Low-volume binary drug therapy for the treatment of hypovolemia

Himanshu Bhattacharjee, Asha Nadipuram, Stanley Kosanke, Mohammad F. Kiani, Bob Moore

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 (Δ8-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.

Original languageEnglish (US)
Pages (from-to)590-596
Number of pages7
JournalShock
Volume35
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Hypovolemia
Dronabinol
Cannabinoid Receptor Agonists
Drug Therapy
Hemorrhagic Shock
Cyclooxygenase 2 Inhibitors
Drug Combinations
Interleukin-1
Blood Vessels
Shock
Abdominal Muscles
Mesentery
Striated Muscle
Therapeutics
Blood Volume
Constriction
Vascular Resistance
Interleukin-10
Sprague Dawley Rats
Arterial Pressure

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Bhattacharjee, H., Nadipuram, A., Kosanke, S., Kiani, M. F., & Moore, B. (2011). Low-volume binary drug therapy for the treatment of hypovolemia. Shock, 35(6), 590-596. https://doi.org/10.1097/SHK.0b013e3182150e80

Low-volume binary drug therapy for the treatment of hypovolemia. / Bhattacharjee, Himanshu; Nadipuram, Asha; Kosanke, Stanley; Kiani, Mohammad F.; Moore, Bob.

In: Shock, Vol. 35, No. 6, 06.2011, p. 590-596.

Research output: Contribution to journalArticle

Bhattacharjee, H, Nadipuram, A, Kosanke, S, Kiani, MF & Moore, B 2011, 'Low-volume binary drug therapy for the treatment of hypovolemia', Shock, vol. 35, no. 6, pp. 590-596. https://doi.org/10.1097/SHK.0b013e3182150e80
Bhattacharjee, Himanshu ; Nadipuram, Asha ; Kosanke, Stanley ; Kiani, Mohammad F. ; Moore, Bob. / Low-volume binary drug therapy for the treatment of hypovolemia. In: Shock. 2011 ; Vol. 35, No. 6. pp. 590-596.
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