scholarly journals The Investigation of Combined Na+/Ca2+ Exchanger and the L-type Ca2+- Channel Inhibition in Langendorff Perfused Isolated Guinea Pig Hearts 

2021 ◽  
Vol 31 (3) ◽  
pp. 537-545
Author(s):  
János PROROK ◽  
◽  
Annamária VEISBART ◽  
Dóra LIPKA ◽  
Norbert JOST ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Ex Vivo ◽  
Cardiac Contractility ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Sodium Calcium Exchanger ◽  
Guinea Pig Heart ◽  
Sodium Potassium ◽  
Channel Inhibition ◽  
Mean Time

Objective: The sodium/calcium exchanger (NCX) and the L-type Ca2+-channel (LTCC) are nowadays considered the major transmembrane transport mechanisms that control Ca2+ homeostasis. In pathophysiological conditions the altered function of these currents may influence the Ca2+ homeostasis and cardiac contractility and thereby, may enhance the development of severe tachyarrhythmias. The blockade of NCX current has been proposed as possible approach in the prevention and/or suppression of arrhythmias; however, this mechanism is not always favourable because the inhibition of both modes of NCX may induce Ca2+ overload. The decrease of the Ca2+ level by partial LTCC inhibition may be beneficial in increasing the antiarrhythmic efficacy. Therefore, the aim of our study was to investigate the antiarrhythmic effects of combined NCX and LTCC blockade in the ex vivo guinea pig arrhythmia model. Methods: We have performed Langendorff experiments in isolated guinea pig hearts. We have recorded electrocardiograms (ECG) and left ventricle pressure. We have applied 1 μM ORM-10962 (ORM), a compound that block NCX current and 30 nM nisoldipine for the inhibition of LTCC. Arrhythmias have been provoked by decreasing the activity of the sodium/potassium pump with 5 μM ouabain. Results: We found that neither LTCC nor NCX blockade alone increased, while the combined inhibition of the two currents significantly delayed (p<0.05) the mean time of appearance of ouabain-induced ventricular fibrillation. The heart f equency was affected by none of the drugs, only the left ventricular pressure (end-systolic and diastolic difference) was significantly elevated by ORM (p<0.001). Conclusion: In the Langendorff-perfused guinea pig heart, specific, combined NCX and LTCC blockade may be favourable than the inhibition of NCX or LTCC alone. However, further investigations are necessary to identify the pathological settings in which this combined cardiac drug therapy may be a potential new approach.

Metabolic correlates of adenosine formation in stimulated guinea pig heart

1991 ◽  
Vol 260 (1) ◽  
pp. H165-H172 ◽  
Author(s):  
J. P. Headrick ◽  
G. P. Matherne ◽  
S. S. Berr ◽  
D. C. Han ◽  
R. M. Berne
Keyword(s):  
Guinea Pig ◽  
Inorganic Phosphate ◽  
Consumption Rate ◽  
Myocardial Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Guinea Pig Heart ◽  
Norepinephrine Infusion ◽  
Myocardial O2 Consumption

Adenosine release into epicardial fluid and coronary effluent of isolated isovolumic guinea pig hearts was examined at baseline and after stimulation with norepinephrine (30 nM) during 31P-nuclear magnetic resonance spectroscopy to monitor myocardial metabolism. At baseline flow (9.6 +/- 0.3 ml.min-1.g-1), epicardial and venous adenosine concentrations were 154 +/- 40 and 17 +/- 5 nM, respectively. The phosphorylation potential (log[ATP]/[ADP][Pi]) and the phosphocreatine-inorganic phosphate ratio ([PCr]/[Pi]) were 5.26 +/- 0.04 and 8.5 +/- 0.7, respectively. Norepinephrine increased left ventricular pressure, heart rate, and myocardial O2 consumption rate by approximately 21, 70, and 45%, respectively, and increased epicardial and venous adenosine to 496 +/- 74 and 461 +/- 94 nM, respectively. Log-[ATP]/[ADP][Pi] and [PCr]/[Pi] declined to 4.57 +/- 0.06 and 1.9 +/- 0.3, respectively. Epicardial [AMP] increased from 54 +/- 13 to 123 +/- 24 nM. AMP was not detectable in the venous effluent. Coronary resistance correlated with epicardial and venous [adenosine] (r = 0.86 and 0.90). Epicardial and venous [adenosine] correlated with log[ATP]/[ADP][Pi], [PCr]/[Pi], and cytosolic [AMP]. Hence, interstitial adenosine is linked to cytosolic metabolism and may regulate coronary vascular resistance. Venous adenosine underestimates epicardial adenosine at baseline but more closely approximates epicardial adenosine during norepinephrine infusion.

