We previously showed that severe inspiratory resistive loads cause acute (<1 h) cardiorespiratory failure characterized by arterial hypotension, multifocal myocardial infarcts, and diaphragmatic fatigue. The mechanisms responsible for cardiovascular failure are unknown, but one factor may be the increased ventricular afterload caused by the large negative intrathoracic pressures generated when breathing against an inspiratory load. Because expiratory threshold loads increase intrathoracic pressure and decrease left ventricular afterload, we hypothesized that anesthetized rats forced to breathe against such a load would experience only diaphragmatic failure. Loading approximately doubled end-expiratory lung volume, halved respiratory frequency, and caused arterial hypoxemia and hypercapnia, respiratory acidosis, and increased inspiratory drive. Although hyperinflation immediately reduced the diaphragm's mechanical advantage, fatigue did not occur until near load termination. Mean arterial pressure progressively fell, becoming significant (cardiovascular failure) midway through loading despite tachycardia. Loading was terminated (endurance 125 ± 43 min; range 82–206 min) when mean arterial pressure dropped below 50 mmHg. Blood samples taken immediately after load termination revealed hypoglycemia, hyperkalemia, and cardiac troponin T, the last indicating myocardial injury that was, according to histology, mainly in the right ventricle. This damage probably reflects a combination of decreased O2 delivery (decreased venous return and arterial hypoxemia) and greater afterload due to hyperinflation-induced increase in pulmonary vascular resistance. Thus, in rats breathing at an increased end-expiratory lung volume, cardiorespiratory, not just respiratory, failure still occurred. Right heart injury and dysfunction may contribute to the increased morbidity and mortality associated with acute exacerbations of obstructive airway disease.
Respiratory Acidosis
