The dose-dependent effect of chronic Verapamil treatment on cardiac function in isolated rat heart with Hypertension

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Verapamil, a calcium channel blocker, is used for treatment of hypertension, paroxysmal supraventricular tachycardia and angina pectoris. It primarily blocks L-type calcium channels preventing excessive influx of calcium into cardiomyocytes, leading to negative inotropic effect, and smooth muscle cells resulting in reduced relaxation of vasculature. With calcium antagonism it also causes negative chronotropic effect. However, there is no data on it’s dose-dependent effects on cardiac dynamic parameters and heart rate on isolated rat heart with hypertension. Purpose To investigate chronic, dose-dependent effects of Verapamil on cardiodynamic parameters in isolated rat heart with hypertension. Methods The present 4-week study was carried out on 24 spontaneously hypertensive Wistar Kyoto male rats (6 weeks old): Control (n = 6), rats treated with 0.5 mg/kg/day of Verapamil (n = 6), rats treated with 5 mg/kg/day of Verapamil (n = 6) and rats treated with 50 mg/kg/day of Verapamil (n = 6). Isolated rat hearts were perfused on Langendorff perfusion apparatus. Results Chronic, low-dose Verapamil treatment significantly depressed function of all cardiodynamic parameters of the hypertensive heart when compared to the rats treated with higher doses of Verapamil (p < 0.001), except on the coronary flow and heart rate when compared to the Control (p= 0.137; p = 1.000, respectively). There was no significant differences between Verapamil in middle dose (5 mg/kg/day) and the Control group in inotropic (p = 0.415) and lusitropic (p = 1.000) effects, while it significantly lowered values of coronary flow (p = 0.002). It achieved significantly lower inotropic, lusitropic and chronotropic effects (p < 0.001) than high Verapamil dose and significantly better inotropic (p = 0.017), lusitropic (p < 0.001), but not chronotropic effects than low-dose Verapamil treatment (p = 0.179). High-dose, chronic treatment with Verapamil significantly intensified function of the isolated rat heart with hypertension when compared to Control and lower doses of Verapamil (p < 0.001), without significant effects on coronary flow (p = 0.363). Conclusions Chronic treatment with Verapamil in high dose achieved better inotropic, chronotropic and lusitropic effects than treatment in low and middle doses of Verapamil, without significant effects on coronary flow. There is dose-depended effect of chronic Verapamil treatment on cardiac function of isolated rat heart with hypertension.

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Mechanisms of antifibrillatory effect of acidic reperfusion: role of perfusate bicarbonate concentration

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.3.h783 ◽

1993 ◽

Vol 264 (3) ◽

pp. H783-H790 ◽

Cited By ~ 2

Author(s):

C. Ibuki ◽

D. J. Hearse ◽

M. Avkiran

Keyword(s):

Heart Rate ◽

Ventricular Fibrillation ◽

Rat Heart ◽

Coronary Flow ◽

Isolated Rat Heart ◽

Acidic Ph ◽

Bicarbonate Concentration ◽

Left And Right ◽

Isolated Rat

Transient (2 min) acidic (pH 6.6) reperfusion with low [HCO3-] solution suppresses reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart. Using this preparation, we tested whether the effect was mediated by the high [H+] or the low [HCO3-] of perfusate. Left and right coronary beds were independently perfused with HCO3(-)-containing (25.0 mmol/l) solution at pH 7.4. Regional ischemia was then induced by stopping flow to the left coronary bed for 10 min. Hearts were subsequently assigned to four groups (n = 12 hearts/group), and the left coronary bed was reperfused with either HCO3(-)-containing (25.0 or 4.0 mmol/l) or HCO3(-)-free (5.0 mmol/l HEPES) solution, at pH 7.4 throughout (control reperfusion) or at pH 6.6 for the first 2 min and at pH 7.4 from 2 to 5 min (acidic reperfusion). Regardless of the buffer, controls exhibited a high (92 and 100%) incidence of VF; this was reduced to 42% in both of the acidic reperfusion groups (P < 0.05). There were no intergroup differences in heart rate, coronary flow, or size of ischemic zone. Thus high [H+], rather than low [HCO3-], appears to mediate the antifibrillatory effect of transient acidic reperfusion.