Ketamine Has Stereospecific Effects in the Isolated Perfused Guinea Pig Heart

1995 ◽  
Vol 82 (6) ◽  
pp. 1426-1437. ◽  
Author(s):  
Bernhard M. Graf ◽  
Martin N. Vicenzi ◽  
Eike Martin ◽  
Zeljko J. Bosnjak ◽  
David F. Stowe
Keyword(s):  
Heart Rate ◽  
Guinea Pig ◽  
Opioid Receptors ◽  
Coronary Flow ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Guinea Pig Heart ◽  
Ringer’S Solution ◽  
Cardiac Depression

Background S(+)-Ketamine is judged to produce more potent anesthesia than either the racemate or the R(-) ketamine isomer because of differential activation of specific cerebral receptors. Other than central nervous system effects, the most important side effects of ketamine occur in the cardiovascular system. We examined the direct cardiac effects of the isomers and the racemate of ketamine in the isolated perfused guinea pig heart. Methods Twenty-three guinea pig hearts were perfused by the Langendorff technique with modified 37 degrees C Krebs-Ringer's solution (97% oxygen and 3% carbon dioxide) at a constant perfusion pressure. Eight animals were pretreated with reserpine to deplete hearts of catecholamines. These pretreated hearts were also perfused with Krebs-Ringer's solution containing propranolol, phenoxybenzamine, and atropine to block any remaining effects of catecholamines and of acetylcholine. Five additional hearts were perfused with naloxone to block cardiac opioid receptors. Ten hearts were not treated. All 23 hearts were then exposed to four increasing equimolar concentrations of each isomer and the racemate of ketamine for 10 min. Heart rate, atrioventricular conduction time (AVCT), left ventricular pressure, coronary flow, and inflow and outflow oxygen tensions were measured. Percentage oxygen extraction, oxygen delivery, and oxygen consumption were calculated. Results Both isomers and the racemate caused a concentration-dependent depression of systolic left ventricular pressure and an increase in AVCT. In the untreated hearts, S(+)-ketamine decreased heart rate and left ventricular pressure and, at higher concentrations, oxygen consumption and percentage oxygen extraction significantly less than R(-)-ketamine independent of blocked or unblocked opioid receptors. Racemic ketamine depressed cardiac function to a degree intermediate to that produced by the isomers. Coronary flow and AVCT were equally affected by the isomers and by the racemic mixture. In the catecholamine-depleted hearts both isomers and the racemate caused equipotent depression of all variables. In these hearts cardiac depression was greater, and AVCT, coronary flow, and oxygen delivery were significantly greater than in untreated and opioid receptor-blocked hearts. Conclusions Lesser cardiac depression by the S(+) isomer is attributable to an increased availability of catecholamines, because previous depletion of catecholamine stores and autonomic blockade completely inhibited these differences. The inability of cardiac tissue to reuptake released catecholamines into neuronal or extraneuronal sites during exposure to ketamine is stereoselective and caused predominantly by the S(+) isomer. Cardiac opioid receptors are apparently not involved in this phenomenon.

