Abstract P144: Effects of Alamandine in Post-ischemic Function

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jonathas F Almeida ◽  
Robson A Santos
Keyword(s):  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Baseline Period ◽  
Left Ventricular ◽  
Biologically Active ◽  
Ventricular Systolic Pressure ◽  
Infarcted Area ◽  
Rat Hearts ◽  
Ischemic Period ◽  
Isolated Rat

Alamandine, a biologically active peptide of the renin-angiotensin system (RAS), was recently described and characterized. Further it has been shown to present effects similar to those elicited by Ang-(1-7). It has been described that Ang-(1-7) decreases the incidence and duration of ischemia-reperfusion arrhythmias and improved the post-ischemic function in isolated perfused rat hearts. In this study we aimed to evaluate the effects of Alamandine in isolated rat hearts subjected to myocardial infarction (MI). Wistar rats weighing between 250-300g were euthanized and their hearts were placed on Langendorff apparatus to evaluate the cardiac parameters. Hearts were submitted to 30min of stabilization, 30min of partial ischemia by occlusion of the left descending coronary artery and 30min of reperfusion. Drugs (alamandine 22pM, d-pro7-ang-(1-7) 220pM) were added to the perfusion setting from the beginning of the experiment until the end. 2,3,5-trypheniltetrazolium chloride were used to evaluate the extension of infarcted area. In control hearts (CON), there was a decrease on the left ventricular systolic pressure (LVSP) on ischemic period (54,6 ± 6,9mmHg) compared to the baseline period (84,6 ± 11,6mmHg). Alamandine (ALA) attenuated that decrease in the ischemic period (66,9 ± 7,9mmHg) vs (82,3 ± 8,9mmHg). Further, ischemia led to a decrease in the left ventricular developed pressure (dLVP), dP/dt maximum and minimum when compared to baseline values. ALA, once more, kept the ischemic parameters of dLVP and dP/dt max and min (58,9 ± 8mmHg; 1629 ± 202,2mmHg/s; 1101 ± 130mmHg/s, respectively) similar to those of baseline period (68,9 ± 8,92; 1682 ± 248,8; 1179 ± 118,6 mmHg, respectively). Ischemia/reperfusion induced an arrhythmia severity index (ASI) in control hearts (4,9 ± 1,26) higher than in hearts treated with ALA (1,10 ± 0,58). ALA also reduced infarcted area (19,64 ± 2,61%) compared with CON (33,85 ± 4,55%). All those effects were blocked by D-PRO7-Ang-(1-7). In conclusion, our data shown that Alamandine exert cardioprotective effects in post-ischemic function in isolated rat hearts by preventing LVSP, dLVP , dP/dt max and min decrease. Furthermore it reduced the infarcted area and I/R arrhythmias, apparently involving MrgD receptor participation.

Abstract P190: Alamandine Improves Cardiac Post-Ischemic Function in Isolated Hearts of TGR(mREN2)27

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jônathas F Almeida ◽  
Robson A Santos
Keyword(s):  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Renin Angiotensin System ◽  
Cardiovascular Function ◽  
Severity Index ◽  
Left Ventricular ◽  
Ventricular Systolic Pressure ◽  
Isolated Hearts ◽  
Infarcted Area ◽  
Ischemic Period

The renin-angiotensin system (RAS) is an important regulator of cardiovascular function. Over the past years, new peptides have been described in this system. Among these new peptides, Alamandine was recently described by Santos and colleagues as an important participant in the control of cardiovascular function through its interaction with MrgD receptors. Our previous studies showed that Alamandine improved post-ischemic cardiac function in normotensive rats. Here we assessed the effects of Alamandine in a more challenging condition using hypertensive rats. TGR(mREN2)27 rats weighing between 250-300g were euthanized and their hearts were placed on Langendorff apparatus to evaluate the cardiac parameters. Hearts were submitted to 30min of stabilization, 30min of partial ischemia by occlusion of the left descending coronary artery and 30min of reperfusion. Alamandine (ALA, 22pM) was added to the perfusion setting from the beginning of the experiment until the end. 2,3,5-trypheniltetrazolium chloride were used to evaluate the extension of infarcted area. In hypertensive (mREN) animals there was an impairment in the baseline (35.57 ± 5.839 mmHg) of left ventricular systolic pressure (LVSP), and this impairment was attenuated by ALA (54.91 ± 6,304mmHg). Maximum and minimum dP/dt in mREN presented a significant reduction in the ischemic period (926.5 ± 172.3 mmHg/s and 682.7 ± 106.1 mmHg/s, respectively) compared to baseline (1761 ± 219.7 mmHg/s and 1242 ± 150.9 mmHg/s, respectively). Ischemia/reperfusion induced an arrhythmia severity index (ASI) in mREN hearts higher than in hearts treated with ALA (4,9 ± 1,26) vs (1,10 ± 0,58). ALA also reduced infarcted area compared to mREN (19,64 ± 2,61%) vs (33,85 ± 4,55%). In conclusion, our data shown that Alamandine exert cardioprotective effects in post-ischemic function in hypertensive rat isolated hearts by preventing LVSP, dP/dt max and min decrease. Furthermore, it reduced the infarcted area and I/R arrhythmias.

