Mona Soliman

Treatment with dipyridamole improves cardiac function and prevent injury in a rat model of hemorrhage

Hemorrhagic shock is a leading cause of death despite the improvement in emergency services. One reason is that the resuscitation policies are designed to reestablish tissue perfusion, but not to prevent the inflammatory response to shock that cause myocardial dysfunction and injury. Dipyridamole is a platelet inhibitor that promotes anti-inflammatory effects. The present study investigated the therapeutic value of treatment with dipyridamole before resuscitation from hemorrhagic shock on myocardial injury and protection. Male Sprague-Dawley rats were assigned to 3 experimental groups (n=6 per group): 1) hemorrhage, 2) hemorrhage treated with dipyridamole, and 3) sham hemorrhage. Rats were hemorrhaged over 60min to reach a mean arterial blood pressure of 40mmHg. After 60min hemorrhagic shock, rats were treated or not by injection of 1mL of (20μg/L) dipyridamole intra-arterially. Resuscitation was made in vivo by reinfusion of the shed blood to restore norm tension for 30min. Arterial blood samples were collected for measurements of TNF-α. Left ventricular generated pressure and +dP/dtmax was significantly higher in dipyridamole treated rats compared to the untreated group. Myocardial biopsy samples were taken for light and electron microscopy. Dipyridamole decreased the number of inflammatory cells and mitochondrial swollen. Dipyridamole also decreased the plasma levels of TNF-α. Our results demonstrate that treatment with dipyridamole before in vivo resuscitation of hemorrhagic shock protect the myocardium against post-resuscitation myocardial dysfunction by decreasing the inflammatory response to shock.

Apelin protect against multiple organ injury following hemorrhagic shock and decrease the inflammatory response.

Introduction: Hemorrhagic shock (HS) result in multiple organ injury and inflammatory response that lead to death. The exact mechanism is not clear. Apelin is an endogenous ligand of orphan G-protein coupled receptor APJ. Apelin has anti-inflammatory effects on the release of inflammatory mediators. Objectives: To examine the protective effects of apelin against multiple organ injury and the possible involvement of inflammatory pathways. Methodology: Male Sprague-Dawley rats (300–350 g) were subjected to hemorrhage over 60 min to reach a mean arterial blood pressure of 40 mmHg. Then, rats were treated or not with 1 mL of 10 nm/L apelin-13 intraarterially resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normotension. Blood samples were collected for measurement of tumor necrosis factor (TNF) using ELISA (R and D systems). Biopsies were obtained from organs for light microscopic examination. Results: HS rats showed significant increase the levels of TNF. Apelin significantly lowered the production of TNF-α. Histological examination of hemorrhagic shocked untreated rats revealed structural damage. Less histological damage was observed in the organs of treated rats. Apelin-treatment decreased the number of inflammatory cells and mitochondrial swollen in cells. Conclusion: Treatment with apelin before resuscitation protects against multiple organ injury in HS by attenuation the inflammatory response and might be a therapeutic target for HS.

Effects of aminoguanidine, a potent nitric oxide synthase inhibitor, on myocardial and organ structure in a rat model of hemorrhagic shock.

Background: Nitric oxide (NO) has been shown to increase following hemorrhagic shock (HS). Peroxynitrite is produced by the reaction of NO with reactive oxygen species, leads to nitrosative stress mediated organ injury. We examined the protective effects of a potent inhibitor of NO synthase, aminoguanidine (AG), on myocardial and multiple organ structure in a rat model of HS. Materials and Methods: Male Sprague Dawley rats (300-350 g) were assigned to 3 experimental groups (n = 6 per group): (1) Normotensive rats (N), (2) HS rats and (3) HS rats treated with AG (HS-AG). Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mmHg. Rats were treated with 1 ml of 60 mg/kg AG intra-arterially after 60 min HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normo-tension. Biopsy samples were taken for light and electron microscopy. Results: Histological examination of hemorrhagic shocked untreated rats revealed structural damage. Less histological damage was observed in multiple organs in AG-treated rats. AG-treatment decreased the number of inflammatory cells and mitochondrial swollen in myocardial cells. Conclusion: AG treatment reduced microscopic damage and injury in multiple organs in a HS model in rats.

