COMPARITIVE STUDY BTWEEN PANTOPRAZOLE AND RANITIDINE ON SOME CARDIOVASCULAR PREPARATIONS

Because of the abundant use of proton pump inhibitors (PPIs) and  histamine H_2- receptors antagonists ( H₂RAs) and considering the hazards of high intravenous (IV) dosing especially in critically ill intensive care unit ( ICU)  patients and in view of controversy about the cardiac effects of these drugs. So it was of interest in the present work to investigate and compare the effects of either pantoprazole or ranitidine on some cardiovascular aspects using both  isolated and intact experimental animal preparations.
The effect of different increasing doses of  pantoprazole or ranitidine on the amplitude of myocardial contraction of isolated perfused rabbit  heart and on NE-induced contraction of aortic spiral strips of rabbits were studied. Their effects on the mean arterial blood pressure (MABP), heart rate (HR) and electrocardiogram (ECG) of anaesthetized cats were also investigated.
This stady showed that, pantoprazole caused a significant dose-dependent reduction in the amplitude of myocardial contraction with mean percentage reductions ranged from 2.5 ± 0.55 to 58.4 ± 3.82, while ranitidine had no effect. The cardioinhibitory effect of pantoprazole was proven to be due to a calcium channel blocking effect. On NE-induced contraction of aortic spiral strips, both pantoprazole and ranitidine produced a significant dose dependent reduction.  The mean percentage reductions ranged from 3.9 ± 0.59 to 40.3 ± 2.13, and8.3 ± 2.45 to 45.4 ± 5.82 for pantoprazole and ranitidine respectively. Intravenous bolus injection of both drugs produced a significant dose-dependent reduction in MABP. The mean percentage reductions ranged from 0.6 ± 0.23 to 16.1 ± 3.15 and  0.7 ± 0.19 to 42.6 ± 3.21 for pantoprazole and ranitidine respectively and were found to be statistically significant. On the other hand, continuous intravenous infusion of pantoprazole 1.5 mg/kg or  ranitidine 2 mg/kg which is equivalent to the human therapeutic dose (HTD), for 2 hours did not produce any change in the MABP, ECG pattern and heart rate of an anaesthetized cat all over the time of infusion.
In conclusion, ranitidine had no cardioinhibitory effect compared to pantoprazole. So, it could be prefered to pantoprazole especially in cardiac patients. On the other hand, the possibility of negative inotropic effect with pantoprazole should be considered carefully especially in patients with myocardial contractility dysfunction.
In the setting where intermittent IV bolus administration of either pantoprazole or ranitidine is needed, pantoprazole seems to be more favourable of the two drugs evident by its less hypotensive effect plus insignificant effect on heart rate and no changes in ECG record even at high doses.
The continuous IV infusion route may be safer and better chosen rather than IV bolus intermittent dosing to avoid any possible cardiovascular side  effects  of either pantoprazole or ranitidine.