Cardiac Effects of Postconditioning Depend Critically on the Duration of Reperfusion and Reocclusion Episodes

2010 ◽  
Vol 13 (1) ◽  
pp. 52 ◽  
Author(s):  
Bruno Botelho Pinheiro ◽  
Alfredo In�cio Fiorelli ◽  
Otoni Moreira Gomes ◽  
Borut Gersak
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ischemic Postconditioning ◽  
Ventricular Pressure ◽  
Maximum Speed ◽  
P Value ◽  
Rat Hearts ◽  
Stabilization Period ◽  
Isolated Rat

Objective: The objective of the present study was to evaluate the effects of ischemic postconditioning on left ventricular function in isolated rat hearts.Methods: The hearts of 24 Wistar rats were were isolated, perfused immediately, and distributed into 3 groups: GI, control (n = 8); GII, three 10-second cycles of postconditioning (n = 8); and GIII, three 30-second cycles of postconditioning (n = 8). After a 15-minute stabilization period, all hearts underwent 20 minutes of global ischemia following 20 minutes of reperfusion. At times t0 (control), t5, t10, t15, and t20 (0, 5, 10, 15, and 20 minutes of reperfusion, respectively), we recorded the heart rate, coronary flow, systolic pressure, +(dP/dt)max (maximum speed of increase in the left ventricular pressure), and -(dP/dt)max (maximum speed of decrease in the left ventricular pressure). Data were analyzed by a 1-way analysis of variance, followed by the Tukey test; a P value .05); however, statistically significant differences in +(dP/dt)max between GII and GI and between GII and GIII occurred at t20 (GI, 1409.0 415.1 mm Hg/s; GII, 1917.3 403.0 mm Hg/s; GIII, 1344.8 355.8 mm Hg/s) (GII versus GI, P = .04; GII versus GIII, P = .02).Conclusion: Ischemic postconditioning with three 10-second cycles of reperfusion/reocclusion was demonstrated effective for preserving +(dP/dt)max in isolated rat hearts that underwent 20 minutes of ischemia following 20 minutes of reperfusion.

Na+/Ca2+ exchange inhibition protects the rat heart from ischemia-reperfusion injury by blocking energy-wasting processes

2005 ◽  
Vol 288 (4) ◽  
pp. H1699-H1707 ◽  
Author(s):  
Hiroji Hagihara ◽  
Yoshiro Yoshikawa ◽  
Yoshimi Ohga ◽  
Chikako Takenaka ◽  
Ken-ya Murata ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mechanical Energy ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Reverse Mode ◽  
Rat Hearts ◽  
Total Mechanical Energy ◽  
Contractile Failure

