Effect of sodium nitroprusside and L-arginine methyl ester on rat hearts stored at 4 °C for 24 h

1998 ◽  
Vol 95 (5) ◽  
pp. 557-564 ◽  
Author(s):  
Oluwole S. FAGBEMI ◽  
Basil J. NORTHOVER
Keyword(s):  
Nitric Oxide ◽  
Cardiac Output ◽  
Methyl Ester ◽  
Sodium Nitroprusside ◽  
Coronary Flow ◽  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphate ◽  
Rat Hearts ◽  
Developed Pressure

1.This study examined the effects of altering nitric oxide levels with sodium nitroprusside or l-arginine in rat hearts stored hypothermically. 2.Hearts were microperfused at 4 ;°C for 24 ;h with a modified Krebs–Henseleit buffer (KHB) that contained either sodium nitroprusside, l-arginine, l-arginine methyl ester or dexamethasone. 3.After hypothermic storage, hearts were rewarmed to 37 ;°C with KHB alone or KHB containing sodium nitroprusside or l-arginine. Cardiac function was then assessed in either Langendorff mode or working heart mode. 4.Compared with values from fresh unstored hearts, hypothermic stored hearts showed a significant decrease in coronary flow and left ventricular developed pressure when the stored hearts were perfused in Langendorff mode. These hearts also produced less aortic flow and cardiac output when perfused in the working mode. 5.Hearts hypothermically microperfused with buffer containing either l-arginine or sodium nitroprusside and then reperfused in the Langendorff mode with untreated KHB buffer had the highest left ventricular developed pressure and coronary flow values. Aortic flow and cardiac output were also higher in these hearts. 6.In all groups of stored hearts, the concentrations of both ATP and creatine phosphate were significantly low, when compared with values from freshly isolated hearts. Addition of dexamethasone to the buffer either during storage or during reperfusion had no beneficial effect on high-energy phosphate loss or cardiac performance of stored hearts. 7.This study showed that the addition of nitric oxide donors to storage buffer significantly improves cardiac function on normothermic reperfusion. The improved functional recovery is unrelated to the high-energy phosphate content of these hearts.

Fasudil prevents KATP channel-induced improvement in postischemic functional recovery

2005 ◽  
Vol 288 (6) ◽  
pp. H3011-H3015 ◽  
Author(s):  
Kenya Nishizawa ◽  
Paul E. Wolkowicz ◽  
Tadashi Yamagishi ◽  
Ling-Ling Guo ◽  
Martin M. Pike
Keyword(s):  
Diastolic Pressure ◽  
Rho Kinase ◽  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphate ◽  
Cellular Processes ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Rock Activity ◽  
Mechanical Recovery

Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.

Myocardial relaxant effect of exogenous nitric oxide in isolated ejecting hearts

1994 ◽  
Vol 266 (5) ◽  
pp. H1699-H1705 ◽  
Author(s):  
R. Grocott-Mason ◽  
S. Fort ◽  
M. J. Lewis ◽  
A. M. Shah
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Coronary Flow ◽  
Systolic Function ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Nitric Oxide Donor ◽  
Vasodilator Activity ◽  
Exogenous Nitric Oxide ◽  
Whole Heart

In isolated myocytes and papillary muscles, both nitric oxide, acting through guanosine 3',5'-cyclic monophosphate (cGMP), and cGMP analogues exert a novel effect on myocardial contraction, influencing mainly the onset of relaxation. We studied the effect of the exogenous nitric oxide donor, sodium nitroprusside (0.1-10 microM), in isolated ejecting guinea pig hearts at constant filling pressure, afterload, and heart rate to identify its direct myocardial effects in the whole heart. Sodium nitroprusside induced concentration-dependent increases in coronary flow as well as premature and faster early left ventricular (LV) pressure decline, but did not change end-diastolic or peak LV pressure or peak rate of rise of LV pressure. There was no correlation between changes in coronary flow and LV pressure decline. Sodium nitroprusside effects were inhibited by hemoglobin, which inactivates nitric oxide. The cGMP-independent vasodilator nicardipine also increased coronary flow but did not influence early LV pressure fall. Thus exogenous nitric oxide exerts novel direct myocardial relaxant effects in the isolated ejecting heart, independent of its known vasodilator activity, and without compromising systolic function.

