Interactions of metoclopramide and ciprofloxacin on electrocardiographic indices in anesthetized normal and hyperthermic rats

The combination of metoclopramide [MCP] and ciprofloxacin [CPX] is not uncommon in clinical practice, as nausea and vomiting are well known during febrile illness. Some reports in the literature have linked both MCP and CPX to serious cardiac adverse effects including QT prolongation and cardiac arrests. In this study we examined the effect of the combination between MCP and CPX on the ECG parameters and serum potassium in normothermic and hyperthermic rats. Thiopental-anesthetized rats were injected i.v. with MCP [0.2 mg/kg] and/or CPX [20 mg/kg] after induction of hyperthermia by intracerebroventricular administration of PGE 2 [0.4-micro g/kg]. ECG recordings were done every 10 min during 90-min duration. Plasma potassium was measured at 0, 20, 40, 60, and 80-min. Small doses of MCP and CPX changed ECG indices in statistically significant manner at normal and elevated body temperatures. MCP produced early bradycardia and prolongation of PR interval although it was less pronounced during hyperthermia possibly due to increased sympathetic nerve discharge. It also produced slight increase in QT interval [-4 ms] in normo- and hyperthermia. On the other hand, CPX caused non-significant effects on HR and conduction velocity but prolonged the QT interval by -4.3 ms during normo- and hyperthermia. Combination of MCP and CPX did not affect the influence of MCP alone on the HR or conduction velocity while it exaggerated their individual effects on the QT and QTc prolongation. This interaction was not affected by hyperthermia. the combination of MCP and CPX should be avoided as it may lead to serious QT prolongation while hyperthermia is not considered a dangerous threat for this interaction

Effect of angiotensin-converting enzyme inhibitors, captopril and lisinopril, on collagen synthesis by cultured rat liver cells

Several studies have documented the role of angiotensin-converting enzyme inhibitors [ACEI] as antifibrogenic and antiproliferative in different tissues in vivo and in vitro but unfortunately non of them has investigated this effect on collagen synthesis by individual liver cells. In this study we focused on the in vitro effect of two ACEI with different pharmacologic properties, captopril and lisinopril, on the synthesis of types I and III collagens by individual liver cells, since these types of collagens are the most abundant ECM molecules both in normal and fibrotic liver. Rat liver cells were isolated, separated according to cell types through density gradient centrifugation in percoll then cultured as separate clones for 24 hours. Types I and III collagens secretion was measured by gel electrophoresis [SDS-PAGE] and computer analysis of their alpha chains after purification from cell culture media. Both captopril and lisinopril significantly reduced types I and III collagens by cultured hepatocytes [HC], liver endothelial cells [EC], and hepatic stellate cells [HSC] with more prominent action for captopril than lisinopril. The present study document the inhibitory effect of ACEI on types I and III collagen synthesis by liver cell sub-population in vitro by a mechanism independent on the systemic angiotensin-converting enzyme inhibition and possibly through a mechanism involving a local renin-angiotensin system or interference with intracellular events involved in collagen synthesis