Insulin treatment before resuscitation following hemorrhagic shock improves cardiac contractility and protects the myocardium in the isolated rat heart

Background: Insulin has been shown to exert positive inotropic effects in several in vivo ex vivo models and in human hearts. Resuscitation following hemorrhagic shock results in myocardial contractile dysfunction. However, the optimal timing for treatment with insulin for the cardioprotection effects is unclear. Objectives: The objective of this study was to test the hypothesis that treatment with insulin before resuscitation provides better cardioprotection than treatment with insulin after resuscitation. Materials and Methods: Rats were assigned to 3 experimental groups (n = 6 per group): (1) Hemorrhagic shock and resuscitation, (2) hemorrhagic shock resuscitated then treated with insulin and (3) hemorrhagic shock treated with insulin before resuscitation. Rats were hemorrhaged for 60 min to rach mean arterial blood pressure of 40 mmHg. Rats were resuscitated in vivo by reinfusion of the shedded blood to restore normotension and monitored for 60 min. Rats were treated or not with insulin 200 μU/g body weight intramuscularly either before or after resuscitation. The maximum of the left ventricular developed pressure (+dP/dt) was measured for 60 min in the isolated perfused hearts using the Langendorff method. Blood samples were obtained for measurements of tumor necrosis factor-alpha (TNF-α). Results: Treatment with insulin before resuscitation following hemorrhagic shock significantly elevated max dP/dt compared with insulin treatment after resuscitation and the untreated group. TNF-α levels were lower in the insulin treatment before resuscitation compared to the treatment after resuscitation and the untreated group. Conclusion: Insulin treatment before resuscitation following hemorrhagic shock provides better cardiac protection than treatment with insulin after resuscitation, as evidenced by the improved myocardial contractility, preservation of myocardial structure. The mechanism of cardiac protection involves decrease in the inflammatory response to shock by lowering the levels of TNF.

Histological and Immunohistochemical Basis of the Effect of Aminoguanidine on Renal Changes Associated with Hemorrhagic Shock in a Rat Model

Acute kidney failure is the main cause of death among patients with severe trauma due to massive blood loss and hemorrhagic shock (HS). Renal cell injury is caused by tissue ischemia. Renal ischemia initiates a complex and interconnected chain of events resulting in cell injury and renal cell necrosis. Nitric oxide plays a crucial role in renal function and can be inhibited by aminoguanidine (AG). We studied whether AG can ameliorate pathological renal changes associated with HS syndrome in a rat model and explored the AG protection mechanism. Rats were intraperitoneally injected with heparin sodium and mean arterial blood pressure was monitored. Animals were divided into three groups: control (without hemorrhage), with or without intra-arterially injected AG; HS (blood continuously withdrawn or reinfused to maintain an MABP of 35–40 mmHg); and HS with AG. We found that AG decreased plasma concentrations of urea, creatinine, and nitrates; ameliorated histological changes of HS-induced rats; and decreased the expressions of inducible nitrogen oxide synthase (iNOS), proapoptotic protein (BAX), and vitamin D receptors (VDR). AG ameliorated kidney injury by inhibiting iNOS resulting in decreased BAX and VDR expressions. Therefore, a therapeutic strategy targeting AG may provide new insights into kidney injury during severe shock.

Protective Effects of Estradiol on Myocardial Contractile Function Following Hemorrhagic Shock and Resuscitation in Rats

Background:Hemorrhagic shock (HS) results in myocardial contractile dysfunction. Studies showed that 17&bgr;-estradiol protects the myocardium against contractile dysfunction. The study investigated the cardioprotective effects of treatment with 17&bgr;-estradiol before resuscitation following 1 h of HS and resuscitation. Methods:Male Sprague-Dawley rats were assigned to 2 sets of experimental protocols: Ex vivo and in vivo treatment and resuscitation. Each set had three experimental groups (n = 6 per group): Normotensive (N), HS and resuscitation (HS-R) and HS rats treated with 17&bgr;-estradiol (E) and resuscitated (HS-E-R). Rats were hemorrhaged over 60-min to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were resuscitated by perfusion in the Langendorff system. In the 17&bgr;-estradiol treated group, 17&bgr;-estradiol 280 µg/kg was added for the first 5 min. Cardiac function was measured. Left ventricular generated pressure (LVGP) and +dP/dt were calculated. In the in vivo group, rats were treated with 17&bgr;-estradiol 280 µg/kg s.c. after 60-min HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30-min to restore normotension. Results:Treatment with 17&bgr;-estradiol before resuscitation in ex vivo treated and resuscitated isolated hearts and in the in vivo treated and resuscitated rats following HS improved myocardial contractile function. In the in vivo treated group, LVGP and +dP/dt max were significantly higher in 17&bgr;-estradiol treated rats compared to the untreated group (LVGP 136.40 ± 6.61 compared to 47.58 ± 17.55, and +dP/dt 661.85 ± 49.88 compared to 88.18 ± 0.85). Treatment with 17&bgr;-estradiol improved LVGP following HS. Conclusions:The results indicate that treatment with 17&bgr;-estradiol before resuscitation following HS protects the myocardium against dysfunction.

Na(+)-H(+) exchange blockade, using amiloride, decreases the inflammatory response following hemorrhagic shock and resuscitation in rats.