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Performance of hypothermic isolated rat heart at various levels of blood acid-base status

Journal of Applied Physiology ◽

10.1152/jappl.1984.56.6.1526 ◽

1984 ◽

Vol 56 (6) ◽

pp. 1526-1532 ◽

Cited By ~ 5

Author(s):

M. Sinet ◽

M. Muffat-Joly ◽

D. Henzel ◽

G. Renault ◽

J. J. Pocidalo

Keyword(s):

Heart Rate ◽

Rat Heart ◽

Coronary Flow ◽

Myocardial Function ◽

Isolated Rat Heart ◽

Acid Base ◽

External Work ◽

Myocardial Oxygenation ◽

Acid Base Status ◽

Isolated Rat

The effects of respiratory-induced pH variation on mechanical function and myocardial oxygenation of isolated, blood-perfused working rat hearts were studied in hypothermia (26 degrees C) and compared with control values (37 degrees C). In these experiments, the change of plasma pH during hypothermia was parallel to the change in pH of neutral water. At 37 degrees C, pH was varied from 7.15 to 7.62; heart rate increased with pH, both cardiac output and external work remaining unaltered. An increase in pH induced a decrease in coronary flow and an increase in the O2 arteriovenous difference. In hypothermia, hemodynamic performance and myocardial O2 consumption decreased proportionately with no change in cardiac efficiency. At 26 degrees C, the cardiac capacity to react to acid-base variations (pH from 7.34 to 7.86) was preserved, i.e., heart rate increased with pH. As at 37 degrees C, regulation of both coronary flow and myocardial oxygenation was maintained. The present data suggest that the myocardial function of a working isolated rat heart undergoing hypothermia was also preserved. Moderate variations in extracellular acid-base status during hypothermia did not impair either myocardial function or the O2 supply-to-demand ratio.

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Inosine transiently decreases coronary flow but potentiates vasodilation by adenosine

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.259.3.h759 ◽

1990 ◽

Vol 259 (3) ◽

pp. H759-H765

Author(s):

P. Van der Meer ◽

J. W. de Jong

Keyword(s):

Heart Rate ◽

Adenosine Deaminase ◽

Rat Heart ◽

Coronary Flow ◽

Isolated Rat Heart ◽

Coronary Vasodilator ◽

Intracoronary Administration ◽

Adenosine Uptake ◽

Adenosine Concentration ◽

Isolated Rat

To test whether inosine interferes with the action of adenosine, we investigated the effects of intracoronary administration of inosine, adenosine, 8-phenyltheophylline, and adenosine deaminase on isolated rat heart. Inosine did not change heart rate or developed tension but increased the effluent adenosine concentration. Inosine also decreased exogenous adenosine uptake and breakdown. After the start of the inosine infusion (20 microM), a transient 30% decrease of coronary flow took place within 0.5 min. The nucleoside caused sustained vasodilation, dependent on the concentration (30-400 microM). After the infusion we observed a transient vasodilation. A nonvasoactive inosine concentration (10 microM) combined with an adenosine concentration that increased flow by 60% (0.1 microM) raised vasodilation by another 60%. Infusion of adenosine, adenosine deaminase, or 8-phenyltheopylline did not influence the inosine-induced transient decrease of flow, suggesting that this decrease is independent of adenosine and its receptor. We conclude that inosine 1) potentiates the vasodilation induced by adenosine and 2) is a coronary vasodilator but probably also a vasoconstrictor.

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Species-dependent hemodynamic effects of adenosine A3-receptor agonists IB-MECA and Cl-IB-MECA

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.6.h2076 ◽

1999 ◽

Vol 276 (6) ◽

pp. H2076-H2084 ◽

Cited By ~ 9

Author(s):

Robert D. Lasley ◽

Prakash Narayan ◽

M. Salik Jahania ◽

Elizabeth L. Partin ◽

Kathleen R. Kraft ◽

...

Keyword(s):

Receptor Antagonist ◽

Rat Heart ◽

Coronary Flow ◽

Receptor Activation ◽

Isolated Rat Heart ◽

Pressure Effects ◽

Hemodynamic Effects ◽

Receptor Agonists ◽

Coronary Dilation ◽

Isolated Rat

The purpose of this study was to compare the hemodynamic effects of the adenosine A3-receptor agonists N 6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-β-d-ribofuranosyl]adenine (IB-MECA) and 2-chloro- N 6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-β-d-ribofuranosyl]adenine (Cl-IB-MECA) in isolated rat and rabbit hearts and in the intact, open-chest pig. Isolated hearts perfused with Krebs-Henseleit buffer at a constant pressure (70 mmHg) were treated with 50 nM of either IB-MECA or Cl-IB-MECA. Neither IB-MECA nor Cl-IB-MECA altered ventricular function or heart rate in the isolated rat and rabbit hearts, and neither agent altered coronary flow in the rabbit. However, 2 min of IB-MECA treatment in the isolated rat heart increased coronary flow by 25%, an effect that did not exhibit tachyphylaxis. The IB-MECA-induced coronary dilation was only partially attenuated by the adenosine A3-receptor antagonist MRS-1191 (50 nM). IB-MECA-induced coronary dilation was completely blocked by the adenosine A2a-receptor antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (Sch-58261, 50 nM). Cl-IB-MECA (50 nM) did not increase coronary flow in the rat, but 100 nM did increase flow by 18%. In pentobarbital sodium-anesthetized pigs IB-MECA (5 μg/kg iv) decreased systemic blood pressure and increased pulmonary artery pressure, effects that did exhibit tachyphylaxis. These results illustrate that adenosine A3-receptor agonists produce species-dependent effects, which in the rat heart appear to be caused by adenosine A2a-receptor activation.

