Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart

Kretzler, Matthias; Tanaka, Shota; Bolling, Steven F.; Simon, Andrè; Su, Tsung Ping; Oeltgen, Peter R.; Haverich, Axel

doi:10.1067/mtc.2001.116950

Cited by 31 publications

(21 citation statements)

References 26 publications

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“…1,5,7,25 Many studies have demonstrated the effects of d receptor agonists to limit myocardial infarct size in models of cardiac ischemia and reperfusion. [5][6][7][8][9][10][11] However, most investigations involving these compounds have examined only their effects on specific receptors, tissues, or organs and have not looked at their impact on systemic processes and whole animal outcomes. 3 In this study, using an animal model of severe hemorrhagic shock, there was significant improvement in hemodynamic stability and a prolonged survival with DADLE treatment.…”

Section: Discussionmentioning

confidence: 99%

“…DADLE (D-Ala2-Leu5-enkephalin) is one of the d receptor agonists that has been extensively studied with regard to its effect on myocardial function and has been used as a tool to investigate the mechanisms of IP. [9][10][11] It differs from other commonly studied opioid agonists in that it stimulates both d 1 and d 2 receptors and possibly has some k and m agonist activity. [12][13][14] There is also evidence that DADLE interacts with nonopioid-mediated cell processes and is antiapoptotic.…”

mentioning

confidence: 99%

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Effect of a δ Receptor Agonist on Duration of Survival during Hemorrhagic Shock

Summers

Hildebrandt

2003

Academic Emergency Medicine

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Objectives: Selective d receptor agonists have been shown to stabilize membrane physiologic processes, reduce metabolic rates, and provide protection against ischemic insults through K ATP channel opening in a variety of organ beds. However, their potential for affecting outcomes in states of generalized ischemia has not been explored. The authors examined the effect of the nonselective d receptor agonist, DADLE (D-Ala2-Leu5-enkephalin), on hemodynamic stability and duration of survival in an animal model of severe hemorrhagic shock. Methods: Conscious Sprague Dawley rats with indwelling catheters were hemorrhaged at a rate of 3.25 mL/100 grams over 20 minutes after half of the group received 1% DADLE (1 mg/kg IV). Following the hemorrhage, all rats were continuously monitored for heart rate (HR), mean arterial pressure (MAP), and life signs for up to three hours (death defined as apnea, systolic blood pressure \ 30 mm Hg without pulsations, and electroencephalographic silence). Survival rates and hemodynamic trends were compared between the control and DADLE-treated groups. Results: In the 14 rats studied (8 DADLE; 6 controls), initial hemorrhage resulted in similar hemodynamic shock (average MAP fall: 118 to 59 vs 119 to 55 mm Hg). Analysis of survival at 3.5 hours revealed statistically significant differences between the control and DADLE groups. While 50% of the DADLE group survived past the three hours, no control animals were still alive at the end of the experimental period. The MAP trended downward and the HR increased for the control group, but all hemodynamic parameters stabilized in the rats treated with DADLE. Conclusions: Most current strategies for treating shock focus on the supply side of resuscitation. The coordinated various actions of DADLE have the potential to work in concert in the intact organism to improve overall survival during severe hemorrhagic shock. In an animal model of severe hemorrhagic shock, there was improvement in hemodynamic stability and a prolonged survival with DADLE treatment. Physiologic manipulation with DADLE appears to be a way to improve survival during shock with possible clinical implications.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of a δ Receptor Agonist on Duration of Survival during Hemorrhagic Shock

Summers

Hildebrandt

2003

Academic Emergency Medicine

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“…Fortgesetzte Untersu chungen auf diesem Gebiet haben nun die Aufmerksamkeit auf endogene Opioi de gelenkt, denen offenbar tatsächlich ei ne umsatzdrosselnde Wirkung bei Win terschläfern und Nichtwinterschläfern zu kommt [33,55] und die in ersten Anwen dungsversuchen sogar einen organprotek tiven Effekt gezeigt haben [22].…”

Section: Schlüsselwörterunclassified

Warum 37°C?

Singer

2007

Anaesthesist

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Homeothermy is the result of an evolutionary process during which every increase in oxygen supply led to a consecutive increase in metabolic rate and, thus, to a new dependence on favorable ambient conditions. In response to the food scarcity of winter months, some inhabitants of temperate zones developed an ability to hibernate which is characterized by a fully thermocontrolled reduction in body temperature down to near zero values. Hibernation thus illustrates that in homeotherms, not only the body shell is poikilothermic, but also the core temperature is more variable than often assumed. However, in contrast to clinical hypothermia, natural torpidity does not consist of a cold-induced reduction in metabolic rate, but of an endogenous metabolic reduction with subsequent lowering of body temperature. As a factor of metabolic suppression, the pH has been suspected which, in hibernators, is kept constant at 7.4 by relative hypoventilation (pH-stat) which differs from its passive shift in the poikilothermic body shell (alpha-stat). In clinical hypothermia, temperature governs the metabolic rate in that, depending on the state of thermoregulation, either a cold defense reaction with an increased metabolic rate (accidental hypothermia) or a cold-induced reduction in metabolic rate (induced hypothermia) occurs. However, as can be learned from hibernators, the lower limit of hypothermia tolerance seems to be due to a uniform minimal metabolic rate rather than to the species-specific body temperature at which this metabolic limit is reached, depending on body size and basal metabolic rate. Accordingly, in judging the sequelae of hypothermia, the degree of cooling should be given less emphasis than the resulting effects on metabolic rate.

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“…Miyokardiyal İÖ oluşumu sırasında etkin olan moleküller; reseptör bağımlı tetikleyiciler (adenozin, bradikinin, opioidler, siklooksijenaz ve lipoksijenaz ürünleri, norepinefrin, anjiotensin, endotelin), reseptör bağımsız tetikleyiciler (serbest radikaller, nitrik oksit, kalsiyum), İÖ medyatörleri (G proteinleri jenle aktive edilen protein kinazlar, ısı şok proteinleri, endotoksin, Janus Kinaz, sinyal transdüktörü ve transkripsiyon aktivatörü yolağı, Rho-Kinaz yolağı) ve İÖ uç efektörleri (adenozin trifosfata duyarlı potasyum kanalları [KATP]) olarak sınıflandırılırlar (9)(10)(11)(12)(13)(14)(15)(16) .…”

Section: Introductionunclassified