Increases in myocardial cyclic GMP attenuate contractile delay in myocardial stunning

2002 ◽  
Vol 80 (8) ◽  
pp. 804-810 ◽  
Author(s):  
Mark W Huang ◽  
Peter M Scholz ◽  
Harvey R Weiss
Keyword(s):  
Cyclic Gmp ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Control Group ◽  
Wall Thickening ◽  
Maximal Rate ◽  
Myocardial Wall ◽  
New Zealand White Rabbits

We tested the hypothesis that the effects of myocardial stunning would be reduced by cyclic GMP in rabbit hearts. In three groups of anesthetized open-chest New Zealand white rabbits, myocardial stunning was produced by 15 min of occlusion of the left anterior descending coronary artery followed by 15 min of reperfusion repeated twice. Either control vehicle (saline plus 1% dimethyl sulfoxide) or 8-bromo-cyclic GMP (8-Br-cGMP (10–4 and 10–3 M)) was topically applied to the left ventricular surface. Hemodynamic (left ventricular and aortic pressures) and functional parameters (wall thickening, delay in onset of wall thickening, and rate of wall thickening) were determined. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine myocardial O2 consumption (VO2). Myocardial stunning was observed in the control group through an increased delay in onset of myocardial wall thickening (29 ± 7 versus 55 ± 16 ms) and decreased maximal rate of wall thickening (20 ± 8 versus 11 ± 3 mm·s–1). After treatment with 8-Br-cGMP 10–4 and 10–3 M, stunning did not increase the delay (37 ± 5 versus 39 ± 7 and 39 ± 7 versus 28 ± 8 ms). Myocardial stunning did not significantly alter V02. 8-Br-cGMP 10–3 M significantly decreased subepicardial V02 (6.2 ± 0.8 versus 3.7 ± 0.6 mL O2·min–1·100 g–1) and insignificantly decreased subendocardial V02 (8.6 ± 0.9 versus 6.3 ± 1.2 mL O2·min–1·100 g–1) when compared with the vehicle-treated rabbits. We conclude that increasing cyclic GMP reduced the effects of myocardial stunning in the rabbit heart by ameliorating the delay in onset of wall thickening and decreasing the local O2 costs in the stunned region. Key words: cyclic GMP, myocardial stunning, O2 consumption, ischemia, reperfusion, wall thickening, rabbit.

Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits

2006 ◽  
Vol 291 (3) ◽  
pp. H1345-H1350 ◽  
Author(s):  
Nicolas Couvreur ◽  
Laurence Lucats ◽  
Renaud Tissier ◽  
Alain Bize ◽  
Alain Berdeaux ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Segment Length ◽  
Wall Thickening ◽  
Area At Risk

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO ( n = 5), 30 s CAR/30 s CAO ( n = 7), and 1 min CAR/1 min CAO ( n = 6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33 ± 4 vs. 34 ± 4%, 30 ± 4 vs. 30 ± 4%, and 33 ± 4 vs. 32 ± 4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39 ± 7%, n = 6 vs. 56 ± 4%, n = 7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.

scholarly journals The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 047-057
Author(s):  
Lei Gong ◽  
Xuyang Wang ◽  
Jinyu Pan ◽  
Mingjun Zhang ◽  
Dian Liu ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Mtor Signaling ◽  
Maximal Rate ◽  
H9c2 Cells ◽  
Mtor Signaling Pathway ◽  
Cardioprotective Effects

AbstractObjectiveThe purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism.MethodsSprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion.ResultsIn vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dtmax), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dtmax) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells.ConclusionThe combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.

Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins

2001 ◽  
Vol 281 (3) ◽  
pp. H1346-H1352 ◽  
Author(s):  
Karyn L. Hamilton ◽  
Scott K. Powers ◽  
Takao Sugiura ◽  
Sunjoo Kim ◽  
Shannon Lennon ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Shock Proteins ◽  
Mnsod Activity ◽  
Over Time

We examined the effects of 3 days of exercise in a cold environment on the expression of left ventricular (LV) heat shock proteins (HSPs) and contractile performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were divided into the following three groups ( n = 12/group): 1) control, 2) exercise (60 min/day) at 4°C (E-Cold), and 3) exercise (60 min/day) at 25°C (E-Warm). Left anterior descending coronary occlusion was maintained for 20 min, followed by 30 min of reperfusion. Compared with the control group, both the E-Cold and E-Warm groups maintained higher ( P < 0.05) LV developed pressure, first derivative of pressure development over time (+dP/d t), and pressure relaxation over time (−dP/d t) throughout I/R. Relative levels of HSP90, HSP72, and HSP40 were higher ( P < 0.05) in E-Warm animals compared with both control and E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts ( P < 0.05). Protection against I/R-induced lipid peroxidation in the LV paralleled the increase in MnSOD activity whereas lower levels of lipid peroxidation were observed in both E-Warm and E-Cold groups compared with control. We conclude that exercise-induced myocardial protection against a moderate duration I/R insult is not dependent on increases in myocardial HSPs. We postulate that exercise-associated cardioprotection may depend, in part, on increases in myocardial antioxidant defenses.

PEG-SOD improves postischemic functional recovery and antioxidant status in blood-perfused rabbit hearts

1992 ◽  
Vol 263 (4) ◽  
pp. H1243-H1249
Author(s):  
Y. Qiu ◽  
M. Galinanes ◽  
R. Ferrari ◽  
A. Cargnoni ◽  
A. Ezrin ◽  
...  
Keyword(s):  
Redox State ◽  
Additive Group ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Control Group ◽  
Sod Activity ◽  
Group A ◽  
Group B ◽  
Developed Pressure ◽  
Postischemic Recovery

The isolated blood-perfused rabbit heart, subjected to 60 min of cardioplegic arrest and 60 min of reperfusion, was used to assess the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) on postischemic recovery of left ventricular developed pressure (LVDP), the tissue activity of SOD, and tissue redox state. The five groups studied were the following: PEG-SOD-free control (group A), PEG-SOD as a pretreatment and as an additive during cardioplegia and reperfusion (group B), PEG-SOD as a pretreatment and a cardioplegic additive (group C), PEG-SOD in cardioplegia alone (group D), and PEG-SOD in reperfusion alone (group E). The results show that pretreatment with PEG-SOD improves postischemic recovery of LVDP (72 +/- 2% and 66 +/- 7 vs. 47 +/- 4% in groups B, C, and A, respectively). This protection was associated with an improved tissue redox state. Thus the ischemia-induced rise in oxidized glutathione was reduced from 313 +/- 26% (group A) to 162 +/- 15 and 138 +/- 14% (groups B and C, respectively), and the fall in reduced glutathione was attenuated from 51 +/- 5% to 35 +/- 6 and 13 +/- 5%, respectively. Tissue Mn-SOD activity was also conserved from 36 +/- 4% (group A) to 71 +/- 6 and 94 +/- 4% (groups B and C, respectively). No significant effect was seen when PEG-SOD was applied in cardioplegia or during reperfusion alone.

TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1

2003 ◽  
Vol 284 (5) ◽  
pp. H1612-H1617 ◽  
Author(s):  
Hongjiang Chen ◽  
Dayuan Li ◽  
Tom Saldeen ◽  
Jawahar L. Mehta
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Left Ventricular ◽  
Blue Staining ◽  
Control Group ◽  
Dependent Manner ◽  
Arterial Blood ◽  
Group I

