The CO/HCO buffer minimizes pH changes in response to acid-base loads, HCO provides substrate for Na,HCO-cotransporters and Cl/HCO-exchangers, and H and HCO modify vasomotor responses during acid-base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO/HCO buffer. Switching from CO/HCO-free to CO/HCO-containing extracellular solution results in initial intracellular acidification due to hydration of CO followed by gradual alkalinization due to cellular HCO uptake. Carbonic anhydrase inhibition decelerates the initial acidification and attenuates the associated transient vasoconstriction without affecting intracellular pH or artery tone at steady-state. Na,HCO-cotransport and Na/H-exchange activity after NH-prepulse-induced intracellular acidification are unaffected by carbonic anhydrase inhibition. Extracellular surface pH transients induced by transmembrane NH flux are evident under CO/HCO-free conditions but absent when the buffer capacity and apparent H mobility increase in the presence of CO/HCO even after the inhibition of carbonic anhydrases. We conclude that (a) intracellular carbonic anhydrase activity accentuates pH transients and vasoconstriction in response to acute elevations of pCO, (b) CO/HCO minimizes extracellular surface pH transients without requiring carbonic anhydrase activity, and

Introduction: Pain can be severe during the first days after arthroscopic surgery, and acute pain is an important outcome in clinical trials of surgical technique or anaesthetic strategy. A standardized, validated method of assessing acute postoperative pain would improve the quality of clinical studies, and facilitate systematic reviews and meta-analyses. A step on the way towards this standard is to investigate the methods most commonly used in recent literature.Methods: PubMed and CINAHL databases were searched, including studies of arthroscopic rotator cuff surgery with a primary pain-related outcome during the first postoperative week, published in English from 2012 to 2017.Results: A total of 47 studies were included, all measuring pain intensity using a pain rating scale. Most frequently used was the visual analogue scale using the anchors “no pain” and “worst pain imaginable”, with recordings at 1, 2, 4, 6, 8, 12, and 24 hours postoperatively. A total of 34 studies recorded analgesic consumption, usually as average cumulated consumption in mg. Time to first analgesic request or first pain were recorded in 11 studies, and 4 different starting points were used.Discussion: This review describes the currently most common methods of assessing acute postoperative pain in clinical trials of arthroscopic shoulder surgery involving rotator cuff repair, and the large variety of methods applied. Based on this study and international guidelines, several recommendations on how to measure and report postoperative pain outcomes in future trials are proposed.

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