Nitric oxide-cGMP pathway is involved in endotoxin-induced contractile dysfunction in rat hearts

2004 ◽  
Vol 96 (3) ◽  
pp. 853-860 ◽  
Author(s):  
Tetsuya Tatsumi ◽  
Natsuya Keira ◽  
Kazuko Akashi ◽  
Miyuki Kobara ◽  
Satoaki Matoba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Myocardial Dysfunction ◽  
Significant Negative Correlation ◽  
Left Ventricular ◽  
No Production ◽  
Contractile Dysfunction ◽  
Cardiac Depression ◽  
Rat Hearts ◽  
Developed Pressure

The mechanisms by which endotoxemia causes cardiac depression have not been fully elucidated. The present study examined the involvement of nitric oxide (NO) in this pathology. Rats were infused with lipopolysaccharide (LPS) or saline, and the plasma and myocardial [Formula: see text] and [Formula: see text] (NOx) concentrations were measured before or 3, 6, and 24 h after treatment. The hearts were then immediately isolated and mounted in a Langendorff apparatus, and left ventricular developed pressure (LVDP) was determined before biochemical analysis of the myocardium. LPS injection effected the expression of inducible NO synthase (iNOS) in the myocardium, a marked increase in plasma and myocardial NOx levels, and a significant decline in LVDP compared with saline controls. The LPS-induced NO production and concomitant cardiac depression were most pronounced 6 h after LPS injection and were accompanied by a significant increase in myocardial cGMP content. Myocardial ATP levels were not significantly altered after LPS injection. Significant negative correlation was observed between LVDP and myocardial cGMP content, as well as between LVDP and plasma NOx levels. Aminoguanidine, an inhibitor of iNOS, significantly attenuated the LPS-induced NOx production and contractile dysfunction. Furthermore, 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, significantly decreased myocardial cGMP content and attenuated the contractile depression, although aminoguanidine or 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one was not able to completely reverse myocardial dysfunction. Our data suggest that endotoxin-induced contractile dysfunction in rat hearts is associated with NO production by myocardial iNOS and a concomitant increase in myocardial cGMP.

Cardioprotective Effects of Propofol and Sevoflurane in Ischemic and Reperfused Rat Hearts 

1999 ◽  
Vol 91 (5) ◽  
pp. 1349-1349 ◽  
Author(s):  
Sanjiv Mathur ◽  
Parviz Farhangkhgoee ◽  
Morris Karmazyn
Keyword(s):  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphates ◽  
Constant Flow Rate ◽  
Rat Hearts ◽  
Reperfusion Period ◽  
Coronary Syndromes ◽  
Cardioprotective Effects ◽  
Developed Pressure

Background Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. Methods Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. Results Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. Conclusion HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.

Effect of Salidroside on Cardiac Functional Recovery

2013 ◽  
Vol 798-799 ◽  
pp. 1030-1032
Author(s):  
Yan Zhang ◽  
Zhong Hua Zheng ◽  
Yue Peng Wang ◽  
Guo Liang Peng ◽  
Liu Hang Wang
Keyword(s):  
Flow Rate ◽  
Functional Recovery ◽  
Rat Heart ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Cardioprotective Effect ◽  
Decrease Rate ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

To investigate the cardioprotective effect of salidroside to rat heart subjected to 8-hour hypothermic storage and 2-hour normothermic reperfusion. Isolated rat hearts were perfused with Langendorff model; after 30 minutes of baseline, the hearts were arrested and stored by St. Thomas solution (STS) without (STS group) or with different concentration salidroside at 4 °C for 8 hours, then reperfused for 2 hours. Compared with STS group, both middle and high dosage in STS greatly improved the recovery of left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (±dp/dt), coronary flow rate (CF). Our study demonstrated that the salidroside was beneficial to improving cardiac functional recovery.

