Analysis of Morphine-Tolerant Mice Exhibit a Profound and Persistent Cardioprotective Phenotype Article - Literature review Example

Name & Student Number Title of the article to be critiqued: Morphine-tolerant mice exhibit a profound and persistent cardioprotective phenotype. Authors: Peart JN and Gross GJ. Journal: Circulation. 2004 Mar 16;109(10):1219-22. Introduction Protection of the cardiac muscles from the effects of ischemia and reperfusion injury could safe many lives. This article reviews various researches that have been undertaken in the field of cardio protection from ischemia and reperfusion injury and takes a critical look at Peart and Gloss cardio protection article. Literature review The cardiac muscles are known to be very sensitive and any exposure to reduced supply of oxygen termed hypoxia or reduced supply of blood termed ischemia for a short period of time often results to pronounced permanent death of tissue. However, research has shown that experiencing ischemia for short periods of time usually results in ischemic preconditioning (IPC) which reduces the severity of the damage to cardiac tissue. Varied number of substances in nature has been found to poses cardio protection ability. For instance Suhendu et al. (2009) found that fresh garlic had superior protection to the cardiac muscles as opposed to the garlic that had been processed. They attributed this ability of fresh garlic to its increased ability to phosphorylate the antiapoptonic proteins such as ERK1/2; its ability to reduce the ratio of Bax and Bcl-2 and its reduced ability to phosphorylate proapoptonic proteins such as JNK and p-38MAPK. This superior ability fresh garlic to provide cardio protection was also related to its ability to enhance redox reaction which was evidenced in form of high levels of p65 subunit of NFkB, Nrf2 and increased PPARα, PPARδ and GLUT4. Therefore, Suhendu et al. (2009) in overall attributed the superiority in cardio protection by fresh garlic to the presence of hydrogen sulphide compounds in it which are absent in processed garlic. Another research by Zeljko in 2007, found that volatile anesthetics could probably have increased cardio protection to patients suffering from reperfusion injury and ischemia. This finding is of great help to patients suffering from coronary thrombosis. The protective ability of volatile anesthetics has been attributed to their ability to reduce the contraction of left ventricles and to depress the function of the sino atrial node. These two actions reduce the demand for oxygen by heart muscles. Zeljko (2007) also attributed this cardio protection of volatile anesthetics to their ability to reduce the energy requirements of heart muscles and therefore there is saving of energy by cellular processes which are dependent on energy. However, previous studies did not identify this as a phenomenon which is not needed for cardio protection. In their review, Dipak and Nilanjana (2006) found that resveratrol provided cardiac protection by attenuating the ischemic heart muscles and reperfusion injuries. They attributed the cardio protection of resveratrol to preconditioning rather than direct effect. Dipak and Nilanjana further points out that resveratrol has scavenging activities which help it to quench reactive oxygen species that might cause injury to heart muscles and thus contributing to the protection of the cardiac muscles. From their review they state that rats infused with resveratrol have reduced incidents of ventricular tachycardia and fibrillation in addition to reduced lactate dehydrogenase (LDH) concentration. These rats are characterized with elevated levels of iNOS expression. However, when the rats protected by resveratrol were infused with iNOS inhibitor, the cardio protection of resveratrol was lost. In addition, mice whose iNOS was knocked out, could not benefit from resveratrol cardio protection. Thus from this review, the protection of resveratrol is dependent on the availability of iNOS. In addition to protecting the heart from reactive oxygen species, resveratrol up regulates the activity of catalase enzyme in the cardiac muscles which scavenges for peroxide radicals hence enhancing its cardio protection ability. Like garlic, resveratrol has the ability to phosphorylate the antiapoptonic proteins such as ERK1/2 which is related to its cardio protective ability. In spite the protection to cardiac muscles, resveratrol has short lived protection of just two to three hours. However, there is another delayed protection which seems to reappear after twelve to twenty four hours which results from an early preconditioning. This delayed protection lasts for a maximum of seventy two hours. This research used both wild type and iNOS null mouse hearts. The results revealed that resveratrol cardio protection was effective in rats with iNOS and poor in those without. From this, it was concluded that mouse hearts could only precondition in presence of iNOS. In addition, rats treated with resveratrol were found have reduced oxidative stress. Therefore, owing to dependence on iNOS for cardio protection, resveratrol offers heart protection through preconditioning. Ryan et al. (1999) on the other hand carried out a research on the effect of exercise on cardio protection. He found that rapid exercise induces the heart muscles to be more ischemia and reperfusion injury resistant. They found that acute exercise improves the post ischemic recovery of cardiac external work and cardiac output. Compared to previous research by Locke et al., Ryan et al. work had reduced time frame to achieve the required cardio protection, that is, one day as compared to three days in Locke et al. work. This was attributed to differences in methodologies. Whereas Locke et al. used a Langendorff preparation of rats and the measurement of pressure to determine the functioning of the heart muscles, Ryan et al. used working heart preparations which are more physiologically relevant. The increased cardio protection was partly attributed to possible increase in HSP 72 protein during the exercise. Previous experiments had found that HSP 72 protein increased during exercise and that an increase in this protein