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Low-volume binary drug therapy for the treatment of hypovolemia.
Shock 2011; 35(6):590-6S

Abstract

The selective regulation of total peripheral circulation in hypovolemic crisis offers a unique approach for treating and preventing hemorrhagic shock. Ideally, such a therapeutic intervention would require targeting of the striated muscle vascular beds without altering the vascular resistance in vital organ vascular beds. We discovered that a combination of cannabinoid receptor agonist, THC (Δ-tetrahydrocannabinol), and cyclooxygenase 2 inhibitor, NS-398, caused selective microvascular constriction in the mouse cremaster muscle manifested by a pronounced and significant 27.4% ± 7.9% decrease in vessel diameter relative to control (P < 0.01). This observation, and the reported lack of microvascular response in the mesentery and brain, led us to hypothesize that the drug combination could favorably redistribute blood volume in hypovolemia and prolong survival. To test the hypothesis, male Sprague-Dawley rats were subjected to a pressure-controlled hemorrhage (mean arterial pressure reduced to 30 ± 13.73 mmHg) then randomly assigned to one of six treatment groups (n = 6 per group). The untreated, NS-398-treated, and THC-treated groups manifested an insignificant difference in survival between groups after shock. The group treated with a combination of THC and NS-398 manifested a significant increase in mean survival from 53 ± 12 to 227 ± 23 min after shock (P < 0.001). The drug combination significantly reduced IL-1α, IL-1β, IFN-γ, and IL-10 production compared with the group resuscitated with normal saline. In addition, histological evaluation indicated that the therapy protects the lungs and liver against hemorrhagic shock-induced damage. The combination of cannabinoid receptor agonist and cyclooxygenase 2 inhibitor represents a potentially new approach to low-volume therapeutic intervention for hypovolemia.

Authors+Show Affiliations

University of Tennessee Health Science Center, Department of Pharmaceutical Sciences, Memphis, Tennessee, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21330941

Citation

Bhattacharjee, Himanshu, et al. "Low-volume Binary Drug Therapy for the Treatment of Hypovolemia." Shock (Augusta, Ga.), vol. 35, no. 6, 2011, pp. 590-6.
Bhattacharjee H, Nadipuram A, Kosanke S, et al. Low-volume binary drug therapy for the treatment of hypovolemia. Shock. 2011;35(6):590-6.
Bhattacharjee, H., Nadipuram, A., Kosanke, S., Kiani, M. F., & Moore, B. M. (2011). Low-volume binary drug therapy for the treatment of hypovolemia. Shock (Augusta, Ga.), 35(6), pp. 590-6. doi:10.1097/SHK.0b013e3182150e80.
Bhattacharjee H, et al. Low-volume Binary Drug Therapy for the Treatment of Hypovolemia. Shock. 2011;35(6):590-6. PubMed PMID: 21330941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low-volume binary drug therapy for the treatment of hypovolemia. AU - Bhattacharjee,Himanshu, AU - Nadipuram,Asha, AU - Kosanke,Stanley, AU - Kiani,Mohammad F, AU - Moore,Bob M,2nd PY - 2011/2/19/entrez PY - 2011/2/19/pubmed PY - 2011/9/3/medline SP - 590 EP - 6 JF - Shock (Augusta, Ga.) JO - Shock VL - 35 IS - 6 N2 - The selective regulation of total peripheral circulation in hypovolemic crisis offers a unique approach for treating and preventing hemorrhagic shock. Ideally, such a therapeutic intervention would require targeting of the striated muscle vascular beds without altering the vascular resistance in vital organ vascular beds. We discovered that a combination of cannabinoid receptor agonist, THC (Δ-tetrahydrocannabinol), and cyclooxygenase 2 inhibitor, NS-398, caused selective microvascular constriction in the mouse cremaster muscle manifested by a pronounced and significant 27.4% ± 7.9% decrease in vessel diameter relative to control (P < 0.01). This observation, and the reported lack of microvascular response in the mesentery and brain, led us to hypothesize that the drug combination could favorably redistribute blood volume in hypovolemia and prolong survival. To test the hypothesis, male Sprague-Dawley rats were subjected to a pressure-controlled hemorrhage (mean arterial pressure reduced to 30 ± 13.73 mmHg) then randomly assigned to one of six treatment groups (n = 6 per group). The untreated, NS-398-treated, and THC-treated groups manifested an insignificant difference in survival between groups after shock. The group treated with a combination of THC and NS-398 manifested a significant increase in mean survival from 53 ± 12 to 227 ± 23 min after shock (P < 0.001). The drug combination significantly reduced IL-1α, IL-1β, IFN-γ, and IL-10 production compared with the group resuscitated with normal saline. In addition, histological evaluation indicated that the therapy protects the lungs and liver against hemorrhagic shock-induced damage. The combination of cannabinoid receptor agonist and cyclooxygenase 2 inhibitor represents a potentially new approach to low-volume therapeutic intervention for hypovolemia. SN - 1540-0514 UR - https://www.unboundmedicine.com/medline/citation/21330941/abstract/Low_volume_binary_drug_ther L2 - http://Insights.ovid.com/pubmed?pmid=21330941 DB - PRIME DP - Unbound Medicine ER -