Systemic administration of analgesic buprenorphine, but not carprofen, affects cardiomyocyte contractility in rodents

Abstract

Rodents are often used in cardiac research, where they undergo a wide variety of procedures. To ensure animal welfare, the rodents are often analgesized before, during and/or after a procedure. Contractility measurements in isolated murine cardiomyocytes are an often used method to assess function; however, little is known about the effects of analgesia on this. Therefore, we investigated the effect of systemic injection of a non-steroidal anti-inflammatory drug, carprofen (N = 3 mice, n = 273 CMs; N = 3 rats, n = 241 CMs) and an opioid, buprenorphine (N = 4 mice, n = 326 CMs; N = 4 rats, n = 308 CMs) on isolated cardiomyocytes using unloaded contractility measurements. We found that buprenorphine prolongs the relaxation of cardiomyocytes, an effect confound to the first 3 h post-isolation, whereas carprofen does not affect contractility. As analgesia might influence the stress response, we assessed the influence of carprofen and buprenorphine on the β-adrenergic receptor (AR) response. The response of cardiomyocytes to both a β-AR agonist and antagonist was not affected by carprofen or buprenorphine. In vitro addition of the analgesics to rat cardiomyocytes (N = 3 rats, n = 197 CMs saline, n = 214 CMs carprofen, n = 211 CMs buprenorphine) revealed that the effect of buprenorphine on contractility is caused by a systemic response rather than a direct response of cardiomyocytes specifically. Collectively, our results suggest that carprofen and buprenorphine do not affect isolated cardiomyocyte contractility if measurements are performed at least 4 h post-isolation.