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STUDY OF DOSE-DEPENDENT EFFECT OF 2-ETHYL-6-METHYL-3 HYDROXYPYRIDINE SUCCINATE ON THE CONTRACTILE FUNCTION OF ISOLATED RAT HEART

RESEARCH RESULT Pharmacology and Clinical Pharmacology ◽

10.18413/2500-235x-2017-3-1-3-9 ◽

2017 ◽

Vol 3 (1) ◽

Author(s):

O.G. Kesarev ◽

◽

L.M. Danilenko ◽

M.V. Pokrovskii ◽

A.S. Timokhina ◽

...

Keyword(s):

Rat Heart ◽

Contractile Function ◽

Isolated Rat Heart ◽

Dependent Effect ◽

Dose Dependent ◽

Dose Dependent Effect ◽

Isolated Rat

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The influence of an essential fatty acid (EFA) deficient diet on coronary flow rate and prostacyclin production of the isolated rat heart

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(77)80337-4 ◽

1977 ◽

Vol 9 (9) ◽

pp. 55-56 ◽

Cited By ~ 1

Author(s):

F TENHOOR ◽

E DEDECKERE

Keyword(s):

Fatty Acid ◽

Essential Fatty Acid ◽

Flow Rate ◽

Rat Heart ◽

Coronary Flow ◽

Isolated Rat Heart ◽

Deficient Diet ◽

Prostacyclin Production ◽

Isolated Rat

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The perfusion of cisplatin and cisplatin structural analogues through the isolated rat heart: The effects on coronary flow and cardiodynamic parameters

General Physiology and Biophysics ◽

10.4149/gpb_2018004 ◽

2018 ◽

Vol 37 (05) ◽

pp. 515-525 ◽

Cited By ~ 1

Author(s):

I. M. Stojic ◽

V. Lj. Jakovljevic ◽

V. I. Zivkovic ◽

I. M. Srejovic ◽

T. R. Nikolic ◽

...

Keyword(s):

Rat Heart ◽

Coronary Flow ◽

Isolated Rat Heart ◽

Structural Analogues ◽

Isolated Rat

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Effect of Temperature and Coronary Flow on the Metabolic and Mechanical Function of the Isolated Rat Heart

Cardiology ◽

10.1159/000175871 ◽

1993 ◽

Vol 82 (4) ◽

pp. 238-248 ◽

Cited By ~ 4

Author(s):

Haywood Blum ◽

Tamas Ivanics ◽

Danning Zhang ◽

Krzysztof Wroblewski ◽

Mary D. Osbakken

Keyword(s):

Rat Heart ◽

Coronary Flow ◽

Isolated Rat Heart ◽

Effect Of Temperature ◽

Mechanical Function ◽

Isolated Rat

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Blood-perfused working isolated rat heart

Journal of Applied Physiology ◽

10.1152/jappl.1976.41.4.603 ◽

1976 ◽

Vol 41 (4) ◽

pp. 603-607 ◽

Cited By ~ 44

Author(s):

M. A. Duvelleroy ◽

M. Duruble ◽

J. L. Martin ◽

B. Teisseire ◽

J. Droulez ◽

...

Keyword(s):

Rat Heart ◽

Coronary Flow ◽

Myocardial Oxygen Consumption ◽

Isolated Rat Heart ◽

Red Cells ◽

Red Cell ◽

External Work ◽

Bicarbonate Buffer ◽

Isolated Rat ◽

Human Red Cells

We describe a method for perfusion of a working isolated rat heart with washed erythrocytes suspended in a Krebs-Henseleit bicarbonate buffer containing bovine albumin (fraction V). With washed pig red cells, as hematocritwas varied between 0 and 40%, coronary flow (CF), aortic flow (AF), external work (W), and myocardial oxygen consumption (MVO2) were measured. Hemodynamic data at a hematocrit of 30% (CF = 5.4 +/- 0.7 ml/min per g, AF = 75 +/- 8 ml/min per g) were identical with those reported for the intact animal.Coronary sinus PO2 was highest with a red cell-free perfusate suggesting that coronary flow is partially shunted. Human red cells obtained from bankedblood, were tried also with success. With careful filtration, the preparation is stable for 2 h and well suited for study of the dynamics of myocardial oxygen delivery.

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