We have recently reported that exposure of rat hearts to high Ca2+ produces a Ca2+ overload-induced contractile failure in rat hearts, which was associated with proteolysis of α-fodrin. We hypothesized that contractile failure after ischemia-reperfusion (I/R) is similar to that after high Ca2+ infusion. To test this hypothesis, we investigated left ventricular (LV) mechanical work and energetics in the cross-circulated rat hearts, which were subjected to 15 min global ischemia and 60 min reperfusion. Sixty minutes after I/R, mean systolic pressure-volume area (PVA; a total mechanical energy per beat) at midrange LV volume (mLVV) (PVAmLVV) was significantly decreased from 5.89 ± 1.55 to 3.83 ± 1.16 mmHg·ml·beat−1·g−1 ( n = 6). Mean myocardial oxygen consumption per beat (Vo2) intercept of (Vo2-PVA linear relation was significantly decreased from 0.21 ± 0.05 to 0.15 ± 0.03 μl O2·beat−1·g−1 without change in its slope. Initial 30-min reperfusion with a Na+/Ca2+ exchanger (NCX) inhibitor KB-R7943 (KBR; 10 μmol/l) significantly reduced the decrease in mean PVAmLVV and Vo2 intercept ( n = 6). Although Vo2 for the Ca2+ handling was finally decreased, it transiently but significantly increased from the control for 10–15 min after I/R. This increase in Vo2 for the Ca2+ handling was completely blocked by KBR, suggesting an inhibition of reverse-mode NCX by KBR. α-Fodrin proteolysis, which was significantly increased after I/R, was also significantly reduced by KBR. Our study shows that the contractile failure after I/R is similar to that after high Ca2+ infusion, although the contribution of reverse-mode NCX to the contractile failure is different. An inhibition of reverse-mode NCX during initial reperfusion protects the heart against reperfusion injury.

Effects of the AT1 Receptor Blocker Candesartan on Myocardial Ischemia/Reperfusion in Isolated Rat Hearts

2014 ◽  
Vol 17 (5) ◽  
pp. 263 ◽  
Author(s):  
C. Murat Songur ◽  
Merve Ozenen Songur ◽  
Sinan Sabit Kocabeyoglu ◽  
Bilgen Basgut
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Relaxation Rates ◽  
Cardioplegic Solution ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Contraction And Relaxation ◽  
Isolated Rat

<p><b>Background:</b> We sought to investigate the effects of the angiotension II receptor blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested isolated rat heart model.</p><p><b>Methods:</b> Ischemia-reperfusion injury was induced in isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute reperfusion protocol. Throughout the experiment, constant pressure perfusion was achieved using a Langendorff apparatus. Cardioplegic solution alone, and in combination with candesartan, was administered before ischemia and 20 minutes after ischemia. Post-ischemic recovery of contractile function, left ventricular developed pressure, left ventricular end-diastolic pressure and contraction and relaxation rates were evaluated.</p><p><b>Results:</b> In the control group, left ventricular developed pressure, rate pressure product, contraction and relaxation rates and coronary flow significantly decreased but coronary resistance increased following reperfusion. With the administration of candesartan alone, parameters did not differ compared to controls. Contractile parameters improved in the group that received candesartan in combination with the cardioplegia compared to the group that received cardioplegia alone; however, the difference between these two groups was insignificant.</p><p><b>Conclusion:</b> In this study, the addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioplegic solution alone.</p>

scholarly journals Myocardial Damage Induced by Uncontrolled Reoxygenation

2000 ◽  
Vol 8 (1) ◽  
pp. 34-37 ◽  
Author(s):  
Antonio F Corno ◽  
Giuseppina Milano ◽  
Michele Samaja ◽  
Ludwig K von Segesser
Keyword(s):  
Systolic Function ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Lactate Production ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Relaxation Rates ◽  
Rat Hearts ◽  
Baseline Conditions ◽  
Hypoxia Reoxygenation

To evaluate myocardial impairment induced by uncontrolled reoxygenation, the effects of hypoxia-reoxygenation were compared with ischemia-reperfusion in isolated rat hearts. After stabilization, 2 groups (n = 8) of Langendorff-perfused rat hearts were exposed to 40 minutes of ischemia (10% of baseline flow) or hypoxia (10% of baseline oxygen content) followed by a sudden return to baseline conditions (reperfusion or reoxygenation). The O2 content was identical for the two groups during baseline conditions, O2 shortage, and O2 readmission. Metabolic (lactate production) and functional parameters (heart rate, peak systolic pressure, left ventricular developed pressure, maximal contraction and relaxation rates, end-diastolic pressure, coronary perfusion pressure) were recorded at the end of stabilization, after O2 deficiency, and after 2 minutes of reoxygenation. Systolic function was significantly depressed after ischemia (p < 0.0001) but completely recovered to baseline values after 2 minutes of reperfusion. In contrast, systolic function was less severely depressed after hypoxia but failed to return to baseline after 2 minutes of reoxygenation. Diastolic function, unchanged during ischemia-reperfusion, remained significantly impaired during hypoxia-reoxygenation.