Factors influencing myocardial response to metabolic acidosis in isolated rat hearts

1987 ◽  
Vol 253 (5) ◽  
pp. H1261-H1270 ◽  
Author(s):  
T. A. Watters ◽  
M. F. Wendland ◽  
W. W. Parmley ◽  
T. L. James ◽  
E. H. Botvinick ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Coronary Flow ◽  
Work Load ◽  
High Energy ◽  
High Energy Phosphates ◽  
Factors Influencing ◽  
Rat Hearts ◽  
Developed Pressure ◽  
High Work Load ◽  
High Work

We assessed the effects of metabolic acidosis in Langendorff rat hearts to identify factors influencing myocardial response to metabolic acidosis. Intracellular pH (pHi), beta-ATP, phosphocreatine, and inorganic phosphate (Pi) content were measured by 31P nuclear magnetic resonance spectroscopy along with simultaneous measurements of coronary flow and developed pressure during 30 min of perfusion at pH = 6.8, followed by 15 min of reequilibration at pH = 7.4. Under high work-load conditions, pHi, high-energy phosphates, coronary flow, and developed pressure were severely reduced during metabolic acidosis. Each of these hearts exhibited a progressive decline in developed pressure and stopped beating during reequilibration. Lowering work load prevented severe biochemical or mechanical deterioration, allowing complete recovery during reequilibration. In the presence of high work load, factors found to improve myocardial tolerance to metabolic acidosis included maintaining base-line or higher levels of coronary flow with vasodilators or substitution of pyruvate for glucose as the energy-producing substrate. Raising perfusate osmolality did not prevent severe decreases in coronary flow and developed pressure during acidosis, but did allow a dramatic recovery during reequilibration. Recovery of biochemical and mechanical performance after 30 min of metabolic acidosis was directly related to 1) ln[ATP]/[ADP]f[Pi] greater than or equal to 4.1, where [ADP]f is the concentration of free ADP; 2) pHi greater than 6.40; and 3) ATP level greater than or equal to 75% of control.

Isoflurane and Halothane Increase Adenosine Triphosphate Preservation, but Do Not Provide Additive Recovery of Function after Ischemia, in Preconditioned Rat Hearts

1997 ◽  
Vol 86 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Ashraf Boutros ◽  
Jun Wang ◽  
Christine Capuano
Keyword(s):  
Adenosine Triphosphate ◽  
Coronary Flow ◽  
Recovery Of Function ◽  
Left Ventricular ◽  
Untreated Group ◽  
Control Group ◽  
Time Control ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

