Fri., 10/19/07 Basic Science, Paper #45, 5:00 pm OTA-2007
Δ Time is Muscle: An Experimental Model of Compartment Syndrome
Abdel Lawendy, MD1; David Sanders, MD, MSc2; Aurelia Bihari, MSc3; Neil Parry, MD2; Daryl Gray, MD2; Amit Badhwar, PhD3;
(all authors: a-OTA/Foundation for Orthopaedic Trauma Resident Research Grant);
1University of Western Ontario, London, Ontario, Canada;
2Victoria Hospital, Lawson Health Research Institute, University of Western Ontario,
London, Ontario, Canada;
3Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada
Purpose: Elevated intracompartmental pressure (ICP) results in microcirculatory impairment and tissue damage. The nature of microcirculatory impairment and the mechanisms by which cellular damage occur are poorly understood. This study determined the effect of increased ICP on skeletal muscle microcirculation, inflammation, and cell viability using intravital videomicroscopy in an animal model. We hypothesized that an elevation in ICP would result in a time-dependent decrease in perfusion and increased cellular damage and inflammation.
Methods: 20 adult male Wistar rats were randomized to four groups: the control group (control) had no intervention, while three experimental groups had elevated ICP maintained for 15 (15m), 45 (45m), or 90 (90m) minutes. Compartment pressure was continuously monitored and controlled between 30 and 40 mmHg in the posterior hindlimb compartment using saline infusion into the anterior hindlimb compartment. Mean arterial pressure was maintained between 80 and 120 mmHg. Fasciotomy was then performed and the extensor digitorum longus muscle studied using intravital videomicroscopy. Perfusion was measured by comparing the number of continuously, intermittently, and nonperfused capillaries. Inflammation was measured by counting the number of activated (rolling and adherent) leukocytes in postcapillary venules. Muscle cellular injury was measured using fluorescent vital staining of injured cell nuclei.
Results:
Perfusion: The number of continuously perfused capillaries decreased from 77 ± 3/mm (control) to 46 ± 10/mm (15m), 40 ± 10/mm (45m), and 27 ± 8/mm (90m) (P <0.05). Nonperfused capillaries increased from 13 ± 1 (control) to 16 ± 4 (15m), 30 ± 7 (45m), and 39 ± 5 (90m) (P <0.05).
Inflammation: Activated leukocytes increased from 3.6 ± 0.7/(100μ)2 (control) to 5.9 ± 1.3 (15m), 8.6 ± 1.8 (45m), and 10.9± 3.0/(100μ)2 (90m) (P <0.01).
Injury: The proportion of injured cells increased from 5 ± 2% in the control group to 12 ± 3 (15m), 16 ± 7% (45m), and 20 ± 3% (90m) (P <0.05).
Conclusion: As little as 15 minutes of 30 mmHg ICP caused irreversible muscle damage and microvascular dysfunction. With increased duration, further decreases in capillary perfusion and increases in injury are noted. A severe inflammatory response accompanies
elevated ICP. The role of inflammation in compartment syndrome is unknown, but may contribute to cell injury and reduced capillary perfusion.
Significance: This study establishes an animal model to examine the microcirculatory and inflammatory changes associated with elevated ICP. Secondly, our understanding of the time-dependent nature of changes in perfusion, inflammation, and cellular injury associated with elevated compartment pressure is improved. Finally, the significant muscle damage associated with a short duration of elevated ICP noted in this study suggests that a time threshold for irreversible muscle injury associated with elevated compartment pressure may not exist; but rather, a time-dependent increase in the amount of muscle cells damaged occurs.
If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.
• The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an “off label” use). ◆FDA information not available at time of printing.