Positive inotropic responses in cardiac muscles: influence of stimulation frequency and species

1982 ◽  
Vol 60 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Peter K. S. Siegl ◽  
John H. McNeill
Keyword(s):  
Right Ventricular ◽  
Species Difference ◽  
Extracellular Calcium ◽  
Stimulation Frequency ◽  
Force Frequency ◽  
Papillary Muscles ◽  
Drug Induced ◽  
Cardiac Muscles ◽  
Inotropic Responses ◽  
Isolated Rat

Inotropic responses to cumulative additions of methoxaminc (10−7 to 3 × 10−4 M), isoproterenol (10−9 to 10−5 M), or calcium (2 to 32 mM) were measured in isolated rat left atria and papillary muscles and rabbit right ventricular papillary muscles at three stimulation frequencies. Cardiac muscles were incubated in oxygenated Chenoweth–Koelle solution (2 mM calcium) at 37 °C. The basal developed force (BDF) before and maximum developed force (MDF) after challenge with methoxamine and isoproterenol were inversely related to stimulation frequency in rat preparations. BDF was directly related to stimulation rate in rabbit papillary muscles while MDF was independent of the rate. Drug-induced increases in force (MDF – BDF) were independent of stimulation frequency in rat and inversely related to stimulation frequency in rabbit. Responses to calcium were similar to the observed adrenergic responses. Also, force–frequency relationships of the rat and rabbit preparations were not similar in the absence and presence of these agonists. These data show that inotropic responses by rat and rabbit hearts are not affected similarly by stimulation frequency and this may reflect a species difference in the utilization of extracellular calcium for contraction.

Dithiothreitol restores contractile function to oxidant-injured cardiac muscle

1989 ◽  
Vol 257 (4) ◽  
pp. H1321-H1325 ◽  
Author(s):  
D. W. Eley ◽  
B. Korecky ◽  
H. Fliss
Keyword(s):  
Free Radicals ◽  
Hypochlorous Acid ◽  
Oxygen Free Radicals ◽  
Contractile Function ◽  
Complete Loss ◽  
Papillary Muscles ◽  
Oxidant Injury ◽  
Sharp Decline ◽  
Cardiac Muscles ◽  
Isolated Rat

Reperfusion injury in ischemic myocardium is caused partially by polymorphonuclear leukocyte oxygen free radicals, the most toxic of which may be hypochlorous acid (HOCl). This study shows that dithiothreitol (DTT), a disulfide-reducing agent, can restore contractile function to cardiac muscles that had been exposed to physiological levels of HOCl. Isometrically contracting isolated rat papillary muscles which were exposed to HOCl (300 microM) showed a rapid and essentially complete loss of developed force, an increase in resting force, and a sharp decline in myocyte protein sulfhydryls (PSH). The addition of DTT (1 mM) after 40 min resulted in a significant (40%) restoration of contractile function. Earlier addition of DTT effected a more complete functional recovery. The DTT-induced recovery was accompanied by a matching increase in cellular PSH levels, suggesting that HOCl injury may be caused primarily by the oxidation of cysteine residues. These data suggest that DTT may prove to be useful in reversing oxidant injury in tissues exposed to oxygen free radicals.

Effects of digitalis and calcium on papillary muscles in normal and hypoxic states

1976 ◽  
Vol 231 (1) ◽  
pp. 66-72 ◽  
Author(s):  
K Taubert ◽  
G Templeton ◽  
JT Willerson ◽  
W Shapiro
Keyword(s):  
Extracellular Calcium ◽  
Muscle Performance ◽  
Inotropic Effect ◽  
Papillary Muscles

The effects of digoxin and ouabain in 2.5 and 4.0 mM extracellular calcium were studied in well-oxygenated and hypoxic isolated, isometrically contracting cat papillary muscles. Muscle digoxin content was measured at the conclusion of the digoxin experiments. In the well-oxygenated environment muscles in the higher Ca bathing media reached peak glycoside inotropic effect sooner and contained 2.7 times more digoxin. During hypoxia and reoxygenation muscles contracting with glycosides performed no differently than those without a glycoside present. Muscle digoxin content was lowered at the end of hypoxia (P less than 0.05) in 2.5 mM Ca; after reoxygenation digoxin content was significantly greater than either before or after hypoxia (P less than 0.001). Hypoxic depression of muscle performance was attenuated in 4.0 mM Ca but muscles in 2.5 mM Ca showed greater improvement during reoxygenation even though the muscles in 4.0 mM Ca had significantly greater digoxin content at the end of reoxygenation (P less than 0.02). It therefore is concluded that, although altered extracellular calcium can alter performance during hypoxia and reoxygenation, muscle performance is not aided by the presence of digitalis and under these conditions performance cannot be correlated with muscle digoxin levels.

