scholarly journals THE CARBON MONOXIDE DONOR, TOPIRAMATE, AND BLOCKERS OF AQUAPORINE RECEPTORS DECREASE MYOCARDIAL ISCHEMIA-REPERFUSION INJIRY

2021 ◽  
Vol 67 (5) ◽  
pp. 30-38
Author(s):  
S.P. Beschasnyi ◽  
◽  
O.M. Hasiuk ◽  
Keyword(s):  
Coronary Flow ◽  
Wave Amplitude ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Ischemic Damage ◽  
Igg Antibodies ◽  
Glucose Intake ◽  
Channel Blocking ◽  
Myocardial Ischemia Reperfusion ◽  
R Wave Amplitude

We investigated the metabolism of mouse isolated heart under the influence of tricarbonyldichlorothenium (II)- dimer (CORM-2 and 2,3-4,5-bis-O-isopropylidene-βD-fructopyranose sulfamate (topiramate) as potential blockers of aquaporine channel (AQP3) of cardiac myocytes. The results were compared with those obtained from the group receiving anti-AQP3 monoclonal antibodies. A decrease in coronary flow was found during the period preceding ischemia (topiramate did not cause this effect). However, at the end of reperfusion, CORM-2 was responsible for its stabilization. This compound did not affect glucose intake (topiramate increased it only at the end of reperfusion), decreased Ca2+ deposition in cardiac muscle (AQP3-IgG antibodies and topiramate had similar effect), decreased creatinine release, AST (especially at the end of reperfusion). The action of CORM-2 increased the amplitude of the R waveform before ischemia and during reperfusion. At the end of reperfusion the R-wave amplitude decreased. The effect of topiramate caused an increase in amplitude only at the beginning of reperfusion. Administration of CORM-2, topiramate and antibodies resulted in prolongation of the interval before and during ischemia. At the same time, the effect of these drugs and antibodies reduced the development of ischemic damage. The results indicate that the released CO from CORM-2 has effects similar to those of anti-AQP3 antibodies. The action of topiramate had signs of calcium channel blocking.

scholarly journals Preconditioning reduces tissue complement gene expression in the rabbit isolated heart

1999 ◽  
Vol 277 (6) ◽  
pp. H2373-H2380 ◽  
Author(s):  
Elaine J. Tanhehco ◽  
Koji Yasojima ◽  
Patrick L. McGeer ◽  
Ruth A. Washington ◽  
Kenneth S. Kilgore ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Membrane Attack Complex ◽  
Global Ischemia ◽  
Mrna Levels ◽  
Similar Reduction ◽  
Complement Components ◽  
Complex Protein ◽  
Myocardial Ischemia Reperfusion

Both preconditioning and inhibition of complement activation have been shown to ameliorate myocardial ischemia-reperfusion injury. The recent demonstration that myocardial tissue expresses complement components led us to investigate whether preconditioning affects complement expression in the isolated heart. Hearts from New Zealand White rabbits were exposed to either two rounds of 5 min global ischemia followed by 10 min reperfusion (ischemic preconditioning) or 10 μM of the ATP-dependent K+(KATP) channel opener pinacidil for 30 min (chemical preconditioning) before induction of 30 min global ischemia followed by 60 min of reperfusion. Both ischemic and chemical preconditioning significantly ( P < 0.05) reduced myocardial C1q, C1r, C3, C8, and C9 mRNA levels. Western blot and immunohistochemistry demonstrated a similar reduction in C3 and membrane attack complex protein expression. The KATPchannel blocker glyburide (10 μM) reversed the depression of C1q, C1r, C3, C8, and C9 mRNA expression observed in the pinacidil-treated hearts. The results suggest that reduction of local tissue complement production may be one means by which preconditioning protects the ischemic myocardium.

Abstract 453: The Role of PD-1/PDL-1 in Myocardial Ischemia Reperfusion Injury.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Mahmood Mozaffari ◽  
Jun Yao Liu ◽  
Babak Baban
Keyword(s):  
Cell Death ◽  
Myocardial Ischemia ◽  
Inflammatory Response ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Cardiac Cells ◽  
Interleukin 17 ◽  
Myocardial Ischemia Reperfusion

