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Because of the abundant use of proton pump inhibitors (PPIs) and histamine H2receptors 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. Az. J. Pharm Sci. Vol. 46, September, 2012. 116 INTRODUCTION Prophylaxis against the development of stress ulcers and subsequent gastric bleeding is a major therapeutic challenge in intensive care medications in the inpatients and intensive care unit settings. Stress related mucosal damage is an acute, erosive gastritis of unclear pathophysiology, representing conditions ranging from stress-related injury to stress ulcer. It is apparent in 75-100% of critically ill patients within 24 hours of admission to an intensive care unit (Grube and May, 2007). Proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) are commonly used in oral and intravenous formulations as prophylaxis against stress-induced gastritis, ulcers, and gastrointestinal bleeding in high-risk patients. Proton pump inhibitors may be also a particularly important intervention after cardiac surgery (Hata et al., 2005). The advantage of PPIs over H2RAs is that, there was no tachyphylactic phenomena reported in patients taking PPIs, resulting in more perdictable and sustained PH control than H2RAs (Pongprasobchai, 2009). They are also commonly prescribed prophylactically to patients with ischemic heart disease including stable angina that have received percutaneous coronary intervention to prevent gastrointestinal bleeding particularly for those patients considered to be at high risk (Wu et al., 2011). In a report, the use of high-dose of ranitidine H2-blocker was associated with several adverse effects such as bradycardia, sinus arrest, atrio-ventricular conduction disturbances, and cardiac decompensation (Hinrichsen et al., 1995). However, another study reported that H2-blocker could modulate heart-rate variability, and has the possibility to inhibit the increase in the sinus rate and prevent ventricular ectopy (Ooie et al., 1999). Moreover the PPI, pantoprazole has been found to depress cardiac contractility at higher concentration in-vitro, although omeprazole administration did not lead to any changes in the cardiac performance of patients with congestive heart disease (Tanaka et al., 2008). MATERIALS AND METHODS Animal doses corresponding to the human therapeutic doses were calculated according to the method given by Paget and Barnes, (1964) who calculated the dose in relation to the animal surface area. I) In-Vitro studies: 1Isolated perfused rabbit heart: The effect of different increasing doses of either pantoprazole (1.5-48 μg/ml) or ranitidine (2 64 μg/ml) on the amplitude of myocardial contractility of isolated perfused rabbit heart was studied by (Modified Langendorff preparation): (Staff of the department of pharmacology. Edinburgh, 1970a) and the site of action was investigated. 2Isolated aortic spiral strips of rabbit:The effect of different increasing doses of either pantoprazole (1.5-48 μg/ml) or ranitidine (2 64 μg/ml) on the NE-induced contraction of isolated rabbit aortic spiral strips was also studied. (Furchgott and Bhadrakom), (Staff of department of pharmacology, Edinburgh, 1970 a). II) In-vivo studies: Effect on the mean arterial blood pressure (MABP), heart rate and ECG of anaesthetized cats. Az. J. Pharm Sci. Vol. 46, September, 2012. 117 The effect of different increasing doses of either pantoprazole (0.37 – 12mg/kg) or ranitidine (0.5-16mg/kg) on MABP, heart rate and ECG pattern and also the effect of IV infusion of either pantoprazole (1.5mg/kg) or ranitidine(2 mg/kg) were studied according to the Staff of department of pharmacology, Edinburgh, 1970 a) and the site of action was investigated. t-test for comparision and of significance (Steel and Torrie 1960).

COMPARITIVE STUDY BTWEEN PANTOPRAZOLE AND RANITIDINE ON SOME CARDIOVASCULAR PREPARATIONS