoxemia, but in both groups there was chronic hypercapnia (PCO2, approximately 51 mm Hg; bicarbonate, 27 to 28 mEq/ml). Hemoglobin was also normal in both groups, confirming the absence of chronic hypoxia. There were no significant differences between obstructed and control rats in lung, liver, and LV weight to body weight ratio. However, RV weight to body weight ratio was increased in obstructed rats compared with that in control rats in both groups by approximately 50% (p < 0.005). Thus, chronic normoxic airway obstruction leads to evidence of RV but not LV hypertrophy. We conclude that the mechanical effects of airway obstruction impose a chronically increased afterload on the RV, probably caused by venous return effects, but they have relatively little effect on the LV.

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

“…(12,13,24,26,27,34,35). Similar to adult CAL rats (12,13,27), our animals did not become hypoxic. Immediately following surgery, inspiratory swings in esophageal pressure increased and respiratory rate decreased, similar to the adult CAL rat model.…”

“…Total body energy balance (V O 2 /daily food intake), hemoglobin and lactate levels, and arterial oxygenation were similar to those of the control group, within normal physiological range (12,27). However, when severe upper airway loading was induced, adult rats exhibited a considerable decrease in body weight immediately after surgery that was related to reduction of food and water intake and hypoxemia (23).…”

“…Our laboratory has previously used a surgical technique to induce CAL (12,13,27,35) in 22-day-old prepuberty Sprague-Dawley rats. The study was approved by the Ben-Gurion University of the Negev Animal Use and Care Committee and complied with the American Physiological Society guidelines.…”

“…Immediately following surgery, inspiratory swings in esophageal pressure increased and respiratory rate decreased, similar to the adult CAL rat model. Thus resistive loading had been produced (12,13,27,34,35). Previously, it was demonstrated that CAL led to decreased respiratory rate and plethysmography inspiratory effort (index for tidal volume) accompanied with elevation of arterial PCO 2 (12,13).…”

“…ONE OF THE CONSEQUENCES OF chronic resistive airway loading (CAL) in adult rats is malfunction in body weight gain (12,27) without effect on longitudinal bone growth (35). The failure to gain weight was not related to decreased caloric intake (12) and was recently attributed to a decline in serum insulin-like growth factor I (IGF-I) levels (35).…”