Ketorolac effectively inhibits ureteral contractility in vitro

C. Charles Wen, Tawnya L Cary Coyle, Travis Jerde, Stephen Y. Nakada

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction: The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range. Materials and Methods: Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM-10 μM) for 90 minutes and compared with indomethacin (1 μM) and dimethyl sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time. Results: Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1 nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 μM, 88.7%; and 10 μM, 98.3%. Ureteral contractility was significantly reduced by 1 μM ketorolac (39.0%; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 μM ketorolac was not significantly different at any time point from any of the higher doses studied. Conclusion: Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 μM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.

Original languageEnglish (US)
Pages (from-to)739-742
Number of pages4
JournalJournal of Endourology
Volume22
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

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Ketorolac
Dimethyl Sulfoxide
In Vitro Techniques
Renal Colic
Urinary Calculi
Cyclooxygenase Inhibitors
Ureter
Muscle Contraction
Transducers
Baths
Indomethacin
Smooth Muscle
Stomach
Buffers
Swine

ASJC Scopus subject areas

  • Urology

Cite this

Ketorolac effectively inhibits ureteral contractility in vitro. / Wen, C. Charles; Coyle, Tawnya L Cary; Jerde, Travis; Nakada, Stephen Y.

In: Journal of Endourology, Vol. 22, No. 4, 01.04.2008, p. 739-742.

Research output: Contribution to journalArticle

Wen, C. Charles ; Coyle, Tawnya L Cary ; Jerde, Travis ; Nakada, Stephen Y. / Ketorolac effectively inhibits ureteral contractility in vitro. In: Journal of Endourology. 2008 ; Vol. 22, No. 4. pp. 739-742.
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abstract = "Introduction: The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range. Materials and Methods: Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM-10 μM) for 90 minutes and compared with indomethacin (1 μM) and dimethyl sulfoxide (DMSO) 0.1{\%}. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time. Results: Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2{\%}; 1 nM, 34.3{\%}; 10 nM, 56.0{\%}; 100 nM, 69.9{\%}; 1 μM, 88.7{\%}; and 10 μM, 98.3{\%}. Ureteral contractility was significantly reduced by 1 μM ketorolac (39.0{\%}; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 μM ketorolac was not significantly different at any time point from any of the higher doses studied. Conclusion: Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 μM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.",
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AU - Wen, C. Charles

AU - Coyle, Tawnya L Cary

AU - Jerde, Travis

AU - Nakada, Stephen Y.

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N2 - Introduction: The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range. Materials and Methods: Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM-10 μM) for 90 minutes and compared with indomethacin (1 μM) and dimethyl sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time. Results: Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1 nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 μM, 88.7%; and 10 μM, 98.3%. Ureteral contractility was significantly reduced by 1 μM ketorolac (39.0%; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 μM ketorolac was not significantly different at any time point from any of the higher doses studied. Conclusion: Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 μM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.

AB - Introduction: The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range. Materials and Methods: Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM-10 μM) for 90 minutes and compared with indomethacin (1 μM) and dimethyl sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time. Results: Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1 nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 μM, 88.7%; and 10 μM, 98.3%. Ureteral contractility was significantly reduced by 1 μM ketorolac (39.0%; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 μM ketorolac was not significantly different at any time point from any of the higher doses studied. Conclusion: Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 μM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.

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