Background Brief ischemic periods render the myocardium resistant to infarction from subsequent ischemic insults by a process called ischemic preconditioning. Volatile anesthetics have also been shown to be cardioprotective if administered before ischemia. The effect of preconditioning alone and combined with halothane or isoflurane on hemodynamic recovery and preservation of adenosine triphosphate content in isolated rat hearts was evaluated. Methods Seven groups of isolated rat hearts (n = 6 each) were perfused in a retrograde manner at constant temperature and pressure. A latex balloon was placed in the left ventricle to obtain isovolumetric contraction. Heart rhythm, coronary flow, left ventricular pressure and its derivative dP/dt (positive and negative), and developed pressure were monitored. The hearts were paced at 300 beats per minute. Each heart was randomly allocated to (1) a time-control group that received no ischemia, (2) an untreated group that received 25 min of normothermic ischemia only. (3 and 4) an isoflurane group and a halothane group that received 40 min of anesthetic (2.2% and 1.5%, respectively) before ischemia; (5) a preconditioning group that received two 5-min periods of ischemia separated by 10 min of reperfusion before ischemia; or (6 and 7) a isoflurane+preconditioning group and a halothane+preconditioning group that received anesthetic for 10 min at concentrations of 2.2% or 1.5%, respectively, before two 5-min periods of ischemia separated by 10 min of reperfusion. All treated groups received 25 min of normothermic ischemia followed by 30 min of reperfusion. Results The time-control group remained hemodynamically stable for the entire experiment, and the adenosine triphosphate content was 18.3 +/- 1.7 (SEM) microM/g at the end of 115 min. The untreated group had depressed recovery after 25 min of normothermic ischemia, and the developed pressure was significantly depressed and recovered only 30 +/- 9% (P < 0.001) of its preischemic value. There was also a significant increase in the incidence of ventricular fibrillation (P < 0.001). Adenosine triphosphate content was significantly lower in this group than in all other groups. Five minutes of ischemia in the preconditioning group had little effect on hemodynamics and decreased developed pressure only 6.4%. Halothane depressed developed pressure by 16 +/- 5% (P < 0.001), and isoflurane increased coronary flow by 145 +/- 9% (P < 0.001) but had no significant hemodynamic effect. The treated groups had significantly better recovery of postischemic function than did the untreated group. In the preconditioning group, developed pressure recovered to 85% of control and dP/dt+ to 87% of control. The addition of halothane or isoflurane to preconditioning did not provide additional functional recovery but did increase the level of adenosine triphosphate preservation (13.1 +/- 1.1 and 12.4 +/- 1.1 microM/g, respectively). Conclusions The results indicate that preconditioning, halothane, and isoflurane provide significant protection against ischemia. The combination of preconditioning and halothane or isoflurane did not improve hemodynamic recovery but did increase preservation of adenosine triphosphate.

Contribution of adenosine to changes in coronary flow in metabolically stimulated rat heart

1988 ◽  
Vol 66 (2) ◽  
pp. 171-173 ◽  
Author(s):  
John Headrick ◽  
Roger J. Willis
Keyword(s):  
Adenosine Deaminase ◽  
Rat Heart ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Extracellular Adenosine ◽  
Mediated Action ◽  
Adenosine Receptor Antagonist ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Metabolic Stimulation

The extent to which endogenous, extracellular adenosine mediates increased coronary flow in crystalloid-perfused, isovolumic rat hearts stimulated with either norepinephrine or isoproterenol was examined. When infused into the coronary circulation, norepinephrine (1 × 10−7 M) rapidly increased left ventricular developed pressure (LVDP) from 81 ± 6 to 235 ± 13 mmHg (1 mmHg = 133.3 Pa) and coronary flow from 12.7 ± 0.8 to 18.4 ± 0.7 mL∙mn−1∙g−1. The presence of either adenosine deaminase (2 U∙mL−1) or the adenosine receptor antagonist, 8-phenyltheophylline (5 × 10−6 M) in the perfusate of norepinephrine-stimulated hearts augmented the increase in LVDP and ±dP/dtmax by 10–20% but reduced the increase in coronary flow by 34%. Doubling the rate of adenosine deaminase infusion, or infusing the enzyme and 8-phenyltheophylline together did not alter their inhibitory effectiveness. Similar results were observed with hearts stimulated with isoproterenol (5 × 10−8 M). These data show that about a third of the vasodilation that results from the metabolic stimulation of rat heart by catecholamines is due to the receptor-mediated action of extracellular adenosine.

Effect of Protein Kinase C Inhibitors and 2,3-Butanedione Monoxime on the Long-Term Hypothermic Preservation of Isolated Rat Hearts

1996 ◽  
Vol 91 (6) ◽  
pp. 745-754 ◽  
Author(s):  
Oluwole S. Fagbemi ◽  
Basil J. Northover
Keyword(s):  
Cardiac Output ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
High Energy ◽  
Left Ventricular ◽  
Protein Kinase C Inhibitors ◽  
Kinase C ◽  
Butanedione Monoxime ◽  
Hypothermic Storage ◽  
Developed Pressure

