Levosimendan Increases Diastolic Coronary Flow in Isolated Guinea-Pig Heart by Opening ATP-Sensitive Potassium Channels

The functional role of ATP-dependent potassium (KATP) in hypoxic cardiac failure was investigated in isolated guinea pig hearts with glibenclamide and rimalkalim as inhibitor and activator, respectively. Monophasic action potential duration at 90% of repolarization (MAP50), left ventricular function, and cardiac energy status (31P nuclear magnetic resonance spectroscopy) were measured during normotoxic (95% O2) and hypoxic (20% O2) perfusion. In normoxic hearts, 1 microM glibenclamide did not affect MAP50, left ventricular function, and coronary flow (n = 4). In contrast, rimalkalim rapidly shortened MAP50 and left ventricular pressure (LVP) in a dose-dependent fashion (e.g., by 60.2 +/- 3.5 and 80.8 +/- 8.2%, respectively, with 0.6 microM rimalkalim). This latter effect was reversed by 1 microM (glibenclamide (n = 4). With hypoxic perfusion, a reduction in LVP was observed, along with a shortening of the action potential (MAP90; 202 +/- 13 vs. 164 +/- 9 ms) and an increase in coronary flow. Glibenclamide (1 microM) reversed the MAP90 shortening and the increase in coronary flow. In addition, glibenclamide increased LVP transiently (n = 4). When coronary flow of hypoxic hearts was kept constant, however, glibenclamide elicited a sustained positive inotropic effect (n = 7). After glibenclamide, an increase in LVP from 54 +/- 4 to 64 +/- 3 mmHg was observed, along with a reduction in the free energy change of ATP hydrolysis from -54.5 +/- 1.9 to -52.9 +/- 0.2 nJ/mol and a further increase in the coronary venous adenosine from 269 +/- 48 to 1,680 +/- 670 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

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ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.2.h818 ◽

1999 ◽

Vol 277 (2) ◽

pp. H818-H825 ◽

Cited By ~ 1

Author(s):

Peter B. Anning ◽

Bernard D. Prendergast ◽

Philip A. MacCarthy ◽

Ajay M. Shah ◽

Derek C. Buss ◽

...

Keyword(s):

Nitric Oxide ◽

Guinea Pig ◽

Coronary Flow ◽

Pyridoxal Phosphate ◽

Left Ventricular ◽

Luciferase Assay ◽

Disulfonic Acid ◽

Vascular Effects ◽

Guinea Pig Heart ◽

Nitric Oxide Release

It has recently been reported that bradykinin induces selective left ventricular (LV) relaxation in isolated guinea pig hearts via the release of nitric oxide. Exogenous bradykinin also induces vasodilation, which is only partly due to nitric oxide release. In the present study we investigated the role of adenyl purines on these bradykinin-induced effects. Isolated ejecting guinea pig hearts were studied. LV pressure was monitored by a 2-Fr micromanometer-tipped catheter. ATP concentrations were measured using a luciferin-luciferase assay. Bradykinin (1 and 100 nM) caused a progressive acceleration of LV relaxation together with a transient increase in coronary flow. These effects were inhibited by the nonselective P2 purinoceptor antagonist suramin (1 μM, n = 6) but were unaffected by the selective P2x purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2′,4′-disulfonic acid (1 μM, n = 6). These myocardial and vascular effects of bradykinin were associated with increased ATP levels in coronary effluent. These data suggest that the selective enhancement of LV relaxation and rise in coronary flow induced by exogenous bradykinin involve endogenous ATP and the subsequent stimulation of P2 purinoceptors.

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ATP‐sensitive potassium channels in capillaries isolated from guinea‐pig heart

The Journal of Physiology ◽

10.1111/j.1469-7793.2000.t01-1-00307.x ◽

2000 ◽

Vol 525 (2) ◽

pp. 307-317 ◽

Cited By ~ 62

Author(s):

Michael Mederos y Schnitzler ◽

Christian Derst ◽

Jürgen Daut ◽

Regina Preisig‐Müller

Keyword(s):

Potassium Channels ◽

Guinea Pig ◽

Guinea Pig Heart

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Effect of Hypoxia on Coronary Flow before and after Disruption of Both NOS and ATP-Sensitive K Channel Activities in the Isolated Guinea Pig Heart

Anesthesiology ◽

10.1097/00000542-200209002-00643 ◽

2002 ◽

Vol 96 (Sup 2) ◽

pp. A643

Author(s):

Kaoru Okazaki ◽

Masayuki Endou

Keyword(s):

Guinea Pig ◽

Coronary Flow ◽

K Channel ◽

Guinea Pig Heart ◽

Before And After

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Effect of Acetaldehyde on the Isolated, Non-working Guinea-Pig Heart: Independence of the Coronary Flow Increase from Changes in Heart Rate and Oxygen Consumption

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y74-078 ◽

1974 ◽

Vol 52 (3) ◽

pp. 602-612 ◽

Cited By ~ 5

Author(s):

Minh-Hau Nguyen ◽

L. Gailis

Keyword(s):

Heart Rate ◽

Oxygen Consumption ◽

Guinea Pig ◽

Gas Phase ◽

Coronary Flow ◽

Constant Pressure ◽

Guinea Pig Heart ◽

Bicarbonate Buffer

Guinea-pig hearts were perfused at constant pressure with Krehs–Henseleit bicarbonate buffer equilibrated with 95% O2 – 5% CO2. Acetaldehyde at 1 and 5 mM increased coronary flow, oxygen consumption, and heart rate. At 0.2 mM, it increased coronary flow and oxygen consumption only. In the rapidly paced heart, 1 mM acetaldehyde increased coronary flow, but not heart rate or oxygen consumption. Acetaldehyde increased coronary flow and oxygen consumption of the potassium-arrested heart. Acetaldehyde increased all parameters of the hypoxic heart (25% O2 gas phase), but the anoxic heart was not affected (coronary flow was already maximal).Reserpine (in vivo) and catecholamine β blockers (dichloroisoproterenol and propranolol) (in vitro) blocked the heart rate increases and moderated the rise in oxygen consumption. Dichloroisoproterenol plus phentolamine blocked the increases of both heart rate and oxygen consumption. None of the compounds affected the increase of coronary flow produced by acetaldehyde. Epinephrine, norepinephrine, and tyramine increased the heart rate and oxygen consumption, but not the coronary flow. Theophylline increased all three parameters. Neither tranylcypromine nor atropine modified the acetaldehyde effect. We conclude that the increase in heart rate is mediated by catecholamine β receptors. The increase in coronary flow is independent of the increase in heart rate or oxygen consumption and is not mediated by catecholamines.

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