Compensatory hypertrophy and failure in gradual pressure-overloaded guinea pig heart

1989 ◽  
Vol 257 (3) ◽  
pp. H1016-H1024 ◽  
Author(s):  
F. M. Siri ◽  
C. Nordin ◽  
S. M. Factor ◽  
E. Sonnenblick ◽  
R. Aronson
Keyword(s):  
Heart Failure ◽  
Left Ventricular Hypertrophy ◽  
Guinea Pig ◽  
Ventricular Hypertrophy ◽  
Significant Proportion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Compensatory Hypertrophy ◽  
Guinea Pig Heart ◽  
Ventricular Afterload

Left ventricular hypertrophy has been produced in the guinea pig by a procedure that gradually increases left ventricular afterload. A mildly constricting band was placed around the ascending aortas of very young guinea pigs (225–275 g). With growth to 500–1,000 g, left ventricular systolic pressure increased and left ventricular hypertrophy developed. In approximately 50% of these animals, the hypertrophy was associated with normal left ventricular function and with no unusual symptoms or evidence of heart failure. The other animals developed dyspnea, which appeared an average of 41 days after banding. Dyspneic animals had normal body weight, markedly increased right ventricular and lung weights, decreased left ventricular norepinephrine content, diminished maximum left ventricular pressure generating capacity, and a significantly higher incidence of left ventricular interstitial and perivascular fibrosis. These findings demonstrate that even when left ventricular overload is imposed gradually by banding the aortas of young animals, myocardial decompensation ultimately ensues in a significant proportion of such animals. The slow imposition of loading, the slow rate of decompensation, and the ability to identify animals in heart failure by clinical dyspnea make this model uniquely valuable for studies on the mechanisms of heart failure.

Muscle metabolism and cardiac function of the myopathic hamster following training

1977 ◽  
Vol 43 (6) ◽  
pp. 936-941 ◽  
Author(s):  
W. L. Sembrowich ◽  
M. B. Knudson ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Cardiac Contractility ◽  
Muscle Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Succinate Dehydrogenase Activity ◽  
Positive Effect

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

scholarly journals Dose-dependent Effects of Perfluorocarbon Based Blood Substitute Perftoran on Cardyodinamics in Animal Model of Ischemia-reperfusion Injury

2021 ◽  
Author(s):  
Vladimir Jakovljevic ◽  
Sergey Vorobyev ◽  
Sergey Bolevich ◽  
Elena Morozova ◽  
Stefani Bolevich ◽  
...  
Keyword(s):  
Growth Rate ◽  
Reperfusion Injury ◽  
Rat Heart ◽  
Ex Vivo ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Isolated Rat

Abstract The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion in ex vivo-induced ischemic-reperfusion injury of an isolated rat heart. The first part of the study aims to determine the dose of 10% perfluoroemulsion (PFT) that will show the best cardioprotective effect in rats on ex vivo-induced ischemic / reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFT, the animals were divided into a control or experimental group, and depending on the application of a dose (8, 12, 16 ml / kg body weight) of saline or PFT. At a dose of 8 ml / kg, the results indicate statistically significantly lower values ​​of the maximum pressure growth rate in the group treated with 10% PFT compared to the control group treated with saline at R5 and R25 points. At a dose of 12 ml / kg, the maximum left ventricular pressure growth rate differed statistically significantly in the PFT group, ie there was an increase in this parameter at points R25 and R30, and the minimum left ventricular pressure growth rate in R15-R30 compared to saline-treated group. At a dose of 16 ml / kg, PFT also had a statistically significant effect on the change in cardiodynamic parameters in an isolated rat heart organ. Based on all the above, we can conclude that Peftoran administered immediately before ischemia (1 hour) has less positive effects on myocardial function in a model of an isolated rat heart compared to earlier administration (10 and 20 hours). Also, the effects of 10% peftoran solution are more pronounced if there is a longer period of time from application to ischemia, ie immediate application of peftoran before ischemia (1 hour) gave the weakest effects on the change of cardiodynamics of isolated rat heart.

