New Pharmacological Approaches to the Prevention of Myocardial Ischemia- Reperfusion Injury

Chin, Kai Yee; Qin, Cheng Xue; May, Lauren T.; Ritchie, Rebecca H.; Woodman, Owen L.

doi:10.2174/1389450116666151001112020

Cited by 26 publications

(20 citation statements)

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“…In the postischemic period, application of an H S donor decreases apoptosis and preserves intestinal architecture (15). Other I/R-related injuries including myocardial infarction, cerebral ischemia, and transplant-associated renal ischemia were also observed to receive therapeutic benefit and end-organ protection with use of H S donors (7,13,21,24). H S likely plays an important role physiologically through cellular signaling and vasodilation.…”

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confidence: 99%

Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

Jensen

Drucker

Khaneki

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hydrogen sulfide (HS) is an endogenous gasotransmitter that has vasodilatory properties. It may be a novel therapy for intestinal ischemia-reperfusion (I/R) injury. We hypothesized that ) HS would improve postischemic survival, mesenteric perfusion, mucosal injury, and inflammation compared with vehicle and ) the benefits of HS would be mediated through endothelial nitric oxide. C57BL/6J wild-type and endothelial nitric oxide synthase knockout (eNOS KO) mice were anesthetized, and a midline laparotomy was performed. Intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using laser Doppler. Intestinal ischemia was established by temporarily occluding the superior mesenteric artery. Following ischemia, the clamp was removed, and the intestines were allowed to recover. Either sodium hydrosulfide (2 nmol/kg or 2 µmol/kg NaHS) in PBS vehicle or vehicle only was injected into the peritoneum. Animals were allowed to recover and were assessed for mesenteric perfusion, mucosal injury, and intestinal cytokines. values< 0.05 were significant. HS improved mesenteric perfusion and mucosal injury scores following I/R injury. However, in the setting of eNOS ablation, there was no improvement in these parameters with HS therapy. Application of HS also resulted in lower levels of intestinal cytokine production following I/R. Intraperitoneal HS therapy can improve mesenteric perfusion, intestinal mucosal injury, and intestinal inflammation following I/R. The benefits of HS appear to be mediated through endothelial nitric oxide-dependent pathways. HS is a gaseous mediator that acts as an anti-inflammatory agent contributing to gastrointestinal mucosal defense. It promotes vascular dilation, mucosal repair, and resolution of inflammation following intestinal ischemia and may be exploited as a novel therapeutic agent. It is unclear whether HS works through nitric oxide-dependent pathways in the intestine. We appreciate that HS was able to improve postischemic recovery of mesenteric perfusion, mucosal integrity, and inflammation. The beneficial effects of HS appear to be mediated through endothelial nitric oxide-dependent pathways.

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confidence: 99%

Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

Jensen

Drucker

Khaneki

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Reperfusion arrhythmias (RA) are the main complications of cardiopulmonary bypass (CPB) in heart surgery. Arrhythmias, such as ventricular tachycardia and ventricular fibrillation, can induce hemodynamic disorders and sudden cardiac death [1, 2]. In the study of arrhythmias, monophasic action potentials (MAPs) is an indicator for changes of cardiac vectors of cardiac arrhythmias, which can describe the repolarization phase of cardiac myocytes intuitively and steadily, and MAPs is an important means to observe the electrical activity of cardiac myocytes [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane Alleviates Reperfusion Arrhythmia by Ameliorating TDR and MAPD₉₀ in Isolated Rat Hearts after Ischemia-Reperfusion

