Respiratory dysfunction in unsedated dogs with golden retriever muscular dystrophy

Abstract

Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation.

Keywords: Blood gas analysis; Flow-volume loop; Golden retriever muscular dystrophy; Muscular dystrophy; Pulmonary function test; Respiratory inductance plethysmography; Spirometry.

Figure 1

Tidal breathing flow-volumes (F-V) loops of 10 representative breaths from two control dogs (A, B) and two GRMD dogs (C,D) displayed on graphs with identical scales. These dogs were selected as representative of their groups based on peak tidal expiratory flows that were closest to the median value for their group. The loops from GRMD dogs show visibly greater expiratory flows (positive values) compared with inspiratory flows (negative values) and compared with expiratory flows from control dogs.

Figure 2

Example RIP tracings and Konno-Mead plots of 1 control dog and 3 GRMD dogs. The raw output (volts) from the rib cage band (Vrc) and the adbomen band (Vab) are plotted against time in the rectangular boxes, and against each other in the square (Konno-Mead) boxes. The raw output was not calibrated or standardized. The control dog shows a synchronous pattern with coordination between rib cage and abdominal motion and the Konno-Mead plot has a positive slope. All control dogs and 3 GRMD dogs had similar patterns. GRMD Dogs 1-3 have two peaks of abdominal motion for each expansion of the rib cage. The first peak occurs at or near peak expansion of the rib cage. The second occurs during expiration. The size of the second abdominal peak is progressively larger compared with the first in these dogs. In total, five GRMD dogs had a pattern similar to GRMD Dog 1. The Konno-Mead plot shows a progressively deeper “C” shape in GRMD dogs 1 through 3. Tracings obtained from GRMD Dogs 2 and 3 without a face mask in place show relatively greater abnormal abdominal motion, with GRMD Dog 2 demonstrating complete paradoxical breathing.