1. This study examines the protective effect of staurosporine, chelerythrine, Ro 31-8220 and 2,3-butanedione monoxime in rat hearts during hypothermic storage. 2. Hearts were microperfused at 4°C for 24 or 48 h with a storage buffer that in some cases contained one of these protein kinase C inhibitors either alone or in combination with 2,3-butanedione monoxime. After hypothermic storage, hearts were rewarmed to 37°C with Krebs—Henseleit buffer. Cardiac function was then assessed in either Langendorff mode or working heart mode. 3. Compared with values from fresh non-stored hearts, hypothermic stored hearts showed a significant decrease in both coronary flow and left ventricular developed pressure when the stored hearts were reperfused in Langendorff mode. The decrease in coronary flow and left ventricular developed pressure was more pronounced in hearts stored for 48 h than in those stored for 24 h. 4. Hearts stored for 24 or 48 h, with or without the protein kinase C inhibitors, and then perfused in working mode generated less aortic flow and less cardiac output than fresh unstored hearts. 5. Hearts preserved in solutions containing staurosporine, chelerythrine, Ro 31-8220 or 2,3-butanedione monoxime had significantly higher left ventricular developed pressure values on reperfusion than hearts stored without any such drug. 6. Addition of 2,3-butanedione monoxime to a storage buffer containing either staurosporine, chelerythrine or Ro 31-8220 further improved left ventricular developed pressure, aortic flow and cardiac output values in these stored hearts. The group of hearts stored in a buffer containing 2,3-butanedione monoxime and chelerythrine gave the highest left ventricular developed pressure value seen during reperfusion. 7. The ATP and creatine phosphate concentrations of hearts stored in buffer alone were significantly lower than those of fresh unstored hearts, irrespective of the duration of storage. ATP concentrations were better preserved in hearts stored in a buffer containing 2,3-butanedione monoxime or/and one of the protein kinase C antagonists than those stored without such antagonists. A positive correlation was found between peak cardiac output values and the concentrations of combined high-energy phosphates in various groups of stored and reperfused hearts. 8. The present study showed that inhibition of protein kinase C during long-term hypothermic storage significantly increased high-energy phosphate concentrations and also improved contractile function during reperfusion.

The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts

2001 ◽  
Vol 79 (3) ◽  
pp. 213-219 ◽  
Author(s):  
Jitka A Ismail ◽  
Kathleen H McDonough
Keyword(s):  
Coronary Flow ◽  
Myocardial Protection ◽  
Myocardial Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Lv Function ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Septic Group

Myocardial function is impaired 24 h after the induction of sepsis, however, recovery of left ventricular (LV) function after 35 min of global ischemia is complete. The mechanisms by which this protection occurs are unknown. Ischemic preconditioning, another form of myocardial protection from ischemia/reperfusion (I/R) injury, has been shown to be modulated by ATP-sensitive potassium (K+ATP) channels. To investigate the role of K+ATP channels in the regulation of coronary flow (CF) and protection from I/R injury in septic rat hearts, we assessed the effects of the K+ATP channel antagonist glibenclamide (GLIB) and the agonist cromakalim (CROM) on pre- and post-ischemic CF and left ventricular developed pressure (LVDP). Although GLIB decreased pre-ischemic CF in both control and septic rat hearts, LVDP was unaffected. After I/R, CF was decreased in GLIB-treated control and septic rat hearts and LVDP was more severely depressed in control rat hearts than in septic rat hearts. CROM increased pre-ischemic CF in the septic group although LVDP was unaltered in both groups. After I/R, control rat heart CF was depressed but LVDP completely recovered. Post-ischemic CF in septic rat hearts was elevated compared with vehicle-treated septic rat hearts, but the recovery of LVDP was not improved. These results suggest that K+ATP channels modulate CF in septic rat hearts, but do not mediate cardioprotection as observed in control rat hearts.Key words: K+ATP channel, preconditioning, ischemia, reperfusion, sepsis.

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