Wang

Dai

Gao

et al. 2019

Anesthesiology Research and Practice

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Objective To investigate the effect of sevoflurane on the monophasic action potentials (MAPs) in isolated rat hearts after ischemia-reperfusion. Methods Twenty-four healthy SD male rats, weighing 280–320 g, were randomly divided into three groups after successful preparation of a Langendorff isolated heart perfusion model with a stabilization period perfusion of 15 min with Krebs–Henseleit (K–H) fluid (n = 8): the control group (group A, continuously perfused with K–H fluid for 105 min), the ischemia-reperfusion group (group B, continuously perfused with K–H fluid for 15 min, and then exposed to 60 min of global ischemia induced by Thomas solution followed by 30 min of reperfusion), and the sevoflurane group (group C, K–H fluid contained 1.0 MAC sevoflurane, and other procedures were same as in group B). Heart rate (HR) and MAPs including time course (MAPD50 or MAPD90) of the epicardium (Epi) and endocardium (Endo) were recorded at the time of balance perfusion for 15 min (T0), continuous perfusion for 15 min (T1), reperfusion for 15 min/continuous perfusion for 105 min (T2), and reperfusion for 30 min/continuous perfusion for 120 min (T3), and the transmural dispersion of repolarization (TDR) was calculated. The incidence of arrhythmia, time for restoration of spontaneous heart beat, and duration of arrhythmia were recorded during the period of reperfusion. Results HR in group B and group C was lower at T2 and T3 than that in group A, while that in group B was significantly lower than that in group A at T2 and T3, and HR in group C was higher than that in group B at T2 and T3 (P < 0.05). There was no difference of TDR in each group at T0 and T1 (P > 0.05), while TDR in group B was increased at T2 and T3 compared with that in group C and group A (P < 0.05). TDR in group C was decreased compared with that in group B at T2 and T3 (P < 0.05), while there was no such difference between group C and group A (P > 0.05). The time for restoration of spontaneous heart beat and duration of arrhythmia in group C were shorter than those in group B (P < 0.05), while cardiac arrhythmia scores in group B were higher than those in group C (P < 0.05). There was no difference of MAPD50 in each group (P > 0.05). The MAPD90 in group B was much longer than that in other groups at T2 and T3 (P < 0.05), while there was no such difference between group C and group A (P > 0.05). The prolonged MAPD90 at T2 and T3 in group B strikingly differed from that at T0 and T1 (P < 0.05). Nevertheless, there was no such difference in other groups at different time points (P > 0.05). Conclusion Sevoflurane alleviates reperfusion arrhythmia induced by myocardial ischemia-reperfusion through the shortening of MPAD90 in isolated rat hearts.

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“… 7 It has most of the IR injury mechanisms, restoring calcium homeostasis, reducing reactive oxygen species (ROS) synthesis, inhibiting the inflammatory response, promoting the preservation of microvascular flow and stabilizing cellular membranes, reducing free radical formation, and promoting angiogenesis following vascular injury. 6 , 8 – 11 However, its systemic administration would bring side effects and limited pharmacological efficiency, and it’s extremely short plasma half-life has hampered its clinical application. 12 – 14 …”

Section: Introductionmentioning

confidence: 99%

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

Yu¹,

Li²,

Yu³

2018

DDDT

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PurposeMyocardial infarction is a major cause of mortality and heart failure worldwide. One of the most effective methods of this injury is direct delivery of cardioprotective drugs to ischemia–reperfusion (IR) myocardium. The aim of the present study was to fabricate an adenosine (Ade) prodrug-based, atrial natriuretic peptide (ANP)-modified nanosystem for the treatment of myocardial infarction.Materials and methodsOleate adenosine prodrug (Ade-OA) and ANP-distearoylphosphatidylethanolamine-polyethylene glycol were synthesized. ANP-modified Ade-loaded lipid nanocarriers (ANP Ade/LNCs) were then self-assembled by using solvent evaporation method. In vitro drug release in the presence of plasma was evaluated. In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics were investigated in rats with ischemic myocardium after intravenous injection.ResultsIn vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics studies in acute myocardial infarction (AMI) rats showed that ANP Ade/LNCs exhibited better efficiency than non-modified Ade/LNCs and free Ade in all respects.ConclusionThese results indicated that the ANP Ade/LNCs can be used as a promising system for the treatment of cardiovascular diseases.

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New Pharmacological Approaches to the Prevention of Myocardial Ischemia- Reperfusion Injury

Abstract: The processes involved in reperfusion injury might provide targets for improved outcomes after myocardial infarction but thus far that aim has not been met in the clinic.

Cited by 26 publications

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Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

Sevoflurane Alleviates Reperfusion Arrhythmia by Ameliorating TDR and MAPD₉₀ in Isolated Rat Hearts after Ischemia-Reperfusion

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

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New Pharmacological Approaches to the Prevention of Myocardial Ischemia- Reperfusion Injury

Abstract: The processes involved in reperfusion injury might provide targets for improved outcomes after myocardial infarction but thus far that aim has not been met in the clinic.

Cited by 26 publications

References 0 publications

Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

Sevoflurane Alleviates Reperfusion Arrhythmia by Ameliorating TDR and MAPD90 in Isolated Rat Hearts after Ischemia-Reperfusion

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

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Sevoflurane Alleviates Reperfusion Arrhythmia by Ameliorating TDR and MAPD₉₀ in Isolated Rat Hearts after Ischemia-Reperfusion