was associated with cardio protection from reperfusion injury or and ischemia. During their research, Ryan et al. were able to inhibit the rise in the HSP 72 protein yet exercise still provided myocardial protection from ischemia and reperfusion injury. Thus other factors involved in cardio protection from ischemia and reperfusion injury seems to be enhanced during exercise other than HSP 72 protein. Ryan et al. could not identify other factor responsible for cardio protection during exercise though they were in agreement that there exist such factors which are still unknown since in their experiments the hearts of the mouse used still had cardio protection from ischemia and reperfusion even when they controlled the levels of HSP 72 protein. The critique Peart and Gross research concerned the effect of morphine tolerance on the cardio protection of the mice. They subcutaneously implanted male mice with morphine pellets and to some with placebo. Their hypothesis was that morphine tolerant mice exhibit improved recovery from ischemia and reperfusion injury. They carried out the research because much research had focused on mechanism of tolerance and dependence of central nervous system on morphine with little research being undertaken on the effects of morphine on other organs. From their research, Peart and Gross found that morphine tolerance in mice helps them to recover faster from ischemia and reperfusion injury than those without prior exposure to morphine. They expected the protection to be short lived like in previous experiments but instead they found that the mice had prolonged protection of the myocardial from ischemia and reperfusion injury. They also observed that LHD was reduced which was in line with research carried out using resveratrol. The authors concluded that chronic exposure to morphine offers cardio protection. As stated by Ryan et al. (1999), better results in relation to cardio protection are obtained when one uses working heart preparation method. This research used working heart method and therefore the results which were obtained credible. The fact that they obtained a reduced lactic dehydrogenase like the one obtained in the resveratrol experiment and the resveratrol also has cardio protection activity arguments the significance of this research. The research also identified a field which had not been much researched on and thus it was valuable in contributing to the literature on cardio protection. It has introduced some new facts about the possibility of the activation of k- and δ-opioid receptors as being behind the cardio protection. In addition this research identified the prolonged protection of the cardiac which had not witnessed before. Thus this holds some promise to patients suffering from coronary thrombosis since previous researches had only identified short lived protection which sometimes reappeared after twenty four hours. Thus this research opens avenues for more research in the medical field and drug development since a drug could be designed to activate the receptors suspected to offer cardio protection. The presentation of data is easy to interpret even to persons who are not knowledgeable in the field which adds to the strength of Peart and Gross research. In spite the strengths of this research, it has some set backs. For instance the choice of male mice for the research is not justified. In addition, this choice could have influenced the outcome and therefore their conclusion should have been that morphine tolerant in male mice offers cardio protection instead of summing them up since we know their exist some physiological differences in male animals and female animals. Thus could have used both female and male mice to have conclusive results instead of using just males and assuming this could be true for both female and male. Furthermore, we are not told the age of the mice which were used. May be the results could be different if a certain age group were adopted. The research has left some questions pending. For instance, the mechanism of protection offered through morphine tolerance is not yet known and thus more research need to be carried out in this area. In addition, there is need for further research to look at the effects found in this research across different sex and age groups. Conclusion Much research concerning cardio protection has been carried out using mice. Most of this research point to preconditioning of the cardiac muscles as a means of providing protection to cardiac muscles. Some of them are short lived up to three hours and a reappearance of protection after twenty four hours while the research under this review found a prolonged protection of cardiac muscles from ischemia and reperfusion. Thus this morphine effects study offers some limelight on the protection of cardiac muscles from ischemia and reperfusion injury that could be useful if well understood. In spite of its few short coming, there is need to do more confirmatory tests using both sex and different age groups since it holds some promise on the future management of human diseases like coronary thrombosis. The mechanisms of action of the protection offered need also to be well understood through further research for any useful application of the knowledge to be utilized. References Dipak Das & Nilanjana Maulik. Resveratrol in cardioprotection: Atherapeutic promise of alternative medicine. Molecular Interventions, 6.1 (2006): 36-47. Garlic is a Superior Cardioprotective Agent than Processed Garlic. J. Agric. Food Chem., 2009, 57.15 (2009): 7137–7144. Roberto Bolli, Lance Becker, Garrett Gross, Robert Mentzer, Jr, David Balshaw, David A. Lathrop. Myocardial Protection at a Crossroads: the Need for Translation Into Clinical Therapy. Circulation Research, 95, (2004): 125-134. Ryan P. Taylor, M. Brennan Harris, and Joseph W. Starnes. Acute exercise can improve cardioprotection without increasing heat shock protein content. 276.3 (1999). Available at http://ajpheart.physiology.org/cgi/content/full/276/3/H1098 Subhendu Mukherjee, Istvan Lekli, Shyamal Goswami† and Dipak K. Das. Freshly Crushed Zeljko J. Bosnjak. Anesthetics and cardioprotection. Signa Vite, 2 Suppl 1, (2007): S6-10. Read More