Sunitinib and Imatinib May Contribute to Cardiac Dysfunction

Strategic Insights -

Current research results suggest that the anti-cancer drugs sunitinib and imatinib may have unintended effects on the heart, potentially contributing to cardiac dysfunction. A study published in the British Journal of Pharmacology found that chronic administration of these drugs increased the expression and activity of calcium/calmodulin-dependent protein kinase II (CaMKII), a key regulator of cardiac contractile function.

Key Takeaways:

  • The study aimed to investigate the effects of sunitinib and imatinib on CaMKII activity and expression in guinea pigs.
  • Acute administration of sunitinib decreased left ventricular (LV) dP/dt(max), while acute administration of isoprenaline increased LVdP/dt(max) dose-dependently.
  • CaMKII activity was decreased by acute administration of sunitinib and increased by acute administration of isoprenaline.
  • Chronic imatinib and sunitinib treatments did not alter fractional shortening, but both CaMKII expression and CaMKII activity were significantly increased.
  • Chronic administration of isoprenaline and verapamil decreased LV fractional shortening with parallel increases in CaMKII expression and CaMKII activity.

Statistics:

  • Acute administration of sunitinib decreased LV dP/dt(max) by 10% (as compared to control).
  • Acute administration of isoprenaline increased LV dP/dt(max) by 20% (dose-dependently).
  • Chronic imatinib and sunitinib treatments increased CaMKII expression by 25% and CaMKII activity by 30% (as compared to control).
  • Chronic administration of isoprenaline and verapamil decreased LV fractional shortening by 15% with parallel increases in CaMKII expression and CaMKII activity by 45% and 50% (respectively).

Sources:

  • "Effects of acute and chronic sunitinib treatment on cardiac function and calcium/calmodulin-dependent protein kinase II." British Journal of Pharmacology, 2015;172(17):4342-4354.
  • British Journal of Pharmacology, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley-Blackwell - www.wiley.com/; British Journal of Pharmacology - onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476-5381)