The effect of 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene on caffeine-induced contractures of skeletal muscle

1981 ◽  
Vol 59 (6) ◽  
pp. 617-620 ◽  
Author(s):  
Ralf G. Rahwan ◽  
Michael C. Gerald
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Calcium ◽  
Extracellular Calcium ◽  
Site Of Action ◽  
Isolated Rat

It has been previously postulated that 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene (pr-MDI) exhibits calcium antagonistic properties with an intracellular site of action. The present investigation further substantiates this hypothesis by providing evidence that pr-MDI inhibits caffeine-induced contractures (which are mediated by intracellular calcium) of the isolated rat hemidiaphragm skeletal muscle both in the presence and in the absence of extracellular calcium.

Reversal of muscle fatigue during 16 h of heavy intermittent cycle exercise

2004 ◽  
Vol 97 (6) ◽  
pp. 2166-2175 ◽  
Author(s):  
H. J. Green ◽  
T. A. Duhamel ◽  
S. Ferth ◽  
G. P. Holloway ◽  
M. M. Thomas ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Muscle Fatigue ◽  
Intermittent Exercise ◽  
Low Frequency ◽  
Quadriceps Muscle ◽  
Stimulation Frequency ◽  
Peak Oxygen Consumption ◽  
Force Frequency ◽  
Reduction In Force ◽  
Before And After

This study examined the effects of extended sessions of heavy intermittent exercise on quadriceps muscle fatigue and weakness. Twelve untrained volunteers (10 men and 2 women), with a peak oxygen consumption of 44.3 ± 2.3 ml·kg−1·min−1, exercised at ∼91% peak oxygen consumption for 6 min once per hour for 16 h. Muscle isometric properties assessed before and after selected repetitions (R1, R2, R4, R7, R12, and R15) were used to quantitate fatigue (before vs. after repetitions) and weakness (before vs. before repetitions). Muscle fatigue at R1 was indicated by reductions ( P < 0.05) in peak twitch force (135 ± 13 vs. 106 ± 11 N) and by a reduction ( P < 0.05) in the force-frequency response, which ranged between ∼53% at 10 Hz (113 ± 12 vs. 52.6 ± 7.4 N) and ∼17% at 50 Hz (324 ± 27 vs. 270 ± 30 N). No recovery of force, regardless of stimulation frequency, was observed during the 54 min between R1 and R2. At R2 and for all subsequent repetitions, no reduction in force, regardless of stimulation frequency, was generally found after the exercise. The only exception was for R2, where, at 20 Hz, force was reduced ( P < 0.05) by 18%. At R15, force before repetitions for high frequencies (i.e., 100 Hz) returned to R1 (333 ± 29 vs. 324 ± 27 N), whereas force at low frequency (i.e., 10 Hz) was only partially ( P < 0.05) recovered (113 ± 12 vs. 70 ± 6.6 N). It is concluded that multiple sessions of heavy exercise can reverse the fatigue noted early and reduce or eliminate weakness depending on the frequency of stimulation.

scholarly journals Tricuspid Valve Dysplasia in a Dog

2019 ◽  
Vol 47 ◽  
Author(s):  
Gabriela De Carvalho Cid ◽  
Luciano Da Silva Alonso ◽  
Ana Paula De Castro Pires ◽  
Mariana Siqueira d'Avila Taïna Gonçalves ◽  
Taïna Gonçalves ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Tricuspid Valve ◽  
Right Atrial ◽  
Pulmonary Insufficiency ◽  
Papillary Muscles ◽  
Ventricular Enlargement ◽  
Pathological Findings ◽  
Chordae Tendineae ◽  
Clinicopathological Findings ◽  
The Right