Ischemia-reperfusion (I/R) is thought to upregulate the expression and activity of matrix metalloproteinases (MMPs), which regulate myocardial and vascular remodeling. Previous studies have shown that transforming growth factor-β1 (TGF-β1) can attenuate myocardial injury induced by I/R. TGF-β1 is also reported to suppress the release of MMPs. To study the modulation of MMP-1 by TGF-β1 in I/R myocardium, Sprague-Dawley rats were given saline and subjected to 1 h of myocardial ischemia [total left coronary artery (LCA) ligation] followed by 1 h of reperfusion ( n = 9). Parallel groups of rats were pretreated with recombinant TGF-β1(rTGF-β1, 1 mg/rat, n = 9) before reperfusion or exposure to sham I/R (control group). I/R caused myocardial necrosis and dysfunction, indicated by decreased first derivative of left ventricular pressure, mean arterial blood pressure, and heart rate (all P < 0.01 vs. sham-operated control group). Simultaneously, I/R upregulated MMP-1 ( P < 0.01). Treatment of rats with rTGF-β1 reduced the extent of myocardial necrosis and dysfunction despite I/R (all P < 0.01). rTGF-β1 treatment also inhibited the upregulation of MMP-1 in the I/R myocardium ( P < 0.05). To determine the direct effect of MMP-1 on the myocardium, isolated adult rat myocytes were treated with active MMP-1, which caused injury and death of cultured myocytes, measured as lactate dehydrogenase release and trypan blue staining, in a dose- and time-dependent manner ( P < 0.05). Pretreatment with PD-166793, a specific MMP inhibitor, attenuated myocardial injury and death induced by active MMP-1. The present study for the first time shows that MMP-1 can directly cause myocyte injury or death and that attenuation of myocardial I/R injury by TGF-β1 may, at least partly, be mediated by the inhibition of upregulation of MMP-1.

Progressive cardiac dysfunction with repeated pacing-induced ischemia: protection by AICA-riboside

1991 ◽  
Vol 261 (5) ◽  
pp. H1570-H1577 ◽  
Author(s):  
M. A. Young ◽  
K. M. Mullane
Keyword(s):  
Blood Flow ◽  
Regional Wall Motion ◽  
Posterior Wall ◽  
Saline Group ◽  
Left Ventricular ◽  
Saline Control ◽  
Regional Myocardial Blood Flow ◽  
Control Group ◽  
Wall Thickening ◽  
Progressive Decline

The effects of repeated episodes of demand-induced ischemia on regional myocardial wall thickening, endocardial electrogram, and regional myocardial blood flow are not well delineated. We studied the cumulative effects of six periods of pacing-induced ischemia in 35 chloralose-anesthetized dogs with circumflex coronary stenosis. Repetitive ischemia of the posterior left ventricular free wall was induced with six 5-min pacing periods separated by 15-min recovery periods. The three groups of dogs studied were 1) saline control, 2) the purine precursor 5-aminoimidazole 4-carboxamide riboside (AICA-r), and 3) nitroglycerin (NTG). During the initial pacing period (before treatment), thickening of the posterior wall declined in the saline group (43 +/- 5% of control), the AICA-r group (47 +/- 8% of control), and the NTG group (55 +/- 3% of control), associated with endocardial S-T segment elevation and a decrease in subendocardial blood flow. Wall thickening continued to decrease in each group with each successive pacing episode. However, during the sixth pacing period wall thickening was significantly (P less than 0.05) less in the saline group (2 +/- 5% of control) than in the AICA-r (31 +/- 7% of control) or NTG (61 +/- 7% of control) group. The progressive decline in wall thickening was accompanied by a further decrease in subendocardial blood flow and a rise in S-T segment in the saline group but not in the AICA-r or NTG group (P less than 0.05). These results demonstrate that sequential periods of ischemia and reperfusion cause a progressive decline in regional wall motion, coincident with a progressive decrease in subendocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressed regional deformation near anterior papillary muscle

1995 ◽  
Vol 269 (1) ◽  
pp. H262-H270 ◽  
Author(s):  
J. W. Holmes ◽  
Y. Takayama ◽  
I. LeGrice ◽  
J. W. Covell
Keyword(s):  
Papillary Muscle ◽  
Insertion Site ◽  
Three Dimensional ◽  
Left Ventricular ◽  
Wall Thickening ◽  
Regional Deformation ◽  
Myocardial Wall ◽  
Muscle Insertion ◽  
Region Data ◽  
Anterior Papillary Muscle

