scholarly journals Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Figueroa-Valverde Lauro ◽  
Díaz-Cedillo Francisco ◽  
García-Cervera Elodia ◽  
Pool-Gómez Eduardo ◽  
López-Ramos Maria ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Perfusion Pressure ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Dependent Manner ◽  
Coronary Resistance ◽  
Testosterone Derivative

Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increasesP=0.05the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibitedP=0.06by indomethacin and PINANE-TXA2  P=0.05at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation.

scholarly journals New Amino-steroid-anthracenone with Biological Activity Against Ischemia-reperfusion Injury in a Wistar Rat Model

2018 ◽  
Vol 8 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Figueroa-Valverde Lauro ◽  
Rosas-Nexticapa Marcela ◽  
Mateu-Armand Virginia ◽  
Herrera-Meza Socorro ◽  
Díaz-Cedillo Francisco ◽  
...  
Keyword(s):  
Biological Activity ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Infarct Area ◽  
Camp Levels

Objective: The main objective of this study was to evaluate the biological activity of an ASA (Amino-Steroid-Anthracenone derivative) against heart failure caused by the ischemia- reperfusion injury (translated as infarct area). Methods: Biological activity exerted by ASA (0.001-100 nM) on infarct area was determined using an ischemia-reperfusion injury model. In addition, to characterize the molecular mechanism involved in the effect exerted by ASA on left ventricular pressure, some drugs such as estrone (0.001-100 nM), tamoxifen (1 nM), butoxamine (1 nM) and ZM-241385 (1 nM) were used. Results: The experimental data showed that ASA decreased the infarction area significantly (p = 0.05) compared to estrone. Other results indicated that ASA decreased left ventricular pressure and this effect was inhibited by ZM-241385. In addition, ASA increased cAMP levels in a time-dependent manner compared to control conditions. Conclusion: The results showed that ASA decreases ischemia-reperfusion injury (translated as infarct area) via A2 adenosine receptor activation and these phenomena involve changes in cAMP levels.

Contribution of extravascular compression to reduction of maximal coronary blood flow

1992 ◽  
Vol 262 (1) ◽  
pp. H68-H77
Author(s):  
F. L. Abel ◽  
R. R. Zhao ◽  
R. F. Bond
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Storage Site

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

Synthesis and Biological Activity of the Pyridine-Hexacyclic-Steroid Derivative on a Heart Failure Model

2021 ◽  
Vol 21 ◽  
Author(s):  
Figueroa-Valverde Lauro ◽  
López-Ramos Maria ◽  
Díaz-Cedillo Francisco ◽  
Rosas-Nexticapa Marcela ◽  
Mateu-Armad Maria Virginia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Pyridine Derivative ◽  
Dependent Manner ◽  
Inotropic Activity ◽  
Heart Failure Model ◽  
Chemical Strategies

Background: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. Objective: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. Methods: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. Results: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. Conclusion: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

scholarly journals Influence of dual ETA/ETB-receptor blockade on coronary responses to treadmill exercise in dogs

2000 ◽  
Vol 89 (5) ◽  
pp. 2041-2048 ◽  
Author(s):  
Masayuki Takamura ◽  
Robert Parent ◽  
Peter Cernacek ◽  
Michel Lavallée
Keyword(s):  
Coronary Sinus ◽  
Adrenergic Receptor ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Receptor Blockade ◽  
Etb Receptor ◽  
Dual Blockade ◽  
The Relationship

We hypothesized that endothelin (ET) release during exercise may be triggered by α-adrenergic-receptor activation and thereby influence coronary hemodynamics and O2 metabolism in dogs. Exercise resulted in coronary blood flow increases (to 1.88 ± 0.26 from 1.10 ± 0.12 ml · min−1 · g−1) and in a fall ( P < 0.01) in coronary sinus O2saturation (17.4 ± 1.5 to 9.6 ± 0.7 vol%), whereas myocardial O2 consumption (MV˙o 2) increased (109 ± 13% from 145 ± 16 μl O2 · min−1 · g−1). Tezosentan, a dual ETA/ETB-receptor blocker, slightly reduced mean arterial pressure (MAP) and increased heart rate throughout exercise. The relationship between coronary sinus O2 saturation and MV˙o 2 was shifted upward ( P < 0.05) after tezosentan administration; i.e., as MV˙o 2 increased during exercise, coronary sinus O2 saturation was disproportionately higher after ET-receptor blockade. After propranolol, tezosentan resulted in significant decreases ( P < 0.05) in left ventricular pressure, the first derivative of left ventricular pressure over time, and MAP during exercise. As MV˙o 2 increased during exercise, coronary sinus O2 saturation levels after tezosentan became superimposable over those observed before ET-receptor blockade. Thus dual blockade of ETA/ETBreceptors alters coronary hemodynamics and O2 metabolism during exercise, but ET activity failed to increase beyond baseline levels.

Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure

1990 ◽  
Vol 258 (6) ◽  
pp. H1889-H1898 ◽  
Author(s):  
R. Krams ◽  
P. Sipkema ◽  
N. Westerhof
Keyword(s):  
Oscillatory Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Ventricular Pressure ◽  
Time Varying ◽  
Waterfall Model ◽  
Developed Pressure ◽  
Phasic Flow

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

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.

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.

Enhanced sensitivity of diabetic hearts to alpha-adrenoceptor stimulation

1983 ◽  
Vol 245 (5) ◽  
pp. H808-H813 ◽  
Author(s):  
S. E. Downing ◽  
J. C. Lee ◽  
R. R. Fripp
Keyword(s):  
Diastolic Pressure ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Response Curves ◽  
Receptor System ◽  
Inotropic Responses

Inotropic responses to alpha-adrenergic stimulation with methoxamine were compared in 12 normal (N) and 12 diabetic (Db) lambs. Diabetes was produced by giving alloxan monohydrate (150 mg/kg iv). Measurements of maximal rate of rise of left ventricular pressure (dP/dtmax), left ventricular end-diastolic pressure (LVEDP), coronary flow, and myocardial O2 consumption were made simultaneously in hemodynamically controlled preparations. All animals were subjected to ganglionic blockade (tetraethylammonium chloride, 100 mg) and beta1-adrenergic blockade (practolol, 4 mg/kg). Methoxamine was given in incremental doses ranging from 0.4 to 6.0 mg/kg. dP/dtmax increased progressively to 126 +/- 4% of initial values in N. However, the increase was twice as large (150 +/- 4%) in the diabetics (P less than 0.005). LVEDP fell in both groups. These changes were abolished by phentolamine (2 mg/kg). Inotropic responses to methoxamine in lambs 2 and 3 wk after induction of diabetes did not differ from those with acute (2 days) diabetes. Dose-response curves obtained by infusing Ca2+ (2-8 mg X min-1 X kg-1) were identical in N and Db. It is concluded that lamb myocardium possesses an alpha-adrenergic receptor system that is stimulated by methoxamine in a dose-dependent manner and blocked by phentolamine. Db hearts are supersensitive to alpha-receptor activation. The mechanistic basis for this latter finding has not been examined but may relate to altered receptor density or nucleotide regulation.

Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia–reperfusion

2012 ◽  
Vol 90 (7) ◽  
pp. 851-862 ◽  
Author(s):  
Ting-Ting Li ◽  
Yi-Shuai Zhang ◽  
Lan He ◽  
Bin Liu ◽  
Rui-Zheng Shi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Clinical Value ◽  
Pharmacologic Inhibition

Myeloperoxidase (MPO) is involved in myocardial ischemia–reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia–reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.

scholarly journals Why is the subendocardium more vulnerable to ischemia? A new paradigm

2011 ◽  
Vol 300 (3) ◽  
pp. H1090-H1100 ◽  
Author(s):  
Dotan Algranati ◽  
Ghassan S. Kassab ◽  
Yoram Lanir
Keyword(s):  
Heart Rate ◽  
Network Flow ◽  
Perfusion Pressure ◽  
Compressive Loading ◽  
Flow Simulation ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
New Paradigm ◽  
Vessel Wall Thickness

Myocardial ischemia is transmurally heterogeneous where the subendocardium is at higher risk. Stenosis induces reduced perfusion pressure, blood flow redistribution away from the subendocardium, and consequent subendocardial vulnerability. We propose that the flow redistribution stems from the higher compliance of the subendocardial vasculature. This new paradigm was tested using network flow simulation based on measured coronary anatomy, vessel flow and mechanics, and myocardium-vessel interactions. Flow redistribution was quantified by the relative change in the subendocardial-to-subepicardial perfusion ratio under a 60-mmHg perfusion pressure reduction. Myocardial contraction was found to induce the following: 1) more compressive loading and subsequent lower transvascular pressure in deeper vessels, 2) consequent higher compliance of the subendocardial vasculature, and 3) substantial flow redistribution, i.e., a 20% drop in the subendocardial-to-subepicardial flow ratio under the prescribed reduction in perfusion pressure. This flow redistribution was found to occur primarily because the vessel compliance is nonlinear (pressure dependent). The observed thinner subendocardial vessel walls were predicted to induce a higher compliance of the subendocardial vasculature and greater flow redistribution. Subendocardial perfusion was predicted to improve with a reduction of either heart rate or left ventricular pressure under low perfusion pressure. In conclusion, subendocardial vulnerability to a acute reduction in perfusion pressure stems primarily from differences in vascular compliance induced by transmural differences in both extravascular loading and vessel wall thickness. Subendocardial ischemia can be improved by a reduction of heart rate and left ventricular pressure.

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