scholarly journals Differential effects of acetylcholine on coronary flow in isolated hypothermic hearts from rats and ground squirrels

1993 ◽  
Vol 185 (1) ◽  
pp. 17-24
Author(s):  
R. F. Burlington ◽  
W. K. Milsom
Keyword(s):  
Coronary Flow ◽  
Systolic Pressure ◽  
Coronary Vessels ◽  
Left Ventricular ◽  
Ground Squirrels ◽  
Similar Treatment ◽  
Ventricular Systolic Pressure ◽  
Spermophilus Lateralis ◽  
Rat Hearts ◽  
Left Ventricular Systolic Pressure

This study was designed to determine whether cholinergic receptors are operative in the coronary vessels of a hibernating species (golden mantled ground squirrel, Spermophilus lateralis) and a nonhibernating species (rat, Rattus norvegicus) under normothermic and hypothermic conditions. Coronary flow and left ventricular systolic pressure were measured in isolated perfused hearts from squirrels at 37, 20 or 7 degrees C and from rats at 37 and 20 degrees C. During cooling, rat hearts became arrhythmic and failed between 15 and 12 degrees C. Squirrel hearts remained functional at 7 degrees C. Bolus injections of acetylcholine (&gt; 1.0 microgram) caused significant coronary vasoconstriction in rat hearts at 37 and 20 degrees C. Similar treatment caused mild coronary vasodilation in squirrel hearts at both temperatures. Squirrel hearts did not respond to acetylcholine at 7 degrees C. The responses in both species were blocked by atropine. Rat coronary vessels appear to contain muscarinic constrictor receptors similar to those described in humans, sheep, cattle and pigs. The coronary vessels of squirrels, by contrast, do not. In this latter species there appears to be a preponderance of muscarinic (possibly endothelial-relaxing-factor-linked) dilator receptors. Given that acetylcholine acts only as a mild vasodilator at higher temperatures in squirrels, parasympathetic regulation of coronary flow in the squirrel heart is unlikely, especially during hibernation.

Coronary autoregulation and metabolism in hypothermic rat and ground squirrel hearts

1989 ◽  
Vol 256 (2) ◽  
pp. R357-R365 ◽  
Author(s):  
R. F. Burlington ◽  
M. S. Dean ◽  
S. B. Jones
Keyword(s):  
Ground Squirrel ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Spermophilus Tridecemlineatus ◽  
Initial Flow ◽  
Ventricular Systolic Pressure ◽  
Langendorff Preparation ◽  
Rat Hearts ◽  
Left Ventricular Systolic Pressure ◽  
Highly Correlated

An isovolumic Langendorff preparation was used to perfuse rat and ground squirrel (Spermophilus tridecemlineatus) hearts at 37, 27, 17, and 7 degrees C. Perfusion pressure (PP) was randomly increased or decreased (40, 60, 70, 110, 120, or 140 mmHg) from a control PP of 90 mmHg. Coronary flow (CF) was measured immediately after each PP change (initial CF) and after stable flow was observed (final CF). Compared with initial flow, final CF was decreased at high PPs or increased at low PPs (autoregulation) in hearts from both species, but rat hearts did not autoregulate CF or develop left ventricular systolic pressure (LVSP) at 7 degrees C. Squirrel hearts generated LVSP at all temperatures and perfusion pressures. LVSP and initial CF were proportional to PP in both species, but squirrel heart LVSP was independent of PP at 7 degrees C. Myocardial O2 consumption (MVO2) was highly correlated with CF in all hearts at 37 degrees C but not at lower temperatures. Squirrel hearts were more efficient (MVO2 vs. HR X LVSP) than rat hearts at low temperatures but less efficient at 37 degrees C. The intrinsic temperature adaptations displayed by squirrel hearts would support continued myocardial function when body temperature and blood pressure fluctuate throughout the stages of hibernation.

Comparison of Functional Load in Rat and Guinea Pig Hearts

Physiology ◽  
1993 ◽  
Vol 8 (4) ◽  
pp. 157-160
Author(s):  
VI Kapelko ◽  
NA Novikova
Keyword(s):  
Guinea Pig ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Structure And Function ◽  
Maximal Volume ◽  
Ventricular Systolic Pressure ◽  
Volume Load ◽  
Rat Hearts ◽  
Left Ventricular Systolic Pressure ◽  
And Function

Isolated rat hearts pump less cardiac output than guinea pig hearts at maximal volume load but develop higher left ventricular systolic pressure at increased resistance. These results allow us to understand the meaning of underlying peculiarities in the structure and function of cardiomyocytes of these two species.