The role of the papillary muscle in left ventricular function has received new attention. We hypothesized that regional mechanics of the left ventricular wall near the anterior papillary muscle are influenced by the papillary muscle insertion. We therefore studied three-dimensional regional mechanics in and near the anterior papillary muscle in anesthetized, open-chest dogs, using implanted radiopaque markers and biplane cineradiography. In seven dogs, deformation differed little between an anterior papillary muscle insertion site (PMA) and a more basal site (PMB) overlying the anterior papillary muscle. However, local shortening and wall thickening were depressed in both locations relative to anterior free wall sites (FWA, FWB) studied in five additional dogs. A distinct structural border was observed at the junction between the myocardial wall and anterior papillary muscle, which may preclude the use of homogeneous strain in that region. Data from within the anterior papillary muscle indicated that uniaxial measurements in the papillary muscle are extremely sensitive to the orientation of the measurement axis, possibly explaining the variety of papillary muscle shortening patterns reported by previous investigators.

scholarly journals Merit of Anisodamine Combined with Opioidδ-Receptor Activation in the Protection against Myocardial Injury during Cardiopulmonary Bypass

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Xuan Hong ◽  
Huimin Fan ◽  
Rong Lu ◽  
Paul Chan ◽  
Zhongmin Liu
Keyword(s):  
Cardiopulmonary Bypass ◽  
Troponin T ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Control Group ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion (MIR) injury easily occurrs during cardiopulmonary bypass surgery in elderly patients. In an attempt to develop an effective strategy, we employed a pig model of MIR injury to investigate the maximum rate of change of left ventricular pressure, left ventricular enddiastolic pressure, and left intraventricular pressure. Coronary sinus cardiac troponin T (TnT) and adenosine-triphosphate (ATP) content in myocardium were measured. The ultrastructures for MIR injury were visualized by transmission electron microscopy (TEM). The role ofδ-opioid receptor activation using D-Ala2, D-Leu5-enkephalin (DADLE) in both early (D1) and late (D2) phases of cardioprotection was identified. Also, the merit of cardioprotection by DADLE in combination with anisodamine, the muscarinic receptor antagonist (D+M), was evaluated. Glibenclamide was employed at the dose sufficient to block ATP-sensitive potassium channels. Significant higher cardiac indicators, reduced TnT and increased ATP contents, were observed in D1, D2, and D+M groups compared with the control group. DADLE induced protection was better in later phase of ischemia that was attenuated by glibenclamide. DADLE after the ischemia showed no benefit, but combined treatment with anisodamine showed a marked postischemic cardioprotection. Thus, anisodamine is helpful in combination with DADLE for postischemic cardioprotection.

scholarly journals Acute Ventricular Wall Thickening: Sepsis, Thrombotic Microangiopathy, or Myocarditis?

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Nicolas De Schryver ◽  
Delphine Hoton ◽  
Diego Castanares-Zapatero ◽  
Philippe Hantson
Keyword(s):  
Thrombotic Microangiopathy ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Wall Thickening ◽  
Ventricular Wall ◽  
Myocardial Oedema ◽  
Ventricular Ejection Fraction

Background. Acute myocardial oedema has been documented in experimental models of ischemia-reperfusion injury or sepsis and is usually investigated by magnetic resonance imaging.Purpose. We describe a case of acute ventricular wall thickening documented by echocardiography in a patient developing sepsis and thrombotic microangiopathy.Case Description. A 40-year-old woman, with a history of mixed connective tissue disease, was admitted with laryngeal oedema and fever. She developedStreptococcus pneumoniaesepticaemia and subsequent laboratory abnormalities were consistent with a thrombotic microangiopathy. Echocardiography revealed an impressive diffuse thickening of the whole myocardium (interventricular septum 18 mm; posterior wall 16 mm) with diffuse hypokinesia and markedly reduced left ventricular ejection fraction (31%). There was also a moderate pericardial effusion. Echocardiography was normal two months before. The patient died from acute heart failure. Macroscopic and microscopic examination of the heart suggested that the ventricular wall thickening was induced by oedematous changes, together with an excess of inflammatory cells.Conclusion. Acute ventricular wall thickening that corresponded to myocardial oedema as a first hypothesis was observed at echocardiography during the course of septicaemia complicated by thrombotic microangiopathy.

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