Na(+)-H(+) exchanger activation on resuscitation following hemorrhagic shock has been shown to result in myocardial injury and dysfunction. Amiloride, an inhibitor of the Na(+)-H(+) exchanger has been shown to protect the myocardium against reperfusion injury in the ischemic hearts. However, the mechanism of protection remains unclear. Na(+)-H(+) exchanger blockers have been implicated in the regulation of inflammatory responses and chemokine production. The present study investigated the therapeutic anti-inflammatory value of amiloride on myocardial contractile function in post-resuscitation following hemorrhagic shock in rats. Male Sprague-Dawley rats were assigned into 3 groups: 1) hemorrhage, 2) hemorrhage treated with amiloride, and 3) sham hemorrhage (n=6 per group). Rats were hemorrhaged over 60min to reach a mean arterial blood pressure of 40mmHg. After 60min of hemorrhagic shock, rats were treated or not by injection of 1ml of 100μM amiloride (0.027mg/ml) intra-arterially. Resuscitation was made in vivo by reinfusion of the shed blood to restore norm tension for 30min. Left ventricular contractile function was measured in the isolated hearts following hemorrhage and in vivo resuscitation using the Langendorff apparatus. Arterial blood samples were collected from all groups at the end of the experimental period (90min) for cytokine measurements (TNF-α). Amiloride decreased the inflammatory response to hemorrhagic shock and resuscitation by lowering the levels of TNF. These results indicate that amiloride protects the myocardium by down regulating the inflammatory response to hemorrhagic shock and resuscitation.

The Reading Habits of Medical Students at Medical College King Saud University

Abstract Background Understanding the reading habits of medical students provide insights and opportunities for medical educators to evaluate the learning needs of the students and improve the teaching methods. The purpose of the present study was to describe the reading habits of King Saud medical students in a fifth year clinical rotation, which previously have not been described. Methods A questionnaire was administered to 96 medical students rotating through their fifth year at the King Saud University College of Medicine during 2008-2009 academic years. The questionnaire focused on issues related to the reading habits. Results Seventy three of 96 (76%) medical students in a fifth year clinical rotation completed the questionnaire. Students reported reading for an average of 4.3(SD 5) (median three hours per week, range zero to 35 hours per week). The most commonly used and useful reading resource were pocket books and medical text books. Approximately 90% of students reported problems in reading about their patients. Conclusions Students spend sufficient amount of time reading medical pocket books and lecture handouts with less time spend on online sources. The majority of students reported problems in reading that medical educators need to address.

Medical students’ perception of the learning environment at King Saud University Medical College, Saudi Arabia, using DREEM Inventory

Background The students’ perception of the learning environment is an important aspect for evaluation and improvement of the educational program. The College of Medicine at King Saud University (KSU) reformed its curriculum in 2009 from a traditional to a system-oriented hybrid curriculum. Objective The objective of the present study was to determine the perception of the second batch (reformed curriculum) of medical graduates about the educational environment at the College of Medicine, KSU, using the Dundee Ready Education Environment Measure (DREEM) scale. Methods The fifth year medical students were asked to evaluate the educational program after graduation in May 2014. The questionnaire was distributed to the graduate students electronically. The DREEM questionnaire consisted of 50 items based on Likert’s scale; and five domains, namely, students’ perceptions of learning, perceptions of teachers, academic self-perceptions, perceptions of atmosphere, and social self-perceptions. Data were analyzed using SPSS. Results A total of 62 students participated in the study. The score for students’ perception of learning among medical students ranged from 2.93 to 3.64 (overall mean score: 40.17). The score for students’ perception of teachers ranged from 2.85 to 4.01 (overall mean score: 33.35). The score for students’ academic self-perceptions ranged from 3.15 to 4.06 (overall mean score: 28.4). The score for students’ perception of atmosphere ranged from 2.27 to 3.91 (overall mean score: 41.32). The score for students’ social self-perceptions ranged from 2.85 to 4.33 (overall mean score: 24.33). The general perceptions of the students in all five sub-scales were positive. Conclusion The overall student’s perception about the educational environment was satisfactory. This study was important to evaluate the students’ perception of the learning environment among medical graduates of the reformed curriculum and provided guidance on areas of improvement in the curriculum.

Use of cross-institutional progress test as a predictor of performance in a new medical college

Background The progress test was initiated by Qassim University in 2000 as a tool to evaluate the educational process among Saudi medical colleges. Princess Nourah Bint Abdul Rahman University (PNU) College of Medicine is a new medical college established in 2012 that implemented the same innovative reformed curriculum of King Saud University College of Medicine. Objectives The objective of this study was to use the progress test to evaluate the rate of knowledge acquisition among a new medical school compared to other long-established medical schools in Saudi Arabia. Materials and methods As part of an ongoing strategy, the progress test was administered before the end of the academic year. Students in PNU were enrolled for 2 years in the progress test. We compared the mean progress test scores for PNU students compared to students at comparable stages in other medical schools in Saudi Arabia. Results The results showed that the rate of knowledge acquisition was similar in students at PNU to students in other well-established medical schools in Saudi Arabia. Conclusion The present study showed that the interinstitutional progress test demonstrated that the level of acquisition of knowledge and performance of students in a new medical school was similar to other medical colleges in Saudi Arabia.