Myocyte and endothelial injury with ischemia reperfusion in isolated rat hearts

1987 ◽  
Vol 252 (6) ◽  
pp. H1211-H1217 ◽  
Author(s):  
K. P. Sunnergren ◽  
M. J. Rovetto
Keyword(s):  
Endothelial Cell ◽  
Time Course ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Endothelial Injury ◽  
Radical Scavengers ◽  
Endothelial Cell Function ◽  
Cell Functions ◽  
Rat Hearts ◽  
Isolated Rat

We determined the time course of ischemic injury, the effects of reperfusion, and the protective effects of prostacyclin, oxygen radical scavengers, and diltiazem on myocardial myocyte and endothelial cell functions in isolated rat hearts. Left ventricular power and coronary microvascular permeability were used as indexes of myocyte and endothelial cell function, respectively. Neither 5- nor 10-min ischemia reperfusion significantly changed power or permeability. However, with reperfusion following 20 and 30 min of ischemia, power was reduced 50 and 60% and permeability increased 70 and 90%. In 30-min ischemic hearts the ischemia-induced increase in permeability was apparent after 4 min reperfusion and further exacerbated at 20 min. Hypoxic reperfusion did not prevent increased permeability. Prostacyclin or a combination of superoxide dismutase, catalase, and mannitol also did not prevent increased permeability, and the radical scavengers did not ameliorate depressed power. In contrast, perfusion with diltiazem during ischemia reperfusion blunted the reduction in power and prevented the increase in permeability. We conclude that ischemia reperfusion causes similar time course of injury to myocytes and endothelial cells; reperfusion contributes to endothelial injury, and diltiazem affords protection to both cell types.

scholarly journals Attenuation of extracellular ATP response in cardiomyocytes isolated from hearts subjected to ischemia-reperfusion

2005 ◽  
Vol 289 (2) ◽  
pp. H614-H623 ◽  
Author(s):  
Harjot K. Saini ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Cardiac Function ◽  
Positive Inotropic Effect ◽  
Ischemia Reperfusion ◽  
Cardiac Contractility ◽  
Extracellular Atp ◽  
Binding Characteristics ◽  
Rat Hearts ◽  
The Status ◽  
Intracellular Ca ◽  
Isolated Rat

Extracellular ATP is known to augment cardiac contractility by increasing intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes; however, the status of ATP-mediated Ca2+ mobilization in hearts undergoing ischemia-reperfusion (I/R) has not been examined previously. In this study, therefore, isolated rat hearts were subjected to 10–30 min of global ischemia and 30 min of reperfusion, and the effect of extracellular ATP on [Ca2+]i was measured in purified cardiomyocytes by fura-2 microfluorometry. Reperfusion for 30 min of 20-min ischemic hearts, unlike 10-min ischemic hearts, revealed a partial depression in cardiac function and ATP-induced increase in [Ca2+]i; no changes in basal [Ca2+]i were evident in 10- or 20-min I/R preparations. On the other hand, reperfusion of 30-min ischemic hearts for 5, 15, or 30 min showed a marked depression in both cardiac function and ATP-induced increase in [Ca2+]i and a dramatic increase in basal [Ca2+]i. The positive inotropic effect of extracellular ATP was attenuated, and the maximal binding characteristics of 35S-labeled adenosine 5′-[γ-thio]triphosphate with crude membranes from hearts undergoing I/R was decreased. ATP-induced increase in [Ca2+]i in cardiomyocytes was depressed by verapamil and Cibacron Blue in both control and I/R hearts; however, this response in I/R hearts, unlike control hearts, was not affected by ryanodine. I/R-induced alterations in cardiac function and ATP-induced increase in [Ca2+]i were attenuated by treatment with an antioxidant mixture and by ischemic preconditioning. The observed changes due to I/R were simulated in hearts perfused with H2O2. The results suggest an impairment of extracellular ATP-induced Ca2+ mobilization in I/R hearts, and this defect appears to be mediated through oxidative stress.

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