Thyroidectomy of SHR: effects on ventricular relaxation and on SR calcium uptake activity

1986 ◽  
Vol 250 (5) ◽  
pp. H861-H865 ◽  
Author(s):  
R. L. Rodgers ◽  
S. Black ◽  
S. Katz ◽  
J. H. McNeill
Keyword(s):  
Ventricular Hypertrophy ◽  
Calcium Uptake ◽  
Ex Vivo ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Mechanical Relaxation ◽  
Ventricular Relaxation ◽  
Uptake Activity ◽  
Wistar Kyoto

Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle relaxation and sarcoplasmic reticulum (SR) calcium uptake activity. A previous report also showed that hypothyroidism does not reverse ventricular hypertrophy (left-to-right ventricular weight ratios) of spontaneously hypertensive rats (SHR). We characterized the effects of thyroidectomy of 8 wk duration on relaxation of ejecting hearts and on SR calcium uptake activity from SHR and nonhypertrophic Wistar-Kyoto rat (WKY) controls. Relaxation was quantified by plotting maximum left ventricular pulse pressure (Pmax) vs. the area under the falling phase of the left ventricular pressure wave at three different pressure loads. Ventricles of euthyroid SHR were characterized by impaired relaxation and depressed SR calcium uptake activity compared with those of euthyroid WKY, confirming earlier studies. Thyroidectomy reduced ventricular relaxation and SR calcium uptake activities to about the same extent in SHR and WKY strains so that these measurements were most depressed in the SHR hypothyroid group. When all groups were considered, the extent of mechanical relaxation ex vivo and the rate of SR calcium uptake in vitro were well correlated.

Hypoxia-induced activation of KATP channels limits energy depletion in the guinea pig heart

1995 ◽  
Vol 269 (2) ◽  
pp. H734-H742 ◽  
Author(s):  
U. K. Decking ◽  
T. Reffelmann ◽  
J. Schrader ◽  
H. Kammermeier
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
Resonance Spectroscopy ◽  
Energy Status ◽  
Guinea Pig Heart

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)

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

1999 ◽  
Vol 277 (2) ◽  
pp. H818-H825 ◽  
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.

Chronic alcohol-induced changes in cardiac contractility are not due to changes in the cytosolic Ca2+ transient

1998 ◽  
Vol 275 (1) ◽  
pp. H122-H130 ◽  
Author(s):  
Vincent M. Figueredo ◽  
Kevin C. Chang ◽  
Anthony J. Baker ◽  
S. Albert Camacho
Keyword(s):  
Cardiac Contractility ◽  
Left Ventricular Pressure ◽  
Alcohol Exposure ◽  
Left Ventricular ◽  
Polyacrylamide Gel ◽  
Chronic Alcohol ◽  
Protein Levels ◽  
Chronic Alcohol Exposure ◽  
Induced Changes ◽  
And Control

Long-standing heavy alcohol consumption acts as a chronic stress on the heart. It is thought that alcohol-induced changes of contractility are due to altered Ca2+ handling, but no measurements of cytosolic Ca2+([Ca2+]c) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced changes in contractility are due to altered Ca2+ handling by measuring [Ca2+]c(indo 1) in hearts from rats drinking 36% ethanol for 7 mo and age-matched controls. Peak left ventricular pressure was depressed (−16%), whereas rates of contraction (12%) and relaxation (14–20%) were faster in alcohol-exposed hearts. Systolic [Ca2+]c(808 ± 45 vs. 813 ± 45 nM), diastolic [Ca2+]c(195 ± 11 vs. 193 ± 10 nM), and rates of [Ca2+]crise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca2+-handling proteins, sarcoplasmic reticulum Ca2+-ATPase and phospholamban, were the same in myocytes isolated from alcohol-exposed and control hearts (SDS-polyacrylamide gel). These data suggest that chronic alcohol-induced contractile changes are not due to altered Ca2+ handling but may be due to changes at the level of the myofilament. As a first step in elucidating the mechanism(s) of alcohol-induced changes at the myofilament, we assessed myosin heavy chain (MHC) isoform content (SDS-polyacrylamide gel). α-MHC was decreased relative to β-MHC ( a/ a+ b = 0.55 ± 0.03 vs. 0.66 ± 0.02; P < 0.02) in alcohol-exposed hearts, which cannot account for the observed alcohol-induced contractile changes. In conclusion, changes of myocardial contractility due to chronic alcohol exposure do not result from altered Ca2+ handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.

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