Programmed Death-1 (PD-1) and its ligand, PDL-1, are expressed on immune cells and have emerged as negative regulators of immune and inflammatory mechanisms. Aside from the contribution of systemic immune and inflammatory mechanisms to myocardial ischemia reperfusion (IR) injury, isolated heart studies have shown that the myocardium is capable of mounting a robust inflammatory response to an IR insult. However, potential involvement of PD-1/PDL-1 in the setting of cardiac IR injury is not established. We tested the hypothesis that an IR insult downregulates PD-1/PDL-1 pathway thereby exacerbating the inflammatory response and cell death. According, Langendorff-perfused rat hearts were subjected to 40 min of ischemia and 15 min of reperfusion; normoxic hearts served as controls. Thereafter, cardiac cells were prepared and subjected to flow-cytometry-based assays. The ischemic-reperfused hearts displayed a marked increase in the pro-inflammatory cytokine interleukin-17 in association with disruption of mitochondrial membrane potential (JC-1 assay) and apoptotic and necrotic cell death. Importantly, the ischemic-reperfused hearts showed a significant increase in PD-1 and PDL-1 positive cells. The results suggest that cardiac PD-1/ PDL-1 pathway likely constitutes an endogenous mechanism whose upregulation in the ischemic-reperfused heart curbs the inflammatory response and associated tissue injury.

Effect of estrogen on global myocardial ischemia-reperfusion injury in female rats

2000 ◽  
Vol 279 (6) ◽  
pp. H2766-H2775 ◽  
Author(s):  
Peiyong Zhai ◽  
Thomas E. Eurell ◽  
Robert Cotthaus ◽  
Elizabeth H. Jeffery ◽  
Janice M. Bahr ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Coronary Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
The Other ◽  
Female Rats ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

We investigated the effects of estrogen on global myocardial ischemia-reperfusion injury in rats that were ovariectomized (Ovx), sham-operated, or ovariectomized and then given 17β-estradiol (E2β) supplementation (Ovx+E2β). Hearts were excised, cannulated, perfused with and then immersed in chilled (4°C) cardioplegia solution for 30 min, and then retrogradely perfused with warm (37°C), oxygenated Krebs-Henseleit bicarbonate buffer for 120 min. The coronary flow rate, first derivative of left ventricular pressure, and nitrite production were all significantly lower in Ovx than in sham-operated or Ovx+E2β hearts. However, coronary flow rates or nitrate production were not consistently different throughout the entire reperfusion period. Ca2+accumulated more in Ovx rat hearts than in sham-operated or Ovx+E2β hearts, and mitochondrial respiratory function was lower in Ovx hearts than in hearts from the other two groups. Marked interstitial edema and contraction bands were seen in hematoxylin-eosin-stained sections of Ovx rat hearts but not in hearts from either of the other groups. Hematoxylin-basic fuchsin-picric acid-stained sections revealed fewer viable myocytes in hearts from the Ovx group than from the sham or Ovx+E2β group. Transmission electron microscopy demonstrated more severely damaged mitochondria and ultrastructural damage to myocytes in Ovx rat hearts. Our results indicate that estrogen plays a cardioprotective role in global myocardial ischemia-reperfusion injury in female rats.

Hydrogen sulfide contributes to cardioprotection during ischemia–reperfusion injury by opening KATP channels

2007 ◽  
Vol 85 (12) ◽  
pp. 1248-1253 ◽  
Author(s):  
Zhifei Zhang ◽  
Haixia Huang ◽  
Ping Liu ◽  
Chaoshu Tang ◽  
Jun Wang
Keyword(s):  
Cardiac Myocytes ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Katp Channels ◽  
Open Probability ◽  
Isolated Hearts ◽  
Heart Perfusion ◽  
Myocardial Ischemia Reperfusion

The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia–reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, ±dP/dtmax, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 μmol/L NaHS) during reperfusion resulted in significant improvement in heart function compared with the I/R group (LVDP recovered to 85.0% ± 6.4% vs. 35.0% ± 6.1%, +dP/dtmax recovered to 80.9% ± 4.2% vs. 43.0% ± 6.4%, and –dP/dtmax recovered to 87.4% ± 7.3% vs. 53.8% ± 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group compared with the I/R group (1.5 ± 0.2 vs. 4.0 ± 0.4, respectively; p < 0.001). The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (KATP) blocker (10 μmol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of KATP channels from 0.07 ± 0.03 to 0.15 ± 0.08 after application of 40 μmol/L NaHS and from 0.07 ± 0.03 to 0.36 ± 0.15 after application of 100 μmol/L NaHS. These findings provide the first evidence that H2S increases the open probability of KATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.

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