Background: Congenital cardiac diseases are a common cause of death in puppies. Tricuspid valve dysplasia is characterized by thickening and displacement of the leaflets of the tricuspid valve, agenesis of the valves, and incomplete separation of valve components. Papillary muscles may fuse and display shortened or absent chordae tendineae that contribute to tricuspid regurgitation. Diagnostic features of tricuspid valve dysplasia include cardiomegaly with massive right atrium enlargement on thoracic radiography and tricuspid insufficiency on an ultrasound. We aimed to describe clinicopathological findings in a dog (Canis familiaris) with tricuspid dysplasia.Case: We aimed to describe tricuspid valve dysplasia in a dog referred for necropsy at the Anatomical Pathology Sector of The Rural Federal University of Rio de Janeiro, Brazil, with a clinical history of abdominal swelling, dyspnea, cyanosis, ascites, and prostration. Echocardiography and abdominal ultrasound revealed right ventricular enlargement, hepatomegaly, and splenomegaly. Examination of the heart showed prominent enlargement, thickening and dilation of the right chambers, thickening of the tricuspid leaflets, and moderately shortened chordae tendineae. The liver was enlarged, with a nutmeg pattern, and foci of clotting and fibrin adhesions in the lateral right lobule.Discussion: Epidemiological, clinical, and pathological findings were consistent with tricuspid valve dysplasia. Although structural abnormalities of the tricuspid and mitral valves are well known in fetuses and neonates, congenital and secondary tricuspid malformations are rare in dogs. The survival rate is associated with the severity of heart lesions. Tricuspid valve dysplasia is mostly observed in large-breed dogs (>20 kg), particularly in Labrador Retrievers, Boxers, and German Shepherds. Regardless, most dogs with tricuspid valve dysplasia are of a pure-breed, which differs from our findings because our dog was a mongrel. Our dog displayed signs of dyspnea, cyanosis, abdominal swelling, prostration, and enlarged liver and spleen on ultrasound examination. Tricuspid valve dysplasia led to heart enlargement and right congestive heart failure, with consequent ascites, abdominal swelling, weakness, lethargy, jugular venous distension, and hepatomegaly. Overall, the heart showed prominent enlargement, thickening and dilation of the right chambers, thickening of the tricuspid leaflets, and moderately shortened chordae tendineae. The liver had a nutmeg pattern. Tricuspid valve dysplasia is characterized by malformation of the tricuspid valve leaflets, chord tendineae, or papillary muscles. Malformed tricuspid valves are known to result in variable degrees of regurgitation, leading to right atrial overflow and ventricular eccentric hypertrophy. Differential diagnosis includes myocarditis, tricuspid valve endocarditis, tricuspid endocardiosis, tricuspid valve prolapse and right ventricular dysplasia, right ventricular enlargement with tricuspidal regurgitation due to pulmonary insufficiency, and arrhythmogenic right ventricular cardiomyopathy. Signs of heart murmurs (irregular sounds of the heart) on clinical examination may indicate an irregular blood flow pattern, and imaging tests may be necessary for assessing the presence and severity of any lesions. The epidemiologic, clinical, and pathological findings were consistent with those of tricuspid valve dysplasia. 

scholarly journals The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium

2015 ◽  
Vol 309 (12) ◽  
pp. H2077-H2086 ◽  
Author(s):  
Nima Milani-Nejad ◽  
Benjamin D. Canan ◽  
Mohammad T. Elnakish ◽  
Jonathan P. Davis ◽  
Jae-Hoon Chung ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Muscle Length ◽  
Human Myocardium ◽  
Force Frequency ◽  
Heart Failure Patients ◽  
Cycling Rate ◽  
Physiological Conditions ◽  
Cross Bridge ◽  
The Right

Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing ( n = 9) and failing ( n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae ( n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization ( P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment ( ktr) in both nonfailing and failing myocardium ( P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length ( P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/d t slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients.

Abstract 17213: Crizotinib Exacerbates the Severity of Pah in a Preclinical Rat Model

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Francois Potus ◽  
Boucherat Olivier ◽  
Provencher Steeve ◽  
Bonnet Sébastien
Keyword(s):  
Right Ventricular ◽  
Small Cell Lung Carcinoma ◽  
Pulmonary Arteries ◽  
Systolic Pressure ◽  
Chemotherapeutic Agents ◽  
Pulmonary Vasculature ◽  
Drug Induced ◽  
Cell Lung Carcinoma ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Arterial

Introduction: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy histologically associated with remodeling of distal pulmonary arteries and right ventricular failure that is drug-induced in approximately 10% of cases. Recently, PAH induced by chemotherapeutic agents such as RTK inhibitors (e.g. dasatinib) has been described. Crizotinib is a new MET inhibitor increasingly used for the treatment of ALK-positive non-small cell lung carcinoma. Interestingly, crizotinib has been shown to induce endothelial cells (EC) dysfunction (e.g. inhibition of EC survival and angiogenesis) and is symptomatically associated with dyspnea and peripheral oedema in many patients, which are cardinal symptoms of PAH. We thus hypothesized that chronic administration of crizotinib exacerbates PAH. Material and results: We observed a significant increase of mortality rate in PAH rats (Sugen/hypoxia model) treated with daily oral administration of crizotinib (100mg/kg/d for 2 weeks) compared to rats treated with vehicle (6/group; p<0.05). Furthermore, we demonstrated that crizotinib treatment was associated with increases in right ventricular systolic pressure, mean pulmonary arterial pressure and pulmonary vasculature resistance; and decreases in cardiac output and stroke volume (right heart catheterizations in closed chest) compared to vehicle-treated rats with Sugen-induced PAH (4 PAH+crizotinib; 6 PAH+vehicle, 5 PAH and 3 control rats; p<0.05). Histologically, crizotinib administration significantly increased pulmonary arteries wall thickness as well as right ventricular fibrosis (p<0.05). Finally, crizotinib increased macrophage accumulation and size within the lungs of PAH rats (p<0.05). Conclusion: We documented for the first time that crizotinib treatment markedly increases vascular remodeling and macrophage activation with concomitantly marked PAH exacerbation in Sugen rats. This study could have major clinical relevance in the management of patients treated with crizotinib.

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