The Anti-infarct Effect of an Adenosine A1-Selective Agonist is Diminished After Prolonged Infusion as is the Cardioprotective Effect of Ischaemic Preconditioning in Rabbit Heart

Tsuchida, Akihito; Thompson, Robert D.; Olsson, Ray A.; Downey, James M.

doi:10.1006/jmcc.1994.1039

Cited by 74 publications

(38 citation statements)

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“…40 Another theoretical problem may be the development of tachyphylaxis to preconditioning agents. Indeed, Tsuchida et al 41 have shown in a rabbit model that continuous infusion of a selective A 1 adenosine receptor agonist led to downregulation of the signaling mechanism and loss of protection. However, more encouraging data have been obtained recently using a different dosing schedule, in which the same drug was administered to rabbits by intermittent dosing over a 10-day period with persistence of myocardial protection assessed 48 hours after the last dose.…”

Section: Discussionmentioning

confidence: 99%

Ischemic Preconditioning in Humans

et al. 1999

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Abstract-Ischemic preconditioning, a powerful form of endogenous protection against myocardial infarction, has been demonstrated in several animal species and, recently, in isolated human cardiomyocytes. For both logistic and ethical reasons, no clinical study can meet the strict conditions of experimental studies on preconditioning with infarct size as the end-point. Nevertheless, the demonstration of adaptation to ischemia observed during in vitro studies on human atrial trabeculae, in patients in the setting of coronary bypass surgery, and in the setting of coronary angioplasty in the absence of collateral vessel recruitment strongly suggests that ischemic preconditioning occurs in humans. This notion is further supported by the observation that in these human models, the adaptation to ischemia is influenced by drugs acting on K ATP channels and on purinergic and ␣-adrenergic receptors, similar to what is observed in accepted experimental models of ischemic preconditioning. This important form of myocardial endogenous protection may also play a role in the warm-up phenomenon and in mediating the beneficial effects of preinfarction angina. The demonstration of ischemic preconditioning in humans and the identification of some of its mediators suggests that in patients at high risk for myocardial infarction, drugs known to block this endogenous form of protection should be used with caution, whereas drugs known to elicit preconditioning might have a relevant therapeutic role. (Circulation. 1999;100:559-563.)

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Section: Discussionmentioning

confidence: 99%

Ischemic Preconditioning in Humans

et al. 1999

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“…A single dose of CCPA is protective either immediately after the removal of stimulus or 48 hours later. A continuous 72 hour administration of this same drug, however, failed to protect the heart immediately following removal of the CCPA (17). Multiple pulses of the drug at 48 hour intervals for 10 days were effective to maintain the protection at 48 hours after the final pulse (18).…”

Section: Can We Infer the Structure And Dynamics Of A Signaling Netwomentioning

confidence: 99%

“…Based on the analyses above, either the single positive forward motif (Fig.3A) or combined ones positive and negative ones, such as the ones shown in Fig.4, can give rise to such a response. However, two early experimental studies (17,18) provide additional information to identify a signaling module driving this protective response. The basic experimental results for CCPA-induced protection are summarized in Fig.5A.…”

Section: Can We Infer the Structure And Dynamics Of A Signaling Netwomentioning

confidence: 99%

“…For example, in the heart, cardioprotection can be induced pharmacologically by administration of the adenosine A 1 receptor antagonist (CCPA), with a single dose resulting in both immediate early and delayed late protection that lasts more than 72 hours in the rabbit (3,4). However, a 72-hour continuous CCPA infusion afforded no sustained protection (17), whereas pulses of CCPA at 48-hour intervals maintained the beneficial response continuously for at least 10 days (18). Therefore, understanding what mechanisms underlie the different forms of memory and how the system responses to additional stimuli is of great importance for therapeutic purposes.…”

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confidence: 99%

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Signal transduction network motifs and biological memory

Han

Vondriska

Yang

et al. 2007

Journal of Theoretical Biology

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Memory is a ubiquitous phenomenon in biological systems, yet the mechanisms responsible for memory, and how to manipulate it at the subcellular level, remain poorly understood. Subjected to transient stimuli, biological systems can exhibit short early responses and/or prolonged (or permanent) late responses. Experimental evidence suggests that early responses ("short-term memory") involve posttranslational modification of existing proteins and/or their intracellular relocalization, whereas late responses ("long-term memory") depend on new protein synthesis. Although this provides an intuitive explanation at the basic molecular level, it does little to clarify the important dynamics that actually maintain memory at the systems level. In this study, we use mathematical modeling to study dynamical mechanisms of biological memory. We first examined the response of four fundamental motifs (positive/negative feedforward and feedback) to external stimuli. Because motifs do not exist in isolation within the cell, we then combined these motifs to form signaling modules to understand how they confer biological memory. These motifs, and different combinations thereof, displayed distinct behavior in response to external stimuli. The principles described in this study have important implications for experimental approaches to identify the mechanisms for biological memory and for the development of therapeutic strategies to modulate signaling network responses in the setting of human disease. Keywords computational biology; protein interactions; dynamicsMany biological systems exhibit biphasic responses to a transient stimulus, in which an immediate brief response is followed, often after a delay, by a substantially prolonged response, conferring a form of biological "memory" to signal transduction. For example, in nerve synapses, a single train of stimuli causes a response lasting a few hours, but multiple trains of stimuli can induce long-term potentiation (LTP) of the response which can last >24 hours or

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“…It may be in this case that insights gained through our studies of the second window of protection could be of benefit. If the second window could be triggered by a pharmacological intervention than it is likely that enhanced anti-ischaemic defences would be in place for at least [70]. Alternative approaches may be treatment with augmenters of endogenous adenosine such as acadesine and draflazine, KATP channel openers such as nicorandil, or modulators of the various intracellular signalling steps.…”

Section: Acute Myocardial Infarctionmentioning

confidence: 99%